Adverse Drug Reaction presentation in PPT

ADR

1. DR. SHABANA ALI

2. Adverse Drug Reactions
(ADR)
Harm associated with the use of a given
medications
OR
Unwanted or harmful reaction experienced
after the administration of a drug or
combination of drugs under normal
conditions of use

3. ADR= significant morbidity & mortality
Range from mild reactions
(drowsiness, nausea, itching& rash);
disappear after discontinuation of drug
OR
Severe reactions (respiratory
depression, neutorpenia, hepatocellualr
injury, hemorrhage, anaphylaxis

4. ADR most common in
Women
Elderly (>60 y old)
Very young (1-4 y)
Patients taking more than one drug

5. Classification of ADR
Rawlin& Thompson classification ABCD
Traditional classification A & B
About 80% of ADR----Type A reactions
1) Type A Reactions
a) Related to pharmacological action of drug
Extensions of the principal pharmacological action
of the drug
Cont.

6. b) Predictable
Relatively easily predicted by preclinical and clinical
pharmacological studies
c) Common
Type A reactions not serious---common
d) Dose-dependent
Usually dose dependent

7. 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 paracetamol
Headache with antihypertensives
hypoglycemia with sulfonylurea;

8. ii) Side Effects
Nearly unavoidable secondary drug effect produced
by therapeutic doses
intensity is dose dependent
Occur immediately after initially taking drug or may
not appear until weeks after initiation of drug use
E.g., sedation with antihistamines

9. iii) Secondary Effects
Secondary pharmacological effect
E.g., development of diarrhea with antibiotic therapy
due to altered GIT bacterial flora
Orthostatic hypotension with a phenothiazine

10. iv) Drug Interactions
When two drugs taken together & they effect each
other’s response pharmacologically or kinetically
E.g., one drug slow metabolism of 2
nd
drug blood
conc.= toxicity
Theophyllinetoxicity in presence of erythromycin

11. 2) Type B Reactions
Unrelatedtoknownpharmacological
actionsofdrug
Unpredictable
Oftencausedbyimmunological&
pharmacogeneticmechanisms
Unrelatedtodosage
Comparativelyrare&causeseriousillness
ordeath cont.

12. Results(morelikely)inwithdrawalof
marketingauthorization
Oftennotdiscovereduntilafterdrugis
marketed
Bothenvironmental&geneticfactors=
importantinthisreaction

13. Type B Reactions (classes)
i) Drug Intolerance
Lower 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

14. iii) Pseudoallergic Reaction
Directmastcellactivation&degranulationby
drugs(opiates,vancomycin&radiocontrastmedia)
ClinicallyindistinguishableformTypeI
hypersensitivitybutnotinvolveIgE(non
immunologicreactions)

15. iv) Idiosyncratic Reactions
Anuncommon&abnormalresponsetodrug
Usuallyduetogeneticabnormality
Affectdrugmetabolism&receptorsensitivity
Harmfulevenfatal,appearinlowdoses
E.g.,Anemia(hemolysis)byantioxidantdrugs
(G6PDdeficiency)
Paralysisduetosuccinylcholine(enzyme
deficiency)

16. 3) Type C (chronic)
Reactions
Associatedwithlong-termdrugtherapy
Wellknownandcanbeanticipated
Adaptationoccurs=discontinuationof
drug=abstinencesyndrome
E.g.opoids,alcohol,barbiturates

17. 4) Type D (delayed) Reactions
Carcinogenic & teratogenic effects
Delayed in onset
Very rare
Carcinogenic Effect
Medication lead to cancer; take >20 y to develop
Teratogenic Effect
Drug-induced birth defects

18. Sign & Symptoms of ADR
Mild, moderate, severe or lethal
Sign & symptoms manifest soon after 1
st
dose or
only after chronic use
e.g.,Allergicreactionsoccursoonafterdrugistaken
usually2
nd
time(itching,rash,eruption,upperor
lowerairwayedemawithdyspnea&hypotension)
Idiosyncratic reactions=any unpredicted symptom

19. Mechanisms of ADR
Type A =non immunological, reversible with reduction
of dose, non serious, extension of pharmacological
effects
Type B
Biochemical mechanism unrelated to
pharmacological
Immunologic=Hypersensitivity(TypeI,II,III,IV)
OR
Non immunologic (direct)= Pseudoallergic,
idiosyncratic, intolerance

20. Mechanism of Type B
Reactions
i) Often mediated by a chemically reactive
metabolite
Non detoxification of metabolite
Direct cytotoxicity
Direct tissue damage + necrosis

21. ii) Bind to NA altered gene product
Bind to a larger macromoleculeinducing
immune response (produce Ab & bind to Ab)

22. 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)