phamacological study of adverse drug reactions in brief

1. Adverse Drug REACTIONS (ADR)Adverse Drug REACTIONS (ADR)
Definition : Harm associated with the use ofDefinition : Harm associated with the use of
agiven medication.agiven medication.
OROR
Unwanted or harmful reaction experienced afterUnwanted or harmful reaction experienced after
the administeration of adrug or combination ofthe administeration of adrug or combination of
drugs under normal conditions of use.drugs under normal conditions of use.
Most common in women ,elderly > 60y old, veryMost common in women ,elderly > 60y old, very
young 1 – 4 y and patients taking more thanyoung 1 – 4 y and patients taking more than
one drug .one drug .

2. Classification of ADR :Classification of ADR :
Rawlin Classification A,B,C,DRawlin Classification A,B,C,D..
Traditional classification A & B. about 80% of ADRTraditional classification A & B. about 80% of ADR
belong to A reaction typebelong to A reaction type..
11((Type A reactions characterized byType A reactions characterized by::
a) Predictable: easily predicted by preclinical and clinicala) Predictable: easily predicted by preclinical and clinical
pharmacological studiespharmacological studies..
b) Related to pharmacological actions of the drugb) Related to pharmacological actions of the drug..
c)Common : type A reactions isnot serious-commonc)Common : type A reactions isnot serious-common
d)Dose dependant : usually dose dependantd)Dose dependant : usually dose dependant..

3. Classes Of Type A REACTIONSClasses Of Type A REACTIONS
1)Side Effects:1)Side Effects:unavoidable secondary drug effect producedunavoidable secondary drug effect produced
by therapeutic doses.by therapeutic doses.
**Its intensity is dose dependant.Its intensity is dose dependant.
*Occur immediately after initially taking drug or may not appear*Occur immediately after initially taking drug or may not appear
until weeks after initiation of drug useuntil weeks after initiation of drug use
*E g : sedation with antihistamines and dryness of mouth with*E g : sedation with antihistamines and dryness of mouth with
atropine.atropine.
2)Secondary effects:2)Secondary effects: ( consequential occur in some people( consequential occur in some people
but not all people) for example: development of diarrheabut not all people) for example: development of diarrhea
with antibiotic therapy due to altered GIT bacterial flora.with antibiotic therapy due to altered GIT bacterial flora.

4. 3) Toxicity of overdose (drug overdose)3) Toxicity of overdose (drug overdose)
An adverse drug rections caused by excessive dosingAn adverse drug rections caused by excessive dosing
E g: hepatic fialure with excessive dose of paracetamole,E g: hepatic fialure with excessive dose of paracetamole,
headache with antihypertensive and hypoglycaemia withheadache with antihypertensive and hypoglycaemia with
sulfonylurea.sulfonylurea.
4)supersensitivity:4)supersensitivity: Exaggerated of normal response toExaggerated of normal response to
adrug due to increase number of receptors (up regulation)adrug due to increase number of receptors (up regulation)
and increase their sensitivity . E g: sympathomimetic drugand increase their sensitivity . E g: sympathomimetic drug
( adrenaline)( adrenaline)
In patients with thyrotoxicosis lead to marked increase in heartIn patients with thyrotoxicosis lead to marked increase in heart
rate than normal individual due to increase number andrate than normal individual due to increase number and
sensitivity of B1 receptors. In this case reducing the dose issensitivity of B1 receptors. In this case reducing the dose is
of significance to avoid marked tachycardia and arrhythmiasof significance to avoid marked tachycardia and arrhythmias
..

5. 5) Cytotoxicity:5) Cytotoxicity: drugs with toxic effects on cells by longdrugs with toxic effects on cells by long
term usage or reaching toxic dosesterm usage or reaching toxic doses
a)a) Cardiotoxic drugs : halothaneCardiotoxic drugs : halothane
b)b) Hepatotoxicity : halothane and paracetamole with toxicHepatotoxicity : halothane and paracetamole with toxic
dose or repeated doses with minimal interval of time (lessdose or repeated doses with minimal interval of time (less
than 2 hrs)than 2 hrs)
c)c) Nephrotoxicity :long term administeration of non steroidalNephrotoxicity :long term administeration of non steroidal
antiinflammatory drugs(NSAIDS) in rheumatoid artheritisantiinflammatory drugs(NSAIDS) in rheumatoid artheritis
and aminoglycosides antibioticsand aminoglycosides antibiotics
d)d) Neurotoxicity :long term administeration ofNeurotoxicity :long term administeration of
aminoglycosides will affect 8aminoglycosides will affect 8thth
cranial nerve causingcranial nerve causing
vertigo and deafnessvertigo and deafness

6. 22((Type B (bizzar) reactionsType B (bizzar) reactions
Characterized by:Characterized by:
**unrelated to drug pharmacological actionsunrelated to drug pharmacological actions
**unpredictableunpredictable
**often caused by immunological & pharmacogeneticoften caused by immunological & pharmacogenetic
mechanismsmechanisms
**unrelated to dosage.unrelated to dosage.
**rare and cause serious illness or deathrare and cause serious illness or death

7. Type B reactions classesType B reactions classes
1)Drug tolerance1)Drug tolerance :: concept describing subjects' reducedconcept describing subjects' reduced
reaction to a drug following its repeated usereaction to a drug following its repeated use..
2) Allergy (hypersensitivity )2) Allergy (hypersensitivity )
*def: abnormal unpredictable drug response due to (Ag – Ab*def: abnormal unpredictable drug response due to (Ag – Ab
reaction) for example : anaphylaxis with penicillinreaction) for example : anaphylaxis with penicillin
3)Pseudoallergic Reaction:3)Pseudoallergic Reaction:direct mast cell activationdirect mast cell activation
and granulation by drug like opiates vancomycinand granulation by drug like opiates vancomycin
&radiocontrast media (NB: NOT IgE mediated> non&radiocontrast media (NB: NOT IgE mediated> non
immunologic reaction)immunologic reaction)

8. 44((Idiosyncrasy ReactionsIdiosyncrasy Reactions
**uncommon& abnormal response to druguncommon& abnormal response to drug usually due to genetic usually due to genetic
abnormality.abnormality.
*Affect drug metabolism & receptor sensitivity*Affect drug metabolism & receptor sensitivity
*Harmful even fatal ,appear in low doses .*Harmful even fatal ,appear in low doses .
**for example:for example:
1)Hemolytic anaemia induced by antioxidant drugs in favisim 1)Hemolytic anaemia induced by antioxidant drugs in favisim
due to genetic defect in G6PDdue to genetic defect in G6PD
2)Paralysis due to succinylcholine ( enzyme deficiency)2)Paralysis due to succinylcholine ( enzyme deficiency)
3) Acute porphyria.3) Acute porphyria.

9. 33((Type C (Chronic) reactionsType C (Chronic) reactions
**Associated with long term drug therapyAssociated with long term drug therapy..
**well known and can be anticipatedwell known and can be anticipated
**Adaptation occur = discontinuation of drug =Adaptation occur = discontinuation of drug =
abstinence syndromeabstinence syndrome
E g : opoids , alcohol , barbituratesE g : opoids , alcohol , barbiturates

10. 44((Type D( delayed) reactionsType D( delayed) reactions
**Carcinogenic & teratogenic effectsCarcinogenic & teratogenic effects..
**delayed in onsetdelayed in onset..
**very rarevery rare..
**Carcinogenic effectCarcinogenic effect::
Medication lead to cancer , taken > 20 years to developMedication lead to cancer , taken > 20 years to develop
**Teratogenic effectsTeratogenic effects::
Drug induced birth defects E g: thalidomide producesDrug induced birth defects E g: thalidomide produces
phocomelia and even ameliaphocomelia and even amelia..

11. Prepared BYPrepared BY::
11//Mohamed Fathy AyadMohamed Fathy Ayad
22//Mohamed Fathy HelmyMohamed Fathy Helmy