Clinical Pharma Part 2

CLINICAL VETERINARY PHARMACOLOGY LECTURE MANUAL/DR. ANNALIE B.
PARAGAS SY 2015-2016
5 FLUID THERAPY
Six questions to consider when instituting fluid therapy
a. When should fluid therapy be instituted?
b. What kind of solution should be used?
c. How much fluid should be administered?
d. How fast should the solution be given?
e. What route of administration should be used?
f. How to evaluate success of fluid therapy?
I. INDICATIONS
1. Dehydration - excessive loss of body water which may be due to hemorrhage, vomiting,
diarrhea, polyuria
a. Types
a. Hypertonic dehydration - results from loss of pure water or hypotonic fluid,
eg decrease water intake
b. Hypotonic dehydration - results from loss of hypertonic solution; there is
reduced osmolality of ECF, eg. Loss of blood, too much perspiration,
Addison's disease ( deficiency in glucocorticoids and mineralocorticoids)
c. Isotonic dehydration - results from loss of water and electrolyte in
proportion similar to ECF, eg. Loss of fluid from GIT.
2. Electrolyte imbalance
3. Acid-base imbalance
a. Metabolic acidosis
i. Extreme diarrhea - loss of NaHC03 via digestive juices
ii. Ketosis - associated with diabetes mellitus and starvation
iii.Chemical poisoning - ingestion of increased NaCl and NH3C1
iv. Circulatory collapse - shock
v. Congestive heart failure
vi. Severe infectious disease
b. Metabolic alkalosis
i. Excessive salivation
ii. Excessive alkaline therapy or use of diuretics
iii.Excessive loss of K+ due to hyperadrenocorticism
iv. Vomiting
c. Respiratory acidosis (retention of C02 due to alveolar hypoventilation)
i. Depression of medullary respiratory center, eg. Anesthetic overdose
ii. Airway occlusion
iii.Pneumonia, pulmonary edema, pneumothorax, emphysema
d. Respiratory alkalosis
i. Fever
ii. Heat prostration
iii.Salicylate intoxication
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CLINICAL VETERINARY PHARMACOLOGY LECTURE MANUAL/DR. ANNALIE B. PARAGAS SY 2015-2016
iv. Decrease oxygen

7. Nutritional imbalance
8. During the peri-anesthetic period
II. KINDS OF SOLUTIONS/FLUIDS
a. Crystalloids - are solutions containing small particles with molecular weight less than a
few 100 mw. Examples
1.Lactated Ringer's solution - an isotonic solution primarily used as rehydration
solution contains lactate which is converted by liver to carbonate
2.Ringer's solution - contains higher concentration of chloride compared to LRS,
hence it is an acidifying solution.
3.
5% Dextrose - is a hypotonic solution, contains only dextrose, no electrolytes,
used as maintenance solution, rehydration fluid for patient with cardiac disease
who cannot tolerate administration of soudium. Can be used in combination with
lactated ringer's solution or NaCl solution.
4.
0.9% Sodium chloride - or normal saline solution (Normosol); is an isotonic
solution which contains sodium and chloride. Indicated in animals with Addison's
disease.
5.
Hypertonic dextrose (10-50%) - is calorigenic solution, example Aminolytic.
Promotes urine flow in patients with oliguric acute renal failure. Given in larger
veins to immediately dilute the hypertonicity of the solution.
b. Colloids -are solutions with large molecules that do not readily cross wall; hence help
maintain intravascular fluid volume. Effective in increasing blood volume in cases of
bleeding or hypoalbuminemia.
1.
Hetastarch
2.
Dextran
Solutions to be used in specific conditions:
• Frequent emesis
• Severe diarrhea
• Plain dehydration
• Ketosis
• Renal insufficiency/ urethral obstruction Oliguria Polyuria
1. 5% Dextrose in Ringer's solution

2. D5LRS
3. 5% Dextrose in 0.3% saline
4. 25% Dextrose
• 10 ml/kg/hr - on succeeding hours or after urine flow is established
• 5-10 ml/kg/hr - under anesthesia
• 4 ml/kg/hr - for neonates
• 10-20 drops/min - IV drop for adults
• 60 drops/min - IV drop for neonate
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2. ROUTE OF ADMINISTRATION
a. IV - most versatile; for emergency situation
Problems:
Must use hygienic equipment and maintain aseptic technique
Some vein are hard to locate
Problem of maintaining of needle such that it will not be dislodged
Clotting and hematoma
Rapid IV administration may overload circulatory system, causing pulmonary
edema and death.
b. Subcutaneous
Rapid and easy to use, useful in very young animals
Not good for emergency cases
Use only non-irritating solutions - isotonic
When edema is present absorption will not occur
c. Intraperitoneal
Practical for large animal
May result to peritonitis and puncture of abdominal organs
d. Oral
a. Easiest, least dangerous; fluids can be administered without restrictions on
volumes tonicity and asepsis; not to be used when animal is vomiting.
3. EVALUATION OF SUCCESS OF FLUID THERAPY
1. Return to normalcy of clinical signs and other normal physiologic parameters.
BLOOD THERAPY
Six questions to consider when instituting blood therapy

a. When should blood therapy be instituted?
b. What kind of blood should be used?
c. How much blood should be administered?
d. Where to collect blood and how much?
e. How to evaluate success of fluid therapy?
INDICATIONS
iv.
Low blood protein (hypoproteinemia) as in severe parasitism or protein-losing
enteropathies.
v.
Low antibodies in the blood or immunodeficiency as in agamma or
hypogammaglobulinemia, in neonates which failed to suck colostrums.
vi.
Bleeding disorders such as in low blood platelets, absence of certain clotting factors.
vii.
Acute blood loss leading to hypovolemic shock.
viii. Severe anemia.
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KINDS OF BLOOD SOLUTIONS
1. Blood and blood components

• Whole blood - contains the plasma proteins, clotting factors including platelets,
red blood cells
a) Therapeutic use: Acute blood loss, concurrent anemia and
hypoprotenemia, clotting defects
b) Easy to collect and store. Stored blood is not as useful as fresh blood.
• Packed RBC - red cell fraction collected by centrifugation of whole blood. Useful
in treating anemia; reduces risk of overload. Reconstitute with equal volumes of
0.9% saline.
• Plasma
i. Types:
• Fresh plasma - contains colloids, active platelet and clotting
factors; useful in treating coagulation defects
• Frozen plasma can be stored for periods up to a year; serve as
source of colloids;
A) Collected from stored whole blood when the red cell
fraction is no longer viable
B) Useful in treating hypoprotenemia and maintaining normal
colloidal osmotic pressure.
d. Cryoprecipitate - formed from fresh frozen plasma that is thawed at refrigeration

temperature until a precipitate forms. Rich in factor VII and von Willebrands
factor indicated in patients with hemophilia and von Willebrands disease.
e. Platelet - collected from plasma shortly after centrifugation of fresh whole blood at
low G-force.
c. Plasma extenders
1.
Acacia (6% solution in 0.9% saline)
2.
Gelatin (6% solution of special gelatin of known molecular size and capable
of being retained in the circulation in a solution of 0.8% saline)
3.
Dextran - a neutral polysaccharide obtained by bacterial fermentation of
sucrose; could be toxic to the horse.
4.
Erythropoietin
d. Oxyglobin - purified bovine hemoglobin in lactated ringer's solution
1.
Doesn't contain red blood cells but a crosslink hemoglobin molecules
2.
Plasma half-life is 30 - 40 hours
3.
Provides oxygen carrying capacity and oncotic pressure, hence improves
oxygenation and provides volume expansion
III. BLOOD TYPING AND CROSSMATCHING
Blood typing (grouping) - is the identification of antigens expressed on the RBC surface.
a. Application of Blood grouping:
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i. Aid in matching of donor and recipients. Antibodies will form if an incompatible

transfusion is administered and these will lead to a serious or fatal reaction on
subsequent transfusions with the same blood type.
ii.Identify breeding pairs potentially at risk of producing hemolytic disease in their
offspring.
b. Predominant Blood group
i. Pig-A d. Sheep-B,R
ii.Cattle - J,B e. Horse - A,C,Q
iii.
Dog - DEA 1.1,1.2 and 7 f. Cat - A,B, AB
• Dogs have several 8 unique antigens on the surface RBC called Dog
erythrocyte antigen or Canine Erythrocyte antigen.
• DEA 1.1 and 1.2 are antigens that are most potent to stimulate antibody
production if transfused in animals that does not posses these antigens
on their own.
• DEA 7 is an antigen against which dogs can have naturally occurring
antibodies (isoantibodies) even if they have never been transfused
before.
Blood Crossmatching - is the mixing of plasma and cells from donor and recipient in order to
determine if the cells and plasma are compatible.
1. Method
a) Collect blood samples from donor and recipient
b) Allow to clot and get both serum
c) Resuspend the clotted erythrocytes with saline solution 9enough to make the
consistency of tomato juice)
d) Requires about 30 minutes to perform, agglutination of cells is the end point
of the cross match that indicates incompatibility.
e) Major test: one drop of donor cell suspension plus 2 drops of recipients
serum
f) Minor test: one drop of recipient's cell suspension plus 2 drops of donor
serum
IV. BLOOD COLLECTION AND TRANSFUSION
9. Criteria for Donor Selection

a. Should be of the same species as the recipient animal
b. Interspecies transfusion is possible and has been used in the past; however the
problems encountered were faster destruction of RBC and the greater
incidence of anaphylactic reactions.
c. Should be healthy, no blood disorders or infections (e.g. Heartworm or
ehrlichiosis, etc.)
d. At least 20 kg in dogs; 5-7 kg in cats with normal PCV
e. Closely related to the patient; with good temperament
f. Negative with DEA 1.1, 1.2 and 7 in dogs
g. Preferably from outside the herd if the problem is affecting the whole herd.
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h. Can be collected 10-15 ml/kg bw every two weeks

10. Blood collection
a. Materials and Methods (Improvised)
1.
Container: Sterilized glass or plastic bottle
2.Anticoagulant: sodium citrate (3 g/L of blood) dusted inside the container before
collection or 3.85% Na citrate solution add 10 ml of solution to each 100 ml
blood
b. Procedure
1.
Anesthesize or sedate the animal if necessary (there is no concern of
transferring sufficient sedative from donor to recipient via the transfused blood)
2.Common venoset plastic tubing may be used and cut as short as possible with
one end attached to a large bore needle (G12-14) and the other to a sterile
container containing anticoagulant.
3. Inset the needle into the preferred blood vessel (e.g. jugular vein) and let the
blood flow. Place a rope around the neck of the animal (choke-rope) to increase
the venous blood pressure. Swirl the bottle while being filled with blood to
ensure even distribution of the anticoagulant.
4. Filter the collected blood through sterile gauze to another sterile container
before administration to the recipient. This is to remove clots, debris or macro
parasites in the blood.
5.Blood can be stored at 4°C for 3 weeks. Blood not used immediately, the
plasma can be removed by centrifugation and stored frozen.
3. Computation for needed blood
Vol. of donor's
Blood (ml) = wt. of animal x blood vol/kg x (desired PCV - recipient's PCV
Donor's PCV
Normal Blood Volume: Dog = 85-90 ml/kg
Cat = 75-75 ml/kg
On the average, transfusion of 10-20 ml/kg will increase the PCV by - 10%
a. Rate of administration
i. Initial rate should be slow for 15 minutes ~1 - 5 ml/kg/hr, if animal does not show
reactions the rate can be increased
ii. Small animals (10 kg dog or 5 kg cat) = 5-10 ml/kg hr
iii.Large animals = 40-60 ml/kg/hr
b. Route of administration
i. IV - especially if the patient is in oligaemic shock
ii. IP - for shock, uncooperative patient, also for newborn calves and baby pigs with
isoimmune hemolytic anemia.
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i. Contraindications:ascites, peritonitis, anbdominal distensions, peritoneal

adhesions, recent abdominal surgery or abdominal distensions due to any
cause.
IV. EVALUATION OF SUCCESS OF BLOOD THERAPY
2. Length of usefulness of transfused RBCs

a) Two days in cattle; two weeks in swine
b) After these periods, the RBCs are destroyed either in the lungs or in spleen
or both and the breakdown products (Fe or Hb) are used to produced new
RBCs
c) In second transfusions, RBCs are destroyed with an hour because of the
immunity already developed by the recipient. A second transfusion is safe if it
is done within seven days after the first. Theoretically, the body needs seven
days or more to develop immunity.
3. Transfusion Problems
a) Blood incompatibilities - rarely encountered in initial transfusion; usually results from
second transfusion.
b) Signs of anaphylaxis:
Tachycardia Muscular trembling Hemoglubinuria

Dyspnea Hyperthermia Coughing
Salivation Abortion Lacrimation
Straining Arching of the back
c) Necropsy lesions are the same as those of animals, which dies of acute anaphylaxis
like pulmonary edema and subserosal petechiation
d) Agglutination or hemolysis. This is due to the presence of blood group substances in
the plasma (anti-a, anti-b, anti-R), which neutralizes injected antibodies before the
latter reach the erythrocytes.
Management of anaphylactic reaction

Discontinue administration of blood
Administer epinephrine (1:1000 solution); ruminants:0.2 - 0.03 mg/kg SC, IM, IV or 4-5
ml IM, or 0.2 - 0.5 ml IV in large animals
Avoid repeated transfusions; transfusion should not be restarted until it is proven that
adverse signs were not a result of hemolytic reaction
Avoid using A+ pig blood, J+ cattle blood, R+ sheep and A+ or C+ horse blood.
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6 INTRODUCTION TO CHEMOTHERAPY
Objectives:
1. To discover the different chemotherapeutics drugs for veterinary use.
2. To classify the chemotherapeutic drugs according to its mode of action,

pharmacokinetics and indications for specific diseases in veterinary medicine.
3. To be familiar in the adverse effects/toxic effects of these drugs.
CHEMOTHERAPY is a branch of pharmacoIogy dealing with drugs that seiectively inhibit or

destroy specific agents of disease such as bacteria, viruses, fungi, protozoan, worms,
arachnids and insects and necplastic cells.
CHEMOTHERAPEUTIC AGENT or anti-infective agent is a drug used for chemotherapy. They

have a selective toxicity, a property of a substance of being more harmful to certain living
organism but not to others.
Examples:
Antibacterial – vs. bacteria
Antiviral – vs. viruses
Antiprotozoan – vs. protozoans
Antifungal (antimycotic) – vs. fungi
Anthelmintics – vs. parasitic worms
Antineoplastic (anticancer) – vs. neoplastic cells
Antimicrobial – a natural or syntheuc drug that acts against microorganism of one or more kinds
AntibiotIc – a substance produced by various species or microorganism (bacteria, fungi, yeast,

etc). which inhibits the growth of another microorganism
THE CHEMOTHERAPEUTIC TRIAD
ANIMAL
CHEMOTHERAPE
UTIC AGENT PATHOGEN
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An effective antimicrobial therapy requiresknowledge of the chemotherapeutic triad,

which consists of the host (patient), the pathogen (disease-causing organism) and the drug
(chemotherapeutic agent), and how they interact with each other.
The pathogen initiates the infection to the host hence stimulating immune response and
disease if unabated; this would necessitate the use of drugs which the pathogen can be
susceptible or resistant. Culture and identification of the organism and antibiotic sensitivity
testing may be necessary to facilitate antibiotic selection.
The drug can act on the pathogen and cause eradication, inhibition of growth, or
selective pressure on it. Dosage regimen and proper route of administration should be selected
to ensure rnaintenance of therapeutic drug levels in affected tissues that can minimize adverse
effects on host such as toxicity, allergy, biological alteration, and immunosuppression.
The host’s physiopathological status is also important to take note because the excretion
and biotransformation of drug relies on this as well as its immune mechanism to resolve the
disease.
PRINCIPLES OF ANTIMICROBIAL THERAPY
Requirements for Successful Antimicrobial Therapy
1. Correct clinical diagnosis

a. Successful therapy requires specific diagnosis, but a reasonable preliminary
diagnosis is often all that is possible initially.
b. Examination of direct smears with Gram stain is also hepful to establish at least the
general type of pathogens involved in the infeclion.
c. Treatment should be aimed at a specific pathogen whenever possible. However,
mixed infections do occur and pose problems in therapy.
d. Conclusive microbial diagnosis oftentimes is difficult, the treatment may be based on
past clinical experience that is a clinician may diagnose an infection by an “educated
guess”.
2. Appropriate choice of chemotherapeutic agent

a. The antibiotic to use for particular bacterial infection must be one, which the infecting
organism is sensitive. Antibiotic sensitivity test provides a sound foundation from
which to proceed with the selection of appropriate antibacterial drugs.
b. Sensitivity test takes time and may not be too important in emergency cases. It is not
always advantageous to wait for the result of bacterial culture and of sensitivity test
before starting an antibacterial therapy.
c. Pseudosensitivity may also occur. This is the occurrence of susceptibility of an
organism to antimicrobial agent in vitro which can not be demonstrated in vivo. This
nay be due to local factors that affect the pharmacokinetics of the agent.
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d. In selecting appropriate antibacteriaal drugs, it is best to consider the following:

i. Probable microorganism involved in infection
ii. Result of sensitivity test (if any)
iii. Pathogenicity of the organism involved
iv. Presence and nature of pathological lesions
v. Acuteness of infection
vi. Pharmacokinetics (physiological disposition) of the drugs
vii. Potential drug toxicity
viii. Organic dysfunction in the host
ix. Drug interactions
x. cost of treatment (especially in treating food animals)
3. Appropriate dosage regimen must be given
a. The dose and frequency of administration must achieve adequate therapeutic levels
at the site of infection for a sufficient period without causing side effects.
b. The dose schedule must be followed for 3 to 5 days or longer to ensure elimination
of pathogens, and to prevent relapse.
c. The drug must be available at the site of infectioni n a concentration above the
minimum inhibitory concentration (MIC) of the drug for the bacterial species involved.
The MIC for an antibacterial for one species may not be the same for another
species.
i. Minimum Inhibitory Concentration (MIC) – the lowest dilution of drug that
prevents visible growth in broth or agar after 18-24 hours of incubation
ii. Minimum Bactericidal Concentration (MBC) – the lowest concentration
dilution of drug that sterilizes the medium or results in a 99.9% decline in
bacterial count
iii. Post-antibiotic Effect (PAE) – inhibition of growth after the antibiotic level
falls off below the MIC
iv. Breakpoint of antimicrobial agent – is the plasma concentration above which
the host is likely to experience toxicity and is dependent on the
pharmacokinetics of the antibiotic in the host
4. Supportive therapy and ancillary treatment
a. Fluid therapy
b. Warmth
c. Rest
d. Good nutrition
Essentials for a successful Antimicrobial Therapy
1. Drug must come in contact with the microorganism

2. Drug must be present in high enough concentration
3. Drug must be present for sufficient length of time
4. The microorganism must be sensitive to the drug
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Reasons for Failure of Antimicrobial Agent
1. Wrong diagnosis was made

2. Organism not susceptible to antibiotic
3. Mixed infection was present and antibiotic is insufficient or ineffective
4. Combination of incompatible antibiotic was administered resulting to decrease
antimicrobial effect
5. Superinfection by a resistant opportunistic pathogen
6. Re-infection by a resistant opportunistic pathogen, by original or other pathogenic
bacteria
7. In surgical infections, drainage was inadequate or foreign body was present
8. Reduction of effectiveness of antibiotic and sulfonamides duen to some changes like
hypoxia, acidosis, accumulation of tissue debris, inflammation, tissue destruction,
abcessation, etc.
9. Defense mechanism of the patient were jeopardized by disease and concurrent therapy
10. Inappropriate route of administration or incorrect dosage side effect
11. Expired or substandard products were used
12. Selected agent had to be withdrawn because of advrse side effects
13. Supportive therapy and nursing care were inadequate
14. Nutritional deficits and predisposing management factors were not corrected
Possible Effects of Antibacterial Therapy
1. No effect
2. Superinfection – new infection arising from the use of broad spectrum antibacterial
3. Induction of bacterial resistance to drugs
4. Toxic effects or adverse reaction with other drugs or with nutrients
5. Allergy
6. Drug residue in animal tissue
7. Bactericidal or bacteriostatic effect
Bacterial Resistance to Antibiotics
Type of Resistance
1. Intrinsic resistance mechanisms are inherited properties of a given species of bacteria

that are based on lack of either antimicrobial target sites or accessibility to them. Ex.
Gram negative bacteria are resistant to penicillin because the latter attack only the cell
wall which gram negative organism lacks
2. Acquired resistance mechanism is based on the alteration of genetic make up of an
organism and become resistant to chemotherapeutic drugs. Result in changing patterns
of sensitivity for many microorganisms hence antibiotic sensitivity testing is a
requirement in the treatment of infection
a. Exchange of genetic information:
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i. Mutation – is a random event where the bacterial chromosomal mutation

may confer resistance when a particular drug’s use is widespread
suppressing the susceptible bacteria hence resistant bacteria predominates.
ii. Transduction – transference of drug-resistant gene by a bacteriophage, it is
particularly important in the transfer of antibacterial resistance among strains
of Staphylococccus aureus
iii. Transformation – this involves the incorporation into bacteria of DNA that is
contained in the environment or release following lysis of resistant organism
iv. Conjugation – is a type of reproduction in which genetic material is
transferred from cell to cell via pillus, which is encoded by a resistance
transfer factor on a plasmid
Mechanism of Bacterial Resistance
1. Enzyme production – organism may produce enzymes via constitutive or inducible

processes that inactyivate the drug
2. Decreased cell wall permeability – this will limit the uptake of drug by the organism
3. Active transport – this will increase the release of drug from the organism
4. Alteratlon of drug receptor – or binding site may result in reduced drug affinity
5. Development of alternative pathways – or synthetic pathways to by-pass or repair the
effects of antimicrobial agents
Combination Therapy
1. Treatment with antimicrobial combinations may be necessary in certain cases. The

administration of 2 or more agents may he beneficial for the following reasons:
a. To treat mix bacterial infections
b. Therapy of severeinfections in which specific cause in unknown
c. Enhancement of antibacterial activity in the treatment of specific infections
d. Prevention of the emergence of resistant microorganism
e. Minimize toxicity in rationally combined drugs
2. Guidelines for combination therapy
a. Generally only antibiotic with similar efficacy should be combined
b. Agents should act at different sites to avoid competing on the same enzyme and
substrate
c. The antibacterial with the narrowest spectrum should be chosen. This induces
selecton pressure for resstance to broad spectrum agents
CLASSIFICATION OF ANTIBACTERIAL AGENTS
1. Spectrum of activity
a. Narrow spectrum – effective only with gram positive or gram negative organism
b. Broad spectrum – effective with both gram positive and gram negative organisms
2. Effect on bacteria
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a. Bactericidal – kill bactena at the minimum inhibitory concentration

i. These agents are more prone to causing superinfection because they may kill
off normal bacterial flora, which normally inhibits pathogens
b. Bacteriostatic – inhibit bacterial growth and replication
i. The normal defense mechanism of the patient must participate in eliminating
infectious bacteria
ii. Bacteriostatic agents may antagonize the action of some bastericidal agents
iii. They may become bactericidal when very high doses are given or when high
concentrations are attained in certain body compartment such as the urinary
tract, but toxic effects on the patient may appear
c. Bacteriolytlc cause dissolution of bacterial cells
3. According to mechanism of action
a. Inhibition of cell wall synthesis
b. Dsruptors of cell membrane
c. Inhibitors of protein synthesis
d. Inhibitors of nucleic acid functions
e. Inhibitors of folate cofactor synthesis
CLASSIFICATION OF ANTIBIOTICS
A. Inhibitors of CelI wall Synthesis

Penicillin Gram (+) cocci and bacilli Bactericidal
Cephalosporins Broad spectrum
Bactericidal
Bacitracin Gram (+) cocci and bacilli Bactericidal
Vancomycin Gram (+) cocci and bacilli Bactericidal
Cycloserine Gram (+) cocci and bacilli Bactericidal
B. Impairment of Cell Membrane

Polymixin B Gram (-) bacilli Bactericidal
Colistin Gram (-) bacilli Bactericidal
Tyrothricin Narrow spectrum Bactericidal
Gramicidin Narrow spectrum Bactericidal
Amphotericin B Broad spectrum Bactericidal
Nystatin Broad spectrum Bactericidal
C. Inhibition of Protein Synthesis

Aminoglycosides
Streptomycin Gram (-) bacilli Bactericidal
Dihydrostreptomycin Gram (-) bacilli Bactericidal
Neomycin Broad spectrum Bactericidal
Gentamicin Broad spectrum Bactericidal
Kanamycin Broad spectrum Bactericidal
Apramycin Gram (-) bacilli Bactericidal
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Spectinomycin Gram (-) bacilli Bacteriostatic

Tetracycline Broad spectrum Bacteriostatic
Macrolide
Tylosin Gram (+) cocci and bacilli Bacteriostatic
Erythromycin Gram (+) cocci and bacilli Bacteriostatic
Spiramycin Gram (+) cocci and bacilli Bacteriostatic
Oleandomycin Gram (+) cocci and bacilli Bacteriostatic
Carbomycin Gram (+) cocci and bacilli Bacteriostatic
Lincosamide
Lincomycin Gram (+) cocci and bacilli Bacteriostatic
Clindamycin Gram (+) cocci and bacilli Bacteriostatic
Tiamulin Gram (+) Bacteriostatic
Virginiamycin Gram (+) Bacteriostatic
D. Inhibitors of nucleic acid

Quinolones Broad spectrum
Bactericidal
Enrofloxacin Bactericidal
Oxolinic Acid Bactericidal
Nalidixic Acid Bactericidal
Novobiocin Gram (+) spectrum Bacteriostatic
Rifamycin Broad spectrum Bactericidal
Nitrofurans Broad spectrum Bacteriostatic
Nitrofurazone
Furazolidone
Furaltadone
E. Inhibitors of Folate Cofactor Synthesis

Sulfonamides Bacteriostatic
Sulfonamide-Trimethoprim Broad spectrum Bactericidal
Trimethoprim Bacteriostatic
Sources of Antibiotics
Apramycin S. tenebrarius
Bacitracin Bacillus subtillis
Cephalosporins Cephalosporium acremonium
Chloramphenicol S. venezuela
Chlortetracycline Streptomyces aureofaciens
Erythromycin S. eythreus
Gentamicin Micromonaspora purpurea
Kanamycin S. kanamyceticus
Lincomycin S. lincolnensis
Neomycin/Tylosin S. fradiae
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Novobiocin S. niveus
Oleandromycin S. antibioticus
Oxytetracycline Streptomyces rimosus
Penicillin Penicillium notatum; P. chrysogenum
Polymixin B B. polymyxa
Spectinomycin S. flavopersicus
Streptomycin Streptomyces griseus
Thiostrepton A. aureus
Tyrothricin Bacillus brevis
Virgiamycin S. virginal
Virginiamycin S. virginiae
Study questions?
1. What is the difference of antibiotic and antimicrobial agents?

2. What are the essentials for successful antibicrobial therapy?
3. What are the factors to consider before choosing an antimicrobial agent?
4. What are the risks with the use of antimicrobial agents?
5. Give one antibiotic and describe its mechanism of action.
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7 PENICILLINS
Penicillins were first produced from Penicillium notatum and were the first antibiotic
available for clinical use. Today, penicillin group of antibiotics represent a large group of
compounds. Only the primary one used in veterinary medicine are covered in this lesson.
Chemistry
1. Penicillins comprise a beta-lactam ring and a thiazolidone ring, attached to amide bond
side chain
2. Cleavage of beta-lactam ring by β-lactamase (penicillinase) destroys antibiotic efficacy
3. Cleavage of the amide bond side yields 6-aminopenicillinic acid (6-APA) nucleus
producing semisynthetic penicillin
Mechanism of Action
1. Penicillins bind to and inhibt the transpeptldase enzyme involved in the crosslinlthng of
peptide-glycan chain of the bacterial cell wall. This is the third and final step in cell wall
synthesis
a. The 1st step of cell wall synthesis is formation of precursors N-acetylglucosamine
(NAGA) and N-acetylmuramic acid (NAMA)
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b. The 2nd step is formation of peptidoglycan chain

2. Loss of cell wall rigdity in the presence of normal high intracellular osmotic pressure
causes lysis of bacterial membrane
3. Penicillin also inhibits other peptidases (penicillin-binding proteins) involved in cell wall
synthesisand blocks inhibition of autoluysins
4. It is bactericidal. Growing bacteria and metabolically active bacterial cells are most
susceptible to this effect
Fig. 1. Companson of the structure and composition of gram (+) and gram (-) cell walls. Stages
of cell wall synthesis are: formation of building blocks; formation of paptidoglycan chain; and
cross-linking chains.
Spectrum of Activity and Therapeutic Uses
1. Natural penicillins
a. Penicillin G (Benzylpenicillin)
b. Penicillin V (penoxymethylpenicillin)
c. They have narrow spectrum of activity, affect gram (+), non-penicillinase producing
pathogens
Streptococcus Staphylococcus Listeria
Erysipelothrix Corynebacterium Clostridium
Bacillus Actinomyces
d. Used in the treatment of Gram-negative infections of the urinary tract. Penicillin G
attains higher plasma concentration in urine. For this reason, it may be useful in the
treatment of urinary tract infection with susceptible bacteria.
2. Penicillinase-stable penicillins
a. Cloxacillin Oxacillin Dicloxacillin
b. Methicillin Nafcillin Quinacillin
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c. Their use is generally restricted to infections caused by penicllinase-producing

bacteria (e.g. Staphylococci)
d. Less active against other Gram (+) bacteria than Penicillin G
e. Clavulanic acid, Sulbactam and Tazobactam are substances that serves as false
substrate for penicillinase. It can protect a penicillin from destruction by penicillinase.
These substances have been combined with amoxicillin, ticarcillin and other penicillin
3. Broad spectrum penicillin

a. Amoxicillin, Ampicillin, Hetacillin affects some Gram (-) aerobic bacteria (E. coli,
Haemophilus. Proteus) but not good for Klebsiella and Pseudomonas. They are acid
stable but not penicillinase-stable
b. Carbenicillin, Indanyl carbenicillin, Ticarcillin are specifically active aganist
Pseudomonas. Can be combined with tobramycin or gentamycin
c. Piperacillin, Azlocillin, Mexlicillin have very broad spectrum of activity; effective
against many gram (-) and gram (+) bacteria including Psuedomonas, Enterobacter
and Klebsiella
Pharmacokinetics
1. Absorption
a. Acid- stable penicillins (Penicillin V, Ampicillin, Amoxicillin, Hetacillin, Oxacillin,
Cloxacillin and indanyl salt of Carbenicillin) are well absorbed orally .
b. Penicillin G, Methicillin, Ticarcillin are acid-labile hence poorly absorbed in the gut.
c. Procaine Penicillin G are slowly absorbed from IM injection and provide therapeutic
levels for 24 hours with single dose, benzathine PCN is even more slowly absorbed
over 48-72 hours. Na or K PCN G may be administered IV or IM q4-6 hours.
2. Distribution
a. They are weak acids with pKa of about 2.76 and tend to distribute into the
extracellular fluid, joint fluid, plueral fluid, pericardial fluid and bile. Low
concentrations are attained n prostate, brain, intraocular fluid and phagocytic cells
b. Inflammation allows entry of penicilfln to blood-brain barrier, placenta and mammary
barriers.
3. Excretion
a. Penicillins are excreted unchanged by renal mechanism, especially by glomerular
filtrationand active tubular secretion. Tubular secretion is inhibited by a competitor
(weak acid) substance such as probenecid.
b. Sufficient concentration of penicillin in urine is needed to affect urinary tract infection
caused by Gram-negative bacteria.
68
c. Some are metabolized by the liver to penicilloic acid derivatives, which may act as
antigenic determinants in penicillin hypersensitivity
Adverse Reactions
1. Allergic reactions ranging from delayed hypersensitivity skin reaction to acute

anaphylaxis may occur. Species most susceptible to allergic reactions are hamsters and
guinea pigs.
2. CNS toxicity occurs with intrathecally administered penicillin G.
3. Nephro-toxicityhave been reported with the use of methicillin in human, may also occur
in animals.
4. Superinfections are most likely to occur with broad-spectrum penicillins. Mild cases of
superinfection results in diarrhea. Overgrowth of toxin-producing bacteria can cause
death. Penicillins are contraindicated in herbivores such as guinea pigs, hamsters,
rabbits and chinchillas for this reason.
Drug Interactions
1. PCN + Chloramphenicol/Tetracycline/bacteriostatic abc = may reduce efficacy of PCN

2. Aspirin/Phenylbutazoneand Sulfonamide can displace PCN at plasma binding sites
3. Presence of food at the GIT decreases the absorption of PCN
Bacterial Resistance
1. Inactivation by bacterial production of beta-lactamase is the most common mechanism

of resistance
2. Alteration in the structure of penicillin-binding proteins result in failure of drug to bind
Dose Rates
Amoxicillin Dog/cat: 20-30 mg/kg PO q8-12h
Poultry: 20 mg/kg in drinking water
40 mg/kg in feeds for 10 days
Amoxicillin trihydrate Horse: 10 mg/kg IM q12h
Ampicillin Dog/cat: 20-30 mg/kg PO q8h
Ampicillin sodium 10-20 mg/kg IM, IV q6-8h
69
Benzathine penicillin 40,000 IU/kg q72h for highly sensitive only
Carbenicillin Dog: 50 mg/kg IM, IV q6-8h
Clavulanic acid-amoxicillin Dog/cat/calf: 14 mg/kg PO q12h
Cloxacillin 40 mg/kg PO, IM q8h
Flucloxacillin Dog/cat: 25 K IU/kg PO q6h
Oxacillin 40 mg/kg IM q8h
Penicillin G sodium 10,000-20,000 IU/kg IV, IM q6h
Ticarcillin 50-75 mg/kg IM, IV q6-8h
Study questions?
1. Who discovered Penicillin and from what source?

2. What is the mechanism of action of Penicillin?
3. Why penicillin can’t be combined with bacteriostatic agents?
4. Describe the pharmacokinetic properties of penicillin?
5. Give clinical indication of Penicillins?
70
8 CEPHALOSRORINS
The cephalosporins were isolated from fungus Cephalosporium acremonium in 1945.

It was isolated from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu.He noticed
these cultures produced substances that were effective against Salmonella typhi, the cause of
typhoid fever, which had beta-lactamase. Since then many derivatives have been developed
with increasing spectrum of activity against many bacteria.
Chemistry
1. The cephalosporins contain a β-lactam ring like the penicillins, but the adjacent ring is
the 6-membered instead of 5-membered
2. The active nucleus of most cephalosporins is 7-aminocephalosporanic acid
Mechanism of Action
1. Similar to Penicillins, cephalosporins inhibit the 3 rd stage of cell wall synthesis by

inhibiting the transpeptidase enzyme, hence are bactericidal
Spectrum of Activity and Therapeutic Use
1. First generation
Oral Parenteral
Cefadroxil Cephaloridine
Cephalexin Cephapirin
Cephaglycine Cephalothin
Cephradin Cephalozine
a. They are the firstalternatives to Penicillins for treating infections caused by gram (+)
aerobes
b. Frequently employed for for antibiotic prophylaxis and treatment of bone and soft
tissue infection due to their good penetration to these organs
c. Not effective against anaerobes; susceptible to β-lactamases (cephalosporinase)
produced by gram (-) bacteria
2. Second Generation
Oral Parenteral
Cefachlor Cefuroxime
Cefoxitin
Cephoxazole
Cefamandole
71
a. Broader than the first generation which includes gram (-) pathogens. The spectrum
also includes: most strains of Klebsiella, Proteus providencia and Enterobacter
b. Enterococci, Pseudomonas, Actinobacter are resistant
c. They are more resistant to gram (-) β-lactamase and are effective against species
that are resistant to the first generation
3. Third generation
Oral Parenteral
Cefmenoxime Cefotaxime
Ceftazidime Cefsulodine
Ceftizoxime Ceftiofur
Ceftriaxone Moxalactam
a. Have extended spectrum against gram (-) organism, are resistant to β-lactamase
b. Wide activity against gram (-) bacteria including Pseudomonas, Proteus vulgaris,
Enterobacter and Citrobacter
c. Able to penetrate blood-brain barrier and are indicated in gram (-) meningitis
d. Ceftiofur is used in the respiratory diseases in cattle
4. Fourth generation
Flomoxef and latamoxef are in a new class called oxacephems
Pharmacokinetlcs
1. Absorption
a. Cephalexin and cafadroxil are acid stable and are well absorbed orally
b. All other cephalosporins must be administered parenterally; some may be given SC
or IM.
2. Distribution
a. They distribute well to the extracellular fluid, reaching therapeutic levels in most
tissues and fluids, including the pericardial fluid, pleural fluid and infected bones
b. Like Penicillin, absence of acute imflammation, cephalosporins do not reach useful
levels in the CSF
c. Cefuroxime, moxalactam, cefotaxime and ceftizoxime penetrate into the CSF in
insufficient concentration to treat meningitis
3. Elimination
a. Metabolismi s minimal. Most cephalosporins are excreted unchanged in the urine by
glomerular filtrationand tubular secretion
b. A few are metabolized by the liver through de-acetylation
Advese Reactions
72
1. Hypersensitivity and allergic reactions are most common. It can be an immediate

reaction, anaphylaxis, bronchospasms or urticaria. Cephalosporins may have cross
reactivity with penicillin hypersensitivity
2. Renal toxicity manifest as renal tubular necrosismay develop with prolonged
administration
3. Other toxicities: gastrointestinal disturbances; local irritation and pain from IM injection;
thromboplebitis from IV injection; drug fever
1. Bacterial β-lactamaseproduction may confer resistance, although ceplalosporins are less

susceptible than penicillin
Dose Rates
Cephalexin Cattle: 7 mg/kg IM daily
Sheep/pig: 10 mg/kg IM daily
Dog/cat: 10-15 mg/kg oral BID
Horse: 10 mg/kg q8-12h IM, IV
Cefadroxil Dog/cat: 22 mg/kg q12h PO
Calves: 12 mg/kg q12h oral
Cefachlor Calves: 3.5 mg/kg q12h PO
Study questions?
1. What is the natural source of cephalosporins?

2. How do penicillin and cephalosphorins differ?
3. Can cephalosporins be combined with bacteriostatic agents?
4. Give clinical indication of cephalosporin.
73
9 BACITRACIN, VANCOMYCIN AND

POLYMIXINS
BACITRACIN
Bacitracin is a liable polypeptide compound isolated from a strain of Bacillus subtilis from a
contaminated compound fracture of a girl named Tracy.
Mechanism of Action
1. Bacitracin inhibits the second step of bacterial cell wall synthesis by blocking
phosphorylase reaction inhibiting peptidoglycan synthesis
2. It is bactericidal
1. Bacteria, susceptible to Bacitrcin include: gram (+) cocci and bacilli; staphylococci
including β-lactamase producers and group A Streptococci; Clostridium, Actinomyces
and Fusobacterium. Spirochetes are susceptible
2. Since it is not absorbed orally, it is used for gut sterilaization before gastrointestinal
surgeryand treats clostridial enteritis
3. It is mainly for topical application for superficial infection of the skin and mucous
membrane and is often combined with polymixin B or Neomycin for this purpose
Pharmacokinetics
1. Bacitracins are not orally absorbed. It is too nephrotoxic for systemic use.
Dose Rates
Zinc Bacitracin Calves/Lambs/pigs: 5-50 g/ton of feed (up to 16 weeks of age); 5-

20 g/ton of feed (16-24 weeks of age); 5-80 mg/ton of feed ( (for
addition to milk replacer)
Zinc Bacitracin Layer Hens: 15-100 g/ton of feed
Broiler chickens/turkeys: 5-50 g/ton of feed (up to 4 weeks of age);

5-20 g/ton of feed (5-26 weeks of age)
74
VANCOMYCIN
Vancomycin, a high-molecular weight glycopeptides, is a fermentation product of

Streptomyces orientalis.
Mechanism of Action
1. Vancomycin blocks the second step of bacterial cell wall synthesis by inhibiting the
transfer of the glycopeptides chain from the phospholipid to the acceptor site during
bacterial cell wall synthesis.
2. Bactericidal in action.
Spectrum of Activity and Thenpeutic Use
1. Bactericidal to most gram (+) aerobic cocci and bacilli

2. Vancomycin ic a reserve antibiotic used intravenously for rnethicillin-resistant
staphylococcal infaections of bone and soft tissue in dogs and cats.
Pharmacokinetics
1. Vancomycin may be administered IV as hydrochloride. It is not absorbed orally.

2. It is distributed to ECF and trancellular fluid
3. Excreted unchanged by glomelular filtration.
Adverse Reactions
1. Nephrotoxic and ototoxic in high doses

2. In humans the adverse effects include hvpersensitivity skin reavtion, pain (IM),
histamine-like reactions (rapid IV)
Dose rates
Vancomycin 20 mg/kg ath interval diluted in at least 200 ml of 5% dextrose

solution
5-10 mg/kg PO BID
75
Study questions?
1. What is the source of bacitracin and vancomycin?

2. How do theseanantibiotics differ with penicillin in terms of mechanism of action?
3. What are the clinical indication of bacitracin and vancomycin, since they are
nephrotoxic?
4. Describe the pharmacokinetic properties of both.
POLYMIXINS
The poIymixns are polytpeptide antibiotic isolated from soil bacteria Bacillus polymyxa. Many
polymixins have been isolated and been named A, B, C, D, E. Polymixin B and E (also called
Colistin from B. colistinus) are the only once used clinically.
Mechanism of Action
1. The polymixins interacts with phospholipid in cell membrane to produce a detergent-like

effect and membrane disruption.
2. They alter osmotic pressure, selective permeability and regulatory properties of cell
membrane resuiting in cell death, hence it is bactericidal.
3. They may be combined with bacteriostatic drugs since their action does not require rapid
multiplication of bacteria
4. They may also have anti-endoloxin and antlpyretic effects. As basic (cationic) drugs,
they may combine with endotoxin, which is anionic.
1. The spectrum of activity of the polymixin is narrow-primarily gram (-) bacteria:

Aerobacter, E. coli, Hemophilus, Klebsiella, Pasteurella, Pseudomonas, Salmonalla,
Shigella
2. Proteus and Serratia spp are resistant
3. They have a synergistic action with tetracyclines chloramphenicol, sulfamethoxazole and
carbenicillin against P. aeroginosa
4. The major clinical application in veterinary medicine: Oral treatment of E. coli and
Salmonella diarrhea; local treatment of Pseudomonas infection such as otitis externa
and superficial lip infection.
Pharmacokinetics
1. Poorly absorbed from the gut and through the skin and mucous membrane but
absorption is rapid following IM and SC administration
76
2. They distribute within the extracellular fluid only, but do not get to the CSF
3. They bind to kidney, liver, lung, heart and skeletal muscle
4. They are excreted unchanged by the kidneys over several days
5. Polymixin B as sulfate is for both oral and parenteral use.
6. Colictin as sulfate is for oral administration and sulfomrthate for parenteral
Adverse Reaction
1. Nephrotoxicity in the form of reduced tubular perfusion may decrease urine output
2. Neurotoxicity such as central nervous depression, anorexia, dose-dependent curare-like
paralysis which is additive with other drugs acting on the neuromuscular junction.
3. Respiratory paralysis due to rapid IV injection
4. No adverse effects have been reported when they are used topically or orally.
Dose Rates
Polymixin B Cow with severe coliform mastitis: 2.5 mg/kg IM
Other animals : 2.5 mg/kg IV q12h; 5 mg/kg PO q12h
Colistin sulfomethate 3 mg/kg IM q12h
Colistin sulfate 5-10 mg/kg oral
Study questions?
1. What is the source of Polymixin?

2. How does its mechanism of action differ from the previous antibiotic?
3. What are the advantages of this antibiotic over the previous antibiotic?
4. Describe the pharmacokinetic properties of both polymixins.
77
10 SULFONAMIDES AND POTENTIATED

SULFONAMIDES
SULFONAMIDES
The sulfonamides are one of the oldest groups of antimicrobial compound. Sulfanilamide, was
the first sulfonamide used clinically. It was derived from azo dye Prontosil, and all sulfonamides
produce structurally resemble it.
Chemistry
1. Sulfonamides are derivatives of p-aminobenzene sulfonic acid and are structurally

related to p-aminobenzoic acid (PABA), an intermediate in the bacterial synthesis of folic
acid
2. Folic acid is important in folic acid synthesis, protein synthesis and microbial replication,
hence they can inhibit growth and are therefore bacteriostatic
1. The spectrum of activity of sulfonamides is broad affecting gram positive and negative
and many protozoal organisms
2. Sulfonamides are commonly used antimicrobials to treat infections of the CNS,
respiratory tract and gastrointestinal tract and particularly urinary tract
3. Preparations:
i. Sulfadimethoxine – long acting therapeutic levels are maintained for 24 hours with
single dose, commonly used in all species for the treatment of systemic and soft
tissue infections and coccidiosis
ii. Sulfamethazine – is used in cattle, sheep and swine in the treatment and
preventions of respiratory infections and to promote growth in swine
iii. Sulfathiazole – used as feed and water additive to treat respiratory and enteric
diseases
iv. Sulfisoxazole and Sulfamethoxazole – are primarily used to treat urinary tract
infections in small animals. Rapidly excreted and very soluble, high concentration
can be achieved in urine with less danger of crystalluria
v. Sulfacetamide – is the only sulfonamide that can be prepared as sodium salt at a
neutral pH and thus beneficial in the treatment of ophthalmic infections
vi. Sulfasalazine – used in the treatment of enteric diseases in dogs and cats
vii. Sulfaguanidine, Sulfaquinoxaline – used in the treatment of gastrointestinal
problems. Good for coccidiosis
viii. Potentiated Sulfonamides – combinations of sulfonamide with trimethoprim or
omethoprim (see below)
78
Pharmacokinetics
1. Absorption
a. Rapidly absorbed from oral administration except sulfathiazole
b. Sulfonamides given parenterally are buffered to reduce perivascular reaction due to
inherent alkalinity of most sulfas
2. Distribution
a. Widely distributed in the body especially in soft tissues including CNS, CSF, joints.
Some have high protein binding ability which increases their half-life
b. Limited distribution in the milk
3. Metabolism and excretion
a. Metabolism by acetylation at the p-amino group and glucoronide conjugation occurs
in most species
b. Unchanged metabolites are excreted via glomerular filtration, active secretion and
passive tubular reabsorption
Adverse Reactions
1. Renal crystalluria, the result of sulfonamide precipitation in neutral or acidic urine

a. This condition occur in large or prolonged doses and inadequate water intake
b. To prevent this problem, pharmaceutical modification has been developed
i. addition of sodium salts (monosodium salt given IV, disodium salt given IM, IP)
ii. use of triple sulfa, comdination of three sulfonamides
iii. Do not use with calcium containing solutions
iv. Alkalinization of urine
2. Keratoconjunctivitis sicca, observed in dogs treated with sulfadiazine
3. Hypothrombinemia, thrombocytopenia, and anemia, hence are not used in animals
with bleeding problems
1. Increase PABA production

2. Decreased affinity of sulfonamide for dihydropteroate synthetase
3. Bacterial metabolism of sulfonamide
79
Dose Rates
Species Initial dose Maintenance Route and

mg/kg frequency
Sulfathiazole Horse, cattle, sheep, 66 66 PO q8h

pig
Sulfamethazine Cattle 220 110 PO, IV q24h
Sulfadiazine All 50 50 PO q12h
Sulfadimethoxine All 55 27.5 PO q24h
Sulfapyridine Cattle 132 66 PO q12h
POTENTIATED SULFONAMIDES
Diaminopyrimidines can potentiate sulfonamides. Sample compounds are Trimethoprim,

Diaveridine, Ormetoprim. They are commonly combined with sulfadiazine, sulfamethoxazole
and sulfachlorpyridazine.
Mechanism or Action
1. The combination results to a synergistic action via sequential blockade of folate

synthesis
2. Trimethoprim inhibits dihydrofolate reductase and thus blocks the formation of
tetrahydrofolic acid from dihydrofolic acid.
Spectrum of activity and Therapeutic uses
1. The combination of trimethoprim and sulfonamide has a broader spectrum of activity and
has a reduced rate of development of bacterial resistance
2. Most sensitive are E. coli, Streptococcus, Salmonella, Pasteurella, Shigella,
Actinomyces, Nocardia and some protozoan parasites
3. Pyrimethamine, diaveridine, and omethoprim may potentiate sulfonamides against
coccidian and protozoan parasites
Pharmacokinetics
1. Trimethoprim is well absorbed orally and much faster than sulfonamides. But it can be
degraded by ruminal fluid
2. It has greater tissue distribution than sulfonamides. High concentration is attained in
tissues especially in the lungs, kidneys, CSF, joint fluid, bone, prostate glands and eyes
80
Adverse Reactions
1. Problems arising from use of sulfonamides may also arise with the potentiated sulfa,
however, it may be lesser
2. Trimethoprim may cause clinical signs of folate deficiency in animal that are borderline
folate deficient
Dose Rates
Trimethoprim – sulfadiazine 15 mg/kg PO q12h

15 -50 mg/kg PO, IV, IM q24h
Trimethoprim – sulfadoxine 16-24 mg/kg V, IM q24h
Ormetoprim – sulfadimethoxine 55 mg/kg PO q24h initial

27.5 mg/kg PO q24hnsubsequent
81
11 AMINOGLYCOSIDES AND SPECTINOMYCIN

AMINOGLYCOSIDES
Amnoglycosides are important antibiotics in the treatment of gram (-) infection. These
compounds are produced from strains of Streptomyces, Micromonaspora and Bacillus
species.
Chemistry
1. The aminogycosides contain aminocyclitol group, with amino sugars attached to

aminocyclitol ring in glycocidic linkages
2. The amino group contributes to basic nature of this class of antibiotic, and the hydroxyl
group on sugar moieties to high aqueous solubility and poor lipid solubility
Mechanism of Action
1. Aminoglycosides inhibit protein biosynthesis by acting directly on the 30s ribosome and
are bactericidal
2. They interfere with proper attachment of messenger RNA to ribosome (30s subunit),
causing misreading of genetic code and cause decrease or abnormal protein synthesis
3. Aminiglycosides penetrates the bacteria by an energy-dependent step that is oxygen-
linked. This uptake is inhibited by an anaerobic or acidic environment and by calcium or
magnesium which competes with the transport system.
Fig 2. Effect of Aminoglycosides on protein synthesis
1. Narrow Spectrum:
a. Streptomycin and Dihydrostreptomycin
82
i. Active against aerobc, gram (-) bacteria: Actinomyces, Pasteurella, E. coli,

Salmonella, Campylobacter, Leptospira, Brucella and Mycobacterium
tuberculosis
ii. Veterinary formulations contain dihydrostreptomycin in combination with
procaine penicillin for IM, SC and Intramammary administration.
iii. Both are especially ototoxic in cats.
iv. Special uses: for eliminating kidney state of leptospirosis in swine, and use
concurrently with minocycline to treat brucellosis. Streptomycin is also used
in the treatment of tuberculosis
2. Broad Spectrum
a. Neomycin
i. It is used orally for GI infections or to suppress GI microflora in hepatic
encephalopathy, and pre-operatively for large bowel surgery. However, it can
cause malabsorption syndrome or GI superinfection
ii. It is commonly used topically in ointments, otic and ophthalmic preparations
and urinary irrigation solution
b. Gentamicin
i. Most active; has the broadest spectrum. Effective against Pseudomonas,
Proteus, Staphylococcus, Corynebacterium spp and Enterobacteriaceae.
ii. They are used in all species in the treatment of septicemia, and all
susceptible infection of skin, respiratory tract, ear, eye, and urinary tract
iii. It is given IV, IM, SC, ophthalmic and otic preparations; and for intra-uterine
infusion in mares
iv. Nephrotoxicity is the general problem
c. Kanamycin
i. Spectrum similar ti gentamicin, but no activity against Pseudomonas
ii. Active against many species of mycobacteria and mycoplasma
iii. Used in dogs and cats to treat gram (-) infections of skin and soft tissue and
urinary tract and respiratory tract
d. Amikacin
i. Synthesized from Kanamycin
ii. Used for gentamicin-resistant gram (-) infections (e.g. Pseudomaonas,
Klebsiella, and E. coli)
iii. Available for intra-uterine infusion in mares
e. Tobramycin
i. Has a spectrum similar to gentamicin but more potent antipseudomonal
activity
ii. Has reduced toxicity and enhanced antibacterial activity compared to
kanamycin
iii. More active than gentamicin against Pseudomonas aeroginosa
83
Pharmacokinetics Features
1. Absorption
a. Poorly absorbed from the gut (<1% of the oral dose) because of their polar and
polyionic nature. Patients with impaired renal function may get toxicity following
repeated oral administration
b. Significant absorption may occur from inflamed gut, or from large burns when applied
topically
c. Rapidly absorbed systematically from serosal surfaces of body cavities and from IM
and SC injection sites
2. Distribution
a. Distributed into extracellular fluid space and to intracellular fluid (e.g. Pleural and
peritoneal fluid)
b. Penetration to CNS, prostate, respiratory and ocular tissue is minimal
c. They tend to accumulate in the renal cortex and otic endolymph predisposing these
tissues to toxicity
3. Excretion
a. Excreted mainly by glomurular filtration with some tubular secretion and tubular
reabsorption
b. Plasma half-lives are 1-3 hours in most species
Adverse reactions
1. Nephrotoxicity is caused by damaged membrane of proximal tubular cells due to binding

of free amino groups of ionized aminoglycosides.
a. Resulting in loss of brush border enzymes, impaired absorption, proteinuria, and
decreased glomerular filtration rate
b. Predisposing factors are: renal disease, old age, dehydreation, and concurrent use
of furosemide (a diuretic)
c. Acute tubular necrosis occurs more likely with prolonged therapy (6-7 days or
longer). Tubular casts and increased protein in the urine are characteristic early
signs of toxicity
d. Gentamicin is the most nephrotoxic of the aminoglycoside
2. Ototoxicity results from progressive damage to cochlear sensory cells (leads to
deafness) and vestibular cells (causes ataxia and incoordination especially in cats with
prolonged exposures).
a. Those with predominantly cochlear (auditory) toxicity are amikacin, kanamycin and
neomycin
b. Those with predominantly vestibular toxicity are streptomycin and gentamicin
3. Neuromuscular blockade is a relatively rare adverse effect of aminoglycosides. It is
caused by pre-junctional blockade of acetylcholine (Ach) release and decreased post-
synaptic sensitivity to Ach. Muscle paralysis and apnea can be treated with Neostagmine
and calcium
84
Drug Interaction
1. Aminoglycosides and penicillins in the same container inactivate each other, except
penicillin G and Strepyomycin
2. Gentamicin shows antagonism with Chloramphenicol, tetracycline and erythromycin
3. Aminoglycosides will potentiate the toxicity of nephrotoxic drugs and neuromuscular
blockade drug
4. It binds to pus, calcium and magnesium; neutralized by acid; 32x more active in alkaline
urine
1. Impaired transport across cell membrane. Because transport process is active and
oxygen-dependent, anaerobic bacteria (Bacteroides and Clostridium) and facultative
anaerobes (Enterobacteria and Staphylococcus) are more resistant when in an
anaerobic environment
2. Enzymatic modification of Aminoglycosides. The numerous amino acid hydroxyl groups
are attack sites of acetylases, phosphorylases and adenylases
a. Amikacin are resistant to most bacterial enzymes that inactivate other
aminoglycosides
3. Reduced affinity of ribosomal binding site due to mutation of specific ribosomal proteins
Dose Rates
Amikacin 5-7.5 mg/kg IM, SC q8h
Gentamicin 1-2 mg/kg IM, SC q8h
Kanamycin 4-5 mg/kg IM, SC q8h
Neomycin 5 mg/kg PO q8-12 hr
Streptomycin 7.5-12.5 mg/kg IM, SC q12h
SPECTINOMYCIN
Spectinomycin is produced by Spectinomyces spaectabilis. It is a non-aminoglycoside

aminocyclitol, and therefore, structurally related to Aminoglycosides. However, it does not
contain aminosugars attached in glycosidic linkages.
85
Chemistry
It is an aminocyclitol, weak organic base with two pKas (6.4 and 8.7). It has low lipid
solubibility, but it is highly water soluble and relatively stable in solution
Mechanism of Action
1. It binds with the 30s ribosome but does not cause misreading of the genetic code
2. Unlike Aminoglycosides, it is bacteriostatic
1. Narrow spectrum, primarily gram (-) bacteria, but not as active as the Aminoglycosides
2. Has some activity against Mycoplasma but none against anaerobes
3. Used in the treatment of respiratory disease caused by gram (-) bacteria
4. It is available in combination with lincomycin. It is used in dogs, cats, horse, swine and
poultry for the treatment of enteric and respiratory diseases
Pharmacokinetics
1. Absorption
a. Poorly absorbed from the gut but rapidly absorbed when given IM and SC
2. Distribution
a. Has low volume of distribution; limited to extracellular fluids because of poor lipid
solubility
b. Tissue concentrations seldom exceed 25-50% of the serum concentrations
3. Excretion
a. Excreted rapidly unchanged in the urine by glomerular filtration
b. 75% of doses is cleared in 4 hours; the half-life is only 60 minutes in most cases
Adverse Reactions
1. Relatively non-toxic even at high doses

2. Neuromuscular blockade is the most significant toxicity but rare. Can potentiate other
neuromuscular blocking agents
3. IM injections may cause pain
86
Resistance
1. Resistant mutants fail to bind aminocyclitols to 30s ribosome

2. Plasmid-mediated resistance, manifested as the production of degrading enzymes, is
less common
Study questions?
1. What are the natural sources of Streptomycin, Dihydrostreptomycin, Gentamycin,

Neomycin, Kanamycin and Spectinomycin?
2. How do aminoglycosides and aminocyclitols differ?
3. Why are aminoglycosides synergistic with bacterial cell wall synthesis inhibitors?
4. Identify the mechanisms of toxicity of aminoglycosides and to minimize their occurrence.
87
12 TETRACYCLINES
The tetracycline antibiotic was the first to be known as “broad spectrum antibiotics”. It was
isolated from a fungus Streptomyces aureofasciens.
Chemistry
1. Tetracyclines are derivatives of polycyclic napthacene carboxamine

2. They are acidic, amphoteric, substances that in aqueous solutions form salt in both acid
and bases
3. They are stable as dry powders but not in aqueous solutions particularly at high pH
ranges
4. They form poorly soluble chelates with bivalent and trivalent cations, particularly Ca, Mg
Al, iron
Mechanism of Action
1. Tetracyclines inhibit protein synthesis by reversibly binding to 30s ribosomal subunit and
prevent the attachmemnt of aminoacyl transfer-RNA to the messenger-RNA receptor
site (A site)
2. They block the addition of amino acids to the growing peptide chain, hence they are
bacteriostatic
3. They become bactericidal when organism seem to lose the functional integrity of the
cytoplasrnic membranes
Fig. 3. Inhibition of bacterial protein synthesis by tetrancline
88
insoluble chelates should be avoided 3 hours before and after oral administration
d. Tetracyclines may be absorbed after IM or SC injection but can be very painful and
damaging to tissues. They are also absorbed following intrauterine or intra-mammary infusion
2. Distribution
a. Tetracyclines have wide distribution in the body, except CNS

b. The highly lipid soluble tetracycline (doxycycline and minocycline) concentrate in tissues
to a greater extent than the less soluble ones and penetrate CNS, eye and prostate at
therapeutic concentrations
c. Reach high concentration in the kidney, bile, liver, lung, and sites of active ossification
d. There is a good penetration in synovial fluid, sinuses, mucosa and milk. They cross the
placenta and enter fetal circulation
e. Can be deposited irreversibly in growing bones, dentine and enamel of unerupted teeth
of young animal
3. Excretion
a. Renal excretion is the major route of elimination of most tetracycline, but small amounts are
excreted into feces via bile or diffusion from blood into the intestine. Alkaline urine increases
excretion
b. Doxycycline is unique in that intestinal excretion is the major route of elimination
Adverse Reactions
1. The Tetracyclines (except Doxycycline) are potentially nephrotoxic and should be

avoided if renal function is impaired. They should not be used with methoxyflourane
anesthesia because acute renal failure may result
2. Permanent staining of unerupted teeth may occur in young animals. Formation of TCN-
Ca phosphate complex in enamel and dentine is the probable cause
3. Superinfection of fungi, yeast, or resistant bacteria may occur in the gastrointestinal tract
with prolonged administration
4. Phototoxicity and hepatotoxicityare rare side effects in animals
5. Oral therapeutic doses may disrupt miminal microflora in adult ruminant or colonic
microflora in horses
6. Rapid IV injection of tetracycline can produce hypotension and collapse. This acute
depression of cardiovascular function appears to be related to the ability of tetracycline
to chelate ionized Ca. Rapid IV administration in cow can precipitate signs of milk fever
(hypocalcemia)
89
7. Tetracyclines are capable of inhibiting leukocyle chemotaxis and phagocytosis when

present in high concentration at sites of infection
1. Decreased penetration of drug into previously susceptible organism due to impaired

uptake into bacteria and active efflux from bacterial cell
Dose Rates
Tetracycline Dog/Cat: 7 mg/kg IM, IV q 12 h; 20 mg/kr oral q8h
Oxytetracycline Dog/Cat: 7mg/kg IM, IV ql2h
Cattle/sheep/pig: 5-10 mg/kg IM, IV q 24h
Calf/foal, Iamb/piglets: 10 – 20 mg/kg oral q8-12h
Horse: 5 mg/kg IV
Doxycycline Dog: 5-15 mg/kg P0 q24h; 5 mg/kg IV q24h
Study questionsns?
1. How do Tetracycline and aminoglycosides differ in protein synthesis inhibition?

2. How broad is the spectrum od activity of TCN, give specific diseases it can treat.
3. What are the adverse effects of the drug and how do we avoid it?
90
13 MACROLIDES AND CHLORAMPHENICOL

AND DERIVATIVES LINCOSAMIDES AND
PLEUROMUTILINS
CHLORAMPHENICOL
Cholamphenicol is produced from Streptomyces venezuela, a soil organism isolated from

Venezuela. Chloramphenicol use in food animals is now banned in the Philippines because it is
known to cause aplastic anemia in humans.
Chemistry
1. Chloramphenicol is a derivative of dichloroacetic acid and contains iorasnphrnirol is a

derivative of dahloroaceric acid and contains a nitrobenzene moiety
2. It is used as freebase or in ester form: neutral-tasting palmitate for oral use and water-
soluble sodium succinate for parenteral use
3. It is highly lipid soluble, only slightly water soluble and very stable
4. Thiamphenicol is a derivative of chloramphenicol wherein one of the hydroxyl groups in
the benzene ring is replaced by a methylsulfonyl group
5. Florfenicol is a derivative of chloramphenicol wherein one of the hydroxyl groups is
replaced by fluorine atom
Mechanism of Action
1. Chloramphenicol and its derivatives inhibit protein synthesisby binding to 50s ribosomal
unit
2. This action prevents the binding of the amino-acid-containthg end of the tRNA to the
active site of petidyl transferase. This prevents elongation of the protein
3. They are primarily bactriostatic
4. They can also inhibit mitochondrial protein synthesis in mammalian cells. The
mammalian erythropoeitic cells seem to be particularly sensitive to these drugs
91
Fig 4. Inhibition of protein synthesis by chloramphenicol
1. Chloramphenicol has a broad spectrum of activity similar to that of tetracyclines with a

good gram negative spectrum including: Haemophilus, Salmonella, E. coli,
Enterobacter, Klebsiella, Proteus, Pasteurella
2. Pseudomonas aeroginosa is resistant
3. It is very useful for Salmonella infections, brain abscesses, bacterial meningitis, intra-
ocular infections
4. In humans, its use is restricted to typhoid fever, or other severe infections against which
no other other antibacterial agents are effective
5. In general, chloramphenicol should probably be used as a second choice antibacterial,
but may be first choice for some deep infections of the eye
Pharmacokinetics
1. Absorption
a. Chloramphenicol is rapidly absorbed after oral administration in monogastric animals
but absorption after IM or SC is unpredictable
b. In adult ruminants, oraIly administered chloramphenicol is inactivated by rumen
microorganism
2. Distribution
a. Chloramphenicol has a very wide disiribution in the body due to high lipid solubility
b. It penetrates intracellular as well as extraccllular fluid. Highest concentrations are
attained in the liver, bile and kidney
c. Therapeutic concentration are attained in the brain, CSF, eye, prostate and milk
d. Chloramphenicol crosses the placenta and may affect the fetus
e. It may penetrate the eye following topical or subconjunctival administration
3. Elimination
a. Primarily excreted through the bile
92
b. Chloramphenicol and glucuronide is the main metabolite excreted (90%), others are
de-acylated or dehalogenated metabolites (2%) and unchanged drug (8%)
Adverse Reactions and Toxicity
1. Chlorampenicol may reduce appetite: cause vomiting, weight loss, dehydration and CNS
depression. These effects are seen more frequently in cats than in dogs
2. Bone marrow suppression (hypoplasia), occurs in most species given high levels of
drug, and is dose-dependent and reversible
a. It is characterized by anemia, leukopenia, and thrombocytopenia. Humans are the
only species that develop non-dose dependent irreversible aplastic anemia because
of chloramphenicol therapy (or exposure to chloramphenicol residues n food).
3. Chloramphenicol inhibits hepatic drug metabolism specifically oxadation and
glucuronidation. Consequently, it prolongs effects of drugs that are dependent on
hepatic microsomal enzymes for their elimination (Phenobarbital, phenytoin, lidocaine)
4. Chloramphenicol can delay wound healing when applied topically in excess because of
inhtbion of protein synthesis. It can also suppress anamestic response
Mechanism of Resistance
1. Plasmid-mediated resistance is very important in gram negative bacteria. A pecific

acetyltransferase acetylates chloramphenicol to an inactive compound
Dose Rates
Cat: 45 - 60 mgJkg P0, IV, IM q12h
Dog: 45 - 60 mg/kg oral,IV, IM q6 - 8h
Horse: 5Omg/kg P0 q6 - 8h; 50 mg/kg IV q2 – 4h
Study questions?
1. Do Tetyracycline and chloramphrnicol differ in protein synthesis inhibition?

2. How broad is the spectrum of activity of Chloramphenicol, give specific diseases it can
treat.
3. Why is it banned for use in food animals?
4. Why it should not be concurrently used with anesthetic and vaccine?
93
MACROLIDES
The macrolides are a group of antibacterials with large lactone structure in these compounds.
Erythromycin is derived from Streptomyces erythreus isolated from the Phillipine soil.
Chemistry
1. Macrolides contain a many-membered lactone ring to which are attached to one or more
deoxysugars.
2. They are weak bases with pKa of 7.1 (tylosin) or 7.8 (erythromycin)
3. They are highly lipid soluble; their salts have good water solubility
Mechanism of Action
1. Macrolides interfere with protein synthesis ith reversibly binding to the 50s subunit of
ribosome. Binding at the donor site, prevents translocation necessary to keep the
peptide chain growing
2. More active in higher pH. Bacteriostatic but can be bactericidal in higher concentration
Fig. 5. Inhibition of bacterial protein synthesis by macrolide antibiotics
Spectrum of Activoty and Therapeutic Use
1. Erythromycin
a. A second-choice antibacterial for most applications; alternatives to penicillins
b. Therapeutic uses: mainly vs gram positive bacteria, including penicillinase
producing staphylococci and streptococci; some garm negative bacteria
(Bacteroides, Haemophilus, Actinobacillus, Bordetella are often sensitive)
94
c. Use for staphylococcal and streptococcal infections in penicillin –allergic patients

d. Mycoplasma infections; foal pneumonia; acute mastitis; enteritis caused by
Campylobacter jejuni
2. Tylosin
a. Also a second-choice antibacterial for most application
b. Less active against bacteria except Treponema hyodysenterae but is more active
agaist Mycoplasma
c. Used primarily in food animal medicine(including poultry) as feed additive
3. Spiramycin
a. Less active than erythromycin
b. Drug of choice against cryptosporidiosis
Pharmacokinetics
1. Absorption
a. Macrolides are readily absorbed from GIT if not inactivated by gastric acid. Oral
preparations are often enteric-coated and are stable esters such as stearate,
lactobionate, glucoheptate, propionate
b. Absorption patterns may be erratic due to presence of food absorption from
rumenoreticulumis usually delayed and unreliable
c. Erythromycin and Tylosin may be also administered IM or IV, absorption is rapid and
swelling occurs at injection sites
2. Distribution
a. Widely distributed, penetrates bone well but not CSF; concentrated in bile and milk
b. Therpeutic concentrations are attained in prostate and prostatic fluid. They can cross
tha placenta
3. Elimination
a. Metabolized via demethylation by HM enzyme. The metabolites are excreted
primarily in bile
b. A small amount of unchanged drug is eliminated in the urine.
1. Gastrointestinal disturbances are the most common reactions and are dose-related.
These are manifested as vomiting, and occasional diarrhea in small animals or diarrhea
in horse. These can also be a problem in guinea pigs, rabbits and hamster
2. Hypersensitivity reactions including anaphylaxis can occur but are rare
3. There can be pain and swelling after IM injections and thrombophlebitis after IV
4. Hepatotoxicity and cholestatic hepatitis occurs occasionally in humans, primarily with
estolate esters
5. E rythromycin can cause increased blood levels and toxicity of theophylline and oral
anticoagulants probably by interfering with their metabolism
95
1. Resistance to macrolides in both chromosomal and plasmid-mediated. The latter is

primarily seen with Staphylococcus spp.
2. The primary mechanism is decreased binding to 50s ribosomal subunit by methylation of
the ribosomal RNA
3. Decreased penetration into bacterial cells
4. Cross-resistance can occur between macrolides and lincosamides
Dose Rates
Erythromycin Cattle: 8 – 15 mg/kg PO q12 – 24h
Cat: 15 mg/kg oral q8h
Foals: 25 mg/kg IM q8h
Tylosin Cattle: 10 – 20 mg/kg IM q12 – 24h
Pig: 10mg/kg IM q12 – 24h

7 – 10 mg/kg oral q8h
Cat: 10mg/kg q12h
Study questions?
1. What arevthe different macrolides?

2. How do they inhibit protein synthesis?
3. What is their primary route of excretion?
4. What arevtheir clinical indications?
LINCOSAMIDES
1. Absorption
2. Distribution
a. They are widely distributed in the body. They can penetrate intracellular fluid but not
the CSF
b. High lipid solubility, ion trapping can result to high concentration of Lincosamides in
some tissues and body fluids
c. High concentrations are achieved in skin, bone and joints. Lincosamides may be the
drug of choice for osteomyelitis
d. High concentrations may also be achieved in milk and bile
e. Generally they are highly protein bound
3. Elimination
96
a. Clindamycin undergoes hepatic metabolism to form inactive metabolites which are

excreted primarily in bile and urine
b. Lincomycin may not be metabolized, but evidence
Aderse Reactions and Toxicity
1. GI disturbances are the major adverse effect, vomiting especially in cats. Dogs are
relatively resistant to GI disturbances
2. Diarrhea resulting from pseudomembranous colitis caused by Clostridium deficile. For
this reason, Lincosamides are contraindicated in the horse, rabbits, guinea pigs, and
hamster
3. Gastroenteritis such as colitis in horses and cattle. Oral lincomycin as low as 7 – 10 ppm
in feeds causes inappetence, diarrhea, ketosis, and reduced milk productions
4. Hypersensitivity reactions is rare
5. They can produce or potentiate neuromuscular blockade in high concentration (can be
reversed by drug withdrawal and calcium injection); additive effect with anesthetic and
skeletal muscle relaxants
6. Some pain in IM injection. Do not administer by rapid IV, may cause cardiac depression
Dose Rates
Lincomycin Cattle: 10 mg/kg IM q12h
Pig: 10 mg/kg IM q12h

7 mg/kg oral in fed
Dog: 20 mg/kg IM q12h
Cat: 12 mg/kg IM q12h
Clindamycin Cat: 10 mg/kg IM, oral q12h
Study questions?
1. What are the different lincosamides?

2. How do they inhibit protein synthesis?
3. What is their primary route of excretion?
4. What are their clinical indications?
97
14 MISCELLANEOUS ANTIBACTERIAL
(QUINOLONES)
QUINOLONES
The original quinolone drugs (nalidixic, oxilinic, and pipimedic acids) had bacterial activity
restricted to gram negative aerobes, and were administered orally for urinary tract infections in
monogastric animals. Their use was limited by the development or resistance and their toxicity.
The fluoroquinolones are the latest and most used quinolones in veterinary medicine.
Chemistry
1. The fluoroquinolones consist of a carboxyl group, fluorine atom and piperazine ring
attached to quinolone ring
2. They are weak acids and are lipophilic. Water soluble salts are used in parenteral
preparations
Mechanism ofAction
1. Quinolones inhibit the activity of DNA gyrase (topoisomerase II). This enzyme is
necessary for relaxing supercoiled DNA and nicking and subsequently closing duplex
DNA strand
2. Inhibition of DNA gyrase leads to degradation of chromosomal DNA as the chromosome
separates during replication
3. They are bactericidal
Fig.6. Schematic diagram of the formation of negative DNA supercoil by DNA gyrase
98
Spectrum of Activity and Clinical Uses
1. FIRST GENERATION QUINOLONES

Nalidixic Acid Oxolinic Acid
a. Spectrum of activity and Clinical Use
i. Effective against most gram-negative aerobes except Pseudomonas
aeroginosa
ii. Inactive against gram positive and aerobic bacteria
iii. Used in the treatment of urinary tract infection caused by gram negative
bacteria
iv. Too toxic to use in dogs and cats
2. SECOND GENERATION QUINOLONES
Flumequine Norfloxacin
Ciprofloxacin Enoxacin
Perfloxacin Ofloxacin
3. THIRD GENERATION QUINOLONES
Enrofloxacin Danofloxacin
a. Spectrum of Activity
i. Very active against Enterobacteriaceae and many other gram negative rods,
including Pseudomonas aeroginosa
ii. Lower but therapeutically useful activity against gram positive aerobes;
inactive against anaerobes
iii. With the exception of flumequine, all have some activity against mycoplasma,
rickettsia
iv. Norfloxacin is less potent than ciprofloxacin, enrofloxacin and danofloxacin
Pharmacokinetics
1. Oral absorption fluoroquinolones is rapid

2. Widely distributed in the CNS, bone and prostate
3. Undergo hepatic metabolism
Adverse Reaction
1. Erosion of articular cartilage in young dogs, hence contraindicated in first 8 months of life
for small breeds and 18 months of life in large breeds
2. Gastro intestinal symptoms – nausea, vomiting, anorexia. Limited available data on
toxicity to animals. May be toxic for dogs and cats
99
Bacterial resistance
1. Rare but may occur in extended exposure of the drug

2. Alteration of topisornerase II
3. Decrease permeability of the drug
4. Increased membrane expression of efflux transporters
Dose Rates
NORFLOXACIN Dog/Cat: 22mg/kg q12h oral

(dog not < 8 months)
ENROFLOXACIN Dog/Cat: 2.5mg/kg q12h oral or IM, SC
Swine: 2.5 – 5mg/kg q24h oral, IM
Poultry: 50 ppm in water oral; 0.5mg/bird SID, IM
CIPROFLOXACIN Dog/Cat: 5 – 8mg/kg q12h oral
FLUMEQUINE Poultry: 12.5mg/kg in drinking water
Study questions?
1. What are the latest Quinolones?

2. Why does bacterial DNA needs to be supercoiled?
3. What is the role of DNA gyrase?
4. What are their clinical indications?
RIFAMYCINS
The rifamycins are group of structularly similar complex of macrocytic antibiotics produced by
Streptomyces mediteranei. Example compounds are Rifamycin, Rifampin, Rifamide.
Mechanism of Action
1. Rifamycins interfere with DNA – dependent RNA polymerase

2. Drug-enzyme complex leads to suppression of initiation of chain formation in RNA
synthesis
100
1. Very active against Mycobacterium tuberculosis, but most other mycobacteria are
resistant.
2. Gram negative bacteria are generally resistant but Brucella and other fastidious
organism are susceptible.
3. Active against Chlamydia. Use in foals to control Corynebacterium equi – induced
pneumonia.
4. Often administered in combination with other antibiotics such as penicillin and
erythromycin due to the ready development of resistance.
1. There is no report of adverse effects in animals but maybe teratogenic.

2. They should not be administered in animals with liver disease.
Dose Rates
RIFAMPIN Horse: 5mg/kg bid oral
Foal: 5mg/kg SID oral
Sheep and calves: 5mg/kg SID oral
Cattle: 10mg/kg IM or IV
NITROFURANS
Nitrofurans comprise of several tsynthetic compounds derived from 5-nitrofuran. Sample

compounds used for veterinary medicine are Nitrofurazone and Nitrofurantoin. Furazolidone
is banned for used in food producing animal.
Mechanism of Action
1. The nitrofurans serves as substrates for bacterial reductase enzymes. They are
degraded to various poorly characterized reduction products
2. These reduction products then cause breakage of bacterial DNA strands and inhibit the
enzymes necessary for carbohydrate metabolism
3. They are bacteriostatic and broad spectrum.
101
1. Spectrum of activity include: gram negative bacteria Escherichia coli, Salmonella,

Klebsiella, some Proteus, gram positive bacteria and Mycoplasma
2. Nitrofurans are also effective against some protozoa (coccidian, trypanosomes), with
activity against Trichomonas vaginalis and Trichomonas fetus of cattle.
3. Nitrofurazone is primarily used topically to treat wounds and infections of the skin, eye,
ear and reproductive tract. It is used as a feed additive in chickens to control coccidiosis.
Water mix and solution are available to treat intestinal infections, primarily in swine.
4. Nitrofurantoin can be used to treat lower urinary tract infections in small animals but it
can be quiet toxic and this limit is true
5. Before it was banned, Furazolidone was used as a feed additive in poultry and swine to
control intestinal infections and coccidiosis.
Pharmacokinetics
1. Absorption and distribution

a. Nitrofurantoin is well absorbed after oral administration, but is rapidly excreted In the
urine.
b. Nitrofurazone and Furazolidone on the otherhand are poorly soluble and are not
absorbed from the gut.
c. The blood and tissue concentrations are too low for treatment of systemic infections.
The mean concentrations attained in the urine are between 50 to 250 µg/ml,
therefore it is quite useful in the treatment of urinary tract infection
2. Metabolism and Excretion. There may be some metabolism. Antibacterial activity is
favored by acidic urine.
Adverse Reactions
1. Toxicity can be severe if drugs are administered parenterally or if a large amount of drug
is absorbed
2. Nausea, vomiting and diarrhea van be common after oral administration
3. Pulmonary toxicity, acute pneumonitis, interstitial fibrosis
4. Polyneuritis and central nervous effects
5. Hemorrhage diathesis with thrombocytopenia, anemia, leukocytopenia and prolonged
bleeding time
6. Local toxixity and hypersensitivity reactions
Resistance is slow to develop and only to a limited degree.
102
Dose Rates
The general dose of livestock is 10 – 12mg/kg for 5 – 7 days. In pigs 100 – 500 ppm in
feeds.
Nitrofurantoin Dog: 4mg/kg oral TId for 5 – 7 days

For urinary tract infection
NITROIMIDAZOLES
Nitroimidazoles are used in veterinary medicine for their activity against aerobic bacteria. They
are similar in spectrum of activity and mechanism of action to the nitrofurans but are not active
against aerobic bacteria. The most commonly used compound is Metronidazole.
Chemistry
1. Nitromidazoles undergo a heterocyclic compounds based on five-membered nucleus

similar to that of Nitrofurans
Mechanism of Action
1. The Nitrimidazoles undergo a non-enzymatic reduction of the nitro group to produce

products that interfere with DNA functions and antibacterial effect.
2. Reduction occurs under anaerobic conditions. Unlike that of the nitrofurans, reduction is
not enzymatically controlled.
Spectrum of Activity and Thenpeutic Use
1. The nitromidazoles are bactericidal to most gram positive and gram negative anaerobic
bacteria
2. Some (such as metronidazole and dimetronidazole) are effective against protozoan
parasites:
a. Tritrichomonas fetus
b. Giardia lamblia
c. Histomonas meleagridis
Pharmacokinetics
103
1. Metronidazole is absorbed after oral administration in monogastric species. In dogs, if

given with food, absorption is enhanced
2. Distributed widely in tissues, penetrates the brain and cerebrospinal fluid
3. Extensively oxidized and conjugated in the liver and excreted in the urine
1. Peripheral neuropathy and epileptiform seizures

2. Nausea and vomiting
3. Rumen dysfunction
4. Hepatotoxixity
5. May have teratogenic and carcinogenic effects
Resistance
1. Resistance is rare among usually susceptible bacteria, a characteristic shared with the
nitrofurans
2. Resistance involves reduced intracellular drug activation
Dose Rates
METRONIDAZOLE Dog: 25 – 50 mg/kg BID oral
Horse: 20 – 25 mg/kg BID oral
Cattle: 75 mg/kg 3x at 12h interval IV

(for trichomoniasis)
Study questions?
1. What are the differences between nitrofurans and nitromidazole?

2. What are their indications?
3. Can they be bought used for food animals?
4. Why antibiotics can be banned for food animals?
104
NOVOBIOCIN
Novobiocin is a dibasic acid derived from coumarin and is utilized clinically as a mono and
dibasic salt form.
Mechanism of Action
1. Produce non-specific cell wall inhibition, inhibition of DNA and RNA synthesis, protein
synthesis, respiration and oxidative phosphorylation suseptible bacteria
2. But non have been shown to be the primary antibiotic effect
1. Very active against Staphylococcus aureus. Less active against Streptococi and the
more fastidious gram negative bacteria (Haemophilus, Brucella)
2. Mycoplasma are moderately susceptible
3. Usually bacteriostatic. Used to treat bacterial mastitis in cows
4. Novobiocin and tetracycline have been combined to treat kennel cough and tonsilitis
Pharmacokinetics
1. Well absorbed from the gut. Mainly excreted in the bile; enterohepatic circulation occurs
Adverse Reaction
1. Inhibition of liver metabolism

2. Eosinophilia, Thrombocytopenia, and leucopenia
3. Skin rashes in cows treated with intramammary infusion of the drug
ISONIAZID
Isoniazid s a hydrazide of isotonic acid, it is the most potent anti-tuberculosis drug used in
humans. The mechanism of action is unknown
Spectrum of Activity and Clinical Use
1. Effective against Mycobacterium tuberculosis, M. bovis, and Actinomyces bovis

2. Used at 11 to 22 mg/kg orally once daily to treat actinomyces in cattle
105
Adverse Reaction
1. Neurotoxic effects resulting from a relative deficiency of pyridoxine, which is inhibited by

isoniazid
VIRGINIAMYCIN
Virginiamycin is a peptolide antibiotic and is a combination of two chemicals produced from

Streptomyces virginiae.
Mechanism of Action: Inhibit protein synthesis at 23S ribosomal subunit, blocking translation
but not transcription. It is bactericidal.
1. Primarily used against gram positive organism, Haemophilus spp and Neiserria spp
bacteria
2. Its main use is as feed additive for growth promotion in swine, turkeys and hens
106
15 ANTIVIRAL AGENTS
Restraints limiting the Use of Antiviral Drugs
I. Concomitant toxicity to the mammalian cells and the virus. A virus is an obligate
intracellular parasite that makes use of the host's genetic machinery to produce new
virus particles; hence drugs that are toxic for viruses are also toxic for mammalian cells.
II. Most antivirals have fewer efficacies against a large number of infectious particles.
Whenever a disease is symptomatic. Antivirals have limited efficacy.
III. Presently available antiviral drugs are virostatic, thus an intact immune response system
is required to maintain the suppression of viral infection.
REPLICATIVE CYCLE
1. Attachment - virus particle attach to the host cell membrane

2. Viropexis - virus penetrates cell membrane
3. Uncoating - protein coat of virus opens and viral nucleic acid is released in
host cell cytoplasm
4. Translocation - polyribosomes form after viral RNA attaches to ribosome and
begins to translate the nucleic acid sequence into proteins
5. Translation - RNA dependent RNA polymerase combined with a strand of
input viral RNA to synthesize a complementary strand to this input RNA
6. Replicative form - double stranded form of the complementary strands serve
as template for viral RNA production
7. Transcription - a new single stranded RNA is produced by 2 RNA polymerase.
The new single stranded RNA can serve as a message for protein synthesis or
as a template for production of more RNA or it may become incorporated into
mature virus
8. Assembly - new RNA and structural protein combine or are assembled into a
mature virus, which released from the cell.
CLASSIFICATION OF ANTIVIRAL AGENTS:
c. ENTRY SITE DRUGS:

1.
Attachement and penetration of virus into the host cell often requires the specific
interaction of viral coat proteins with receptor proteins of the host cell membrane.
2.
Analog viral binding proteins can bind host cell receptor proteins thereby competing with
actual viral particle from binding.
3.
Not safe for clinical use.
d. TRANSCRIPTION DRUGS:
1 .Idoxuridine and Trifluridine - Thymidine analogs
i.Active only against DNA virus primarily herpesvirus and poxvirus
ii.Used topically in the treatment of herpetic keratitis.
107
i. Cytarabine - nucleoside analogs of cytosine

ii. Vidarabine - nucleoside analogs of adenine
a. They have in vitro activity against certain DNA viruses: (herpesvirus, poxvirus,
vaccinia, rabies, cytomegalovirus and hepatitis B virus).
iii. Ribavirin - purine nucleosamide analog
a. It inhibits the replication of a wide range of RNA and DNA viruses in vitro.
b. Preparation: Virazole (indicated in hepatitis, influenza and measles)
iv. Acyclovir - purine nucleoside
a. Inhibits viral DNA polymerase. Has antiviral activity against herpes virus simplex
types 1 and II.
b. Can be administered IV, also available as ophthalmic ointment and cream and
oral preparation e.g. Zovirax
v. Forcasnet - pyrophosphate analog which exhibits antiviral activity against a variety of
DNA and RNA viruses.
3. ASSEMBLY DRUGS:
Amanthidine and Rimantadine
1. These are water- soluble cyclic amine with antiviral activity against
2. narrow range of RNA viruses, including myxovirus, paramyxovirus, togavirus and most
strains of influenza A virus.
3. They were thought to prevent viral penetration and uncoating but this have
4. been recently refuted.
5. Their antiviral activity is now thought to involve inhibition of late-stage
6. assembly of the virus.
HOST RESISTANCE:
Interferon (Intron A®, Roferon A®)
1. Protenaceous substances released from mammalian cells with ability to

cause other cells to resist viral infection.
2. Activity of interferon is released to production of a second protein;
inhibits activity of RNA dependent polymerase brought into the cell by a virus
or attenuates ribosome so they cannot read viral RNA.
3. Inhibits the replication of wide variety of viruses:
a. RNA - Togavirus, Rhabdovirus, Orthomyxovirus, Paramyxovirus,
Reovirus, Picornavirus, Onconavirus
b. DNA - Poxvirus, Herpes simplex types 1 and 2, Cytomegalovirus
Isoprinosine - interferon inducer
108
VACCINES
Vaccine is any agent (antigen) that can induce an immune response (production of
antibodies).
Vaccination is the process of administration of vaccines (antigen) so that an animal mounts

a specific immune response and achieve resistance to that agent. • Take - successful immune
response resulting in protection after vaccination
Other forms of vaccine:

1. Toxoids - are toxins whose poisonous substances have been removed. It has the
antigenic property but not the poisonous properties of toxin. Eg. Clostridium pefringes
toxoid.
2. Bacterins are suspensions of bacteria which have been inactivated by physical
and chemical means.
Functions of vaccines:
1) It is an aid to stimulate an immune response in animal, and in that manner help the
animal protect itself. It is the immune response of the animal that protects it, not the
vaccine.
2) The immune response of the animal depends on many factors, therefore the protection
conferred by the immune response is not absolute.
a) Vaccines can be used to control disease in a population
3) Vaccination of some animals in the herd may produce herd immunity which refers to
increase resistance of a group because of the presence of some immune animals in the
group, which reduces the chance of susceptible animal to be infected.
• Characteristics of a good vaccine

1. Should confer prolonged and strong immunity in the vaccinated animal
2. Should not cause adverse side effects
3. Should be stable and adaptable to mass vaccination
4. Should stimulate an immune response distinguishable from the natural infection
5. Should be inexpensive
• Dose:
a. Generally, a higher dose will stimulate a greater immune response (up to a
point)
b. Minimum protective dose - dose of vaccine required to protect 90% of
vaccinates against challenge 3 weeks post vaccination. While 90% of non-
vaccinated controls will show clinical signs when challenged.
Routes of administration
ii. Local: Spray, intranasal, intraocular or water administration
iii. Parenteral: IM,SC
109
TYPES OF VACCINE:
1. Live vaccine
a. Contains living organism that is usually harvested from the growing and multiplying
medium which is usually liquid
b. The vaccine may be frozen or freeze-dried
c. Peak immune response after vaccination with a live vaccine occurs 2-4 weeks after
vaccination
7. Advantages of live vaccines

a. Few inoculating doses required
b. Adjuvants unnecessary
c. Less chance of hypersensitivity
d. Induction of interferon
e. Rapid development of immunity
f. Development of local immunity
g. Can be mass administered
h. Relatively inexpensive
a. Disadvantage of live vaccines
a. Often in completely applied
b. Short duration of immunity
c. May revert to virulence
d. May mimic actual disease under certain conditions
e. Needs considerable care in the preparation, storage, and
handling
2. Inactivated vaccine (killed)
i. Contains organism that have been inactivated by chemical agents.

ii. Peak immune response after vaccination with an inactivated vaccine occurs 4- 6
weeks after vaccination.
iii. It can be given with adjuvant or without
• Adjuvant - material that is added to antigens to enhance the normal immune
response by:
allowing the antigen to be released slowly, providing
longer lasting, continuous exposure to the antigen and
- causing local granulomatous mononuclear inflammatory response,
further stimulating the immune response of the antigen.
Advantages of inactivated vaccines

1. Stable on storage
2. Unlikely to cause disease through residual virulence
3. Unlikely to contain contaminating organism
110
4. Long duration of immunity, if properly primed

5. May be more economical in certain circumstances
6. Disadvantage of inactive vaccines

7. Reaction to adjuvant may occur
8. Slow development of immunity
9. Little development of local immunity
10. Cannot be mass administered
11. Expensive
3. Modified live vaccines
a. These viruses have been attenuated by serial passages through unnatural host
or tissue cultures.
i. Lapinized - vaccines produced from rabbits
ii. Avianized - vaccines produced from hens
iii. Tissue cultured
b. The virus lose their virulence, they retain their antigenic properties and act as a
vaccine. They produced a solid and lasting immunity.
Classification of vaccines:
a. Monovalent vaccine contains only one virus.
b. Multivalent vaccine contains a mixture of viruses.
Factors to consider before using vaccine:

1. Actual cause of the disease must be determined.
2. Establishment that an appropriate immune response can protect against the
disease.
3. Risk of vaccination must not exceed those caused by the disease itself.
Handling of vaccines:
1. Vaccines are manufactured under strict control. They are pure uncontaminated. Livestock
field assistants are expected to maintain them in this condition. Careless handling, improper
storage, and poor techniques all contribute to rapid vaccine deterioration and loss of potency.
The following are the rules in handling of vaccines.

(i) Vaccine is perishable product. Keep them under refrigeration always and
keep them in a cool place during transit. Frozen vaccine below 0°; freeze
dried and inactivated vaccines - 2 to 7 °C.
(ii) When lyophilized products are reconstituted with the diluents, used them
immediately or they will deteriorate rapidly.
(iii) Open vaccine aseptically and use only distilled water as diluents.
111
2 Discard containers with multiple doses when used unless they are aseptically opened
and kept under refrigeration.
3. Vaccine has varying dates of expiration. Do not use them beyond the prescribed period.
1. Use only clean sterilized needles and syringes.
2. Administer biological in accordance with producer's direction. Then follow all instruction
correctly.
3. Do not use vaccines that are outdated or improperly stored. They have lost part of their
antigenic properties.
4. Burn or immerse in strong disinfectant empty virus containers. Carelessly discarded
bottles are potential sources of disease outbreaks.
5. In mass vaccination, have a liberal supply of disposable needles. Disease can be
transmitted when the same needle is used to vaccinate numerous animals.
6. Maximum active immunity is not reached until at least 10 days following vaccination.
Administer the antiserum simultaneously with the vaccine if the animal has been
recently exposed to the etiologic agent. In some cases, such simultaneous
administration may interfere with long term immunity. Thus, another vaccination is
needed.
7. When live, unmodified, fully virulent viruses are used, remember that the vaccinated
animal may become a carrier and shed the virus for varying periods. Susceptible stock
should not come in contact with vaccinates until after the period of elimination has
passed.
Causes of vaccination failure:

1. Animal as a cause
i. Vaccine was given too late, the animal is already incubating the disease
ii. Animal is incapable of responding
iii. Animal is previously passively immunized
iv. Animal is unhealthy or immunocompromised/immunosuppressed
2. Vaccine as a cause
iv. Death of supposedly live vaccine
v. Inadequate dose or poor administration including failure to give vaccine
vi. Inappropriate strain or organism
vii. Ineffective vaccine
2. ROUTE OF ADMINISTRATION
a. IV - most versatile; for emergency situation Problems:
Must use hygienic equipment and maintain aseptic technique
Some vein are hard to locate
Problem of maintaining of needle such that it will not be dislodged
Clotting and hematoma
Rapid IV administration may overload circulatory system, causing pulmonary
edema and death.
b. Subcutaneous
112
Rapid and easy to use, useful in very young animals

Not good for emergency cases
Use only non-irritating solutions - isotonic
When edema is present absorption will not occur
c. Intraperitoneal
Practical for large animal
May result to peritonitis and puncture of abdominal organs
d. Oral
a. Easiest, least dangerous; fluids can be administered without restrictions on
volumes tonicity and asepsis; not to be used when animal is vomiting.
SCHEDULE FOR VACCINATION AGAINST COMMON DISEASE OF LIVESTOCK AND

POULTRY
DISEASE CAUSATIVE VACCINE 1ST 2ND SUBSEQUE REMARKS

AGENT TYPE DOSE DOSE NT DOSE
(mo)
CATTLE/CARAB
AO
Foot and mouth Aphthovirus Inactivate 2-3 6-8 Annual
A,O,C types d in alum
hydroxide
Anthrax B. anthracis Spore 4-6 Annual In anthrax
vaccine zone
Hemorrhagic P. multocida Bacterin 2-3 6-7 Annual
septicemia
Blackleg/Maligna Cl. chauvei Mixed 4-6 Annual
nt edema Cl. septicum bacterin
POULTRY
Mareks Herpesvirus Live Day old Single
avirulent dose
turkey
virus
Newcastle Paramyxovir Live mild, 1st-2nd 3rd-5th Booster
disease us in oil week week shot during
emulsion egg
production
Infectious Coronavirus Mild live, 1st-2nd 3rd-5th
Bronchitis monovale week week
nt or
bivalent
Fowl pox Avian pox Modified 3rd-4th
virus live week
chicken
pigeon
virus
Fowl cholera Pasteurella Killed 8-10 wk 12-14
113
multocida bacterin wk
SWINE
FMD Aphthovirus Inactivate 1-2 mo 3-4 mo Semi annual During
d oil outbreaks
emilsion
Hog Cholera Pestivirus Modified 1-2 mo 3-4 mo Annual
live
Pseudo rabies Porcine Inactivate 4-5 mo 6-7 mo 3 wks before For
herpesvirus d in alum farrowing breeders
hydroxide only
Piglet scours E. coli Bacterin 4wks 1-2 wks For
before before breeders
farrowin farrowin only
g g
Salmonellosis Salmonella Bacterin 2-4 wks 3-4 mo For
cholerasuis after fattening
weanin stocks
g
Pasteurellosis Pastuerella Bacterin 2-4 wks 3-4 mo Repeat
multocida after dose
weanin before
g breeding
Leptospirosis Leptospira Polyvalen 1 wk 3-4 mo
t bactrin before
weanin
g
CANINE
Distemper Paramyxovir MLV 6-8 wks 10-12 14-16 wks Annual
us (SC/IM) wks revaccinati
on
Infectious canine Adenovirus MLV 6-8 wks 10-12 14-16 wks Annual
Hepatitis (SC/IM) wks revaccinati
on
Parvoviral Parvovirus MLV 6-8 wks 10-12 14-16 wks Annual
enteritis (SC/IM) wks revaccinati
on
Leptospirosis Leptospira MLV 6-8 wks 10-12 14-16 wks Annual
(SC/IM) wks revaccinati
on
Rabies Lyzavirus MLV/ 12-16 Annual
Inactivate wks
d
FELINE
Panleukopenia Panleukope Inactivate 6-8 wk 12-14 Annual
nia virus d (SC/IM) wk
Viral Inactivate 8-10 wk 12-14 Annual
Rhinotracheitis d wk
Rabies Inactivate 8-10 wk 12-14 Annual
d wk
114
ANTISERUM
Antiserum - hyper immune serum, a serum which contain high concentration of specific
antibodies.
7. Passive immunization - involves the production of antibodies in one animal by

active immunization and transfer of these antibodies to susceptible animals to
confer immediate production.
a. Natural - transfer of materNal antibody to offspring via placenta of
colostrums
b. Artificial - involves the use of antiserum
8. Types of antiserum
a. Antitoxic serum - antiserum prepared against toxin or toxoids
1.Tetanus antitoxin (TAT) - tetanus immune globulin confer
immediate protection against tetanus.
2. Dose:
e.1500 - 3000IU for horse and cattle
f.500 IU in calves, sheep, goat and pigs
g.250 IU in dogs
h.Exact amount varies with the amount of tissue damage,
degree of wound contamination and the time elapsed since
injury.
i.Antibacterial sera - contains antibodies that induce specific reactions by
the bacteria when the two are brought in contact.
i. Examples
o Agglutinins which causes agglutination o Precipitins - which
precipitates the bacteria o Bacteriolysins - which lyses or liquefy
the bacterial bodies
o Bacteriotropins - induce phagocytosis of bacteria by
leukocytes
c. Antiviral sera- contains antibodies against virus
• Example: Antisera against canine distemper, feline
panleukopenia
3. Adverse effects of antisera
9. Allergic reaction which is more common in heterologous antisera
10. Anaphylaxis
11. Serum sickness
NON - SPECIFIC IMMUNOTHERAPY:

Immunoproteins - agents that stimulate the normal immune response to enhance protection
and or treat immunosuppressive conditions.
a. Adjuvant - material; that enhance an immune response when administered with an

antigen
1.
Function by slowing the release of antigen into the body and thereby
prolongs immune response.
115
2. Examples:
a. Aluminum hydroxide, aluminum phosphate, potassium, aluminum
sulfate (alum)
b. Slow release adjuvant: Beryllium sulfate, silica, kaolin, carbon
i. Immunostimulants - induce non-antigenic specific enhancement of immune system;
need not be administered together with antigen.
2. Useful when treating chronic diseases in which there is immunosuppression.
1. Examples: equine sarcoid, staphylococcal pyoderma or
demodicosis, feline panleukopenia
3. Bacteria as immunostumulant
i. BCG (Bacillus of Calmette Guerin) - the live attenuated vaccine strain from
Mycobacterium bovis. Produce generalized enhancement of both B and T cell
mediated response, and of phagocytosis, graft rejection and resistance to
infection.
j. MDP (Muramyl dipeptide) and TDM (Trehalose dimycolateO - contained in a
mycobacterial cell wall and enhance antibody production and activates
macrophages.
• Propionibactrium acnes - cellwall of this organism conatains MDP and
has been used to increase resitance in dog with pyoderma and
horses with respiratory disease.
k. Bacterial endotoxins - (gram negative bacteria), enhance immune activity by
promoting release of interferon from cells
i. Complex carbohydrates - e.g. Zymosan, glucan. Dextran sulfate, and
lentinans, activates macrophages
i. Interferons
ii.Levamisole - brod spectrum anthelmintic, stimulates T-cell differentiation
and response to antigen.
116
16 ANTIFUNGAL AGENTS
Fungal infections are classified according to the location of the infection
1. Dermatophytic infections (dermatophytosis) are the most common fungal (mycotic)

infection
a. Possible causes: Microsporum gypseum, M. canis, Trichophyto mentagrophytes
b. Affects hair, skin and nails
c. Most dermatophytes can be treated with topical antifungal agents
2. Mucocutaneous infections
a. Possible causes: Candida albicans
b. These involve the moist skin and mucus membrane (GIT, perianal and vulvovaginal
areas)
c. Treatment is topical application of Amphotericin B, miconazole, Clotrimazole,
Nystatin and with oral ketoconazole for chronic infection
3. Systemic infection. Occur less frequently, and is usually chronic in nature
a. Example: Histoplasmosis, Blastomycosis, Aspergillosis, Cryptococcosis
b. They are rather difficult to diagnose. Treatment is the parenteral amphotericin B and
ketoconazole for chronic infection.
TOPICAL ANTIFUNGAL AGENTS
Pharmaceutical preparations vary
a. For skin: solution, lotion, spray, powder or ointment

b. For intravaginal use: irrigant solution, ointment, tablet, and suppository
Preparations
a. Undecyclic Acid USP is fungistatic used for superficial infections involving skin areas
with little hair. Available as powder or 10% alcoholic solution, it is used in combination
with zinc and salicylanilide for improved efficacy. (Desenex ointment or powder®)
b. Caprylic Acid and Propionic Acid are used to treat dermatophytoses. Propionic acid is
also incorporated in manufactured animal feeds to help control fungal growth (in animal
feeds)
c. Benzoic Acid is the main ingredient in Whitfields ointment (formula: 6% benzoic acid,
3% salicylic acid). It has a fungistatic as well a s a keratolytic property
d. Salicylic Acid is used in the treatment of chronic superficial skin infections. It has
moderate fungistatic activity but with good keratolytic action. lncluded in many topical
antifungal preparations, it requires the presence of water to produce keratolytic effects. It
may cause skin irritation
117
e. Ciclopirox olamine has a broad-spectrum antifungal activity. It is effective against

Candida (yeast), Epidermophyton, Microsporum and Trichophyton but has a limited
penetration of epidermis. It is available as 1% solution
f. Tolnaftate is used against Epidermophyton, Microsporum and trichophyton infections. It
has no effect on bacteria and on Candida spp. Tolnaftate may be administered with
griseofulvin for more immediate topical effect. It is available as 1% cream, solution or
powder (Quadriderm®)
g. Canidicin is a fungicidal polyene antibiotic, and is used primarily for moniliasis
h. Haloprogin is a synthetic antifungal agent used against Trichophyton, Microsporum and
Candida. It is available as 1% cream or solution
i. Iodochlorhydroxyquin has both antifungal and antibacterial activity. It is used for
localized dermatophytoses complicated by bacterial infection. It is available as 3%
cream ointment or powder
j. Natamycin is also known as Pimaracin. It is a fungicidal polyene antibiotic, effective
against a wide range of filamentous and dimorphic fungi, and yeasts. lt is used for local
application against ringworm, in udder for yeast maistitis and on the eyes for mycotic
keratitis. It is available as 2.5% to 5% solution
k. Cuprimycin is a broad spectrum antifungal with antibacterial activity. After application,
the myxin component is effective against Trichophyton, Microsporum and Candida
l. Nystatin. A polyene antibiotic, binds to sterols in fungal cell membrane, resulting in
increased membrane permeability, and cell destruction. Used against Candida,
Aspergillus and Microsporum
Dose: Dog  22,000 units/kg/day; Poultry  62.5-250 ppm in drinking water
m. Clotrimoxazole, an imidazole, is used for topical treatment of Epidermophyton,
Microsporum, Tricophyton and Candida. It is available as 1% cream or solution
(Canesten®)
n. Ketoconazole, also an imidazole, is a broad spectrum antifungal, and is used for dermal
and systemic fungal infection
i. Spectrum of Activity: It is effective against Coccidiodes immitis, Cryptococcus
neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, Candida spp,
Aspergillus spp and Sporothrix spp
ii. It has an antagonistic effect with amphotericin B. For Blastomycosis in dogs, use
30 mg/kg daily for 2 months
o. Thiabendazole, a benzimidazole, has antifungal as well as anthelmintic activity. It may
reduce aflatoxin formation in infectedfeed. It is effective against Blastomyces, Fusarium,
Candida, Penicilium and Trichophyton
p. Iodine Preparations include Tincture of Iodine, Potassium Iodide and Iodophores
q. Dyes
i. Carbol-Fuschin solution – 0.3% basic fuschin; 4.5% phenol; 10.5% resorcinol;
5% acetone; 10% ethyl alcohol
ii. Gentian Violet – Used for candidiosis and other fungal infections. Used alone or
in combination with Benzathonium Chloride (a disinfectant)
118
SYSTEMIC ANTIFUNGAL AGENTS
1. These are used for treatment of systemic mycosis but may also be used for
dermatophytoses when distributed into skin
2. Preparations
2.1 Griseofulvin. An oral fungistatic antibiotic derived from Penicilium griseofulvum
a. Mechanism of Action: Inhibit fungal cell mitosis by binding to mircotubules,
disrupting the mitotic spindles. Fungicidal in rapidly developing fungi
b. Pharmacokinetics
i. Administered orally. Absorption from the gut is variabIe; depends greatIy
on particle size. Absorption is enhanced by high fat meal
ii. Distributes to growimg nails and skin binding to keratinand make the cells
resistant to fungal infection
iii. Only new skin, hair and nail growth is protccted against the fungal
infection
iv. Biotransformed in the liver. Excreted in the urine
c. Spectrum of Activity and Clinical Use: Used against Microsporum,
Epidermophyton, Tricophyton and Sporothrix. Must be given for prolonged
period, usually for several weeks to months
d. Adverse reactions
i. Occasional diarrhea and nausea
ii. Hepatic toxicity has been reported
iii. Teratologic effects in cats
e. Dose
i. GRISEOFULVIN Horse: 10mg/kg daily for days; oral
Dog/Cat: 7-20 mg/kg/day for 3-4 weeks; oral
Cattle: 7.5 mg/kg for 7 days (in feed)
2.2 Amphotericin B: A polyene antibiotic or systemic infections derived from
Streptomyces nodosus
a. Mechanism of action
i. Binds to ergosterol, the principal sterol of the fungal cell membrane and
causes cell destruction. Active in both growing and resting cells.
ii. Additionally, it causes oxidative damage to fungal cell in vitro, and
enhances cell-mediated immunity in the host
b. Pharmacokinetics
i. Not absorbed by oral administration. Administered slow IV for systemic
effect
ii. Thought to bind to plasma protein to be released slowly from the sites.
Little amphotericin B penetrates the CSF
iii. Excreted in the urine and bile
c. Spectrum of activity and therapeutic use
i. Broad spectrum of activity including Candida albicans, Histoplasma
capsulatum, Blastomyces dermatitidis, Cryptococcus neoformans,
Aspergillus spp. and Coccidiodes immitis
119
ii. No activity against protozoa and bacteria

iii. It has been the most important drug available for the treatment of
systemic fungal infections, but its place is being challenged by
ketoconazole
d. Adverse reaction
i. Fever
ii. Reversible renal toxicity leading to azotemia
iii. Hypochromic normocytic anemia may be observed
iv. Cardiac arrhythmias
v. Concurrent use of flucytosine decreases the dose required to treat
crypococcal infection
e. Dose
i. AMPHOTERICJN
a) Dog: 5mg/kg IV 3 times a week; on the first day dilute the total dose in
20 ml of 5% dextrose and 5ml is given. If no acute anaphylactic
response develops give the remainder over 45 seconds. Then give
the total dose over I minute in 20 ml of 5% dexlrose for 6-12 weeks 3
times aweek. Dilute further if to be given to debilitated dogs
b) Cat: for Cryptococcus neoformans, incremental doses beginning with
1mg/day up to 50mg on the 75th day.
c) Horse: 0.5 to 1.5 mg/kg every other day; IV diluted in 1 liter of 5%
dextrose
2.3 Flucytosine: A fluorinated pyrimidine derivatives
a. Mechanism of Action
i. Converted in sensitive fungi to 5 fluorouracil
ii. Mammlian cells do not convert flucytosine to fluorouracil. This is further
biotransformed to 5 fluoride oxyuridylic acid, an inhibitor of thyrimidylate
synthesis, and thus DNA synthesis
b. Pharmacokinetics
i. Well absorbed from the gut. Excellent penetration into tissues and the
CSF. Minimally bound to plasma protein
ii. Largely excreted in the urine unchanged
iii. Amphotericin B, which can reduce renal function, may increase the
toxicity of flucytosine when they are used in combination
c. Spectrum of Activity and Therapeutic Use
i. narrow spectrum of activity
ii. Active against most C. neoformans, 80-90% of Candida and most
Turolopsis and Cladosporium
iii. The majority of yeast isolates from bovine mastitis are resistant
iv. Major application is for treatment of cryptococcal infection in cat
d. Adverse reactions
i. Reversible anorexia, nausea, vomiting and diarrhea
ii. Thrombocytopenia and leucopenia due to depression of bone marrow
120
iii. Toxicity is more frequent in case of azotemia or when administered

concurrently with Amphotericin B
2.4 Ketoconazole
a. Mechanism of Action
i. Inhibits the enzyme sterol 14-alpha demethylase and therefore interfere
with biosynthesis of ergosterol and bind phospholipids in the fungal cell
membrane. This results in cell leakage
ii. They also interfere with cytochrome C. oxydase and peroxidase, resulting
in increased in intracellular peroxide and cell death
b. Pharmacokinetics
i. Well absorbed after oral administration. Absorption is decreased by
simultaneous administration of histamine receptor H 2 antagonist (e.g.
cimetidine and antacids). Food does not affect absorption
ii. Biuotransformed in the liver and excreted in the bile and urne
c. Spectrum of Activity
i. Generally fungistatic against a wide range of filamentous fungi, including
dermatophytes, yeast and dimorphic fungi
ii. About 75% of yeast isolated from bovine mastitis is sensitive to
Ketoconazole
d. Adverse Reactions
i. Relatively well tolerated particularly when compared to Amphotericin B
ii. Inappetence, pruritus, alopecia and reversible lightening of the hair of
dogs
iii. Cats are more sensitive, may develop anorexia, depression, diarrhea and
fever
iv. May be embryotoxic and teratogenic; not to be given to pregnant animals
e. Dose
i. KETOCONAZOLE Dog/Cat: 5-10 mg/kg oral for 4-5 weeks; for
ringworm
10 mg/kg oral 3 times daily; for systemic infection
121
17 ANTHELMINTIC AGENTS
Anthelmintic agents are drugs that are selectively toxic to worms. They are classified
based on the helminthes they affect as well as the mechanism of action. The helminthes
affected are roundworms, flatworms and flukes. Newer drugs have broader spectrum of activity.,
affecting different species of worms. However, resistance to various anthelmintics is now
reported in mot farms as a problem.
CLASSIFICATION OF ANTHELMINTICS
1. Mechanism of Action
a. Interfere with energy metabolism
i. Inhibitors of glucose transport
ii. Disruptors of glycogen metabolism
iii. Inhibitors of glycolysis
iv. Inhibitors of mitochondrial reaction
v. Uncouplers of oxidative phosphorylation
b. Interfere with neuromuscular coordination
i. Cholinesterase inhibitors
ii. Cholinergic agonists
iii. Potentiators of inhibitory neurotransmitters
iv. Agents causing muscle hyperpolarization
2. Spectrum of Activity
a. Anti-nematodal – against roundworms
b. Anti-cetodal – against flatworms
c. Anti-trematodal – against flukes
3. Effect o the parasite
a. Larvicidal – kill larval stages of the worm
b. Ovicidal – inactivate the egg of the worm
c. Adulticide – kill the adult stage of the worm
BENZIMIDAZOLES
These are group of anthelmintics with wide range of parasitic action, high degree of efficacy,
good margin of safety and versatility of administration. The first to be discovered is
Thiabendazole. Structural modification of the drugs produced the different Benzimidazole as
below:
Albendazole Cambendazole Oxibendazole

Fenbendazole Flubendazole Mebendazole
OxfendazoIe Thiophanate
Netobimin Febantel
122
Chemistry
1. All Benzimidazoles have the diamino-benzene as central structure

2. All are insoluble in water
Mechanism of Action
1. Benzimidazoles bind to bimeric tubulin, which prevents its polymerization during

microtubule assembly. Microtubules are cytoskeletons that are involved in cellular
motion
2. Disruption of microtubule may consequently interfere with enrgy metabolism such as
inhibition of cellular transport (mebendazole) and inhibition of fumarate reductase which
catalyze formation of ATP (other BZM)
Fig. 7. a) Schematic diagram of microtubule and b) a top view of triplets of microtubule

struct
ANTHELMINTIC AGENTS
A. Interference or energy metabolism

Inhibitors of glucose transport Dithiazanine Anti-trematodal
Mebendazole Anti-cestodal/nematodal
Flubendazole Anti-nematodal
Disruptors of glycogen metabolism Niridazole Antitrematodal
Inhibitors of glycolysis Clorsulon Antitrematodal

Arsenicals Antinematodal
Inhibitors of mitochondrial rxns Benzimidazole Broad

Uncouplers of oxidative Salicinilides Antitrematodal
phosphorylation Closantel
123
Oxyclosanide
Brotianide
Niclosamide
Substituted Phenols
B. Disruptors of Neuromuscular coordination

Cholinesterase inhibitors Organophosphates Antinematodal
Dichlorvos
Trichlorfon
Coumaphos
Cholinergic agonist Imidazothiazoles Antinematodal

Levamisole
Tetramisole
Butamisole
Pyrimidines Antinematodal
Pyrantel
Morantel
Potentiates inhibitory Ivermectin Antinematodal

neurotransmitter GABA Milbemycin
Piperazine
Phenothiazine
Spectrum of Activity
1. Thiabendazole – has ovicidal and larvicdal acitivity
Cattle All GIT roundworms, except Nematodirus and

Trichuris, lungworms and filariae
Horse Large and small strongyle; Pinworms
Pigs Hyostrongylus rubidus; Strongyloides ransoni;

Oesophagostomum dentatum
Dog/Cat Stronglodes
2. Cambendazole Fenbendazole Oxfendazole
Cattle Adult and immature roundworm (Dictyocaulus)
Horse Strongyles; Pinworms (Oxyuris); Small pinworm
124
(Probstmayria); Trichostrongylus axei
Pigs Hyostronylus; Strongylus ransoni; Oesophagostomum

dentatum; Ascaris; Stephanurus
3. Parbendazole Mebendazole
Horse Ascaris; Lungworm; Tapeworm (Anoplocephalia)
Dogs/Cats Hookworms; Ascaris; Whipworm; Tapeworm
4. Albendazole – broad spectrum
Pharmacokinetics
1. Absorption
a. BZM has poor solubility to water (except Thiabndazole, Albendazole and
oxfendazole), hence not readily absorbed from GI tract
b. Full stomach enhance absorption
a. Degree of metabolism varies. Most BZM is hydroxylated at C5
b. Mebendazole is poorly metabolized, excreted in the urine unchanged
c. Oxfendazole, fenbendazole, thiophanate and febantel are biotransformed in the liver
and resecreted into the alimentary tract as active metabolite
d. Drug residues persist for 1-3 weeks. Withdrawal perion in cattle is 27 days for
albendazole, 8 days for fenbendazole and 7 days for oxfendazole
Adverse Effects
1. These agents generally safe, although albendazole and oxfendazole may be

teratogenic. Tratogenic activity was observed in cattle and sheep during the first 45 days
of pregnancy
2. Hepatotoxic, may be due to repeated a dministration
Dose Rates
Cattle Horse Pig Dog/cats
Thiabendazole 66mg/kg 44 mg/kg

110 mg/kg 66-75 mg/kg
(severe parasitism)
125
Cambendazole 25 mg/kg 20 mg/kg 20 mg/kg
Fenbendazole 7.5 5 5 50 for 3 days
Mebendazole --- 8.8 1.25 22 for days
Albendazole 7.5 --- 5-10 25 mg/kg
Oxfendazole 4.5 10 3 – 4.5 ---
Febantel > 6 mo = 10 mg/kg

for 3 days
pups = 15 mg/kg
IMIDAZOTHIAZOLES
These are broad antinematodal agent that can be used in large number of host. These agents
can be given as pour-on or subcutaneous injection. It can also be administered in feeds, oral
suspension or bolus.
Levamisole Tetramisole Butamisole
Chemistry
1. Levamisole is an isomer of tetramisole, while Butamisole is a derivative of Levamisole

2. It is formulated with hydrochloride (drench) and phosphate (injectable)
Mechanism of Action
1. Levamisole act as a ganglion stimulant (cholinomimetic) causing sustained contracture

of muscle leading to paralysis of nematodes
1. Levamisole
Ruminants a) All major mature GIT roundworms:
Haemonchus; Ostertagia; Cooperia;
Trichostrongylus; Bunostomum;
Eosophagostomum
b) Lung worm ((Dictyocaulus)
c) Eye worm (Thelazia)
10 mg/kg as pour-on
5-8 mg/kg oral or SC
126
Horses a) Ascarids; lungworms and adult worms

10-15 mg/kg oral or SC
Pigs a) Nodular worms (Oesophagostomum);

b) Intestinal worms: Ascarids, Stronyloides
ransomi and Metastrongylus
Lung worm
Kidney worm
8 mg/kg PO or SC
Dogs a) Microfilaricide for heartworm

5.5 mg/kg bid for 6 days for heart worm
b) Ascarids and hookworms but not whipworms
7.5 mg/kg SC
Chicken a) Ascaridia; Heterakis; Capilaria and Oxyspirura

mansoni
40 mg/kg in half the daily consumption of
drinking water
2. Tetramisole
a. Practically the same as levamisole except for higher dose required and higher
likelihood of toxic reactions
3. Butamisole
a. Injectable, for treatment of whipworm and hookworm I dogs
b. Not safe for pups
c. Dose: 2-4 mg/kg
Pharmacokinetics
1. Absorption
a. Excellent absorption following gastrointestinal, topical or parenteral administration
a. Approximately 40% will be excreted from the urine 12 hours after administration
b. Elimination from the feces accounts the remaining dose within 8-day period
c. Withdrawal period in cattle and pig are 7 and 3 days, respectively
Adverse Effects
1. Levamisole is one of the most toxic anthelmintics. It has low margin of safety, especially
when given injection
127
2. Signs of levamisole include parasympathetic stimulation, convulsion, CNS depression,

asphyxia
3. Atropine cannot counteract levamisole-induced depolarizing blockade of skeletal muscle
4. Co-administration of levamisole and pyrantel increases toxicity
5. Butamisole can cause renal and hepatic problems to debilitated patients hence are
contraindicated for these patients
Modulation of Host Immune System
1. Anthelmintic treatment with Levamisole is enhanced with immune responsiveness of

host especially in critically ill and old patients
2. Can enhance immune response, stimulates cell mediated immune reactivity by
potentiating the rate of T-lymphocytes differentiation, responsiveness to antigens and
mitogens. Promotes maturation of precursor T-lymphocytes
Study questions?
1. What are the differences between Benzimidazoles and Imidazothiazoles?

2. Enumerate the anthelmintics within the family of Benzimidazoles and Imidazothiazole.
3. Can you recall the worms affected by these anthelmintics?
4. Levamisole is toxic but it is good for debilitated animal, explain why.
TETRAHYDROPYRIMIDINES
These broad spectrum antheImintic was initially ised for GIT parasite of sheep; subsequently it
has come to be used in cattle , swine, horses and dogs.
Pyrantel Morantel
Chemistry
1. Pyrantel is an imidazothiazole derivative, while morantel is the methyl ester analog of

pyrantel. It is readily inactivated by sunlight
2. Pyrantel salts are tartrate or pamoate, while morantel are are available with furmarate or
citrate salt
128
Mechanism of Action
1. Like levamisole, pyrantel and morantel paralyze the worms by causing depolarizing
neuromuscular blockade, with less larvicidal activity
Spectrum of Activity
1. Has a broad spectrum of activity against gastrointestinal parasites of ruminants, pigs,

horse, dogs and cats
Horses Strongyles; ascarids and pinworms; effective against

tapeworm Anoplocephala if used in double dose
Pigs Ascarids and Oesophagostomum
Dogs Hookworms and ascarida; not effective against whipworms
Cattle/Sheep Morantel is effective against stomach worm,

nodular worm, and other intestinal worms
Pharmacokinetics
1. Absorption
a. Pyrantel tartrate is water soluble, absorbed systematically following oral
administration. The tartrate salt is well absorbed in pig and goat
b. The pamoate salt is less soluble in water and therefore stays in the gut
a. The absorbed pyrantel and morantel are rapidly metabolized and excreted, mostly
via feces, but some in urine
b. Pre-slaughter withdrawal requirement is 1 day for pyrantel tartrate in swine and 14
days for morantel in cattle
Adverse Effects
1. Less toxic than OP’s and levamisole; safe in pregnant horses and weanlings
2. Not to be given in debilitated animals
3. Emesis may occur in dogs and pigs
Dose Rates
Pyrantel tartrate Horse: 12.5 mg/kg
129
Pig: 22 mg/kg, max of 2 g /animal

Ruminants: 25 mg/kg
Pyrantel pamoate Horse: 6.6 mg base/kg

Dog: suspension 5 mg base/kg for dogs > 2.2 kg
15 mg/ kg for dogs < 2.2 kg
Morantel Tartrate Sheep 10 mg/kg

Cattle: 8.8 mg/kg PO; 2% ointment for Telazia eyeworm
ORGANOPHOSPHATES
These compounds are frst used as pesticides and subsequently have found use as
anthelmintics.
Dichlorvos Trichlorfon Naphthalopos

Haloxon Coumaphos Crufomate
Mechanism of Action
1. Inhibition of nematodal acetylcholinesterase resulting in paralysis of adult worms

2. Unrestrained Ach of the parasite accumulate leading to neuromuscular malfunction
1. DichIorvos
a. Approved for use in horses, pigs and dogs
b. It is effective against whipworm, nodular worm, Strongyloides, hookworms and
ascarids in dogs and pigs
c. It has little or no activity against migrating larvae of ascarids and hookworms
d. It is effective against bots, strongyles, ascarids and pinworms
2. Coumaphos is approved for use in cattle to control stomach worms, whipworms and
cooperia
3. Trichlorfon is used mainly in horses with similar activity to Dichlorvos
Pharmacokinetics
1. Dichlorvos is rapidly absorbed from the digestive tract, detoxified in the liver
2. Coumaphos’ pharmacokinetics is not well understood
3. Trichlorfon is a white crystal with poor water solubility. It is metabolized rapidly after oral
dosing and may inhibit Ach for 2-3 weeks
130
Adverse Effects
1. Overdose leads to muscarinic and nicotinic signs. Animals that are debilitated or
parasitized are more prone to its toxic effects
2. Chronic effect may include demyelinationi ncluding neurotoxicity
3. Acute death may result from respiratory paralysis and cardiovascular arrest
4. Antidote for OP poisoning: atropine sulfate (0.2 mg/kg; ¼ dose IV, the rest IM) and
pralidoxime (10-50 mg/kg IM)
Dose Rates
Dichlorvos Trichlorfon Coumaphos
Cattle 2 mg/kg/day for 6 days

top dressing
15 mg/kg single drench
Horse 31-41 mg/kg 40 mg/kg for

nematode and bots
Foals 20 mg/kg for

ascarids
10 mg/kg for
bots
Swine 11.2 – 22.6 mg/kg
Dogs 27-33 mg/kg 75 mg/kg
Puppies/Cats 11 mg/kg
MACROLIDE ENDECTOCIDE
These compounds have activity against internal and external parasites, specially nematodes
and arthropods. They have no activity against cestostode, trematodes, and protozoa.
Avermectins: Ivermectin, Abamectin, Doramectin
Milbemycin: Milbemycin
Nemadectin: Moxidectin
131
Chemistry
1. Macrolides endecticides are 16-membered macrocyclic lactones

2. Avermectins are fermentation product of Streptomyces avermitilis, Milbemycin are
from Streptomyces hygroscopicus aureolacrimosus, and Nemadectins are from
Streptomyces cyaneogriseus noncyanogenus
Mechanism of Action
1. These compounds open chloride channels in invertebrates via specific site that is
glutamate-gated, which is in close proximity to GABA-gated sites, hence potentiate
GABA-gated sites as well
2. Chloride-ion influx lowers cell membrane resistance and causes a slight
hyperpo!arization leading to worm paralysis
3. It is observed to interfere with reproduction of parasites causing reduced oviposition in
ticks; abnormal egg formation in nematodes and sterility of fiIariaI worm
Spectrum of Acivity and Therapeutic Use
1. Ivermectin is approved for use in humans, horses, cattle, sheep, goat, pig, dogs, and
camels
a. Ruminants: effective agairtst all major gastrointestinal worms and lung worms
b. Horses: effective against bots, stomach worm, strongyles, pinworms and ascarids
c. Pigs: used against mature and immature stages of gastrointestinal worms, lung
worm and kidney worm
d. Dogs: effective against ascarids, hookworms, whipworms, used as mmicrofilaricide
and heartworm preventives
2. Formulations: Ivomec injection is a sterile solution containing 1% ivermectin in an
organic vehicle containing 60% prppylyn glycol and 40% glycol formula, given SC to
ruminants. Paste preparation for oral administration (Eqvalan paste®)
3. Abamectin is approved for use in cattle, effective against mature and immature stages
of gastrointestinal worms, sucking louse and ticks
4. Milbemycin is approved for use in dogs only and effective against the infective larvae of
D. immitis, hookworm, whipworm and ascarids
Pharmacokinetics
1. After administration of Ivermectin it is metabolized in the liver. The plasma half-life is 3

days in cattle. Ivermectin remains in tissues with long persistency, 1 dose is effective for
2-4 weeks
2. Withdrawal period is 18 days in swine and 35 days in cattle
132
3. Orally administered milbemycin, approximately 90% passes through the GIT unchanged
while 10% is absorbed and excreted in the bile
Adverse Effects
1. Local irritation may occur following subcutaneous administration to swine

2. At high doses, Ivermectin may evoke CNS depression
3. Collie dogs and Murray grey cattle are most susceptible to toxic effects of lvermectin
Dose Rates
Ivermectin Abamectin/ Milbemycin

Doramectin
Cattle 0.2 mg/kg PO or SC 0.2 mg/kg
Horse 0.2 mg/kg PO or SC
Swine 0.3 mg/kg
Dogs (Not for Collies) 0.5 mg/kg per mo.

0.2 mg/kg – ascarids, (heartworm)
hookworm and for all breeds
whipworm including collies
6-12 µg/kg
heartworm preventive
50 µg/kg
microfilaricide
PIPERAZINE
This one of the earliest nematodal agent used. Piperazine compounds have a wide margin of
safety to animals.
Chemistry
1. Piperazine is a diethylenediamine that is freely soluble in water and glycerol

2. Stability is accomplished using salts of citrate, tartrate and hydrochloride
133
Mechanism of Action
1. It has an anti-cholinergic action at myoneural junction in worms, producing a

neuromuscular block
2. Anticholinergic activity is thought to be due to either stimulation of GABA or nonspecific
blockade of Ach receptors
3. Worms are said to be narcotized and would regain its motility if the compound is readily
excreted from the gut
1. Piperazine is effective against ascarids and nodular worms in all species

2. Mature worms are more susceptible in young ones. Lumen dwelling larvae and
immature worms are sufficiently susceptible to be eliminated however; tissue dwelling
larval stages are not readily affected
Pharmacokinetics
1. Piperazine and its simple salts are readily absorbed from GIT
2. Some piperazine is metabolized in the liver and the remainder (30-40%) is excreted in
the urine
3. Can be excreted within 1-8 hours after administration and urinary excretion complete
within 24 hours
Adverse Effects
1. Piperazine is a very safe drug but large doses may induce vomiting, diarrhea, ataxia and
head pressing in cats and dogs
Dose Rates
Piperazine
Cattle/sheep, goat, swine 110 mg/kg
Horse 110 mg/kg
Poultry 32 mg/kg in feeds or

water for 2 days
Dogs/Cats 45-65 mg/kg
134
Study questions?
1. Among the antitrematodal agents, which has the most broad spectrum activity against
nematodes?
2. Which of the antitrematodal agents is safest to use? Most commonly used in what
domestic animal?
3. Differentiate the mechanism of action of Ivermectin from Piperazine, Pyrantel.
Mebendazole, Levamisole and Albendazole.
4. Give the chemical indication of each anthelmintic
DRUGS USED FOR HEARTWORM PREVENTION AND THERAPY
1. Heartworm infection is commonly caused by Dirofilaria immitis, and rarely Dipetalonema

reconditum
2. Clinical signs
a. Initially there is no apparent clinical sign, weight loss, ascites
b. Pneumonitis may be manifested by coughing especially at night
c. Severe signs includes cardiovascular dysfunction, edema
3. Diagnosis
a. History, physical exam
b. Blood examination (usually done late in the afternoon as microfilaria concentrate in
the peripheral circulation)
4. Treatment and Prevention
a. Removal of adult heartworm with the use of adulticidal agents
b. Interruption of the life cycle requiring microfilaricide. This is ususlly initiated 4-5
weeks after adulticide treatment
c. Prevention of infection using larvicide. Usually given daily especially during mosquito
season and for 2 months thereafter
ADULTICIDES
1. Sodium thiacetarsamide (Na caparsolate, Filaramide®)

a. Chemistry: a trivalent arsenic compound
b. Mechanism of Action: Denatures enzymes by binding to the sulfhydryl group of
cysteine residues
c. Pharmacokinetics
i. Given IV and distributed widely in the body, but is concentrated in the liver
and kidneys
ii. Metabolized in the liver. After administration 85% of the dose is eliminated
with 48 hours primarily in the feces
d. Adverse effects
135
i. Very irritating when injected extravascularly. Tissue sloughing and phlebitis

may occur. In case of extravascular injection, dilute drug by infiltration of
injection site with normal, saline solution, and glucocorticoids
ii. Hepatotoxicity and renal toxicity
iii. Thromboembolic pneumonia may may result as dead heartworms
accumulate usually in caudal lung lobes. Signs may include dyspnea,
coughing, hemoptysis, fever, anorexia and lethargy. Can be treated with
aspirin and glucocorticoids for 2 weeks. Antibiotic may be administered to
prevent secondary bacterial infection
iv. Keep dog confined and quite 1 to 2 weeks after treatment to prevent spread
of embolic problems
e. Dose rates: 2.2 mg/kg IV 2x a day for 2 days
2. Melarsomine hydrochloride
a. Chemistry: A new organoarsenical adulticide with efficacy superior to
thiacetarsamide
b. Mechanism of Action: Denatures enzymes by binding to the sulfhydril group of
cysteine residues
c. Pharmacokinetics
i. Given deep IM and its absorption half-life is 2.6 minutes with a peak
concentration of blood in 8 minutes
ii. Distributed in plasma and red blood cells
iii. Body clearance is 3x lower than thiacetarsamide
d. Adverse effect
i. Mild localized edema may occur following intramuscular injection
ii. Hepatotoxicity and renal toxicity may be milder than thiacetarsamide
iii. Thromboembolic pneumonia may be as severe as thiacetarsamide
iv. Overdose may result in distress, restlessness, pawing, salivation, vomiting,
tachycardia, tachypnea, dyspnea, abdominal pain, hindlimb weakness and
recumbency
v. Toxicity can be reversed by IM injection of 3 mg/kg dimercaprol within 3
hours of the onset of symptoms
e. Dose Rates: 2.5 mg/kg IV once a day for 2 days
i. The first injection should be administered in the right lumbar muscle and the
second in the left
ii. This regimen can eliminate all worms in 60-80% of dogs, however, it can be
repeated in 4 months to increase efficacy to 98%
iii. For dogs with severe infection, a single dose of 2.5 mg/kg is followed the full
2-dose treatment 1 month later
136
MICROFILARICIDES
1. Dithiazanine iodide
a. Given orally continuously until microfilariae disappear from the blood. Give for 1
week then check for microfiariae
b. If still positive, give another course of therapy
c. If still positive, give another course of therapy at a higher dose
d. Toxicity: Gut disturbances and potential to nephrotoxicity
e. Dose: 6.6-11 mg/kg/day for 7-10 days
EXTRA LABEL MICROFILARICIDES
1. Levamisosle: Dose: 11mg/kg/day up to 5 days

2. Fenthion: Pour on OP insecticide, applied topically of dorsal midline once a week; no
longer used because of toxic fatalities
3. Ivermectin: Dose: 0.05 mg/kg POb or SC
4. Milbemycin: Dose: 0.5 mg/kg PO, repeated after 2 weeks
PREVENTIVES
1. Diethylcarbamazine (DEC)
a. Kills the L3 larvae thereby eliminating the stages L3-L5 of the heartworm life cycle.
Also active against ascarid and hookworms in dogs and cats
b. Chemistry: It is a piperazine derivative
c. Pharmacokinetics
i. Readily aborbed after oral administration
ii. 10-30% ofdose is excreted as unchanged drug in the urine, the rest are
excreted as metabolites
iii. Maintenace of effective blood level during mosquito season prevents
development of larvae following mosquito bite
d. Dose Rates: 2.5-3 mg/lb/day PO during and 2 month after the mosquito season
i. Puppies are started on therapy at weaning
ii. Do not give to animals with existing heartworm infestation. Sudden massive
destructionof microfilariae may produce anaphylactic reaction. DEC
“opsonizes” the microfilariae to the action of antibodies
2. Ivermectin: Dose: 0.006 mg/kg once a month prevents infestation
3. Milbemycin oxime: Dose Rates: 0.5 mg/kg PO once a month
Study questions?
1. What are the different species of heartworm and where is their predilection site?
137
2. What are the clinical signs of heartworm infection?

3. Why is adulticide given first before microfilaricides?
4. What are the complications of heartworm treatment?
ANTICESTODALS
These are drugs against tapeworms. They are referred to as taenicides if they cause
death of tapeworm in situ or taeniafuge if they facilitate tapeworm expulsion. The aim of
satisfactory treatment of tapeworms is to completely remove the parasite. A retained scolex is
likely to regenerate another body after 3 weeks. Control of intermediate host (fleas and rodents)
is also necessary
1. BUNAMIDINE (Bunamidine HCl)

a. Spectrum of Activity: Effective against all tapeworms of dog and cat including
Echinococcus granulosis, Dipylidium caninum
b. Mechanism of Action: Disrupts integument down to the level of fibrous basal lamina
thereby decreasing glucose uptake
c. Pharmacokinetics: Administered PO in tablet form. Tablets should not be dissolved
in liquid prior to administration, since irritation of oral mucous membrane occurs
d. Toxicity: occasional emesis/transient diarrhea
e. Dose: Dog/cat: 25-50 mg/kg 3-4 hrs fast before Tx and feed 3 hrs after treatment
2. NICLOSAMIDE
a. Spectrum of Activity
i. Dog: Dipylidium caninum, Taenia pisiformis, T. hydatigena, T. taeniaformis
ii. Cattle/Sheeep/Goats: Monieza; effective also against flukes
iii. Horses: Anoplocephala
iv. Mice: Hymenolepsis nana
b. Mechanism of Action: Inhibit absorption of glucose by the tapeworm and uncouple
oxidative phosphorylation process in the mitochondria of cestodes
c. Pharmacokinetics
i. Poorly absorbed from the host GIT
ii. Small quantities absorbed are transformed into an inactive metabolite
d. Dose
i. Dog/Cats: 100-157 mg/kg PO
ii. Ruminants: 50 mg/kg ns drench
iii. Sheep/Goat: 100 mg/kg
e. Drug interaction: Can be administered in conjunction with several other drugs such
as tetramisole
3. BITHIONOL
a. Spectrum of activity
i. Used for tapeworm of dogs, cats and poultry
ii. Rumen flukes of sheep, cattle and goats (adult paramphistomum)
iii. Ruminant tapeworms (Monieza, Thysanosoma)
138
b. Pharmacokinetics
i. Absorbed from the host digestive tract
ii. Has a cholinimimetic effects in the intestinal tract of host, this stimulates
purgation
c. Dose: Dogs/Cats/Sheep/Goats: 200 mg/kg
4. PRAZIQUANTEL
a. Spectrum of Activity: Has excellent activity against all spp of schistosomes and
larval cestodes
b. Mechanism of action: Increase cell membrane permeability to calcium
subsequently causing muscle paralysis. Produce vacoulation of the tegument
c. Pharmacokinetics: Completely absorbed from alimentary canal following oral
administration. Quickly metabolized into inactive forms. Excreted in urine and feces
d. Dose
i. Dog >4 wks old 25 mg/kg for 2 days
Spirometra, Diphyllobotrium
5 mg/kg T. pisiformis, D. caninum
ii. Cat >6 wks old 4.2-12.7 mg/kg
iii. Ruminant 10-15 mg/kg Monieza, Stilizia, Avetilina
5. BENZIMIDAZOLES
a. Mebendazole 22 mg/kg/day for 5 days Taenia for dogs and cats
22 mg/kg/day for 5 days T. hydatigena of pigs
b. Fenbendazole 10 mg/kg Thysamosoma of sheep
c. Oxfendazole 7.5 mg/kg Raillitina of chicken
ANTITREMATODALS
Against adult flukes
1. HEXACHLOROPENE
i. Has high efficacy against mature flukes (at least 12 weeks old): F. hepatica,
F. gigantica
ii. They are not against immature flukes from the liver parenchyma where they
are bath withblood. This drug binds with proteins in the blood reducing the
availability to immature flukes
b. Dose: Sheep/Goat/Cattle: 25 mg/kg PO
2. BITHIONOL SULFOXIDE
a. Spectrum of Activity: In addition to its anticestodal properties, bithionol is effective
against rumen and liver flukes of domesticated ruminants (F. hepatica, F. gigantic;
Fascioloides magna and Paramphistomum)
b. Dose
i. Sheep/ Goat/Cattle: 60 mg/kg
ii. Can be combined with:
139
1) Hexachloropene 5 mg/kg + Bithionol 30 mg/kg – sheep/cattle

2) Levamisole 1.5% + Bithionol 50 mg/kg – sheep
3. BROMSALANS (Dibromsalans, Tribomsalan)
a. Spectrum of Activity: 100% effective against immature flukes (6-10 week range)
b. Dose: Sheep 30-60 mg/kg
4. OXYCLOSANIDE
i. Effective against liver fluke
ii. It has poor activity against rumen fluke (Paramphistomum) unless treated
twice with a 3-day interval
iii. It can be used in debilitated and pregnant animals without side effects
b. Mechanism of action: Uncouplers of oxidative phosphorylation. Only adult flukes
are affected
c. Pharmacokinetics
i. Following absorption, it reaches the highest concentration at the liver, kidney
and intestines
ii. Excreted as an active glucoronide metabolite into bile
d. Dose: 15-20 mg/kg oral for adult flukes;
45 mg/kg for immature flukes (acute fasciolosis)
5. NICLOFOLAN
a. Spectrum of activity: Can be used against mature Fasciola, it is also effective
against immature forms but in higher doses
b. Pharmacokinetics: Usually administered as tablet. Can be metabolized in the
rumen
c. Dose: Cattle 3 mg/kg
6. NITROXYNIL
a. Spectrum of activity: Can be used against F. hepatica, F. gigantica; Hemonchus
contortus; Parafilaria bovicola
b. Pharmacokinetics: Injectable fasciolicide Nitroxinil is slowly eliminated from the
body in urine and feces for 31 days
c. Dose: 10 mg/kg SC only
7. RAFOXANIDE
i. Adult F. hepatica and gigantic, but also against immature flukes
ii. Repeat treatment is necessary at 3-week intervals to eliminate maturing
flukes
iii. It is also effective in the treatment of Hemonchosis, Bunostomiasis and sheep
nasal bots
b. Pharmacokinetics
i. After oral dosing, rafoxanide is absorbed intothe blood stream
ii. It is not metabolized; it becomes bound to plasma protein. It persists in the
plasma for a longer period hence may affect immature flukes
c. Toxicity
i. Higher dose (80 mg/kg) may cause inappetence and diarrhea
140
ii. Doses 45 mg/kg can cause ocular pathologic changes in sheep; may lead to
blindness
iii. Contarindicated in lactating animals whose milk products are to be used for
human consumption and animals intended for slaughter within 28 days
d. Dose: 7.5 mg/kg for sdult (100% effective), for immature (50% effective); available
combination with thiabendazole
8. CLORSULON
a. Spectrum of activity: Has poor efficacy against rumen fluke Paramphitomum.
Effective against adult F. hepatica; higher doses are required for immature flukes (15
mg/kg)
b. Pharmacokinetics
i. Formulated as drench for sheep and cattle, or in combination with ivermectin
as a SC injection for cattle
ii. Approved for use for beef and lactating and non-lactating dairy cattle
iii. Milk discard time is 72 hours after treatment
c. Dose
3.7mg/kg (adult flukes); 15 mg/kg (6 weeks); 30 mg/kg (8 weeks)
With Ivermectin (0.2 mg/kg) + clorsulon 2 mg/kg SC
9. CLOSANTEL
a. Spectrum of activity: Used against F. hepatica, Haemonchus contortus
b. Mechanism of action: Uncoupler of oxidative phosphorylation
c. Dose: Cattle/Sheep 10 mg/kg against 8 wk old fasciola
10. BENZIMIDAZOLE
a. Albendazole
Sheep 7.5 mg/kg
Cattle 10 mg/kg F. magna, F. hepatica
15 mg/kg Dicrocoelium dentriticum
b. Fenbendazole: Not as effective against F. hepatica as Albendazole but has good
activity against Dicrocoelium in sheep
Dose: 100 mg/kg
c. Triclabendazole
Goat 5 mg/kg
Sheep 10 mg/kg
Cattle 12 mg/kg
Against Immature Flukes
11. DIAMFENETIDE
a. Spectrum of activity: Highest activity against youngest immature stages of F.
hepatica and Dicrocoelium lanceolatum. Used to treat acute fascioliasis
b. Pharmacokinetics: Absorbed in the blood and distributed throughout the body after
oral administration. Greatest concentration in the liver and gallbladder
c. Dose: 100% against flukes from 1 day to 9 wks old at a dose of 100 mg/kg
141
RECOMMENDED DEWORMING SCHEDULES
ANIMAL SCHEDULE REMARKS

LARGE RUMINANTS
Calves 2wks-1mo Use anthelmintic effective against
Repeat after 3mo threadworms and large ascarids
Adult (>1 yr old) Once a year preferably onset of Follow up should be given after 3
rainy season weeks to preclude establishment
of larvae
Separate defluking schedule:
every 3 mo on the 1st year and Subsequent dosing may be
every 6 mo on 2nd year and yearly based from monitoring of parasite
thereafter load
SMALL RUMINANTS
Pregnant animals 2 wks-1 mo Use anthelmintic that is effective
against all stages of worms a
Repeat after 3 mo month before onset of rainy
season
2 wks before expected parturition
SWINE
Piglets 4 wks of age Broad spectrum dewormer may
I wk after weaning be used
Grower/Fattener 5-6 wks after last deworming Routine fecalysis may be helpful
Sow/Gilt 2 wks before breeding Hygiene and sanitation also play
2 wks before farrowing important role
2 wks after weaning litter
Boar/Replacement At least 2x a year (3-4 mo interval)
Breeder
POULTRY
Layer and breeder 2x before onset of lay
EQUINE
Start at 2 mo of age
Min of every 8 wks thereafter
DOG/CAT
Pup/kitten 2,4,8 and 12 wks of age, every 3 Control of roundworms and
mo thereafter hookworms
At 3 mo of age,treat every 6-8 wks For whipworm

>1 year Once a mo
2 wks before breeding and before
parturition
Study questions?
1. Name species of worm affecting the different species of animal.

2. Identify the indicated anthelmintic for specific worm in animal.
3. What are included in the proper control of worm infection in animals?
4. Which is more practical to use, broad spectrum or narrow spectrum anthelmintic?
Explain.
5. Is there a need to eliminate worm population in animals? Why?
142
ANTIPROTOZOAN AGENTS
Protozoa differ at some extent from pathogenic bacteria and fungi. Many protozoan
require arthropod intermediate hosts for complete development. They are generally closer in
biochemical make up to the mammalian cells than are the pathogenic bacteria and fungi, hence
may pose as problem with regard to the selective toxicity of the antiprotozoal agents.
Most antiprotozoal agents possess a narrow spectrum of activity. Antiprotozoal agent

discussed below will be classified based on the protozoan agent they affect.
DRUGS AFFECTING AMOEBAE AND FLAGILLATES
1. NITROMIDAZOLE
Metronidazole Dimetrinidazole
Ipronidazole Tinidazole
a. Mechanism of action: After appropriate drug metabolism, the intermediate product
may interfere with nucleic acid synthesis by binding to DNA
b. Therapeutic Use
i. Metronidazoles are approved for use in canine, feline and equine giardiasis.
Also for the treatment of trichomoniasis, histomoniasis and amebiasis
ii. Before treatment of trichomoniasis in bulls with Ipronidazole (IM), the bulls
should receive a course of broad spectrum antibacterial to reduce preputial
commensal bacteria, which might inactivate the drug
c. Pharmacokinetics
i. It is absorbed well from the GIT and reaches high concentration in tissues
ii. It has 8 hours t ½ and less than 20% bind to proteins
iii. Metabolized in the liver, primarily excreted in the kidney
d. Dose
i. DIMETRIDAZOLE
1) Cattle: 50 mg/kg oral daily for 5 days or 10 mg/kg IV for 5 days for bovine
trichomoniasis
2) Turkey: 0.0125% in feeds for histomoniasis
ii. METRONIDAZOLE
1) For feline amebiasis: 10-25 mg/kg BID for 5-7 days
2) Canine giardiasis and amebiasis: 15-30 mg/kg BID for 5-7 days
3) Equine giardiasis: 5 mg/kg TID for 10 days
iii. TINIDAZOLE
Canine giardiasis: 44 mg/kg OD for 3 days
2. NITOFURANS
Nifurtimox Nitofurazone Furazolidone
a. Mechanism of action: Inhibit DNA synthesis by breaking DNA strands
b. Therapeutic use
143
i. Nitofurazone. Has an anticoccidial and antibacterial activity. Used as

preventive anticoccidial (0.0005%) in feed. As a curative anticoccidial
(0.002%) may cause nervous signs when treatment is continued for more
than 12 days
ii. Furazolidone. Use to treat feline giardia infection at 4 mg/kg BID for 7-10
days. Was used to treat histomoniasis (given in feed at 0.022%)
iii. Nifurtimox. For treatment of Chagas disease caused by Trypanosoma
3. QUINACRINE HYDROCHLORIDE
a. Clinical use. Used in the treatment of canine giardiasis at 6.6 mg/kg BID for 5 days
4. PHENANTHRIDINES or AMINOPHENANTHRIDIUMS
Homidium Bromide (Ethidium BrO, Dimidium Br, Pyrithidium Br and
Isometamidium)
i. Inhibit DNA polymerase and DNA-primed RNA polymerase as a result of
intercalation of the drugs with DNA
ii. This causes a local unwinding and lengthening of the DNA helix and thus
interferes with its function as a primer in the nucleic acid synthesis
b. Therapeutic use: Used for trypanosomiasis (Trypanosoma congolense, and T.
vivax). Less effective against T. brucei, inactive against T. evansi
c. Dose
i. HOMIDIUM Br: 1 mg/kg as a single IM injection curative and prophylactic for
a month
ii. PYRITHIDIUM: 2 mg/kg IM
5. AMINOQUINOLONES
Chloroquin Quinacrine
a. Mechanism of action: Quinine and chloroquin act in the same way as the
phenanthridines, although chloroquin is primarily concerned with inhibition of
hemoglobin degradation causing amino acid starvation of the parasite
b. Therapeutic Use
i. Both quinine and chloroquin are used for malaria.
ii. Chloroquin in addition has an anti-inflammatory property. Also used for
rheumatoid arthritis and discoid lupus erythematosus
iii. Quinacrine: Used for giardiasis in dogs
c. Dose
i. For large breeds: 200 mg/dog TID on the first day and BID on the subsequent
6 days
ii. For small breeds: 100 mg/dog BID for 6 days
6. ALBENDAZOLE and MEBENDAZOLE

a. Therapeutic use: Albendazole was found to be 30 fold more effective than
metronidazole in treating canine giardiasis at 25 mg/kg q 12h for 2 days
144
7. TETRACYCLINE
a. Therapeutic use: They have been found to be effective against amoebae, mucosal
flagellates, coccidian, malaria, and babesia
b. Mechanism of action: The antiprotozoal activity of tetracycline is associated with
their lipophilic properties and reflects better uptake of lipophilic agents by passive
diffusion of protozoans
AGENTS AFFECTING COCCIDIA, HAEMOSPOROZOANS AND PIROPLASMS
1. SULFONAMIDES and SUBSTITUTED PARA-AMINOBENZOIC ACID

Sulfadiazine Sulfaquinoxaline
Sulfadimethoxine Sulfaguanidine
Sulfadoxine Sulfamethazine
Sulfamethoxazole Sulfanitran
Ethopabate
i. As analogues of the growth factor p-amonobenzoic acid (PABA), blocks the
synthesis of tetrahydrofolate
ii. Affecting mostly the asexual stages of coccidian
b. Therapeutic use: Widely used for coccidiosis, malaria and bacterial infections
c. Adverse effect: Prolonged use can cause hemorrhagic syndrome in birds
d. Dose
i. Sulfamonomethoxine: also for leucocytozoonosis in birds: 1g/L of drinking
water
ii. Ethopabate: Usually combined with amprolium for prevention of coccidiosis in
poultry. Given at 0.0004 to 0.004%
AGENTS AFFECTING COCCIDIA, HAEMOSPOROZOANS AND

PIROPLASMS
3. SULFONAMIDES and SUBSTITUTED PARA-AMINOBENZOIC ACID:

Sulfadiazine Sulfaquinoxaline Sulfadimethoxine
Sulfaguanidine Sulfadoxine Sulfamethazine
Sulfamethoxazole Sulfanitran Ethopabate
a. MOA:
i. As analogues of the growth factor p-aminobenzoic acid (PABA), block
the synthesis of tetrahydrofolate
ii. Affecting mostly the asexual stages of coccidian.
b. Therapeutic use: Widely used for coccidiosis, malaria and bacterial
infections
c. Adverse effect: Prolonged use can cause hemorrhagic syndrome in birds.
145
d. Dose:
i. Sulfamonomethoxine - also for leucocytozoonosis in birds; 1 g/liter of
drinking water
ii. Ethopabate - usually combined with amprolium for prevention of
coccidiosis in poultry. Given at 0.0004 to 0.0004%.
2. DiAMINOPYRIMIDINES
Diarveridine Ormetoprim
Pyrimethamine Trimethoprim
a. MOA:
Inhibit synthesis of tetrahydrofolate at the tetrahydrofolate reductase level.
Cosequence of tetrahydrofolate inhibition: disruption of one- carbon
transfer reactions important in protein and DNA synthesis.
Synergistic with sulfonamides.
b. Therapeutic Use:
Diaveridine and pyrimethamine - coccidiostats in combination with
sulfadimidine or sulfaquinoxaline.
Pyrimethamine - drug of choice for toxoplasmosis. Also used for
leucocytozoonosis.
POLYETHERIONOPHORES
Monensin Lasalocid Salinomycin Narasin Maduromicin
l. MOA:
i. They have the ability to form lipophilic complexes with alkali metal cations
and transport these cations across the biological membrane
ii. Acts against extracellular sporozoites and merozoites.
m. Therapeutic use:
i. For treatment of coccidiosis in poultry
ii. Acts on the first sexual cycle by preventing the development of first
generation schizonts
iii. Retards the development of immunity to coccidiosis. Suitable for addition
to broiler feed.
n. Special considerations
i. Should not be mixed with the feed for laying birds
ii. Do not feed to horses and other equines
iii. Must not be used together with other coccidiostat
iv.Fatal when used with the therapeutic levels of tiamulin d.
Dose:
i. Monensin 0.01-0.0121% in feed
ii. Lasalocid 0.005 - 0.0075% in feed
iii. Salinomycin 0.01% in feed
iv. Narasin 0.07%
v. Maduromicin 0.0005 - 0.0006%
146
b. MOA: Acts as structural analogue of thiamine or vitamin Bl, a cofactor of a

number of decarboxylase enzymes.
c. Therapeutic Use
1. An anti coccidal. Acts chiefly on the first generation schizonts; effective in
the early stages of infection.
2. Used as a preventive and therapeutic drug against Eimeria tenella and E.
acervulina broilers.
3. Used as preventive drug in layers.
d. Adverse reaction
1. Bleeding disorders.
2. Vitamin K in the diet reduces mortality.
e. Dose: Amprolium 20 % - 5g/4gal water for 305 days.
o. CLOPIDOL
i. MOA. Interfere with cytochrome-mediated electron transport in the
parasites mitochondria.
ii.
Therapeutic use.
i. Active against sporozoites and interfere with second generation
schizogony, gemetogony ad sporulation of coccidian.
p. ROBENIDINE
i. MOA. Undetermined. Its peak activity is on the first generation schizonts.
ii. Therapeutic Use. Use in chicken to prevent outbreak of coccidiosis in
chicken.
q. DECOQUINATE
i. MOA. Decoquinate is a quinolone and blocks DNA synthesis by inhibiting
DNA gyrase.
ii.
Therapeutic Use.
i.Used in calves, young goats, and broilers for prevention of coccidiosis. Not
effective for treating clinical cases.
ii.It is effective against bovine Eimeria, E. bovis and caprine E. christenseni.
AGENTS AFFECTING BABESIA AND THEILERIA
AROMATIC DIAMIDINES
Pentamidine Stilbamide Phenamidine Imidocarb Diminazene aceturate
f. MOA. Blind with DNA. Disrupts phosphogylcerate synthesis.

g. Therapeutic Use.
1. Diminazene aceturate:
a.
Treatment of equine and bovine babesia infection 6-12 mg/kg bid;
canine babesiosis 3.5 mg/kg SC.
147
b. Also against Trypanosoma congolense and T. vivax, less

effective against T. brucei and T. evansi.
2. Phenamidine is used against babesiosis in equine and bovine at 8.8

mg/kg bid.
CHEMOTHERAPY OF SOME PROTOZOAN DISEASES
COCCIDIOSIS
There are two important genera: Eimeria and Isospora. Coccidia may enter cells in
liver (rabbit) and intestine (cattle, sheep, pigs , goats, dogs, rabbits and fowls). Infection is
self-limiting.
The parasites undergo two stages of multiplication: asexual (schizogony) and sexual
(sporogony). The rapid multiplication during sporogony is the most pathogenic stage.
Repeated infection may cause host immunity.
a. Goat and sheep coccidiosis: infection is chiefly confined to young (4 - 6 mo old), a. Tx.
i. Sulfaguanidine - 2 g/day for 6 days
ii. Nitrofurazone - 7 - 10 mg/kg daily for 7 days maybe given in feed at
0.0165% or 0.008% in drinking water.
iii.
Amprolium - 50 to 62.5 mg/kg in water or feed for sheep; 100 mg/kg for 4
days or longer for goats
b. Catlle coccidiosis: infection common in 3 weeks to 6 mo. Old a. Tx.
i.Lincomycin HC1 -1 g/calf in water for 21 days
ii.Amprolium - most effective drug at present; 20-25 mg/kg in feed daily for
4-5 days.
c. Poultry coccidiosis: The clinical disease is dependent upon the number of oocyst ingested
by individual birds. No cross immunity between species of coccidian.
r. Protection is more important in fast-growing birds than the egg-laying type where
immunity and caging alter the demands for anticoccidial drugs.
s. To prevent development of resistance, switch from one class of anticoccidial to
another
t. Curative regimen
i. Sulfadimidine - 0.2% in drinking water for two periods of 3 days separated by 2 days
without treatment.
i. .Sulfaquinoxaline - 5% mixed in feed
ii. Nitrofurazone with furazolidone - 0.0126% given over 7 day period; maybe
repeated after 5-day interval.
i. Dog coccidiosis a. Treatment
a. Sulfadimethoxine - 50 mg/kg for 10 days
b. Sulfaguanadine -5-10 mg/kg
c. Amprolium - 300 - 400 mg/kg for 55 days
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TOXOPLASMOSIS
Caused by Toxoplasma gondii. Definitive hosts are domestic cat, and other felines.
Intermediate host are almost all warm-blooded animals, a. Tx: aim to reduce shedding of
oocysts
i. Pyrimethemine - 0.025 - 0.5 mg/kg dogs and cats
ii. Clindamycin - cat 8-17 mg/kg PO or IM q8h for 2 weeks
Dog - 3-13 mg/kg PO or IM q8h for 2 weeks
TRYPANOSOMIASIS
Caused by Trypanosoma spp. Most species undergo cyclical changes in arthropod
vectors.
a. Tx.
d.Suramin: Horse; 4g/45 kg IV
Dog; 0.03 g/kg IV for 6 days
e. Pyrithidium Br.
Cattle: used as 1-2.5% solution at 1 mg/kg IM
Protection lasts for about 5 weeks
BABESIOSIS
Caused by Babesia spp. Transmitted by arthropods; acute, often fatal infections;
characterized by fever, hemolytic anemia, jaundice, CNS signs and HBnuria. a. Treatment
i. Tetracycline
ii. Diminazene aceturate Horse: 3-5 mg/kg IM Dog: 3-5 mg/kg IM
iii. Imidocarb Bovine: 1-3 mg/kg IM or SC Horse: 1-2 mg/kg 2x
ql2h Dog: 5 mg/kg IM
.ANAPLASMOSIS
a. Treatment:
2.Tetracycline: 11 mg/kg for 10 days
3. Tetracycline LA 22 mg/kg, administered 4 doses 3 days apart
4. Imidocarb proprionate 4 mg/kg 2 weeks apart or daily for 3 days at 5
mg/kg
LEUCOCYTOZOONOSIS
a. Prophylactic medication
a. Pyrimethamine (1 ppm) and sulfadimethine (10 ppm)
b. Clopidol may also be used at 1.25 to 2.5 ppm
c. Quinacrine and Chloroquine phosphate
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EXTERNAL ANTIPARASITICS
External antiparasitics (pesticides) are agents that reduce parasite burdens to a

tolerable level by killing or inhibiting their growth. Pesticides include insecticides or agents
that affect insects and acaricides, agents that affect arachnids.
CLASSIFICATION OF ECTOPARASITES:
Arachnids
2. Ticks - affect mainly ruminants but may also affect horses, dogs and poultry.
3. Mites:
i. Sarcoptidae includes mange mites - Chorioptes, Notoedres,
Otodectes, Psorergetes, Psoroptes and Sarcoptes.
ii. Demodicidae includes parasites causing demodectic mange.
iii. Gamasidae includes the n orthern and red mites of poultry.
6. Insects
a. Diptera (flies)
b. Anopleura (lice)
c. Siphonaptera (fleas)
Methods of application of pesticides:

1.
External application
a.
Dipping
b.Spraying
c.
Application by hand as dust, ointment, spray, foams, mist spray, aerosol,
pour-on, spot-on
d.
By tags, collars, and strips
2.
Systemic application
a.
As feed additive
b.
By injection
c.
By stomach tube
d.
By intranasal administration (for Oestrus ovis)
Pesticide Toxicity:
i.All pesticides are poisons and can be toxic to both warm blooded and cold-
blooded animals. Acute signs of poisoning usually result from over-dosage.
ii.Factors affecting pesticide toxicity
2. Age - younger animals are more susceptible
3. Health - healthy animals are least likely to be affected
4. Stress
5. Species
a. Cats are very sensitive to effects of pesticides because of their
grooming behavior and deficient drug biotransforming
capacity.
b. Horses show extreme sensitivity to various pesticide
formulations. They may develop urticaria and hyperemia.
6. Environment - animals confined to poorly ventilated areas are
150
more likely to be affected 3.

Precautions to prevent toxicity
4. Do not apply pesticides in combination unless specified by the manufacturer.
5. Precautions must be taken to prevent poisoning of the person administering
pesticides. Handlers must wear protective cloth, ing including rubber gloves and
mask especially when handling spray, dust and solutions of organophosphate and
organochlorine compounds
6. Should contamination occur, wash off insecticide immediately. Medical assistance
maybe called in contamination that is more serious when signs of poisoning are
present.
7. Precautions must be practiced to prevent contamination of human food supply and
environment.
8. Waste solutions or empty containers should be carefully disposed of to avoid
contamination of streams, ponds and patures.
9. Do not re-use empty pesticide containers.
CLASSIFICATION OF PESTICIDE
According to mode of action

i. Stomach poisons must be eaten by parasites to be effective.
ii. Contact poisons enter the body of parasites through the skin.
iii. Fumigants are released into the atmosphere as a gas or a mist; enters the parasites
by the respiratory system.
According to chemical structure

1.Chlorinated hydrocarbons. These are becoming less popular because of persistence in
the environment.
a. Examples: Lindane, Bromocyclen, Methoxychlor, DDT and Chlordane
b. Lindane, Bromocyclen and methoxychlor are still used such as against mange
mites in pigs.
c. DDT and Chlordane are no longer approved for use.
2.Organophosphates
d. Examples: Chlorpyriphos Chlorvinphos, Crotoxyphos, Coumaphos (Asuntol
™), Cythioate, Diazinon, Dichlorvos, Dioxanthion, Famfur, Fenthion,
Malathion, Phosmet, Tetrachlorvinphos, Trichlorfon (Neguvon®),
Dichlorofenthion (Gusanex®)
e. MOA: OPs are both contact and stomach poisons. They inhibit
cholinesterase enzymes.
f. Pharmocokinetics: Ops are subjected to biotransformation in animal
tissues resulting in inactivation. The enzymes responsible for this
inactivation are not present in ectoparasites.
g. Adverse effects: All Ops are toxic to humans and animals. By virtue of
their cholinesterase inhibitory activity. Cholinesterase inhibition by Ops is
relatively less readily reversible, if not totally irreversible.
151
3.Carbamates
h. Examples: Carbaryl (Sevin®) and Propoxur Methylcarbamate (Negasunt®)
i. MOA: They reversible inhibit cholinesterase enzymes.
j. Therapeutic Use: Use as powders or sprays on animal to reduce ticks,
fleas and lice.
4.Pyrethrins and Pyrethroids
i.pyrethrins are naturally occurring: extracted from chrysanthemum flower.
ii. pyrethroids: examples, cypermethrin , decamethrin, resmehtrin, allethrin, fenvanlerate. They
are synthetic compounds and have greater potency than pyrethrin.
iii.MOA: blocks the nicotinic receptor and increases GABA realease.
iv. Therapeutic uses: rapid breakdown effect with low residual activity on insect. Often mixed
with synergists to enhance.
5.Rotenone
i. A naturally occurring compound obtained from debris roots. Largely superseded but still use in
mixtures with other pesticides.
ii.MOA. Inhibits cellular respiratory metabolism by blocking electrin generation.
iii.Therapeutic Use: Use for ear mite and demodectic mange in dogs. It has a fast knock
down action on all arthropod with little persistence.
6. Formamidines
i. Examples: Amitraz (Ectodex®; Tactic®) is an acaricidal compound.
ii. MOA. Kills parasite by inhibiting monoamine oxidase.
iii. Therapeutic use:
a) Offers an alternative for treatment of ticks, lice and mange mites in dog, swine, cattle
where resistance to Ops has developed
b) 3-6 biweekly treatment may be used to control demodectic mange.
a. Dose: Ectodex® - 5 -10 ml/L water; no rinsing needed
1. Tactic® - 400 ml/100 L water
7. Synergists
ii. Examples: Piperonyl butoxide, N-octyl-bicycloheptene dicarboxamide
(MGK 264), Sesamin and Sesamolin.
iii. MOA. They prolong the activity of a wide range of pesticide by inhibiting
microsomal enyzymes of insects.
iv. Therapeutic uses: They are often included in formulations of topical
preparations particularly those containing pyrethrin.
a. Insect growth regulators.
152
i. Example: Methoprene; Cyromazine; Fenoxycarb,

Pyriproxyfen,Lufenuron
ii. MOA. Mimic the action of juvenile hormones of insects thereby maintaining
the larvae in immature stage and interfere with reproductive organ
differentiation.
iii. Therapeutic Use:
• Lufenuron is used in dogs and cats older than 6 weeks of age to
control flea. It is effective against eggs and immature fleas, but has
no proven effects on adult fleas. Administered orally once a month.
• Cycromazine is used as feed premix to control fly larvae
a) Repellants
i. Examples; Dimethyl phthalate; Deet (N-N-diethyl-m-toluamide), D-
Limonence, Linalool, Crude citrus oil extract
ii. Used in veterinary medicine not yet established.
b) Endectocides (Macrolides)
i. Example: Ivermectin,Abamectin, and Doramectin. Selamectin
ii. MOA. Enhance the inhibitory neurotransmitter GABA.
iii. Therapeutic Use: Use in the treatment of Sarcoptes and Demodectic
mange.
iv. Dose: Ivermectin: 0.02 mg/kg 2x, 2 wks apart for sarcoptes
7. MOA. Inhibits cellular respiratory metabolism by blocking electrin

generation.
8. Therapeutic Use: Use for ear mite and demodectic mange in dogs. It has a
fast knock down action on all arthropod with little persistence.
C Formamidines
a. Examples: Amitraz (Ectodex®; Tactic®) is an acaricidal compound.
b. MOA. Kills parasite by inhibiting monoamine oxidase.
c. Therapeutic use:
u.
Offers an alternative for treatment of ticks, lice and mange mites in dog,
swine, cattle where resistance to Ops has developed
v.
3-6 biweekly treatment may be used to control demodectic mange.
i. Dose: Ectodex® - 5 -10 ml/L water; no rinsing needed
Tactic® - 400 ml/100 L water
7. Synergists
i. Examples: Piperonyl butoxide, N-octyl-bicycloheptene dicarboxamide
(MGK 264), Sesamin and Sesamolin.
ii. MOA. They prolong the activity of a wide range of pesticide by inhibiting
microsomal enyzymes of insects.
153
iii. Therapeutic uses: They are often included in formulations of topical

preparations particularly those containing pyrethrin.
a. Insect growth regulators.
i. Example: Methoprene; Cyromazine; Fenoxycarb,
Pyriproxyfen,Lufenuron
ii. MOA. Mimic the action of juvenile hormones of insects thereby maintaining
the larvae in immature stage and interfere with reproductive organ
differentiation.
iii. Therapeutic Use:
• Lufenuron is used in dogs and cats older than 6 weeks of age to
control flea. It is effective against eggs and immature fleas, but has
no proven effects on adult fleas. Administered orally once a month.
• Cycromazine is used as feed premix to control fly larvae
a) Repellants
i. Examples; Dimethyl phthalate; Deet (N-N-diethyl-m-toluamide), D-
Limonence, Linalool, Crude citrus oil extract
ii. Used in veterinary medicine not yet established.
b) Endectocides (Macrolides)
i. Example: Ivermectin,Abamectin, and Doramectin. Selamectin
ii. MOA. Enhance the inhibitory neurotransmitter GABA.
iii. Therapeutic Use: Use in the treatment of Sarcoptes and Demodectic
mange.
iv. Dose: Ivermectin: 0.02 mg/kg 2x, 2 wks apart for sarcoptes
Selamectin: 0.60 mg/kg 5x, 7 days apart for demodex. Benzyl

benzoate
i. An acaricide used as an adjunct in the treatment of sarcoptic mange in dogs. Toxic to
cats.
Examples: Sublimed sulfur, Precipitated sulfur, and Monosulfiram Therapeutic use:
ii. For years was the best external treatment for mange until the advent of chlorinated
hydrocarbons. Still used for routine baths for dogs.
iii. Maybe applied as ointments or oily suspension at a concentration of 1:8
iv. As powders diluted with talc, kaolin, etc. or as dispersible bath powders combined
with soaps and wetting detergents
MOA:
v. Acts as a non-competitive inhibitor of GABA, an essential neurotransmitter of the
CNS of the invertebrates.
vi. By binding to a receptor site inside the chloride channel, fipronyl inhibits the
intracellular flow of chloride ions, thereby inducing a rapid and sure death of the
ectoparasite due to hyper-excitation.
Therapeutic Use: Available as spray or spot-on preparation, and maybe applied on a monthly
basis against ticks and fleas.
154
18 ANTINEOPLASTICS
Neoplastics are agents that cure or control cancer or neoplastic growth.
Factors to consider in Cancer therapy:

1. Dosage calculation - body surface area is used to calculate the dosages
Duration of treatment - should continue beyond cessation of clinical signs to achieve total cell
kill
ii. Treatment is discontinued if WBC count is below 3000/mm 3 or platelet count is
below 50,000/ mm3
Combination therapy Adjunct therapy Resistance
iii. Decreased cellular permeability or uptake of drug
iv. Increased production of enzymes that degrade the drug
v. Increased capacity to repair or bypass the effects of drugs
vi. Decreased binding of drug to receptors or target enzymes
1. ANTINEOPLASTIC AGENTS:
Chemistry: Contain alkyl group which react with DNA base in the double helix and form
a cross-link.
MOA:
1. These agents produce alkalytion, the substation of an alkyl group for an active
hydrogen atom in an organic compound.
2. Alkylation of DNA inhibits replication and increases breakdown.
3. Alkylation aof proteins also inhibits transcription.
Preparation:
1. Cyclophosphamide - given PO or IV
2. Chlorambucil - given PO every 2 days
3. Melphalan - given PO 3x weekly
4. Thiotepa
5. Carmustine
6. Busulfan
Therapeutic Uses:
1. Lymphoreticular neoplasia
2. Carcinomas
3. Sarcomas
4. Multiple myelomas
5. Mast cell tumors
155
2.ANTIMETABOLITE
Chemistry: Antimetabolites are structurally similar to folic acid, pyrimidines or purine
MOA: Compete with metabolites in the formation of DNA synthesis.
W Preparations:
1. Methotrexate - use for lymphomas, carcinomas, sarcomas, TVT
2. 5-fluorouracil - use for canine carcinomas of GIT, mammary glands, liver and
lungs, given once weekly.
3. Cytosine arabinoside
4. Mercaptopurine
5. 6-Thioguanine
Therapeutic Use:
1. Lymphomas
2. Carcinomas
3. Sarcomas
4. Transmissible Venereal Tumor
ANTIBIOTICS
Preparations:
10. Doxorubicin
w. MOA: Cleaves DNA chain and induces free radicals which damage cell
membrane.
x. Therapeutic Use: Given IV q21 days to treat carcinomas and sarcomas
i. Bleomycin
y. MOA: Generates fee radicals which destroys DNA
o Therapeutic Use: Given IV o.d. for 3-4 days, then once weekly to
treat testicular tumors, squamous cell carcinoma, lymphoma
• Actinomycin D
z. MOA: Binds with DNA and blocks transcription by RNA polymerase
aa.Therapeutic Use: Given IV once weekly to treat lymphoreticular
neoplasms, rhabdomyosarcomas, choriocarcinomas
5. HORMONES
Preparations:
11. Glucocorticoids (Prednisone, Prednisolone, Dexamethasone)
bb.MOA: Decrease the circulation lymphocytes and increase circulating RBC
cc.Therapeutic Use: Lymphoreticular neoplasms, enhance appetite and well
being
i. Estrogen (Diethylstilbestrol, Estradiol cypionate)

dd. MOA: Mechanism of action: Inhibits gonadotropin secretion in the male,
decreasing androgen levels
Therapeutic Use: Treat prostatic hypertrophy and perianal adenomas
156
19 VITAMINS
Vitamins are organic dietary essentials needed in small amounts by animals so that normal
body functions (health and growth) can proceed.
Classification:
Based on Solubility
12. Water soluble vitamins

i. Composed of Vitamin B complex (thiamine,riboflavin, niacin, pantothenic acid,
Vit. B6, biotin, B12 and folic acid) and Vit. C.
ii. In most cases, these are ingested as natural dietary constituent or maybe
synthesized by gastrointestinal organisms.
iii. These are absorbed into the hepatic portal vein and any excess is excreted in
the urine
iv. There is little storage of free vitamin, hence to be supplied in the diet.
6. Some storage of folic acid occur in the liver
7. Depletion may take several months for ascorbic acid and years for B12
v. Excess intake is generally well tolerated except for side effects occurring with
large doses of niacin, ascorbic acid or pyridoxine
13. Fat soluble vitamins

i. Vit. A,D,E,K
ii. Digested with fat and absorbed by the intestine and incorporated in
chylomicrons
iii. They are transported in the liver which serves as major storage for Vit. A,D, and
K and adipose tissue for Vit. E.
iv. In obstructive jaundice and pancreatic disease, deficiencies of fat-soluble
vitamins can develop even if their intake is adequate.
v. Not excreted in the urine and are toxic in excess amount
FAT SOLUBLE VITAMINS
1. Vitamin A
ee.Vit. A1 (Retinol) - formed in animal tissue from various plant carotenoids (P-
carotene)
ff.Vit. A2 (Dehydroretinol) - found in freshwater fish
Physiologic Function:
a. Epithelial cell integrity: Maintain normal structure and function of epithelial cells;
it acts to decrease keratinization and to stimulate production and differention of
mucous-secreting cells. Affects the lining of respiratory, genitourinary and
gastrointestinal system.
157
b. Vision: P-carotene of plants is cleaved by p-carotene dioxygenase to form

retinaldehyde which binds with opsin to form rhodopsin (visual purple). The
visual purple reacts with light and activates the visual neural pathway.
c. Reproduction: Necessary for spermatogenesis in males and maintenance of
pregnancy and fetal development in females.
d. Bone remodeling: Support osteoclast and osteoblast activity and bone
growth.
e. Immunity: Promotes phagocytic and bacteriocidal function of
neutrophil;produce resistance to infectous disease
f. Hematopoiesis: Vit. A enhance incorporation of iron in erythrocyte.
g. Antioxidant and cancer prevention: Its antioxidant function removes the free
radicals and inhibits lipid peroxidation.
Deficiency Symptoms:
a) Alteration of epithelial surfaces with increased keratinization and surface lesions
b) Anasarca in cattle
c) Night blindness (nyctalopia) followed with excessive lacrimation in
cattle,sheep,horses,pigs and dogs.
d) Corneal keratization;xeropthalmia
e) Decreased reproductive efficiency; abnormalities in piglets
Toxicity:
a) Diarrhea
b) Increase mucus secretion
c) Teratogenic effects; cleft palate; deformities in joints
Food Sources:
1. Fish liver oils
2. Eggs
3. Butter
4. Liver
5. Milk
6. Green and yellow vegetables
Dietary requirement: 1000 - 2000 IU daily for most species
Vitamin D
a. Vit. D2 (Ergocalciferol) - plant provitamin
b. Vit. D3 (Cholecalciferol/calcitrol) - formed in animal tissue
Physiologic function:
i. Maintain circulating levels of calcium in the blood and parathyroid hormone
secretion
ii. Normal bone calcification
iii.Participate in immune system regulation
158
To maintain circulating levels of blood calcium, it acts on:

2. Bone - by mobilizing Ca and P
3. Intestine - by activation of intestinal epithelial cells; stimulate Ca and P absorption
4. Kidney - by increasing reabsorption of PO4 and Ca
Deficiency symptoms:
a) Rickets
b) Lactation paresis in sow
c) Parturient paresis
d) Osteomalacia
Toxicity:
Decrease bone mineralization, calcification of some soft tissues
Vasoconstriction leading to hypertension and ischemic tissue damage
Food sources:
a) Fish liver oils
b) Dairy products
c) Eggs
d) Sunlight
e) Hay
Dietary requirement: 125 - 1000 IU/kg diet Vitamin E (Tocopherola,p,y)

Physiologic functions:
a) Antioxidant - protective effect against oxidation of fatty acids, certain types of liver
degeneration, erythrocytes, hemolysis, anoxia, and hypoxia of the lungs
b) Role in normal functionvof kidney, muscle, respiratory system, enzyme and
pituitary
c) Role in formation of dental enamel and liver tissue
d) Potentiate immune mechanism of body, increase resistance to bacterial/viral
challenges
e) For normal reproductive function
a) Decreased hatchability of eggs due to embryonic death
b) Encephalomalacia and exudative diathesis in young chicks
c) Muscular dystrophy in poultry, pigs,dogs,cattle,sheep and goat
d) Steatites or yellow fat disease in carnivores or omnivores which eat fish by-
products; hepatosis dietetica
14. Mulberry heart disease, fibrinoid degeneration of arterioles, thrombi in mycardial

arteries
15. Enhance iron toxicity
Food sources:
159
i. Vegetable oil
ii. Eggs
iii. Wheat
iv. Cereals
v. Green leafy vegetables
Dietary requirement: 10,000 - 20,000 IU/tons feed in swine + 0.33 ppm selenium
Vitamin K
a. Menadione - parent compound
6. Stimulate production of coagulation factors X,IX, VII,II essential to normal blood
clotting
7. Antidote for dicoumarol-type drug
8. Has a role in the synthesis of bone protein, osteocalcin
a. Delayed clotting time
b. Spontaneous hemorrhage
Deficiency occurs during:

1.Liver disease
2.Prolonged antibiotic therapy
3.Exposure to antivitamin K (coumarin,sweet clover, and rodenticide)
Food source:
a.
Green leafy vegetables
b.
Tomatoes
c.
Cured roughage
d.
Liver
Dietary requirement: 0.05 - 2 mg/kg

WATER SOLUBLE VITAMINS
i. Vitamin Bi
Thiamine - active forms: Thiamine diphosphate (TDP); Cocarboxylase
2.
Prosthetic group in metabolism of CHO, keto-acids
3.
Essential in energy metabolism of neurons and cardiac muscle
4.
Essential to production of acetylcholine
5.
Necessary in conversion of pyruvate to acetyl-CoA
a. Neuromuscular incoordination and tremors (beri-beri)
b. Convulsion, cardiac failure
160
Thiamine-destroying agents:
Bracken fern
Carp (Hemin-partially degraded Hb metabolite)
Amprolium
Thiaminase - synthesize by Clostridium sporogenes and mold
Food source:
gg.
Brewer's yeast
hh.
Pork
ii.
Fresh green vegetables
jj.
Whole grain
kk.
Liver
Dietary requirement: 0.8 - 2 mg/kg
i. Vitamin B2 - Riboflavin
i.Activated into coenzymes flavin mononucleotide (FMN) and flavin adenine
dinucleotide (FAD) or otherwise known as flavoproteins which are necessary in
many reduction processes
ii.
Necessary for normal growth and development of fetus
iii.
Essential to health of tissues of ectodermal origin, including CNS
iv.
Has a role in release of ACTH
v.Share with vitamin A and nicotinamide in visual purple
a. Seborrheic lesions
b. Exhaustion
c. May occur with pellagra
d. Curl toe paralysis in chickens
Food source:
1. Yeast
2.
Milk
3.
Leafy vegetables
4.
Liver
5.
Meats
6. Egg white
Dietary requirement: 1.8-4 mg/kg Niacin,
Nicotinic acid, Nicotinamide

161
a. Prosthetic group of coenzyme I (Nicotinamide adenine dinucleotide) and II (NAD-

Phosphate) which serve as hydrogen carriers in glycolysis; Kreb's cycle and oxidative
phosphorylation
b. Has a role with Vitamin B in maintaining healthy CNS, skni, and GIT
i. Pellagra in humans
ii. Blacktongue in dogs
iii.Oral lesions in most species
Food source:
2. Yeast
3. Eggs
4. Liver
5. Milk
6. Corn
Dietary requirement: 11 - 70 mg/kg of diet Biotin
a. Coenzyme for certain carboxylations, decarboxylation; and deamination
b. Necessary for utilization of panthotenic acids
c. Important in ectodemal metabolism
d. May involve in biosynthesis of fatty acids, amino acids and proteins
Fatty liver
Kidney syndrome
Food source:
a. Present in all food
b. Raw egg white contains avidin which can bind with Biotin Dietary
requirement: 100-300 ng/kg of diet
16. Choline - derived from methionine
a. Base components of neurohumor acetylcholine essential for all cholinergic
neuromuscular transmission
i. Perosis
162
ii. Decrease reproductive efficiency in sows Dietary requirement: 400 - 1,900 mg/kg
of diet
17. Folic acid
i. Provitamin
ii. Associated with Vitamin B12 in nucleic acid synthesis and nucleoprotein function
iii. Active in metabolism of amino acids, purine, and pyramidine
iv. Necessary to utilization of pathothenic acid by organisms
v. Essential to growth and reproduction
vi. Important in erythropoiesis Deficiency symptoms:
a. Growth failure and megaloblastic anemia
Food source:
6. Green leafy vegetables
7. Kidney
8. Yeast
9. Liver
Dietary requirement: a. 0.25 -

1 mglkg
a. Pantothenic acid
1. Component of coenzyme A
2. Important to adrenal function, antibody production and epidermal growth Dietary
requirement: 8-16 mg/kg

b. Vitamin B6 - Pyridoxine, Pyridoxol
1. Acts as coenzyme in many steps in amino acid metabolism
2. Has a role in synthesis of unsaturated fatty acids from protein
3. Necessary to health of entire organism, especially CNS and skin
Suggested clinical application:

a.Idiopathic and metabolic neurological disorders, certain dermatosis, prolonged
vomiting, radiation sickness
b.B-complex deficiencies
Food source:
163
i. Yeast
ii. Meat
iii. Whole grains
iv. Legumes
v. Liver
vi. Fish
vii. Corn
Dietary requirement: 1 -6 mg/kg
2. Vitamin B12- Cyanocobalamin
a. Has a role in synthesis of methionine, choline andproduction of purine and
pyrimidines
b. Essential to normal metabolism of carbohydrates, fats, and proteins
c. Important to RBC, neural function and growth
Deficiency symptoms: a. Pernicious

anemia
Food source:
Liver
Beef
Eggs
Organ meats
Pork
Dairy products
ll. Vitamin C - Ascorbic acid
a. Function in the synthesis of hydroxyproline, an important component of collagen
and connective tissue
vii. Important in redox system and certain other metabolic process
viii. Essential to normal growth, especially of bones and teeth
ix. Role in anti-stress factor, including effects of adrenals and anti-infectious in action
x. Essential for normal wound healing
xi. Antioxidant
xii. Anticarcinogenic
Suggested clinical application:

6. Scurvy
7. Supportive in infectious disease
8. Possible prevention of common cold
Food source:
164
a. Citrus fruits
b. Green peppers
c. Parsley
d. Vegetables of cabbage family
165
20 ANTISEPTIC AND DISINFECTANTS

Antiseptic is a substance that is applied to skin or tissues to inhibit the rate of reproduction or
growth of microorganisms.
Disinfectant or germicide is a substance used to destroy bacteria or other infective organism

and is usually applied to inanimate surfaces
Sanitizer is a substance that reduces the number of bacterial contaminants to population

judged safe by public health interpretations
Sterilization refers to complete destruction of all forms of microbial life by chemical or

physical processes.
Properties of ideal antiseptic:

1. Wide spectrum of antimicrobial activity
2. Non-irritating
3. Low toxicity
4. High penetrability
5. Activity in the presence of pus and necrotic tissue
6. Non-interference with normal healing processes
7. Non-corrosive for certain types of surgical instrument
8. Should have color to define areas to which it is applied
9. Low cost
Properties of ideal disinfectant:

a. Ability to penetrate crevices, cavities and films of organic matters
b. Maintain lethal concentration in the presence of organic matter, blood, soil and fecal
matter
c. Compatible with soap and other chemical
d. Chemically stable
e. Odorless and economical
Factors affecting effectiveness of antiseptic or disinfectant:

i. Concentration
ii.Time exposure
iii.
Temperature
iv.Susceptibility of microbe
v. Protective effects of organic matter
Types of disinfectant:
1. Based on target microorganism
a. Low level - kills most bacteria, some viruses and fungi but not tubercle bacilli
or bacterial spores
2. Intermediate - inactivate tubercle bacilli, most viruses and fungi but not bacterial
spores
166
3. High level - destroys all microorganism except in high number of bacterial

spores
2. Based on risk of infection

a. Critical - disinfection of materials use to penetrate skin and mucous membranes
b. Semi- critical - those that touch mucous membranes
c. Non-critical - those that do not touch mucous membrane but may contact intact
skin
Mode of action:
Alteration of plasma membrane permeability
Protein coagulation
Poisoning or interference of vital metabolic enzyme system
Removal of free sulfhydryl group of bacteria
TYPES OF ANTISEPTIC AND DISINFECTANTS:
mm. PHYSICAL AGENTS

i. Heat
i.Moist heat - produces its germicidal effect by protein coagulation, more effective
than dry heat
ii.
Dry heat - oxidize and incinerate microorganisms. Requires higher temperature
and longer exposure period
ii. Light
• Ultraviolet light - electromagnetic radiation having a wavelength shorter than
visible light but longer than x-ray. Use to sterilized food and medical equipment.
a) CHEMICAL AGENTS A. Alcohols

i. Preparations
i.
Ethyl alcohol (ethanol)
i.
Isoprophyl alcohol - more potent than ethanol; less corrosive
i. Rubbing alcohol - crude distillates of alcohol that contains mostly isoprophyl
alcohol
i. Methyl alcohol - produced by distillation of wood
ii. Mechanism of action
i. Damage bacterial membrane and precipitate protoplasmic protein; act on
vegetative cells but not destroy bacterial spores and non- enveloped
viruses
9. Uses
a. Excellent when used at 70-95% concentration for disinfection of instruments,
though it is not recommended for high level disinfection.
b. Skin antiseptic, 1-3 minutes contact time can eliminate 80% of organism. Though
rapid evaporation can limit contact time, residual effect decease bacterial
contaminant.
10. Adverse effects
167
i. After prolonged and repeated use alcohols can damage shellac mountings of
lensed instrument and can swell or harden rubber and plastic tubings.
B. Halogens a. Iodine
a. Preparations:
1.Iodine tincture - 2% iodine, 2.4% potassium iodide, dissolved in 50% ethanol
2.Iodine solution (Lugol's solution) - 2% iodine, 2.4% KI in aqueous solution
3.Iodophors (tamed iodine) - iodine in solubilized surfactant
• Solubilizing carrier - Polyvinyl pyrrolidone (PVP), or otherwise known
as povidone
b. Mechanism of action:
It exerts lethal effects by diffusing into the cell and interfering with the
metaboYic reactions and pioXem
nucleic acid structure and synthesis. 2. Eliminates both enveloped and
non-enveloped virus, fungi, bacteria and algae
c. Uses:
1.
Applied on skin surfaces before surgical incisions or hypodermic injections
2.
Treatment of various skin disease caused by fungi or ectoparasites
3.
Counterirritant for the treatment of equine lameness
d. Undesirable properties:
1.
Tissue irritant
2.
Allergic or toxic reactions
3.
Stains
4.
Corrosive to certain metals
5.
Inactivated in the presence of organic matters, needs multiple application.
b. Chlorine
i. Preparations:
1. Hypochlorites - may contain Na and Ca
2. Organic chlorides - Chloramine T, Chloroazodin, Chlorinated lime)
a. Mechanism of action:
1. Release of free chlorine and formation of hypochlorous acid from water can
inhibit cellular enzymatic processes, protein denaturation and inactivation of
nucleic acids
b. Uses:
i. low level of disinfection such as disinfection of non-metal base surfaces at
clinics, sanitize dairy equipment, animal quarters and non-critical items.
ii. Low concentration of free chlorine is active against M. tuberculosis (50 ppm)
and vegetative bacteria.
iii. Can sanitize water supply at 1 -3 ppm.
c. Undesirable properties:
1. Corrosive to metals, destroys many fabrics and have strong odor
168
C. Acids
nn. Inorganic acids
i.
Hydrochloric acids - cidal at pH<3
ii.
Sulfuric acid
iii.
Boric acid - non-irritating to tissue, applied to delicate areas (2-5% aqueous
solution)
oo. Organic acids
i.
Salicylic acid - combined with other drugs in dermatologic preparations for its
keratolytic activity
ii.
Benzoic acid - constituent of Whitefields ointment used in treating fungal infections
iii.
Acetic acid - 1% solution used in surgical dressing: 0.25% for UTI infection
D. Alkalies - alter enzyme activity of microorganisms

i. Lye (soda lye) (NaOH) - kills pathogen causing fowl cholera, pullorum disease and
anthrax in high concentration
ii. Sodium carbonate and trisodium phosphate - primarily used as cleansing agent
iii.Lime (calcium oxide - "apog", quickname) - powdered lime is used as general
disinfectant
iv. Ca hydroxide (hydrated or slaked lime)
v. Ca hydroxide solution (lime water)
a. Alkali combinations
i. 1% sodium hydroxide + 8% sodium hydrochlorite + 3-5% formaldehyde - inactivates
TGE virus within 5 minutes
ii. 2% calcinated sodium carbonate + 98% sodium chloride - inactivates FMD virus on
cattle hides
iii. 2% sodium hydroxide and 2 % cresol - inactivate hog cholera virus in excreta
b. Aldehydes
i. Formaldehyde
i. Preparation:
Formaldehyde solution - bactericidal in concentration of 1% - 2% of gas within a
few minutes of exposure
Formalin - contains 37 - 40% formaldehyde in aqueous solution with variable
amounts of methyl alcohol to prevent ploymerization
i. Mechanism of action:
i. Inactivates microorganism by alkylating the amino and sulfhydryl groups
ofprotein and ring nitrogen atoms of purine bases
i. It is effective but slow bactericide, virucide, fungicide, require 6-12 hr. contact
time
i. It is effective against M. tuberculosis, bacterial spores and most animal
viruses
i. Uses:
i. For fumigation of building: 35 ml of commercial formaldehyde in a vessel for
each 100 cubic feet of space plus potassium permanganate in the proportions of 17.5 g/100 cu.ft.
Close the building for 65 hours at a temperature of 70°F. This kills viruses, bacteria and molds.
i. Disinfection of surfaces
169
i. Glutaraldehyde
i. Preparation:
1. Glutaral - (glutaraldehyde) l%-2% alkaline solution in 70% isopropanol; more
potent than 4% formaldehyde; used to sterilized surgical and endoscopic
instrument and plastic rubber apparatus.
i. Mechanism of action:
Inactivates microorganism by alkylating the sulfhydryl groups, hydroxyl, carboxyl, and amino
groups affecting RNA and DNA and protein synthesis.
It has better bactericidal, virucidal, sporicidal activity than formaldehyde. Variable activity with
tubercle bacilli.
iii. Uses:
18. For high level of disinfection, a minimum of 1% GLT should be used
19. Disinfection of surfaces c. Propylene
oxide and Ethylene oxide
i. Gaseous fumigants used for sterilizing animal and human food and surgical
equipment
i. Chlorhexidine
6. It is a synthetic cationic compound. Chlorhexidine in detergent base as 4% solution
of 2% liquid foam.
7. Mechanism of action
a. Kills bacteria by disrupting the cell membrane and precipitating cell contents.
b. With better activity against gram positive than negative bacteria. Effective
against fungi, fairly active against M. tuberculosis, poor activity in viruses.
c. Retain activity in the presence of blood, pus, but inactivated by hard water,
nonionic surfactants and soaps.
8. Uses
1. Widely used as presurgical antiseptic, wound flush and teat dips.
ii. Oxidizing agents

pp.
Preparations
i.Hydrogen peroxide
ii.
Potassium permanganate
iii.
Sodium perborate
qq.
Mechanism of action
i.Release of nascent oxygen which irreversibly alters bacterial proteins. Effervescent
action mechanically removes pus and cellular debris.
ii.
Conflicting reports on its efficacy were reported. Has a high bactericidal, virucidal
and fungicidal activity.
rr.
Uses
i.Use should b e restricted to initial treatment of recently contaminated wounds
suspected of Clostridial spores.
ii.
3% H2O2 has been shown to be damaging to tissues including fibroblast, hence
not suitable for routine wound care.
170
i. Phenols and related compounds a.

Preparation
a. Phenols (carbolic acid)
b. Cresol
c. Pine tar
d. Hexachlorophene
1. Mechanism of action
a. Denatures bacterial proteins and it is a general cytoplasmic poison.
b. With wide spectrum of activity including M. tuberculosis.
2. Uses
i. Disinfection of non-critical item. It has a long residual property on porous
materials.
J. Surface active agents

ss. Preparations
i. Anionic surfactants - soaps
ii. Cationic surfactants - quaternary ammonium compounds with germicidal
activity
iii.Benzalkonium chloride (Zephiran chloride)
iv. Benzalthonium chloride (Phemerol chloride)
v. Cetylpyridinium chloride (Cepryn chloride)
tt. Mechanism of action
i. Cleansers or surfactants (detergents) remove dirt and contaminating
organism by solubilization and physical means
uu. Uses
i. Disinfection of non-critical item
K. Dyes
• Azo dyes - scarlet or Sudan IV, stimulate epithelial growth
• Acridine derivatives - useful in wounds characterized by copious serious
exudates but little bleeding or pus formation.
• Acriflavine HC1, Proflavine
• Rosaniline dyes
• Crystal violet (Triphenylmethane dye) - funghicidal agent, active against gram +
organism; incorporated in skin applications as a coloring substance with
bacteriostatic effect.
• Brilliant green - for infected wounds and burns.
DISINFECTANTS COMMONLY USED TO INACTIVATE VIRUSES:

a) Newcastle disease virus: Formaldehyde, formalin, chloramines, chlorinated lime
b) Fowl pox virus: Formaldehyde, formalin, methyl bromide, phenethyl alcohol
c) TGE virus: Formaldehyde, mixture of Na hydroxide 1% and Na hypochlorite 8%
d) FMD virus: Formaldehyde, Na hydroxide, potassium permanganate, hexachlorophenol,
Na hypochlorite
e) Marek's disease virus: Formaldehyde, phenol, cryselic acid, chlorine yielding
compound, Na hydroxide
f) Myxovirus and Orbivirus: Phenethyl alcohol
171
172
21 EUTHANIZING AGENT
Euthanasia - (eu - good; thanatos - death) is the act of inducing humane death inanimal by
specially trained personnel. It is done with the highest degree of respect, with emphasis on
making death as painless and distress free as possible.
Objective of euthanasia:
6. To prevent or stop suffering of animals from incurable or painful conditions.
7. To avoid dangerously aggressive or behavior problems.
8. To minimize or control population of animals.
Properties of an ideal euthanizing agent:

a. It should not cause undue anxiety, alarm, fear behavior, struggling, vocalization, muscle
spasms or clinical signs of autonomic activation
b. It should be painless or as nearly so as possible under the circumstance of the moment
c. It should be fast acting, i.e. cause unconsciousness and death instantaneously within
minutes.
d. It should be reliable i.e. cause death every time when properly used.
e. It should be safe and easy for a properly trained person to use
f. It should not be known as a drug of abuse in human beings.
g. It should be aesthetically acceptable to use.
h. It should be compatible with the overall reason and purpose of euthanizing the animals
i.e. it should be practical
i. It should be economical
j. It should not create a problem of sanitation or environmental contamination
k. It should not cause tissue changes that might complicate the postmortem examination.
Modes of action of euthanizing agent:

1.Hypoxia, direct or indirect
a. Causes loss of consciousness at different levels
b. Loss of consciousness should precede loss of motor activity
c. Loss of motor activity may not be equated with loss of consciousness
d. Motor activity after loss of consciousness is a reflex not perceived by the
animal
2.Direct depression of neurons necessary for life function
a. Example of these agents are anesthetic
b. Produce loss of consciousness, death may be caused by cardiac arrest or
hypoxemia.
3.Physical disruption of brain activity and destruction of neurons
a. Induce rapid death due to destruction of brain or electrical depolarization of
neurons
b. Exaggerated muscular activity can follow loss of consciousness, that may be
distressing to observer but the animal may not experience pain and distress.
173
Accepted Euthanizing Agents/Methods:

1. Barbiturates - e.g. pentobarbitone sodium (Nembutal), thiopentone sodium,
thialbarbitone sodium, thiamylal sodium
2. cause smooth and rapid onset of unconsiousness
3. Chloral hydrate - not recommended when used alone because of sloe onset of action
and production of gasping, spasm of muscles and vocalization. This may be used
following premedication with a tranquilizer.
4. Barbiturate - chloral hydrate - magnesium sulfate - commonly used in large animal
5. T-61 euthanasia solutions
6. Inhalant anesthesia - in small animal species (chloroform, halothane, methoxyflurane)
7. Carbon dioxide - this can be carried out in CO chamber, at 30-40% concentration may
induce deep anesthesia
8. Electricity - in large species - not pleasant to watch, dangerous, time-consuming
9. Bullets - not pretty to watch, bullet has to be aimed properly
10. Captive bolt weapons - in these instruments, a 22 caliber black cartridge is used to
proper a steel bolt against the skill of a large animal. It takes an expert to use this
properly.
11. Concussion - done by a sharp blow to the head, followed by thoracotomy or
exsanguinations
12. Vaccum - use of high altitude chamber
13. Guillotine, cervical dislocation - done by quickly chopping off the head or by quickly
breaking or crushing the cervical spinal cord
14.15% formalin IV
Unacceptable Euthanizing Agents:

i. Inhalant anesthetics in large species - difficult and expensive
ii. Magnesium sulfate - it is a neuromuscular blocking agent and myocardial depressant
and not a CNS depressant. When given IV along, it causes excitement, alarm,
struggling, and vocalization.
iii. Narcotic analgesics - some species are rendered maniacal by large dosages
iv. Curariform drugs - e.g. 8-tubocurarine, gallamine, decamethonium, suxamethonium
(succinylcholine), consciousness not affected
v. Tranquilizer and sedatives - causes hypotension and degree of central nervous
depression but there is no analgesia
vi. Central muscle relaxants - large dosages are required to depress the brain
vii. Strynhine - it is a convulsant poison, it does not depress consciousness
viii. Nicotine
ix. Cardiac drugs
x. Electricity in small species
xi. Water (drowning) - not condone as a means of euthanasia
xii. Exsanguinations
xiii. Volatile anesthetics given IV
xiv. Air embolism
174
Acceptable agents and methods of euthanasia by species:

Species Accepted Conditionally accepted
Birds Barbiturates,inhalant Cervical dislocation,
anesthetics,C02,CO, gunshot (free- decapitation, thoracic
ranging) compression (small birds)
Cats Barbiturates, inhalant anesthetics,
C02, CO, KC1 in conjuction with
general anesthesia
Dogs Barbiturates, inhalant anesthetics,
C02, CO, KC1, in conjunction with
general anesthesia
Fish Barbiturates, inhalant anesthetics, Decapitation and pithing,
C02, tricaine methane sulfonate (TMS) stunning and
decapitation/pithing
Horses Barbiturate, KC1 in conjunction with Chloral hydrate, gunshot,
general anesthesia, penetrating electrocution
captive bolt
Rabbits, rodents and Barbiturates, inhalant anesthetics, Cervical dislocation
other small animals C02,C0, KC1 in conjunction with
general anesthesia
Ruminants Barbiturates, KC1 in conjunction with Chloral hydrate, gunshot,
general anesthesia, penetrating electrocution
captive bolt
Swine Barbiturates,KC1 in conjunction with Inhalant anesthetics, CO, IV
general anesthesia, penetrating chloral hydrate, gunshot,
captive bolt electrocution, blow to the
head
175

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CLINICAL VETERINARY PHARMACOLOGY LECTURE MANUAL/DR. ANNALIE B.

iv. Decrease oxygen

II. KINDS OF SOLUTIONS/FLUIDS

Solutions to be used in specific conditions:

1. 5% Dextrose in Ringer's solution

3. EVALUATION OF SUCCESS OF FLUID THERAPY

1. Return to normalcy of clinical signs and other normal physiologic parameters.

Six questions to consider when instituting blood therapy

KINDS OF BLOOD SOLUTIONS

1. Blood and blood components

d. Cryoprecipitate - formed from fresh frozen plasma that is thawed at refrigeration

III. BLOOD TYPING AND CROSSMATCHING

a. Application of Blood grouping:

i. Aid in matching of donor and recipients. Antibodies will form if an incompatible

IV. BLOOD COLLECTION AND TRANSFUSION

9. Criteria for Donor Selection

h. Can be collected 10-15 ml/kg bw every two weeks

3. Computation for needed blood

Normal Blood Volume: Dog = 85-90 ml/kg

Cat = 75-75 ml/kg

i. Contraindications:ascites, peritonitis, anbdominal distensions, peritoneal

IV. EVALUATION OF SUCCESS OF BLOOD THERAPY

2. Length of usefulness of transfused RBCs

Tachycardia Muscular trembling Hemoglubinuria

Management of anaphylactic reaction

1. To discover the different chemotherapeutics drugs for veterinary use.

2. To classify the chemotherapeutic drugs according to its mode of action,

3. To be familiar in the adverse effects/toxic effects of these drugs.

CHEMOTHERAPY is a branch of pharmacoIogy dealing with drugs that seiectively inhibit or

CHEMOTHERAPEUTIC AGENT or anti-infective agent is a drug used for chemotherapy. They

AntibiotIc – a substance produced by various species or microorganism (bacteria, fungi, yeast,

THE CHEMOTHERAPEUTIC TRIAD

An effective antimicrobial therapy requiresknowledge of the chemotherapeutic triad,

PRINCIPLES OF ANTIMICROBIAL THERAPY

Requirements for Successful Antimicrobial Therapy

1. Correct clinical diagnosis

2. Appropriate choice of chemotherapeutic agent

d. In selecting appropriate antibacteriaal drugs, it is best to consider the following:

Essentials for a successful Antimicrobial Therapy

1. Drug must come in contact with the microorganism

Reasons for Failure of Antimicrobial Agent

1. Wrong diagnosis was made

Possible Effects of Antibacterial Therapy

Bacterial Resistance to Antibiotics

1. Intrinsic resistance mechanisms are inherited properties of a given species of bacteria

i. Mutation – is a random event where the bacterial chromosomal mutation

Mechanism of Bacterial Resistance

1. Enzyme production – organism may produce enzymes via constitutive or inducible

1. Treatment with antimicrobial combinations may be necessary in certain cases. The

CLASSIFICATION OF ANTIBACTERIAL AGENTS

a. Bactericidal – kill bactena at the minimum inhibitory concentration

A. Inhibitors of CelI wall Synthesis

B. Impairment of Cell Membrane

C. Inhibition of Protein Synthesis

Spectinomycin Gram (-) bacilli Bacteriostatic

D. Inhibitors of nucleic acid

E. Inhibitors of Folate Cofactor Synthesis

1. What is the difference of antibiotic and antimicrobial agents?

b. The 2nd step is formation of peptidoglycan chain

Spectrum of Activity and Therapeutic Uses

c. Their use is generally restricted to infections caused by penicllinase-producing

3. Broad spectrum penicillin

1. Allergic reactions ranging from delayed hypersensitivity skin reaction to acute