1. ADVERSE DRUG REACTIONS

2. DEFINATIONS
Adverse drug reactions (WHO):
Any response to a drug that is noxious and unintended
and that occurs at doses used in man for prophylaxis,
diagnosis or therapy of disease or modification of
physiological states.

3. No Drugs are
Dangerous if
used properly
All Drugs are
Dangerous
Some drugs
have a low
therapeutic ratio
Some drugs have a
low incidence of
horrendous effects
Some drugs are
dangerous in
acute poisoning
but not when
used
therapeutically
The most
dangerous drugs
have the greatest
potential for
benefit
Some adverse
effects occur
after a delay or
after stopping
BAD
GOOD
How dangerous a drug is
depends on the skill of the
prescriber
Some adverse
effects can be
predicted if you
know the
pharmacology
(Type A); some
are not (Type B)

4. The Risk to Benefit Ratio
When prescribing drugs a doctor must assess
risk to benefit ratio in the individual patient by
•Choosing an appropriate class of drug then an
appropriate individual agent
RISK
BENEFIT
•Is it effective ?
•What are the chances of adverse effect ?
•Are there features in this patient which
affect choice eg other drugs, organ failure,
aged
•Tailoring the dose
•Considering duration of treatment

5. Epidemiology
4% of hospital admissions
1 in 1000 deaths in medical wards
10 to 20 % of in-patients
5% of patients in general practice

6. More frequent in elderly:
erratic drug taking
multiple pathology
altered pharmacokinetics
increased sensitivity of CNS
and CVS

7. Drugs - anti-coagulants,
NSAIDs,corticosteroids, antihypertensives, anti-biotics, diuretics
and insulin.

8. Occur in circumstances related to
drug’s pharmacology, predisposing
factors in the patient and care taken
in choosing the drug and the dose.

12. SIDE EFFECTS Pharmacological effects produced with therapeutic dose of drug.
 Troublesome in one condition but useful in others.
 Ex. atropine
UNTOWARD EFFECTS Undesirable effects with therapeutic dose of the drug ,if severe requires
caessation of treatment.
 Ex.tetracyclines,aspirin
TOXIC EFFECTS Effects produced by large & / repeated doses
 Ex. morphine

13. ADR
TYPES
QUANTITATIVE
QUALITATIVE
(Type A)
(Type B)
IDIOSYNCRASY
Genetic
ALLERGY
Unknown
I
II
III
(HYPERSENSITIVITY)
IV

14. Comparison –type A &B
Type A
Type B
1.Nature
augmented/ attenuated normal Totally abnormal, bizarre
response
2.Mechanism
Hyper/ hypo response
Genetic, immunological,UK
3. Predictable
Yes
No
4.Incidence
high
Low
5.Mortality
Low
High
6. Treatment
Adjust dose
Stop the drug
7.Dose dependent
Yes
No

15. IDIOSYNCRASY
GENETIC
• G6PD DEFECIENCY
• ATYPICAL PSEUDOCHOLINESTRASES
UNKNOWN
Chloramphenicol –Aplastic anaemia

16. ALLERGIC REACTION
FEATURES
1. Ranges from mild- severe (anaphylaxis)
2. Prior sensitization requried
3. Immunologically mediated
4. Low incidence , unpredictable, dose
independent.

17. Hypersensitivity
Hypersensitivity is an immune reaction to
innocuous antigens that results in tissue injury
and/or disease
An antigen that causes allergy is an allergen

18. TYPES OF ALLERGIC REACTIONS
I.IgE MEDIATED REACTION AND
ANAPHYLAXIS-(immediate hypersensitivity)
• Systemic anaphylaxis- ex.penicillin.
Antigen + IgE antibodies—influx of ca++ ----degranulation of mast
cells ,basophiles—release of histamine---anaphylaxis
• Local anaphylaxis -Hay fever
-Asthma
-Diarrhea, gi.Pain.
-Skin rash

19. Allergy (type I hypersensitivity mediated
by IgE on mast cells)

20. Mast cell degranulation by antigen (allergen)
cross-linking of FceR-bound IgE

21. Mast cell activation has many effects

22. TYPE II ALLRGIC REACTION
Cytotoxic type reactionAntibodies binds to antigen present on the cell surface
promotes phagocytosis of cell or cell destruction by
polymorphs, macrophages or by lymphoid killer cells.
ExamplesTransfusion reactions
Rh incompatibility
• drugs-antigenic complex with blood cells----increase
humoral antibodies----cytotoxic –
haemolysis / agranulocytosis / thrombocytopenia

23. Type II hypersensitivity (IgG-mediated anticell-associated antigen response) is rare
Immune response to certain drugs (e.g.,
penicillin) where drug binds to cell surface and
antibody cause removal of the cells (usually
by macrophages).

24. TYPE III
IMMUNE COMPLEX MEDIATED REACTIONS
ANTIGEN+HUMORAL ANTIBODIES
IMMUNE COMPLEXES
Ab EXCESS
Ppt.NEAR SITE OF ENTRY
SKIN-ERYTHEMA,EDEMA, ETC.
ARTHUS REACTION
Ag EXCESS
DEPOSIT IN SKIN, JOINTS
KIDNEY
SERUM SICKNESS

25. Arthus Reaction: acute antibodymediated hypersensitivity to soluble
antigens

26. TYPE IV
CELL MEDIATED REACTION-(Delayed hypersensitivity)
 Inflammatory reaction initiated by T cells.
 Delayed-secondary cellular response occurs after 48
hrs of antigen exposure.
 Examples1.montoux reaction-i.d. tuberculin inj.
2.Sulphonamides

27. Four Types of Hypersensitivities

28. MANIFESTATION OF ADR
1. Haemopoetic toxicity
2. Hepatotoxicity –direct / immunological
3. Nephrotoxicity
4. Abnormality in taste & smell
5. Occular toxicity
6. Ototoxicity
7. Behavioural toxicity
8. Iatrogenic diseases
9.Teratogenicity

29. Risk Factors for Adverse Drug Reactions
Simultaneous use of several different drugs
– Drug-drug interactions
Very young, or very old in age
Pregnancy
Breast Feeding
Hereditary Factors
Disease states which may effect drug absorption,
metabolism, and/or elimination
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30. Risk Factors Examples: Simultaneous Drug Use or
Drug-Drug Interactions
Cerivastatin-Gemfibrozil interactions in
hypercholesterolemia patients (rhabdomyolysis)
Coumadin-NSAID interactions (increased inhibition of
platelet aggregation)
Venlafaxine-indinavir interactions in depressed HIVinfected patients (decreased indinavir concentrations)
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31. Risk Factors Examples: Age Related Issues
Children are often at risk because their capacity to
metabolize drugs is usually not fully developed
– Newborns cannot metabolize or eliminate chloramphenicol, an
antibiotic
– Children younger than 18 may be at risk of developing Reye’s
syndrome if given acetylsalicylic acid (aspirin) while infected with
chickenpox or influenza
– Central nervous system effects of topiramate in children
(seizures, tremor, and dizziness)
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32. Risk Factors Examples: Age Related
Issues
 ADRs, including drug interactions, are a common cause of
admission to hospitals in the elderly
 Reasons for ADRs in the elderly:
– Concomitant use of several medications
– Disease states leading to drug ADME changes
– Decreased drug ADME activity due to age
 These conditions are exacerbated by malnutrition and
dehydration, common in the elderly
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33. Risk Factors Examples: Pregnancy
 Use of sulfonamides (antibiotic) can lead to
jaundice and brain damage in the fetus
 Warfarin use for anticoagulation can lead to birth
defects, and increased risk of bleeding problems in
newborns and mothers
 Lithium, for bipolar disorder, can lead to defects of
the heart, lethargy, reduced muscle tone, and
underactivity of the thyroid gland
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34. Risk Factors Examples: Breastfeeding
 Similar concerns, as for other children with
underdeveloped capability to metabolize or excrete
xenobiotics
 Many drugs can be passed from mother to infant
via breast milk
– Amantadine (antiviral)
– Cyclophosphamide (antineoplastic)
– Cocaine (Schedule 2 FDA drug)
– Carisoprodol (skeletal muscle relaxant)
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35. Risk Factors Examples: Hereditary
Factors
 Genetic polymorphisms may play a role
– Evident in CYP2C9 and 2C19, especially in the Asian population
(phenytoin)
– May lead to impaired metabolism in mutation of enzymes
 Higher risk of hemolysis in some populations, such as
African, Middle Eastern, and South East Asian races
– Quinolones
– Antimalarials
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36. Risk Factors Examples: Disease States
 Metabolism (Phase I or II) may be impaired with
hepatic disease
– Cirrhosis
– Hepatic Carcinoma
 Renal Insufficiency
– Acute or Chronic Renal Failure
– Decreased glomerular filtration rate (GFR)
 Drug levels may become toxic if too high, so
dosing modifications may be indicated
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