DRUG INTERACTIONS OF VETERINARY IMPORTANCE WITH REFERENCE TO FLUID THERAPY

DRUG INTERACTION

The modifications of the effects of one drug by the prior or concomitant administration of another drug/ 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 ofAbsorptionDistribution 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

-AntagonismButyrephenones, 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 FQs Chloramphenicol Fluconazole Clotrimazole Erythromycin Itraconazole,ketoconazole Metronidazole Miconazole Protease inhibitors (indinavir,

nelfinavir, ritonavir).

Omeprazole Phenobarbitone Carbamazepine Glucocorticoids Sulfadimidine Phenyl butazone,

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)DoxycyclineErythromycin estolateGriseofulvin, ketoconazoleMetronidazole, nitrofurantoin Irritant drugs