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Adverse drug reaction. An adverse drug reaction (ADR) is any undesirable effect of a drug beyond its anticipated therapeutic effects occurring during clinical use ,drug therapy has been recognized as a significant cause of harm since the earliest time.
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Adverse drug reaction An adverse drug reaction (ADR) is any undesirable effect of a drug beyond its anticipated therapeutic effects occurring during clinical use ,drug therapy has been recognized as a significant cause of harm since the earliest time
Hippocrate warned about the dangerous of drugs recommended that they should never be prescribed unless the patient had been thoroughly examined . In 1785 William Withering described the benefits of digitalis ,he also described the vomiting , alteration of vision ,brady cardia ,convulsion and death it could cause In 20th century great therapeutic advances were a accompanied by a growing awareness of the problems of adverse reaction to medicine among both health care professionals and consumers.
In particular ,the thalidomide tragedy in 1960 was the seminal event leading to the development of modern drug regulation ,thalidomide prescribed as a safe hypnotic to many thousand of pregnant women ,caused a severe form of limb abnormality known as phocomelia in many of the babies born to these women.
Classification There are several ways to classifying adverse reactions, the simplest is to separate them into type A and B . Type A reactions are the result of an exaggerated ,but otherwise normal ,pharmacological action of a drug given in the usual therapeutic doses . e.g. hypoglycemia with sulphonylurea .Type A reaction is predictable from drug known pharmacology and usually dose dependant . Some type A reaction have a long latency ,e.g. include teratogenicity ,chloroquine retinopathy etc.
Type B reaction in contrast are not predictable on the basis of drug pharmacology , e.g. malignant hyperthermia of anesthesia . Type B reactions are generally unrelated to dosage, and although comparatively rare, they are more likely to result in serious illness and death . This type of reaction is often not observed during the pre-marketing clinical trial programme for a medicine and consequently account for many drug withdrawals from the market .
Characteristics of type A and type B reaction:- Type A Type B Pharmacologically yes no predictable Dose dependent yes no Incidence high low morbidityhigh low Mortality low high Management dosage adjustment stop
Predisposing factors Multiple drug therapy:- The incidence of adverse drug reactions and interaction has been shown to increase sharply with number of drugs taken. This suggest that effect of multiple drug use are not simply additive ,but the concept of confounding by multiple disease state must be born in mind..
Age:- The very old and the very young are more susceptible to ADRs .the elderly often have multiple and chronic disease and so are more likely than younger people to be taking several medicines at any one time .they are particularly vulnerable to the adverse effect of drugs because of the physiological changes that a company aging. It is difficult to determine whether age alone renders these patients more susceptible to ADRs or whether this simply reflect increased drugs exposure, multiple disease states and age-related pharmacokinetic change.
All children , and particularly neonates differ from adults in the way that they handle and respond to drugs Specific example of concern in children are Reys syndrome with aspirin and hepatotoxicity with sodium valproate.
Gender:- Women are thought to be at greater risk of ADRs than men , female appear to have a 1.5 to 1.7 fold greater risk of developing an ADRs .The reasons for this are not entirely clear but may include gender –related differences in pharmacokinetics, immunological and hormonal factors.
Intercurrent disease:- Patient with impaired renal or hepatic function are at substantially increased risk of developing ADRs to drugs eliminated by this organs. There are specific disease states which may be predispose to adverse drug reaction such as HIV infection, critical illness and trauma .
Genetics causes:- Until recently ,many adverse reactions that could not be easily classified were termed “idiosyncratic”it is apparent that many have a genetic basis.
Mechanisms of ADRs:- There is great variability in in the individual response to drug therapy. This is manifest either as different dose being required to produce the pharmacological effect or different response to a defined dose .Such interindividual variation is the basis of many ADRs, such reaction may occur because of variation in the pharmaceutical, pharmacokinetic or pharmacodynamics properties of drug and are often due to underlying disease state of pharmacogenetics characteristics of the patient .In some cases a combination of these causes may be responsible .
Delayed adverse effect of drug:- A number of adverse effect may only become apparent after long term treatment ,e.g. development of vaginal carcinoma in the daughters of women given stilboestrol during pregnancy for the treatment of threatened abortion and immunosuppressive and chemotherapeutic agent which can induce malignancies that may not apparent until years after treatment has been given.
ADRs associated with drug withdrawal:- Some drug cause symptoms when treatment is stopped abruptly, e.g. benzodiazepine withdrawal syndrome ,rebound hypertension following discontinuation of anti hypertensive such as colondine ,and the acute adrenal insufficiency that may be precipitated by the abrupt withdrawal of corticosteroids.
