PHARMACOVIGILLANCE:

ADVERSE DRUG REACTION

MONITORING(=ADRM)

Herri S.Sastramihardja

Deparment of pharmacology & therapy

Medical school-padjadjaran university
Introduction
 Any drug has the potential to do harm
 Almost all effective drugs, no matter
how skillfuly used, may cause ADR
 ADRs are a cost of modern medical
therapy

4,5 – 14 % of total cost of

hospital care is related to ADRs
Introduction (continued…)

 Incidence of ADRs:
 Responsible for 3-5% of hospital
admission
 Resulting in 300.000 hospitalizations
annually in the USA
 Once hospitalized, patients have about
a 30% change of an ADR
 Attributable risk to course of drug
therapy is about 5%
Introduction (continued…)

 The seriousness & frequency of ADRs

& the nature of the disease being
treated will determind how acceptable
the risk is in a particular patient
 Ampicillin frequently causes skin rashes which
are seldom serious
 Phenylbutazon causes lifethreattening aplastic
anemis
 Cytotoxic drugs causes major ADRs but the
seriousness of the diseases justifies their use
Terminology
 Drug :
Any subtance or product which is to
prevent, relieve or cure a pathological state
or to explore or influence physiological or
pathological mechanism for the benefit of
the patient
 ADR:
unintended response to a drug which may be
harmful to the recipient, at the doses
normally given for prophylactic, diagnostic
or therapeutic purposes
Terminology (continued…)

 ADR monitoring :
The systematic reporting, recording
and evaluation of certain or all
adverse reactions to drugs
 Pharmacovigillance :
The detection, assessment and
prevention of drug effects in human
 Classification of ADRs

Characteristic A type B type

 Normal pharmacological action + -

 Dose related + -
 Predictability ++ +
 Morbidity ++
 Mortality + ++
A = Augmented B= Bizarre

(Rawlins & Thompson, 1977)

Classification of ADRs (continued…)

Type Characteristic
A Augmented, Predictable
Bradycardia due to ß-blocker
B Bizzare, unpredictable
Anaesthetic-induced hyperthermia
C Chronic effect
Choroquine induced retinopathy
D Delayed effect
Diethylstilbesterol induced vaginal adenocarcinoma
E End of treatment effect
Steroid induced cushing syndrome

(Bateman, 1999)
Classification of ADRs (continued…)

 Unpredictable ADRS
 20-30%
 Often unavoidable

 Predictable ADRS
 70-80%
 preventable
Classification of ADRs (continued…)
 Inherent anomalies in patient response
 Allergic or idiosyncratic
 All reactions due to genetic factors
 Acquired patient abnormalities
 Due to intercurrent ilness
 Anomalies of drug administration
 Exesive dosage or inappropriate administration
 Alteration of bioavailability
 Drug interaction
 Table genetically-determined ADRs
Mechanism Result
1. Altered drug metabolism :   Risk of drug induced
 Slow acetylation of lupus
hydralazine, INH,
sulfonamide  Prolonged apnoea following
 Abnormal plasma succinylcholine
pseudocholinesterase

2. Atypical response  Drug induced hemolysis

 G_6 PD deficiency (antimalarials, sulphonamide)
 Abnormal H6 (H6_M)  Drug induced Met_H6
(nitrites, phenacetin,
sulphonamides)
 Anaesthetic induced
 Malignant hyperthermia hyperthermia
Fig. General Processes Involved In Drug Allergy
Classification of allergic responses
 Anaphylactic reactions (type I)
 Immediate type & largely IgE-mediated
 Acute systemic anaphylactic or localised (skin,
respiratory tract, G1-tract)
 Penicillin-G, iodinated contrast
 Cytotoxic reaction (type II)
 Involve IgG or Ig M antibodies
 Quinine, sulphonamides, phenybutazone
 Auto immune haemolytic anaemia due to
α-M Dopa & mefenamic acid

Gell & Coombs

Classification of allergic responses
(continued…)

 Serum sickness (type III)

 IgG and IgM reacts with antigen which is in
excess of antibody concentration
 Fever, skin rashes, lymphadenopathy & joint
swelling
 ATS, penicillin, streptomycin, PAS &
sulphonamides
 Delayed hypersensitivity (type IV)
 Due to interaction of antigen with sensitised
lymphocytes leading to skin inflammation
(contact dermatitis)
 penicillin
Predisposing factors of ADRs
 Onset of reaction
• Acute-anaphylactic shock due to
penicillin inj.
• Chronic-retinopathy due to
chloroquine
 Age
• Frequency in very young/old people 
 Pathophysiological condition
• Diseases-alter pharmacokinetic and
pharmacodynamic fact.
Predisposing factors of ADRs (continued…)

 Drug administration
• High and prolong dose (relative
overdose)
 Sex
• Female
 History of allergy
 Multiple drug therapy
 Racial or genetic factors
 Criteria of drug-ADR relationship

Grade
Criteria
HP Pro Pos Rem

Onset: ?? + + + -
Associate to response + + - -
Dech.- Rechallenge + - - -
Rare,due to drug exp. - - + -
Could be happens at clinical condition - - + -
Summary of important principles
 ADRs are a mojor cause of iatrogenic
diseases
 Dose_related ADRs can be predicted
 Idiosyncratic ADRs are also dose
related but only in some individuals
 Immune_mediated ADRs are not
dose_related & the effect are not
related to the known pharmacological
properties of the drugs
THANK YOU