Adverse Drug Effects PDF

Dr.Dalia ElEbeedy 11/7/22 1  Adverse drug effects — Any unwanted or unintended consequence of drug administration. — In abroad term “ includes all kinds of noxious effect- trivial , serious or even fatal” — All drugs are capable of producing adverse effects...

Dr.Dalia ElEbeedy 11/7/22 1  Adverse drug effects — Any unwanted or unintended consequence of drug administration. — In abroad term “ includes all kinds of noxious effect- trivial , serious or even fatal” — All drugs are capable of producing adverse effects and whenever a drug is given a risk is taken. The magnitude of risk has to be considered along with the magnitude of expected therapeutic benefit in deciding whether to use a particular drug in a given patient. 11/7/22 2  Adverse drug effects — Even risk of bone marrow depression may be justified in treating cancer while mild drowsiness caused by an antihistaminic in treating common cold may be unacceptable. — Adverse effects may develop promptly or only after prolonged medication or even after stoppage of the drug. — Adverse effects are not rare, an incidence of 10-25% has been documented in different clinical settings. — They are more common with multiple drug therapy and in elderly. 11/7/22 3 Classification of ADR 1) Predictable (Type A) reactions: these are based on pharmacological prosperities of the drug. Ex. Side effects , toxic effects, consequences of drug withdrawal. They are more common, dose related and mostly preventable drugs 2) Unpredictable (type B) reactions: refers to totally abnormal effects, unrelated from the drug’s known pharmacological actions. Based on the patient not the drug. Ex. allergy Less common, often non-dose related , generally more serious and require withdrawal of the drug. 11/7/22 4 Severity of adverse drug reactions — Minor: No therapy, antidote or prolongation of hospitalization is required. — Moderate: requires change in drug therapy, specific treatment or prologs hospital stay by at least one day. — Sever : potentially life threatening, causes permanent damage or requires intensive medical treatment. — Lethal : directly or indirectly contributes to death of the patient. 11/7/22 5 Prevention of adverse effects to drugs 1. Avoid all inappropriate use of drugs in the context of patient's clinical condition. 2. Use appropriate dose, route and frequency of drug administration based on patient's specific variables. 3. Elicit and take into consideration previous history of drug reactions. 4. Elicit history of allergic diseases and exercise caution. 5. Rule out possibility of drug interactions when more than one drug is prescribed. 6. Adopt correct drug administration technique (e. g. NSAIDs not to be given on empty stomach). 7. Carry out appropriate laboratory monitoring. 11/7/22 6 1. Side effects These are unwanted but often unavoidable pharmacodynamics effects that occur at therapeutic doses. They can be predicted from the pharmacological profile of a drug and are known to occur in a given percentage of drug recipients. Reduction in dose generally reduce the symptoms. A side effect may be based on the same action as the therapeutic effect, 1) e. g. atropine is used in preanaesthetic medication for its antisecretory action produces dryness of mouth as a side effect 2) antiinflarnmatory as well as gastric mucosal damaging effects of NSAIDs are due to inhibition of prostaglandin synthesis. 11/7/22 7  Side effect may also be based on a different mode of action, 1. e.g. promethazine produces sedation which is unrelated to its antiallergic action; 2. estrogens cause nausea which is unrelated to their antiovulatory action. An effect may be therapeutic in one context but side effect in another context, 1. e.g. codeine used for cough produces constipation as a side effect but the latter is its therapeutic effect in traveller's diarrhoea; 11/7/22 8 2. Secondary effects These are indirect consequences of a primary action of the drug, e.g. 1) suppression of bacterial flora by tetracyclines paves the way for superinfections. 2) corticosteroids weaken host defense mechanisms so that latent tuberculosis gets activated. 11/7/22 9 3. Toxic effects These are the result of excessive pharmacological action of the drug due to overdosage or prolonged use. Overdosage may be absolute (accidental, homicidal, suicidal) or relative (i.e. usual dose of gentamicin in presence of renal failure). Toxic effects are predictable and dose related. They result from 1. functional alteration (high doses of atropine causing delirium) or 2. drug induced tissue damage (hepatic necrosis from paracetamol overdosage). Toxicity may result from extension of the therapeutic effect itself, e. g. hypoglycaemia due to insulin. — Another action may be responsible for toxicity, e. g. Morphine (analgesic) causes respiratory failure in overdosage. 11/7/22 10 4. Intolerance It is the appearance of characteristic toxic effects of a drug in an individual at therapeutic doses. It is the converse of tolerance and indicates a low threshold of the individual to the action of a drug. Examples are: — Only few doses of carbamazepine may cause ataxia in some people(neurological sign consisting of lack of voluntary coordination of muscle movements). — One tablet of aspirin may cause gastric bleeding. 11/7/22 11 5. Idiosyncrasy It is genetically determined abnormal reactivity to a chemical. Certain adverse effects of some drugs are largely restricted to individuals with a particular genotype. — certain uncharacteristic effects due to an individual variations. — Examples: 1) Quinine/ quinidine cause cramps, diarrhoea, asthma and vascular collapse in some patients. 2) Barbiturates cause excitement and mental confusion in some individuals. 11/7/22 12 6. Drug allergy It is an immunologically mediated reaction producing stereotype symptoms which are unrelated to the pharmacodynamics profile of the drug and are largely independent of dosage. — This is also called drug hypersensitivity; but does not refer to increased response which is called supersensitivity. 11/7/22 13 Treatment of drug allergy — The drug must be immediately stopped. — Most mild reactions (like skin rashes) subside by themselves and do not require specific treatment. — Antihistamines are beneficial in some reactions (urticaria, rhinitis, swelling of lips). — In case of anaphylactic shock it’s recommended to do the following: 1. Put the patient in reclining position, administer oxygen at high flow rate and perform cardiopulmonary resuscitation if required. 2. Administer antihistaminic i.m or slow i.v. 3. Intravenous glucocorticoid should be added in severe/recurrent cases. it acts slowly, but is specially valuable for prolonged reactions and in asthmatics. 11/7/22 14 7- Photosensitivity — It is a cutaneous reaction resulting from drug induced sensitization of the skin to UV radiation. The reactions are of two types: 1. Phototoxic Drug or its metabolite accumulates in the skin, absorbs light and undergoes a photochemical reaction followed by a photobiological reaction resulting in local tissue damage(Sunburn like) i.e. erythema, edema, blistering. 2. Photoallergic Drug or its metabolite a cell-mediated immune response which on exposure to light of longer wavelengths (UV). produces a papular or contact dermatitis. 11/7/22 15 11/7/22 16 8. Drug dependents Drugs capable of altering mood and feelings are liable to repetitive use to derive euphoria, withdrawal from reality, social adjustment. Drug dependence is a state in which use of drugs for personal satisfaction is accorded a higher priority than other basic needs, often in the face of known risks to health. 11/7/22 17 the following may serve to describe different aspects of the problem. Psychological dependence It is said to have developed when the individual believes that optimal state of wellbeing is achieved only through the actions of the drug. It may start as liking for the drug effects and may progress to compulsive drug use in some individuals. Examples: opioids, cocaine, benzodiazepine. 11/7/22 18  Physical dependence: It is an altered physiological state produced by repeated administration of a drug, which necessitates the continued presence of the drug to maintain physiological equilibrium. Discontinuation of the drug results in a characteristic withdrawal syndromes. Since the essence of the process is adaptation of the nervous system to function normally in the presence of the drug, it has been called ‘neuroadaptation'. Examples: 1) CNS depressant (opioids, barbiturates) 2) CNS stimulant (amphetamines) 11/7/22 19  Drug abuse: Refers to use of a drug by self medication in a manner and amount that deviates from the approved medical and social patterns in a given culture at a given time. Drug addiction: lt is a pattern of compulsive drug use characterized by excessive involvement with the use of a drug. taking the drug and using it takes precedence over other activities. Even after withdrawal most addicts tend to relapse. Physical dependence, though a strong force for continued drug use, is not an essential feature of addiction. 11/7/22 20  Drug habituation: It denotes less intensive involvement with the drug, so that its withdrawal produces only mild discomfort. Consumption of tea, coffee, tobacco, social drinking are regarded habituating, physical dependence is absent. Basically, habituation and addiction imply different degrees of psychological dependence and it maybe difficult to draw a clearcut line of distinction between the two. Therefore, it is better to avoid using these terms in describing drug dependence and related conditions. 11/7/22 21 9. Drug withdrawal reactions Sudden interruption of therapy with certain other drugs also results in adverse consequences. mostly in the form of worsening of the clinical condition for which the drug was being used, e. g.: (i) Acute adrenal insufficiency may be precipitated by abrupt stopping of corticosteroid therapy. (ii) Frequency of seizures may increase on sudden withdrawal of an antiepileptic. These manifestations are also due to adaptive changes and can be minimized by gradual withdrawal. 11/7/22 22 10. Teratogenicity — It refers to capacity of a drug to cause fetal abnormalities when administered to the pregnant mother. The placenta does not strictly constitute a barrier and any drug can cross it to a greater or lesser extent. The embryo is one of the most dynamic biological systems, and in contrast to adults, drug effects on embryo are often irreversible. — Ex. The thalidomide cause seal-like limbs. 11/7/22 23  The type of malformation depends no the drug as well as stage of exposure to the teratogen. It is, therefore, wise to avoid all drugs during pregnancy unless compelling reasons exist for their use regardless of the assigned pregnancy category, or presumed safety. Only emergency dental treatment should be undertaken during the first trimester of pregnancy. 11/7/22 24 11. Carcinogenicity and mutagenicity lt refers to capacity of a drug to cause cancer and genetic defects respectively. Usually, oxidation of the drug results in the production of reactive intermediates which affect genes and may cause structural changes in the chromosomes. Chemical carcinogenesis is a well-recognized phenomenon but generally years. Ex : tobacco 11/7/22 25 12.Drug Induced Diseases Caused by drugs which persist even after the offending drug has been withdrawn and largely eliminated. Ex: Peptic ulcer by salicylates and corticosteroids. 11/7/22 26 11/7/22 27