DRUG INTERACTIONS OF VETERINARY

IMPORTANCE WITH REFERENCE TO FLUID

THERAPY
DRUG INTERACTION

 The modifications of the effects o

f one drug by the prior or concom
itant administration of another dr
ug/ substance : food
supplements
 Introduction

 Interaction with foods

 Interaction with drugs
 May diminish the effectiveness of drug
 Reduce the absorption of food nutrients.
 The effect of one drug is altered by the
presence of another drug in the body.
 The drug-drug interactions occurring in-vitro as
a result of having been mixed before
administration: Incompatibility.
 In vivo interactions
Consequences
 Reduces the effect of the ‘ primary/target drug”
(the drug already there) - /loss of efficacy
 Increases the toxicity of the target drug – often
perceived as an adverse effect
 Beneficial in increasing the overall activity on
very few occasions unfavorable.
 Drug interference on certain laboratory tests
procedures -distinguish false +ve/-ve test
results.
Incompatibility
 Mixing of certain drugs together in the same
syrienge or with IV fluids
 Physical incompatibility (change in turbidity or
colouration)
 Chemical reactions (viz; hydrolysis, oxidation,
reduction or complex formation) and thereby
loss of pharmacological activity.
 The vehicle/ stabilizers /preservations used
Incompatibility…contd
 Therapeutic: when drugs are combined which
have antagnostic physiologic actions.
 Chemical : combination of two or more drugs,
a new and undesired chemical compound
results.
 Pharmaceutical : when drugs are combined
which form, either immediately or later, cloudy,
precipitated or decomposed solutions.
 Closely related ones
Incompatibility…contd
 Failure to get desired response
 Untoward responses like febrile response
 Venous thrombosis or phlebitis
 Extravasation and hypervolemia.
Normal saline : the most compatible IV fluid
 General Rule: Drugs should not be mixed in
infusion containers or syrienges unless the
componments are of known compatibility.
Incompatibility…contd
 FQs: IV not to be mixed with Na, Ca,Al,
Mg,Fe,cation-containing fluid solutions
 TCs: Ca containing solutions -precipitation.
 Salts of hydrochloric acid (HCl) (e.g.,
dobutamine HCl, dopamine HCl, and
epinephrine HCl) with alkaline solutions.
 Vitamin B1: should not be mixed with
alkalinizing solutions, carbonates, or
citrates
Incompatibility…contd

 Potassium containing solutions: in

digitalized patients
 Solutions containing lactate ions should
be used with caution as excess
administration may result in metabolic
alkalosis.
 Always better to discard unused portion
of the solution
Drug-drug Interactions

 Pharmacodynamic
 Act agonistically at the same receptor sites
leading to potentiation or may act
antagonistically at the same receptor leading to
antagonisim.
 Pharmacokinetic -At the level of
 Absorption
 Distribution

 Metabolism

 Excretion of the drug.

Drug-drug Interactions

The net result…..

 Increase
 Decrease in the concentration of
primary drug in plasma/blood
 potentiating /inhibiting action at the site
of action/infection
 Resulting in the toxicity due to reduced
clearance from the body
Penicillins

Chloramphenicol, tetracyclines ,
sulfonamides; NSAIDS(phenyl butazone)
Antagonistic: Reduced efficacy; reduced
distribution
 Oral- Antacids- Decrease absorption
Fluoroquinolones

 Na+ and Cl-. Aluminum, Iron, calcium, and

Mg+2 ,Antacids : Decr absorption

 Theophylline (methyl xanthines)- CNS

stimulation , Convulsions
 NSAIDS - Increased risk of seizures
Tetracyclines

 Antacids , Calcium supplements, Milk,

Fe supplements, Mg, Sodium
bicarbonate: Chelation and reduced
absorption
 Phenobarbitone, Microsomal enzyme
inducers: Reduce efficacy
Linocomycin

 Antidiarrhoeals-kaolin, pectate-
Decreased absorption
 Chloramphenicol, erythromycin,
neostigmine : Antagonistic-reduced
efficacy
 Opioid analgesics : Potentiate
respiratory depression
Aminoglycosides

 Cephalosporins: Cephaloridine,
cephalothin
 polymixins, furosemide,, anaesthetics,
amphotericin: Nephrotoxicity
 Curare like drugs- neuromuscular
blockade
Cephalosporins

 Antacids, H2 recpetor amatagonists-

Reduced efficacy
 Nephrotoxic medications-
Aminoglycosides, Diuretics -Potentiate
nephrotoxicity
 Anticoagulants -Potentiate bleeding
Macrolides

 Chloramphenicol , Florfenicol,
Lincosamides, penicillins- Antagonistic:
Reduced efficacy
 Xanthines- Increased toxicity
Corticosteroids
 Acetazolamide- Increased hypokalemic risk
 Antidiabetic drugs- Antagoniosm of
hypoglycaemia
 Barbiturates- Increased risk of hypokalemia
 Diuretics- Antagonism of diuretic effect,
Increased risk of hypokalemia
 Metoclopramide –Aggression
 NSAIDS - Risk of gastrointestinal ulceration
Drug-drug Interactions…contd

Antihistamines
 Barbiturates, tranquilizers, CNS depressants :
Increased sedative effects

Antidiarrhoeal medications
 tranquilizers (e.g., diazepam), sedatives-
increased effect of tranquilizers, sedatives
NSAIDS

 Anticoagulants, corticosteroids- Risk of

excessive bleeding
 Diuretics,beta blockers,ACE inhibitors-
Reduced antihypertensive effect ;
 Sulfonylureas -Increased
hypoglycaemic effect
Metoclopramide

 Antimuscarinic drugs, opioid analgesics

-Antagonism
 Butyrephenones, phenothiazines,
corticosteroids -Increased
Extrapyramidal signs risk
 Aspirin, paracetamol -Increased
absorption
Drug-drug Interactions…contd
Zinc salts
 Iron salts, tetracyclines : Reduced absorption
Levamisole
 Organophosphorous compounds,
diethylcarbamazine
Enhanced toxicity
Antibiotics administered per os in ruminants
 Atropine -Decreased bioavailability
Microsomal biotransformation
enzymes Inhibition
 Hepatic microsomal biotransformation
enzymes may be inhibited by certain drugs
 The inhibition: via a competitive binding to
form an inactive drug-enzyme complex.
 A metabolite of the drug that is responsible for
enzyme inhibition.
 Noncompetitive inhibition also is possible
when the drug is not a substrate for the
enzyme.
 Enzyme
Inhibitors Inducers
 Cimetidine  Omeprazole
 FQs  Phenobarbitone
 Chloramphenicol  Carbamazepine
 Fluconazole  Glucocorticoids
 Clotrimazole  Sulfadimidine
 Erythromycin  Phenyl butazone,
 Itraconazole,ketoconazole
 Metronidazole
 Miconazole
 Protease inhibitors (indinavir,
nelfinavir, ritonavir).
Food drug interactions
 Diminish the effectiveness of the ingested drug
 Reduce the absorption of food nutrients.
 Generally, food may delay or reduce the
absorption of the drug resulting in their
reduced efficacy and slower onset of action.
 For very few agents: food may help in
increasing the absorption of the drugs.
 Drugs in turn may alter/hinder the nutrients
absorption from the food
Food drug interactions…contd

Factors
 Dosage of the drug
 Age, size
 State of health of the patient
 Time of food and medicine intake.
As a general rule
 Irritant drugs- along with food
 Other drugs- adm. 1-2 hours after food intake.
Food drug interactions…contd
Drugs preferably administered with food
for enhancing bioavailability/reducing the
gastric irritation
 chloramphenicol palmitate(cats)
 Doxycycline
 Erythromycin estolate
 Griseofulvin, ketoconazole
 Metronidazole, nitrofurantoin
 Irritant drugs
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