adverse drug reactions

22
DR. SHABANA ALI

Upload: riddhi-jain

Post on 29-Jan-2016

7 views

Category:

Documents


0 download

DESCRIPTION

powerpoint presentation for adverse drug reaction

TRANSCRIPT

Page 1: Adverse drug reactions

DR. SHABANA ALI

Page 2: Adverse drug reactions

Adverse Drug Reactions (ADR)

Harm associated with the use of a given medications

ORUnwanted or harmful reaction experienced

after the administration of a drug or combination of drugs under normal

conditions of use

Page 3: Adverse drug reactions

ADR= significant morbidity & mortalityRange from mild reactions

(drowsiness, nausea, itching& rash); disappear after discontinuation of drug

ORSevere reactions (respiratory

depression, neutorpenia, hepatocellualr injury, hemorrhage, anaphylaxis

Page 4: Adverse drug reactions

ADR most common in

WomenElderly (>60 y old)Very young (1-4 y)Patients taking more than one drug

Page 5: Adverse drug reactions

Classification of ADR

Rawlin & Thompson classification ABCDTraditional classification A & BAbout 80% of ADR----Type A reactions

1) Type A Reactionsa) Related to pharmacological action of drugExtensions of the principal pharmacological action

of the drugCont.

Page 6: Adverse drug reactions

b) PredictableRelatively easily predicted by preclinical

and clinical pharmacological studies

c) CommonType A reactions not serious---common

d) Dose-dependentUsually dose dependent

Page 7: Adverse drug reactions

Type A reactions (classes) i) Toxicity of overdose (Drug overdose)An adverse drug reaction caused by excessive

dosing

e.g., hepatic failure with dose of paracetamolHeadache with antihypertensiveshypoglycemia with sulfonylurea;

Page 8: Adverse drug reactions

ii) Side EffectsNearly unavoidable secondary drug effect

produced by therapeutic doses

intensity is dose dependentOccur immediately after initially taking drug

or may not appear until weeks after initiation of drug use

E.g., sedation with antihistamines

Page 9: Adverse drug reactions

iii) Secondary EffectsSecondary pharmacological effect

E.g., development of diarrhea with antibiotic therapy due to altered GIT bacterial flora

Orthostatic hypotension with a phenothiazine

Page 10: Adverse drug reactions

iv) Drug InteractionsWhen two drugs taken together & they

effect each other’s response pharmacologically or kinetically

E.g., one drug slow metabolism of 2nd drug blood conc.= toxicity

Theophylline toxicity in presence of erythromycin

Page 11: Adverse drug reactions

2) Type B ReactionsUnrelated to known pharmacological

actions of drugUnpredictableOften caused by immunological &

pharmacogenetic mechanismsUnrelated to dosage Comparatively rare & cause serious

illness or death cont.

Page 12: Adverse drug reactions

Results (more likely) in withdrawal of marketing authorization

Often not discovered until after drug is marketed

Both environmental & genetic factors = important in this reaction

Page 13: Adverse drug reactions

Type B Reactions (classes)

i) Drug IntoleranceLower threshold to normal pharmacological

action of a drug e.g., tinnitus (single average dose of aspirin)

ii) Hypersensitivity (immunological reaction)

Immune mediated response to a drug agent in sensitized patient

e.g., anaphylaxis with penicillin

Page 14: Adverse drug reactions

iii) Pseudoallergic Reaction

Direct mast cell activation &

degranulation by drugs (opiates, vancomycin

& radiocontrast media)

Clinically indistinguishable form Type I

hypersensitivity but not involve IgE (non

immunologic reactions)

Page 15: Adverse drug reactions

iv) Idiosyncratic Reactions

An uncommon & abnormal response to drugUsually due to genetic abnormalityAffect drug metabolism & receptor

sensitivityHarmful even fatal, appear in low doses

E.g., Anemia (hemolysis) by antioxidant drugs (G6PD deficiency)

Paralysis due to succinylcholine (enzyme deficiency)

Page 16: Adverse drug reactions

3) Type C (chronic) Reactions

Associated with long-term drug therapy

Well known and can be anticipatedAdaptation occurs = discontinuation

of drug=abstinence syndrome

E.g. opoids, alcohol, barbiturates

Page 17: Adverse drug reactions

4) Type D (delayed) ReactionsCarcinogenic & teratogenic effectsDelayed in onset Very rareCarcinogenic EffectMedication lead to cancer; take >20 y to

develop

Teratogenic EffectDrug- induced birth defects

Page 18: Adverse drug reactions

Sign & Symptoms of ADRMild, moderate, severe or lethalSign & symptoms manifest soon after 1st

dose or only after chronic usee.g., Allergic reactions occur soon after drug

is taken usually 2nd time ( itching, rash, eruption, upper or lower airway edema with dyspnea & hypotension)

Idiosyncratic reactions=any unpredicted symptom

Page 19: Adverse drug reactions

Mechanisms of ADR

Type A =non immunological, reversible with reduction of dose, non serious, extension of pharmacological effects

Type BBiochemical mechanism unrelated to

pharmacologicalImmunologic = Hypersensitivity (Type I, II, III,

IV)OR

Non immunologic (direct)= Pseudoallergic, idiosyncratic, intolerance

Page 20: Adverse drug reactions

Mechanism of Type B Reactions

i) Often mediated by a chemically reactive metabolite

Non detoxification of metabolite

Direct cytotoxicity

Direct tissue damage + necrosis

Page 21: Adverse drug reactions

ii) Bind to NA altered gene product

Bind to a larger macromolecule inducing immune response (produce Ab & bind to Ab)

Page 22: Adverse drug reactions

Drug Hypersensitivity (allergic) Reaction

Common form of adverse response to drugs

Classification (Gell & Coombs) Type I reactions (IgE-mediated)

Type II reactions (cytotoxic)Type III reactions (immune complex)Type IV (delayed, cell mediated)