Useful for MBBS students

1. ADVERSE DRUG REACTIONS
Dr.SUMITHA A MBBS.,MD
Assistant professor of Pharmacology
Acs Medical college

2. ADVERSE DRUG REACTION
Any response to a drug that is noxious and
unintended and occurs at doses used in man for
prophylaxis,diagnosis or therapy

3. ADVERSE DRUG EVENT (ADE)
Any untoward occurrence that may present during
treatment with a medicine
But
Does not necessarily have a causal relationship
with the treatment

4. • Incidence of ADR
– Polypharmacy
– Elderly
– Children
– Patient with multiple diseases
– Pregnancy
– Malnourished
– Immunosuppression
– Drug Abusers and addicts

5. GRADING OF SEVERITY OF ADVERSE DRUG REACTIONS :
Minor : No therapy, antidote or prolongation of
hospitalization is required.
Moderate: Requires change in drug therapy, specific
treatment or prolongs hospital stay.
Severe: Potentially life-threatening, causes permanent
damage or requires intensive medical treatment.
Lethal : Directly or indirectly contributes to death of
patient.

6. CLASSIFICATIONS OF ADR
• A (Augmented)
• B (Bizarre)
• C (Continuous)
• D (Delayed)
• E (Ending Use)
• F (Failure of Efficacy)
Broadly
Type- A (Predictable)- Based on pharmacological properties
Type- B (Non-predictable) – Based on Immunological response
and genetic makeup of person

7. TYPE A- AUGMENTED
• These are based on the pharmacological
properties of the drug .Predictable.
• They are common and account for 75% of
ADRs
• Dose related and preventable mostly
reversible.
Predictable

8. • TYPE A Adverse drug reactions
SIDE EFFECTS SECONDARY TOXIC EFFECTS
EFFECTS

9. SIDE EFFECTS
Unwanted often unavoidable pharmacodynamic
effects that occur at therapeutic doses.
Not serious.
Predicted from pharmacological profile of drug.
Reduction in dose –ameliorates symptoms

10. Side effects
• May be based on same action as therapeutic
effect.
• Eg:Atropine used in pre anaesthetic
medication for its antisecretory action.
produces dryness of mouth as side effect.
• Promethazine produces sedation –unrelated
to its antiallergic reaction.
• Estrogen cause nausea –unrelated to
antiovulatory action.

11. Effect may be therapeutic in one context but side
effect in another.
Codeine used for cough produces constipation as
side effect ,latter is its therapeutic effect in
travellers diarrhoea.
Serendipity:
Early sulphonamides used as antibacterial :
hypoglycemia and acidosis as side effects-
development of hypoglycemic sulphonylureas
and carbonic anhydrase inhibitor.

12. SECONDARY EFFECTS
• Indirect consequences of a primary action of the
drug.
• E.g. corticosteroids weaken host defence
mechanisms so that latent tuberculosis gets
activated.

13. TOXIC EFFECTS
• Over dose or prolonged use.
• The effects are predictable and dose related.
• The CNS, CVS, kidney, liver, lung, skin and bone
marrow are most commonly involved in drug
toxicity.

14. • Toxicity resulting from extension of therapeutic
effect:
• Coma by barbiturates
• Bleeding due to heparin
• Morphine-respiratory depression in overdosage
• Imipramine overdosage –cardiac arrhythmia
• Streptomycin- vestibular damage on prolonged use

15. TOXICITY TO ORGAN SYSTEMS
• Hepatotoxicity-ATT drugs
• Nephrotoxicity-
analgesics,aminoglycosides,cisplatin
• Ototoxicity-aminoglycoside, furosemide
• Cardiovascular system-digoxin,doxorubicin

16. TYPE B- BIZZARE OR UNPREDICTABLE
Unrelated to the primary pharmacological effects of
drug.
• Develop on the basis of:
– Immunological reaction on a drug (Allergy)
– Genetic predisposition (Idiosyncratic reactions)
Un-predictable

17. IDIOSYNCRASY
• It is genetically determined abnormal reactivity to
a chemical.
• Reaction is restricted to individuals with particular
genotype.
Example :
• Chloramphenicol produces nondose-related
serious aplastic anaemia.
• Barbiturates cause excitement and mental confusion
in some individuals.
Un-Predictable

18. DRUG ALLERGY
• It is also called drug hypersensitivity.
• It is an immunologically mediated reaction.
• unrelated to the pharmacodynamic profile of the drug.
• It generally occur even with much smaller doses and
have a different time course of onset and duration.
Un-Predictable

19. TYPES OF ALLERGIC REACTIONS
A) HUMORAL
1. Type I/ anaphylactic reactions.
2. Type-II / cytolytic reactions.
3. Type-Ill / retarded or Arthus reactions.
B) CELL MEDIATED
Type-IV (delayed hypersensitivity) reactions.

22. Treatment of drug allergy
• Offending drug immediately stopped.
• Inject adrenaline 0.5 mg(0.5 ml of 1 in 1000) solution
for adult i.m.
• H1 antihistaminic (10-20 mg )i.m.
• Intravenous glucocorticoid (200 mg) in severe cases.
Glucocorticoids are only drugs for type 2,3,4 reactions.
Penicillin,sulphonamides,cephalosporins are some
drugs causing allergic reactions.

23. TYPE C – CHRONIC (CONTINOUS) USE
• They are mostly associated with cumulative-long
term exposure
Example:-
Analgesic (NSAID)– interstitial nephritis, papillary
sclerosis, necrosis.
Cushing syndrome
Predictable

24. TYPE D – DELAYED
Occur long after stopping treatment.
Eg:leukemia following treatment of hodgkins lymphoma
Teratogenic effects
Predictable

25. TYPE E – END OF USE
Due to sudden discontinuation of a drug after prolonged use.
– Example – sudden withdrawal of long term therapy with
-blockers can induce rebound tachycardia and
hypertension
Predictable

26. INTOLERANCE
• It is the appearance of characteristic toxic
effects of a drug in an individual at therapeutic
doses.
• It indicates a low threshold of the individual to
the action of a drug
• Example:- Only few doses of carbamazepine
may cause ataxia in some people.
Triflupromazine-muscular dystonia.
Un-Predictable

27. PHOTOSENSITIVITY
It is a cutaneous reaction resulting from drug induced
sensitization of the skin to UV radiation.
The reactions are of two types:
a) Photo-toxic :- (T-S)
a) Drug or its metabolite Accumulates in the skin,
b) absorbs light and undergoes a Photochemical reaction
followed by
c) Photobiological reaction resulting in
d) Tissue damage (sunburn-like),
a) i.e. erythema, edema, blistering , hyper pigmentation, desquamation.
The shorter wave lengths (290-320 nm, UVB) are responsible

28. • Drugs causing acute photo toxic reaction are
tetracycline.This reaction more common than
photoallergic reaction.
Drugs causing chronic and low grade sensitisation are
nalidixic acid, sulponamides,amiodarone.

29. (b) Photo-allergic: (A-L)
Drug or its metabolites induce a cell mediated immune
response which on exposure to
Light of longer wave lengths (320-400 nm, UV -A)
Produces a papular or eczematous contact dermatitis like
picture.
Drugs involved are sulfonamides, sulfonylureas, griseofulvin,
chloroquine, chlorpromazine

30. DRUG DEPENDENCE
Physical dependence It is an altered physiological state
produced by repeated administration of a drug which
necessitates the continued presence of the drug to maintain
physiological equilibrium.
• Discontinuation of the drug results in a characteristic
withdrawal (abstinence) syndrome.
opioids, barbiturates alcohol and benzodiazepines

31. • Psychological dependance
When individual believes optimal state of well
being is achieved only through actions of drug.
Psychological dependance varies from desire to
craving.
Opioids and cocaine are strong
reinforcers.Benzodiazepines are weak
reinforcers.

32. • Drug abuse :
Refers to use of a drug by self medication in a manner and
amount that deviates from the approved medical and social
patterns in a given culture at a given time.
Two patterns of drug abuse:
Continuous use: opioids,alcohol,sedatives.
Occasional use:
cocaines,amphetamines,cannabis,solvents(inhalation)
• Drug addiction
It is a pattern of compulsive drug use characterized by
overwhelming involvement with the use of a drug.
Procuring the drug and using it takes precedence over other
activities.eg: amphetamines,cocaine,cannabis,LSD

33. • Drug habituation
It denotes less intensive involvement with the drug,
so that its withdrawal produces only mild
discomfort.
• Consumption of tea, coffee, tobacco, social drinking
are regarded habituating, physical dependence is
absent

34. TERATOGENICITY
• Drug to cause foetal abnormalities when administered to the pregnant
mother.
• Drugs can affect the foetus at 3 stages-
(i) Fertilization and implantation-conception to
17 days-failure of pregnancy which often goes unnoticed.
(ii) Organogenesis-18 to 55 days of gestation most vulnerable period,
deformities are produced.
(iii) Growth and development-56 days onwards
developmental and functional abnormalities
can occur,
e.g. ACE inhibitors , Thalidomide(seal like limbs)
, Warfarin, Barbiturates

37. • Type of malformation depends on drug as well
as stage at which exposure to teratogen
occured.
• Frequency as well as drug induced
malformations reduced by folate therapy
during pregnancy.

38. MUTAGENICITY AND CARCINOGENICITY
• Cause genetic defects and cancer respectively.
• Oxidation of drug-reactive intermediates which affect genes
and may cause structural changes in the chromosomes.
• Covalent interaction with DNA –modify it to induce mutations
,manifest as heritable defects in next generation.
• Even without interacting directly with DNA, certain
chemicals can promote malignant change in genetically
damaged cells, resulting in carcinogenesis.
• Examples- anticancer drugs, radioisotopes, estrogens, tobacco

39. DRUG INDUCED DISEASES
• These are also called iatrogenic (physician induced)
diseases, and are functional disturbances (disease)
caused by drugs .
• Hepatitis by isoniazid and Rifampicin
• Peptic ulcer by salicylates and corticosteroids
• Parkinsonism by phenothiazines and other
antipsychotics.

40. PHARMACOVIGILANCE
The 'science and activities relating to the detection,
assessment, understanding and prevention of
adverse effects or any other drug related
problems’
The Uppsala Monitoring Centre (Sweden) is the
international collaborating centre.

41. PREVENTION OF ADVERSE EFFECTS TO DRUGS
• Avoid inappropriate use of drugs .
• Appropriate drug administration (Rational Therapeutics)
– Dose
– Dosage form
– Duration
– Route
– Frequency
– Technique
• Ask for previous history of drug reactions and allergies
• Always suspect ADR when new symptom arises after
initiation of treatment. ( No new drug for new symptom).
• Ask for laboratory findings like serum creatinine etc.

42. Thanks