UNIT II

ANTI-MICROBIAL DRUGS
 Antimicrobial therapy

• An antimicrobial therapy kills or inhibits the growth

of microorganisms such as bacteria, fungi, or
protozoans.
• Therapies that kill microorganisms are called
microbiocidal therapies
• and therapies that only inhibit the growth of
microorganisms are called microbiostatic therapies.
 Antimicrobial therapy
• Empiric
– Infecting organism(s) not yet identified
– More “broad spectrum”
• Definitive
– Organism(s) identified and specific therapy chosen
– More “narrow” spectrum
• Prophylactic or preventative
– Prevent an initial infection or its recurrence after
infection
 Gram Positive vs. Gram Negative Bacteria

• Most bacteria can be broadly classified as Gram positive or Gram

negative.
• Gram positive bacteria have cell walls composed of thick layers of
peptidoglycan.
• Gram positive cells stain purple when subjected to a Gram stain
procedure.
• Gram negative bacteria have cell walls with a thin layer of
peptidoglycan. The cell wall also includes an outer membrane with
lipopolysaccharide (LPS) molecules attached.
• Gram negative bacteria stain pink when subjected to a Gram stain
procedure.
• While both Gram positive and Gram negative bacteria produce
exotoxins, only Gram negative bacteria produce endotoxins.
5
 Cont….
• Infection: the invasion and multiplication of pathogenic microorganisms
in body tissues, causing disease by local cellular injury, secretion of a
toxin or by antigen–antibody reaction in the host.
• Sepsis: The presence of bacteria (bacteremia), other infectious organisms,
or toxins created by infectious organisms in the bloodstream with spread
throughout the body. It is a potentially life-threatening complication of an
infection. Sepsis occurs when chemicals released into the bloodstream to
fight the infection trigger inflammatory responses throughout the body
damage multiple organ systems.
• Bacteremia : Bacteremia or Septicemia is the presence of viable bacteria
in the circulating blood.
• Super infection: a new infection occurring in a patient having a preexisting
infection; for example, bacterial infection may occur in patients with viral
respiratory disease.

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 Principles of Antimicrobial Therapy

• Antimicrobial therapy takes advantage of the

biochemical differences that exist between
microorganisms and human beings.
• Antimicrobial drugs are effective in the treatment of
infections because of their selective toxicity;
• that is, they have the ability to injure or kill an
invading microorganism without harming the cells of
the host.
 Definitions
• Chemotherapy: It means using chemical agents that are selectively toxic
to the causative agent of the disease, such as a microorganisms or
malignant cells.
• Chemotherapy means the use of drugs to eradicate micro-organisms
and parasitic worms or malignant cells in the body is called
chemotherapy
• Antimicrobial drugs: Drugs that are used to treat infections with micro-
organisms are known as antimicrobial drugs.
• Antibiotics: Antibiotics are chemical substances produced from various
microorganisms (bacteria and fungi) that kill or inhibit the growth of
other microorganisms.
• Antibiotic resistance: Antibiotic resistance is the ability of bacteria/fungi
to resist the effects of an antibiotic.

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 Selection of Antimicrobial Agents

• Selection of the most appropriate antimicrobial

agent requires knowing
1) the organism’s identity,
2) the organism’s susceptibility to a particular agent,
3) the site of the infection,
4) patient factors,
5) the safety of the agent, and
6) the cost of therapy.
• However, some patients require empiric therapy
(immediate administration of drug(s) prior to
bacterial identification and susceptibility testing).
 A) Identification of the infecting organism

• Characterization of the organism is central to selection of the

proper drug.
• A rapid assessment of the nature of the pathogen can
sometimes be made on the basis of the Gram stain, which is
particularly useful in identifying the presence and
morphologic features of microorganisms in body fluids that
are normally sterile.
• However, it is generally necessary to culture the infective
organism to arrive at a conclusive diagnosis and determine
the susceptibility to antimicrobial agents. Thus, it is essential
to obtain a sample culture of the organism prior to initiating
treatment.
B) Empiric Therapy Prior to Identification of The
Organism
• Ideally, the antimicrobial agent used to treat an
infection is selected after the organism has been
identified and its drug susceptibility established.
• However, in the critically ill patient, such a delay
could prove fatal, and immediate empiric therapy is
indicated.
 Cont…
• Timing: Acutely ill patients with infections of
unknown origin—for example, a neutropenic patient
or a patient with meningitis—require immediate
treatment.
• Selecting a drug: Drug choice in the absence of
susceptibility data is influenced by the site of
infection and the patient’s history
• Broad-spectrum therapy may be indicated initially
when the organism is unknown or polymicrobial
infections are likely.
 C. Determining antimicrobial susceptibility of
infective organisms
After a pathogen is cultured, its susceptibility to specific
antibiotics serves as a guide in choosing antimicrobial
therapy
1. Bacteriostatic versus bactericidal drugs:
Bacteriostatic drugs: Which arrest the growth &
replication of bacteria at serum levels achievable in the
patient. Bactericidal agents: Which kills bacteria at
serum levels achievable in patients. For example,
linezolid is bacteriostatic against Staphylococcus
aurous and enterococci but is bactericidal against
most strains of S. pneumoniae.
 C. Determining antimicrobial susceptibility of
infective organisms
After a pathogen is cultured, its susceptibility to specific
antibiotics serves as a guide in choosing antimicrobial
therapy
1. Bacteriostatic versus bactericidal drugs:
Bacteriostatic drugs: Which arrest the growth &
replication of bacteria at serum levels achievable in the
patient. Bactericidal agents: Which kills bacteria at
serum levels achievable in patients. For example,
linezolid is bacteriostatic against Staphylococcus
aurous and enterococci but is bactericidal against
most strains of S. pneumoniae.
• 2. Minimum concentration: Minimum
inhibitory
Inhibitory Concentration (MIC) is the lowest
concentration of antibiotics that inhibits bacterial
growth.
• To provide effective antimicrobial therapy, the
clinically obtainable antibiotic concentration in body
fluid should be greater then the MIC.

• 3. Minimum Bactericidal concentration: the

minimum bactericidal concentration (MBC) is the
lowest concentration of antimicrobial agent that
results in a 99.9 percent decline in colony count
after overnight broth dilution incubations.
 What is antimicrobial resistance?

• Antimicrobial resistance is the ability of microbes to

resist the effects of drugs in same dosage. When the
drug loose the ability to either kill or inhibit the
growth of microbes and the microbes gain the ability
to survive in the presence of drug to which they were
previously susceptible this is called resistance.

16
 Intrinsic resistance
• Intrinsic resistance is the innate ability of a bacterial species
to resist activity of a particular antimicrobial. This can also be
called “insensitivity” since it occurs in organisms that have
never been susceptible to that particular drug.
• Lack of affinity of the drug for the bacterial target
for example penicillin's are not effective against
mycobacterium tuberculosis, as the later does not contain
peptidoglycan in cell wall. Inaccessibility of the drug into the
bacterial cell
For example: Gram –ve bacteria are naturally resistant to
vancomycin and penicillin G/V. Because of inability to
penetrate outer membrane.
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 Acquired resistance
• Acquired resistance means when the microbes gains
the ability to grow in the presence of a drug.
Acquired resistance develops when micro-organisms
no longer respond to a drug to which they were
previously susceptible.
• β-Lactamase activity: This family of enzymes
hydrolyzes the cyclic amide bond of the β-lactam
ring, which results in loss of bactericidal activity
• Altered PBPs: Modified PBPs have a lower affinity for
β-lactam antibiotics
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19
 D. Effect of the site of injection on
therapy
• The blood Brain Barrier: this barrier is formed by the
single layer of tail-like endothelial cells fused by tight
junctions that impede entry from the blood to the
brain of virtually all molecules, except those that are
small and lipophilic.
• The penetration and concentration of an
antibacterial agent in the CSF is particularly
influenced by the following:
1. Lipid soluble drug, such as quinolones and
metronidazole, have significant penetration into
the CNS.
• In contrast, β-lactum antibiotics, such as
penicillin, are ionized at physiologic PH and have
low solubility in lipids.
• They therefore have limited penetration through
the intact blood brain barrier under normal
circumstances.

2. Molecular Weight of the drug

3. Protein binding of the drug

 E. Patient factors

1. Immune System
2. Renal Dysfunction: serum creatinine levels are frequently
used as an index of renal function for adjustment of drug
regimens.
3. Hepatic dysfunction
4. Poor perfusion
5. Age
6. Pregnancy
7. Lactation
F. Safety of the agent
G. Cost of the therapy
 Spectrum of Antibiotics

A. Narrow-Spectrum antibiotics: Isoniazid

is active only against mycobacteria

B. Extended-Spectrum: agains
gram positive and acts
Ampicillin some t
bacteria
gram negativ
e
C. Broad-Spectrum Antibiotics: Tetracycline and
chloramphenicol affect a wide variety of
microbial species
Spectrum
.

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 Requirements for treatment success
(using conventional dosage of antibiotic)

– to achieve serum antibiotic concentrations above

MIC

– to maintain this concentrations for enough long

period after adminstration
The lower the MIC,
the better the therapy
Amount of antibiotic above MIC

The greater the AUC,

the better the therapy
Time above MIC
 Antimicrobial drugs

Common microbes causing diseases

• Bacteria......anti bacterial
• Viruses……anti viral
• Fungi………anti fungal
• Protozoa ……antiprotozoal

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 History of antibiotics
• Before penicillin introduction there was no effective treatment
for treating infections.
• In 1928 penicillin, the first true antibiotic, was discovered by
Alexander Fleming, Professor of Bacteriology at St. Mary's
Hospital in London.
• Alexander Fleming was a bit disorderly in his work. He left his
petridishes uncovered. Upon returning from holidays he noticed
that a fungus, Penicillium notatum, had contaminated a culture
plate of Staphylococcus bacteria. The fungus had created
bacteria-free zones wherever it grew on the plate.

28
 Cont…

• Fleming isolated and grew the mould in pure culture.

He found that P. notatum proved extremely effective
even at very low concentrations, preventing
Staphylococcus growth even when diluted 800 times.
• Fleming published his findings in the British Journal
of Experimental Pathology in June 1929.
 Classification of Antimicrobials
•• Alter
Inhibitnucleic
cell wallacid metabolism
synthesis
–
– Quinolones
Penicillins
– Cephalosporins
– Carbapenems
• Inhibit folate metabolism
– Monobactams (aztreonam)
–
– Trimethoprim
Glycopeptides (Vancomycin)
– Sulfamethoxazole
• Inhibit protein synthesis
– Chloramphenicol
– Tetracyclines
– Macrolides
– Oxazolidinones (linezolid)
– Aminoglycosides
31
32
 Cell wall synthesis inhibitors

• Penicillins are antibiotics derived from several

strains of common moulds.
• All penicillin's and cephalosporin's have beta lactam
ring, therefore they are called beta lactam
antibiotics.

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 Carbapenems

Monobactams
Clavulanic acid

Penicillins
Cephalosporins
 Cell wall synthesis inhibitors
A number of drugs inhibit cell wall synthesis.
1. Beta lactam antibiotic
2. cycloserin
3. Bacitracin
4. Vincomycin
 The β-lactams, e.g., penicillins and
cephalosporin's, which block polymer cross-
linking.
 Penicillins

1. Natural penicillins
2. Penicillase-resistent pencillins
(anti-staphylococcal).
3. Aminopenicillin

3. Carboxypencillins and ureidopencillins

(anti-pseudomonal)
 1. Natural Penicillin
• Penicillin (PCN or pen) is a group of antibiotics,
derived originally from common moulds
known as Penicillium moulds;
• which includes penicillin G (intravenous use),
penicillin V (use by mouth), procaine penicillin,
and benzathine penicillin (intramuscular use).
• Narrow spectrum
• Short half-life: dosage 3-6 times/day
• Renal excretion: dose adjustment with renal
funciton
 2. Penicillase-resistant penicillins (iv, po)
(meticillin sensitivity)

Penicillinase resistant penicillins are antibiotics, which are not inactivated by

the penicillinase enzyme.
Staphylococcus bacteria produce beta lactamse enzyme, which destroy beta
lactam ring.
Penicillinase resistant penicillin includes
 methicillin
 Cloxacillin
 dicloxacillin and
 nafcillin.

• Very narrow spectrum-

– Indication: MSSA, S.pyogenes (cellulitis)
• Short half-life
• Hepatal elimination (bile excretion)
 3. Aminopenicillins (iv, im, po)

2a. Amoxycillin , Ampicillin

• Moderate spectrum:
– Gram-positive: Streptococci., Enterococci,
– Gram-negative: E.coli, Salmonella, Haemophilus influenzae
• Short half life
• Renal excretion.
2b. Amoxycillin-clavulanate , Ampicilin-sulbactame

• Broader spectrum with addition of:

– Meticillin sensitive Staphylococcus aureus (MSSA)
– -lactamese producing gram-negative bacteria:
• H.influenzae,
 4. Carboxypenicillins and Ureidopenicillins (iv)
(anti-pseudomonal)

• Carbencillin
• Ticarcillin
• Piperacillin
• Azlocillin
Nowdays market- only with -lactamase inhibitors:
Activity aganist:
• Tikarcilin-clavulanate • Gram-negative bactera
• Piperacilin-tazobactam • Anaerobes (+ B.fragilis)
• MSSA

Intrabdominal infections.
Mixed soft tissue infections
 Mechanism of action penicillin's and cephalosporins

• The synthesis of cell wall of bacteria depends upon

an enzyme named as transpeptidase (Penicillin
binding proteins (PBPs)). This enzyme cross-
links peptidoglycan chains to form rigid cell walls.
• Penicillins and cephalosporin's inhibits
transpeptidase and block the peptidoglycan of
bacteria cell wall

44
 Important to know
• They are inactive against organisms lacking of cell
wall(peptidoglycan), such as mycobacteria, protozoa, fungi, and
viruses.
• Production of autolysins: Many bacteria, particularly the gram-
positive cocci, produce degradative enzymes (autolysins)
• Thus, the antibacterial effect of a penicillin is the result of both
inhibition of cell wall synthesis and destruction of the existing cell
wall by autolysins.
• In general, gram-positive microorganisms have cell walls that are
easily reached by penicillins, and, therefore they are easily
targeted.
• Gram-negative bacteria have water-filled channels (called porins)
to drug entry.

45
 Penicillin's Resistance
• Penicillins are inactivated by β-lactamases (penicillinases) that
are produced by the resistant bacteria
• Antistaphylococcal Penicillins: Methicillin, nafcillin, oxacillin,
and dicloxacillin are β-lactamase (penicillinase)-resistant
Penicillins. Their use is restricted to the treatment of
infections caused by penicillinase-producing staphylococci
• Clavulanic acid, sulbactam , and tazobactam are β-lactamase
inhibitors
• Antipseudomonal Penicillins: Piperacillin and ticarcillin are
called antipseudomonal penicillins because of their activity
against Pseudomonas aeruginosa
 Therapeutic uses

• Bacterial infections (only Peptidoglycan cell walled

bacteria)
• Streptococcal infections: pharyngitis, sinusitis, otitis
media and cellulitis etc.
• Syphilis
• Diphtheria

47
 Adverse reactions

• Skin rashes, urticaria

• Hypersensitivity: Approximately 5% percent of
patients have some kind of reaction, ranging from
rashes to angioedema (marked swelling of the lips,
tongue) and anaphylaxis. Cross-allergic reactions
occur among the β-lactam antibiotics.
• Diarrhea: Diarrhea is a common problem that is
caused by a disruption of the normal balance of
intestinal microorganisms.

48
 Cephalosporin

• Cephalosporin drugs are beta lactam antibiotics that

inhibit the cell wall of bacteria. Cephalosporin C was
first isolated from a fungus named as
Cephalosporium acremonium by Dr. Abraham in
1948. These are bactericidal antibiotics as they kill
the micro-organisms when used at therapeutic dose.
• Mode of Action: As penicillin

49
 First Generation
• First Generation: The optimum activity of all
first generation cephalosporin drugs is against
Gram-positive bacteria such as
staphylococci and streptococci.
Drugs:
 Cefazolin
 Cefadroxil
 Cephradine
 Cephalexin
 Second Generation
• The second generation drugs have more activity
against Gram-negative bacteria (Haemophilus
influenzae, Enterobacter aerogenes) in comparison
to the first generation. Their Gram positive spectrum
is less than the first generation.
• Drugs:
 Cefamandole
 Cefoxitin
 Cefaclor
 Cefpodoxime
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 Third Generation:

Third generation cephalosporin drugs are broad

spectrum and the effective against both Gram positive
and gram negative bacteria.
Drugs:
 Cefotaxime
 Ceftriaxone
 Ceftazidime
 Cefixime
 Fourth Generation

• Fourth Generation:
• These are extended spectrum antibiotics. They are
resistant to beta lactamases.
Drugs:
 Cefipime
 Fifth Generation

• Ceftaroline, and Ceftobiprole are broadspectrum,

advanced-generation cephalosporins that is
administered IV. They are the only commercially
available β-lactam in the United States with activity
against MRSA and is indicated for the treatment of
complicated skin and skin structure infections and
community-acquired pneumonia. The unique
structure allows ceftaroline to bind to PBP2a found
with MRSA and PBP2x found with Streptococcus
pneumoniae.

54
 Important about cephalosporins

• The cephalosporins are β-lactam antibiotics that are

closely related both structurally and functionally to the
penicillins
• The first-generation cephalosporins are effective against
staphylococcal infections
• The third-generation cephalosporins have enhanced
activity against gram-negative bacilli
• Cefepime is classified as a fourth-generation
cephalosporin and must be administered parenterally.
• Ceftaroline is a fifth generation, and is effective against
MRSA
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 Adverse effects

• Hypersensitivity (rarely anaphylaxis)

• The patient may be informed that diarrhea is a
common problem caused by antibiotics which usually
ends when the antibiotic is discontinued.
• They should be used cautiously in patients with a
history of or suspected allergy
• Cross allergy with cephalosporins should be
considered.
• Nephrotoxicity may occur rarely

56
 Carbapenems
• Carbapenems are a class of highly effective antibiotic agents
commonly used for the treatment of severe or high-risk
bacterial infections. This class of antibiotics is usually reserved
for known or suspected multidrug-resistant (MDR) bacterial
infections.
• Carbapenems (meropenem, imipenem) are beta lactam class
of antibiotics, which kill bacteria by binding to penicillin-
binding proteins, thus inhibiting bacterial cell wall synthesis.
• However, these agents individually exhibit a broader spectrum
of activity compared to most cephalosporins and penicillins.
Furthermore, Carbapenems are typically unaffected by
emerging antibiotic resistance, even to other beta-lactams.
 Uses of Carbapenems

• Intra-abdominal infections
• Complicated urinary tract infections
• Pneumonia
• Bloodstream Infections

Side effects: Nausea, vomiting and rashes are common

side effects and rarely, seizures have also been reported
 Monobactams
• Monobactams are monocyclic and bacterially-
produced β-lactam antibiotics. The β-lactam ring is
not fused to another ring, in contrast to most other
β-lactams.
• Monobactams are effective only against
aerobic Gram-negative
bacteria (e.g., Neisseria, Pseudomonas).
• Aztreonam is a commercially available monobactam
antibiotic.
• Adverse effects to monobactams can include skin
rash and occasional abnormal liver functions.
 Glycopeptide antibiotics (Vancomycin)

• Vancomycin is in a class of medications called

glycopeptide antibiotics.
• Vancomycin acts by inhibiting proper cell wall
synthesis in Gram-positive bacteria.
• It is recommended intravenously as a treatment
for complicated skin infections, bloodstream
infections, endocarditis, bone and joint
infections, and meningitis caused by methicillin-
resistant Staphylococcus aureus
 Side effects
• Common side effects include pain in the area of
injection and allergic reactions.
• Occasionally, hearing loss, low blood pressure,
or bone marrow suppression occur.
• Ototoxicity
• Nephrotoxicity
• Red man syndrome
2. Proteins synthesis inhibitors

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 Aminoglycosides
• Mechanism of action: aminoglycosides
irreversibly bind to the 30S ribosomal subunit of
bacteria. This binding inhibit protein synthesis.
• Aminoglycosides are mostly used against Gram-
negative enteric bacteria(gram-negative rods
that inhabits the gastrointestinal tract. V.
cholera, Escherichia coli )
• They can be used in combination with a β-
lactam antibiotic to extend coverage (synergism)
63
 Spectrum of activity
Broad spectrum but NOT effective against
anaerobic bacteria

Aerobic Gram-negative & Gram-positive bacteria

Oxygen dependent active transport (this required step makes aminoglycosides

ineffective against anaerobic bacteria).

64
 Clinical Uses
• Mycobacterial Infections:
• Brucellosis: Brucellosis is a zoonotic infection caused by the
bacterial genus Brucella. The bacteria are transmitted from
animals to humans by ingestion through infected food
products, direct contact with an infected animal. Other
names Malta fever, gastric remittent fever, and undulant
fever
• Plague : it is a disease that affects humans and other
mammals. It is caused by the bacterium, Yersinia pestis.
• Tularemia: it is a serious infectious disease caused by the
intracellular bacterium Francisella tularensis

65
 Important to remember about aminoglycosides

 Aminoglycosides are poorly absorbed from the gastro intestinal tract.

 They are not well absorbed orally and have to be given parenterally.
 As the aminoglycosides are strongly polar molecules, they do not
distribute to the CNS
 They are eliminated by the kidneys, therefore, in kidney patients dose
needs to be adjusted
 Aminoglycosides are bactericidal
 Aminoglycosides are more effective against aerobic Gram-negative
 Aminoglycosides do not cross the blood brain barrier, but can cross
placental barrier
 Renal damage is associated with aminoglycosides (nephrotoxic)
 Check renal function: BUN and creatinine

66
67
 Macrolides
• Macrolides are protein synthesis inhibitors.
• Macrolide antibiotics do so by binding
reversibly to the P site on the 50S subunit of
the bacterial ribosome. This action is
considered to be bacteriostatic.
• Macrolides are actively concentrated within
leukocytes, and thus are transported into the
site of infection.

68
 Tetracyclines
Mechanism of action: They are protein
synthesis inhibitors
Tetracyclines bind reversibly to 30S subunit
and block the binding of the amino acid
containing tRNA on the mRNA-ribosome
complex.
Tetracyclines prevent binding of tRNA.

69
 Anti bacterial spectrum
Tetracyclines are active against many
Gram-positive and Gram negative
bacteria, including certain anaerobes,
rickettsiae, chlamydiae, and mycoplasmas.

70
 Important to learn
• Tetracyclines bind to calcium in newly formed teeth in young children.
This can result in a brown to yellow discoloration (enamel dysplasia).
• Tetracyclines can bind to calcium in growing bone, resulting in deformity.
• Tetracycline & doxycycline can cause phototoxic skin reactions due to
their ability to absorb UV radiation present in sunlight.
• They are bacteriostatic.
• Calcium in the milk binds the Tetracyclines and prevents gut absorption.
Other metal which affect the absorption of tetracyclines are aluminum, ,
magnesium, iron)
• Tetracyclines cross the placenta, enter fetal circulation, accumulate in
fetal bones, and, if used during the 2nd or 3rd trimester, may cause
permanent discoloration of the fetus's teeth.

71
Mechanism of action

72
 DNA synthesis inhibitors
(Fluroquinolones)

General properties:
 Synthetic antimicrobials
 Bactericidal
 Broad spectrum
 Quinolones can enter cells easily and, therefore,
are often used to
treat intracellular pathogens such as Legionella
pneumophila and Mycoplasma pneumoniae.

73
 Drugs
1. Ciprofloxacin (Cipro)
2. Gemifloxacin (Factive)
3. Levofloxacin (Levaquin)
4. Moxifloxacin (Avelox)
5. Norfloxacin (Noroxin)
6. Ofloxacin (Floxin)
75
76
 Mechanism of action
Fluroquinolones block bacterial DNA synthesis by
inhibiting bacterial topoisomerase II (DNA
gyrase) and topoisomerase IV.
Inhibition of DNA gyrase prevents the relaxation
of positively supercoiled DNA that is required for
normal transcription and replication. Inhibition
of topoisomerase IV interferes with separation of
replicated chromosomal DNA into the respective
daughter cells during cell division.

77
 Clinical uses
• Urinary tract infections
• Upper and lower respiratory tract infections
• Bacterial diarrhea
• Tuberculosis
• Soft tissues, bones, and joints and in intra-abdominal and
respiratory tract infections, including those caused by
multidrug-resistant organisms such as Pseudomonas(diabetic
foot).
• Ciprofloxacin is a drug of choice for prophylaxis and treatment
of anthrax
• Gonorrhoea (norfloxacin, ofloxacin).
• Bacterial prostatitis
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 Adverse effects self study
The most frequent side-effects are:
• Gastrointestinal reactions (nausea, dyspepsia,
vomiting)
• CNS reactions such as dizziness, insomnia and
headache.

79
 Folate antagonists
(Cotrimoxazole(trimethoprim + sulfamethoxazole)

• These drugs stop bacterial cells from

using folic acid to make DNA

80
 sulfamethoxazole
• Dihydrofolic acid: Dihydrofolic acid is a folic acid derivative
which is converted to tetrahydrofolic acid. tetrahydrofolate
is needed to make both purines and pyrimidines, which are
building blocks of DNA and RNA
• Dihydrofolate synthase: it is the enzyme which convert the
Dihydrofolic acid to tetrahydrofolate
• In many microorganisms, dihydrofolic acid is synthesized
from p-aminobenzoic acid (PABA),
• Sulfonamides are a synthetic analogs of PABA, the
sulfonamides compete with PABA for the bacterial enzyme,
dihydropteroate synthetase.
81
 Trimethoprim
• Trimethoprim prevent the conversion of
Dihydrofolate to tetrahydrofolate
• The enzymatic reaction is inhibited by
trimethoprim,
• Ultimately, there is decreased availability of
the tetrahydrofolate cofactors required for
purine, pyrimidine, and amino acid synthesis

82
Pyrimethamine

83
• They are eliminated kidney, require dose adjustments
for renal dysfunction
• Crystalluria is a major side effect of sulfonamides.
Avoid Vitamin C use. It acidifies urine
• Megaloblastic anemia, leukopenia, and
thrombocytopenia may occur with use of Cotrimoxazole
• Hemolytic anemia is encountered in patients with
glucose-6-phosphate dehydrogenase (G6PD)
deficiency.
• Due to the danger of kernicterus, sulfa drugs should
be avoided in newborns and infants less than 2
months of age,
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 Antimycobacterial drugs
• Drug use to treat “ Tuberculosis”
• It is the type of drugs used to treat mycobacterium
infection.
• TUBERCULOSIS
• It is common and in many cases lethal
infectious disease caused by various strains of
mycobacteria usually mycobacterium tuberculosis.
• Tuberculosis attack the lungs but also effects other
parts of the body, spread through air when people have
mycobacterium tuberculosis, cough, sneeze or otherwise
transmit their saliva through the air.
 CLASSIFICATION

• 1st line drugs • 2nd line drugs

 Ethambutol  Tobramycin
 Isoniazid  Capreomycin
 Pyrazinamide  Cycloserine
 Rifampicin  Ciprofloxacin
 Streptomycin  Ofloxacin
 Claritromycin
 Azithromycin
 MECHANISM OF ACTION
• Rifampicin produces the antimicrobial activity by
inhibition of DNA dependent RNA polymerase
(RNAP) either by sterically blocking the path of
the elongating RNA at the 5′ end or by
decreasing the affinity of the RNAP for short RNA
transcripts. It specifically inhibits the microbial
RNAP and has no action on the mammalian
enzyme, thereby decreasing the number of
adverse effects it can cause in humans.
 ANTI-FUNGALS

• All those drugs used against fungal infections are called anti-fungal.
CLASSIFICATION
• Anti fungal drugs are classified into two groups
1. DRUGS USE FOR SUBCUTANEOUS AND SYSTEMIC MYCOSES
• Amphotericin-B
• Caspofungin
• Fluconazole
• Flucytosine
• Itraconazole
• Ketoconazole
• Micafungin
• Posaconazole
• Voriconazole
2. DRUGS FOR CUTANEOUS MYCOSES
• Butoconazole
• Clotrimazole
• Econazole
• Griseofulvin
• Miconazole
• Nystatin
• Terbinafine
 MECHANISM OF ACTION

• It binds with ergosterol (enzyme of fungi) in

the plasma membrane of fungi cells.
Amphotericin-B then produce pores in plasma
membrane and disrupt the membrane
functions, all the electrolytes are allowed to
leak out from fungal cells, resulting cell death.
 ANTI-VIRAL DRUGS

• All those drugs use against viral infections are

called anti-viral drugs.
 CLASSIFICATION

A. FOR RESPIRATORY INFECTIONS

VIRAL INFECTIONS  Adefovir
 Amantadine  Entecavir
 Oseltamivir  Interferon
 Ribavirin  Lamivudine
 Rimantidine  Telbivudine
 Zanamivir
B. FOR HEPATIC VIRAL
C. FOR HUMAN IMMUNE DEFICIENCY VIRUS
(HIV) INFECTION
• Abacavir
• Atazanavir
• Darunavir
• Delavirdine
• MECHANISM OF ACTION
• Acyclovir binds with viral
DNA-polymerase enzymes and inactivates
these enzymes thus causing premature DNA
chain termination.
 ANTI-MALARIAL DRUGS

• All those drugs use in malaria are called anti

malarial agents
 CLASSIFICATION

1. 4-aminoquinolines
• Chloroquinsulphate
• Chloroquin phosphate
• AmodiaquinHcl
2. Cinchona alkaloids
• Quinine bisulphate
• Quinine dihydrochloride
3. 8-aminoquinolines
• Primaquine phosphate
4. 2,4-diaminopyrimidines
• Pyrimethamines
5. 4-Qinoline carbinolamines
• Mefloquines
6. 9-aminocardine
• Quinacrine
 M.O.A of antimalarial drugs
• The major action of chloroquine is to inhibit
the formation of hemozoin (Hz) from the
heme released by the digestion of hemoglobin
(Hb). The free heme then lyses membranes
and leads to parasite death.
Chloroquine resistance is due to a decreased
accumulation of chloroquine in the food
vacuole.
 Antiparasitic agents
• Antiparasitic agents are drugs used to treat
parasitic diseases. Parasites can live on or in a
host and feed off of it. Human parasites
include protozoa, flatworms, roundworms .
 Antipharasitic drugs
• Metronidazole (Flagyl). Metronidazole is the most
commonly used antibiotic for giardia infection. Side
effects may include nausea and a metallic taste in the
mouth. Don't drink alcohol while taking this medication.
• Tinidazole (Tindamax). Tinidazole works as well as
metronidazole and has many of the same side effects, but
it can be given in a single dose.
• Nitazoxanide (Alinia). Because it comes in a liquid form,
nitazoxanide may be easier for children to swallow. Side
effects may include nausea, gas, yellow eyes and brightly
colored yellow urine.
 M.O.A of antipharasitic drug
• These drugs are neurotoxic to parasites by
potentiating glutamate-gated chloride ion
channels in parasites. Paralysis and death of
the parasite are caused by increased
permeability to chloride ions and
hyperpolarization of nerve cells.