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ADVERSE DRUG REACTIONS Definition: unwanted ,harmful effect produced by administration of a drug or combination of drugs under normal conditions Pharmacodynamics effect

Desirable/beneficial

undesirable/not beneficial

(TYPE A) PREDICTABLE UNDESIRABLE

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Side effect genetic effect

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TYPEB(SERIOUS EFFECT)

secondary effect

toxic effect

idiosyncratic effect

allergic effect

TYPE-1

TYPE-2

TYPE-3

TYPE4

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ADR can be reduced by 1. Treatment 2. Discontinuation of drugs 3. Future precautions Occurrence 1. 2. 3. 4. 5. immediately After discontinuation prolonged use poly pharmacy Visit of multiple doctors

Prevention of ADR

In appropriate use of drugs Right use of dose ,route, drugs& frequency of administration Multiple use usage of drugs Avoid multi visit of doctors Right usage of technique Should know the drug history & patient history to know about allergic reaction

Types of adverse drug reactions Type A ( augmented) Type B ( Bizarre) Type C ( chronic) Type D (delayed) Type E ( prolonged) Type F (failure therapy)

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Morphine on prolonged use cause respiratory disease Type A : response: a)Quantitatively normal b)Quantitatively abnormal Dose related correct by dose adjustment Common to less toxic

Type B:

due to patient peculiarities i.e., allergy, Idiosyncratic reaction Serious ,so withdrawal of drug

Type C: due to long term treatment

e.g: on benzodiazepines/ barbiturates intake, it cause on dependence On analgesic intake, it causes nephropathy On verapamil, severe constipation On INH B6 deficiency i.e. peripheral neuropathy Type D: carcinogenicity & teratogenicity

Initiators Ex: estrogens Androgens

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proactivators i.e increase tumor spread Ex: smoking

Type F: especially in case of T.B , leprosy

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Severity of ADR Minor no treatment >no hospital No antidote Moderate drug changes if necessary, therapy if necessary hospitalized serious life threatening ,so treated Damage occurs

Lethal

Direct Indirect

In type I ,II,&III drug +receptors ( treated as foreign body) Complex

Hap ten/antigen produce specific AB On secondary exposure ag+ Ab reaction occurs Release of cytokines allergy Symptoms of allergy : Urticonia, hypertension, bronchoconstriction, swelling of soft tissues, angloedma Laryngo edema, anaphalytic shock, Stevenson Johnson syndrome, lupus erethematous Tetracylins ,amiodonone,sulfnomides photo allergic

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leads to death

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Thalidomide, warfarin etc are tetracylins Side effects: Drug Atropine morphine Promethazine Side effect as use Drug Atropine morphine cideine Secondary effect: Side effect Dryness of mouth constipation constipation Use General anesthetic increase secretion sedation sedation Desirable Peptic ulcer Analgesic Anti allergic Undesirable Dryness of mouth constipation sedation

Tetracycline---------------------- staphylococcal diarrhea Antibiotics-------------------------super infection by inhibiting intestinal bacteria Corticosteroids-------------------- increase immunity Diuretics------------------------------Hypokalemic Toxic effects: Morphine(high dose)-------------------> respiratory failure Barbiturates& atropine( high dose)---------------> coma& cvs failure Methyldopa on prolonged use --------------------->hemolytic anemia Gentamycin---------------------------------------------->nephrotoxicity Atropine-------------------------------------------->delirium ,hyperpyrexia, photophobia

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Hemolytic anemia is diagnosed by positive coombs test Warfarin ------------------------------------> bleeding problem Intolerance Triflupromazine (A tranquillizer) ------- causes muscular dystopia Carbamazepine ( tegretol) ataxia IDIOSYNCRACY: Abnormal response, no specific genotype is identified. Ex: single dose of aspirin -----------------------anaphylactic shock Dihydrostreptomycin -----------------------otoxicity

Single dose of diclofenac -----------------------kidney damage

Barbiturates -------------------------------------------mental confusion Chloramphenicol--------------------------------------aplastic anemia Primaquine & salicylate----------------------------- hemolytic anemia due to deficiency

Note : - NO2 containing drugs cause bone marrow i.e. aplastic anemia Drug allergy: Type I : urticaria( rashes) ACTHAngioedema, caused by penicillin, heparin,streptokinase,localanaestheti c,chlorhexidine

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anaphylactic shock, asthma

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Type III: arthralgia ,Stevens Johnsons syndrome caused by hydralazine Type II: thrombocytopenia---------------quinine:heparin Agranulocytosis Aplastic anemia clozapine ( antipsychotic) carbimazole( antithyroid) Sulfonamides: NSAID Lupus erthyma : hemolytic anemia Type IV: control dermatitis Photosensitization amiodarone, sulfonamides, penicillin, Carbamazepine

Drug dependence :

psychological ex: caffeine contents nicotine Physical ex:

TERATOGENECITY: Drugs with effect off spring. Generally there is defect in limbs , lips,head,ears Ex: thalidomide------phoeomelia ( defects in limbs) D- penicillamine treated by Wilsons disease i.e. metal poisoning cu+2 disorders antidote for heavy metal poisoning warfarin, valporic acid tetracylins

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amphetamine, heroine,cocaine ,barbiturates, narcotic analgesics

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CAERCINOGENCITY: Mutations------>changes of alteration of DNA& suppression of proncogenes or tumor suppressor genes. Initiators & proactivators are responsible for further damage Ex : hydrocarbons: estragons--------------- breast& uterine cancer Androgens ------------prostate cancer Cigarette smoking-------lung cancer sodium .cyclamates( a sweetener) Photo toxic allergy: amiodarone, peniciilin, sulfonamides

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