Adverse Drug Reactions | Pharmacology

Any noxious, undesired and unintended response appearing following prophylactic, diagnostic or therapeutic use of a drug administered at an appropriate dose level and that occurs within a reasonable time frame of administration of the drug is known as an adverse drug reaction.

Adverse drug reactions are more commonly observed in human medical practice and such true drug related disorders are uncommon in veterinary practice, but it is obvious that such reactions occur. The incidences of drug induced disorders are lower in veterinary practice because of shorter duration of therapy and economic constrains put pressure to use limited number of drugs.

However, use of modern and effective drugs has increased the risk. The veterinarians can Probably reduce the frequency of drug induced disorders in animal patients by correct use of drugs in a particular case.

It is generally advisable to employ drugs which have been proven relatively safe in veterinary use. However, use of acetaminophen in cats, indomethacin and ibuprofen in dogs, and phenylbutazone in ponies has resulted in fatal drug reactions.

The clinician should always keep in mind that all pharmacologically active compounds pose some risk to the patient. Risk to benefits associated with the use of drug is to be judged and accordingly the patient is to be treated.

Owner of the patient should be well informed about the possible adverse drug reactions so that he can seek help in emergency, and the drug can be withdrawn or the dosage can be modified at an early stage.

Factors Associated with Adverse Drug Reactions:

Adverse drug reactions (ADR) observed with a drug in a particular animal may not be duplicated in another animal of the same species as genetic make is different and circumstances are also not the same.

While managing a case of adverse drug reactions the following factors associated with ADR are also to be considered:

(A) Drug Factors:

Vehicle of some preparation may cause adverse reactions. Propylene glycol used as vehicle of some injectable causes haemolysis, heart block and hypotension when injected intravenously; it causes extensive edema by its osmotic effect when injected subcutaneously. Benzyl alcohol employed as preservative in injection of Vitamin B 12, causes allergic reactions.

Many adverse reactions are observed due to change in product, incorrect route of administration, alteration in dosage regimen and modification in pharmacokinetic behaviour of drug. Barbiturates, chloral hydrate, levarterenol and some other irritant drugs administered subcutaneously causes sloughing of skin.

Oral dosage forms given intravenously may cause sudden death. Severe pulmonary embolism and death ensue following intravenous administration of particulate suspension intended for intramuscular administration.

(B) Animal Factors:

I. Age:

Incidence of adverse drug reactions are more in young and very old animals because of differences in body composition, rate of biotransformation and alteration in protein binding of the drug.

II. Body Mass:

Fat disposition in obese animals introduces error in calculating the dose of drug on the basis of body weight. Digoxin, being low fat soluble do not distribute in body fat and hence causes toxicity in obese dog if it is given on weight basis. The rate of biotransformation of drug and its distribution may modify in very lean, severely starved and ill animals.

III. Sex:

It is not known whether a sex of domesticated animal influences on development of adverse drug reactions. However, pregnancy and parturition play role on disposition of drug. Potential adverse effects on embryo and foetus is to be considered before administering a drug in a pregnant or recently parturated animal.

IV. Species and Breed:

Species differences, breed characteristics and some congenital disorders predispose the animal to adverse drug reactions. Doberman, pinschers and German Shepherds are prone to bleeding in response to anticoagulants and non-steroidal anti-inflammatory drugs.

V. Disease:

Presence of renal or hepatic and other system disorders alter the pharmacodynamics and pharmacokinetic behaviour of drug. Renal disease greatly modify elimination rate of some drugs. Hepatic coma may be observed with certain drugs administered to animals with hepatitis.

VI. Presence of Other Drug:

The concomitant use of drugs is often essential to obtain a desired therapeutic response. However, the incidence of adverse drug reactions increases dramatically with such a practice. The mechanisms that lead to adverse reactions between drugs involve changes in the pharmacokinetic profile.

(C) Environmental Factors:

Animals live in a more complex environment now than that of several years ago. Various environmental factors like feed additives, agricultural chemicals, insecticides, atmospheric and water pollutants and other chemicals may contribute in development of adverse reactions to drugs by one way or other. Crowding of animals, extremes of ambient temperature and altitude are also the factors to be considered.

Timing of Adverse Drug Reactions:

Adverse drug reactions can occur at any time during therapy. Cardiac failure may occur immediately, anaphylactic reactions develop within minutes to administration of the allergen. Reactions to other drugs may require weeks to develop and some may require months.

Allergic Drug Reactions:

Allergic drug reactions are adverse effects of drugs based on immunologic mechanisms. They are also called hypersensitivity reactions. The true incidence of allergic reactions to drugs in veterinary practice is unknown. Allergic reactions are manifested as an immediate hypersensitivity, serum sickness and haematologic manifestations.

Direct toxic effects of drugs may be manifested as nephrotoxicity, hepatotoxicity, aplastic anaemia, retinopathy, ototoxicity and other organ toxicities. A smaller percentage of adverse drug reactions are idiosyncratic and generally unpredictable.

In the management of an adverse reaction to a drug:

(i) Provide life support.

(ii) Stop administration of the drug,

(iii) Enhance elimination of the drug.

(iv) If the drug is to be continued, modify the dosage regimen or change to another drug and,

(v) If possible, administer drug antagonists or antidotes.

The clinician must be able to recognize that an adverse reaction has occurred, so that, he can stop treatment to prevent further damage, and can plan a course of action for dealing with the reactions.