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
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