An adverse drug effect (ADE) is any harmful or unintended response to a medication or drug therapy. These effects can range from mild symptoms, such as nausea or headache, to severe or life-threatening reactions, such as anaphylaxis or organ damage. ADEs can occur due to various reasons, such as allergic reactions, drug interactions, dosage errors, or individual variations in drug metabolism or tolerance. Monitoring and managing ADEs are essential in ensuring the safety and efficacy of drug therapies. Healthcare professionals can take measures to prevent or minimize ADEs, such as proper patient screening, careful medication selection and dosing, and close monitoring of drug effects and side effects. Patients can also play a role in reducing ADEs by following medication instructions, reporting any symptoms or concerns to their healthcare provider, and informing their provider of any other medications or supplements they are taking.An adverse drug reaction (ADR) is a type of adverse drug event (ADE) that involves an unexpected, harmful, or unwanted response to a medication or drug therapy. ADRs can occur at any dose and can range from mild to severe or life-threatening. These reactions may be caused by various factors, such as drug interactions, allergic reactions, dosage errors, or individual variations in drug metabolism or tolerance. ADR can be classified into two types: type A and type B. Type A ADRs are predictable and occur at a relatively high frequency, such as gastrointestinal upset or drowsiness. Type B ADRs, on the other hand, are less predictable and occur at a low frequency, such as allergic reactions, drug-induced liver injury, or blood disorders. Monitoring and managing ADRs are crucial in ensuring the safety and efficacy of drug therapies. Healthcare professionals can take measures to prevent or minimize ADRs, such as proper patient screening, careful medication selection and dosing, and close monitoring of drug effects and side effects. Patients can also play a role in reducing ADRs by following medication instructions, reporting any symptoms or concerns to their healthcare provider, and informing their provider of any other medications or supplements they are taking. Toxicity refers to the degree to which a substance or agent can harm or damage living organisms, such as humans, animals, or plants. It can be caused by various factors, such as chemical composition, dosage, duration of exposure, and individual susceptibility. Toxicity can be classified into acute or chronic. Acute toxicity occurs when a substance or agent causes harmful effects rapidly after a single exposure or within a short period. Symptoms of acute toxicity may include nausea, vomiting, headache, dizziness, seizures, or coma, depending on the type and dose of the toxic substance. Chronic toxicity occurs when a substance or agent causes harmful effects after repeated or long-term exposure. Chronic toxicity may lead to gradual or cumulative damage to organs

1. D R J ER IN J AM ES
ADVERSE DRUG
REACTION

2. DEFINITION
 Any response to a drug, which is noxious ,
unintended and
 which occurs at doses normally used in man for the
prophylaxis , diagnosis or therapy of disease or for
the modification of physiological function ,
 requires treatment or decrease in dose or indicates
caution in future use of same drug

3. INCIDENCE OF ADR
 5% of hospital admission due to ADR
 10% to 20% experience during hospital stay
 0.1% drug related death in Medicine IP
 2% to 30% incidence of ADR in general practice
 Any drug can cause ADR

4. HISTORY OF ADR
 1870 and 1890 Chloroform – Cardiac toxicity
 1937 in USA 107 people died due to sulfanilamide
which contains diethylene glycol as a solvent
 1959-1961 Thalidomide incident – seal like limbs
 Phenacetin – Analgesic nephropathy
 Fenfluramine – Cardiac valvular defects
 Trpglitazone – Hepato toxicity
 Rofecoxib- Cardio toxicity

5. CLASSIFICATION
 Type A/Augmented/expected undesirable effects
 Type B/unexpected undesirable effects
 Type C/chronic effects
 Type D/delayed effects
 Type E/End of treatment effects
 Type F/Failure of drug to produce desired effect

6. TYPE – A ADRs
 Common , less serious , dose related
 Corrected by dose adjustment
 Includes : side effects
secondary effects
toxicity

7. SIDE EFFECTS
 Mild , manageable
 Undesirable effects observed with therapeutic doses
of drug
 eg: Cetrizine - sedation

8. SECONDARY EFFECTS
 These are indirect consequences of the main action
of the drug
 Eg: development of superinfection after supression
of bacterial flora by antibiotics
 Weakening of host defenses after use of
corticosteroids

9. TOXICITY
 These are exagerrated form of side effects which
occur due to overdose or after prolonged use of drug

10. TYPE B ADRs
 Unexpected undesirable effects/Bizarre effects
 These occur unexpectedly even when drug is used in
therapeutic doses , by a mechanism unrelated to
the main pharmacological effect of the drug
 Three types :
1. drug allergy
2. Genetically determined abnormal responses
3. Idiosyncratic drug responses

11. DRUG ALLERGY/HYPERSENSITIVITY
REACTIONS
 Immunologically mediated
 Independent of dose
 Prior sensitization required
 1-2 weeks after first dose.
 Drug act as an antigen or hapten
 Chemically related drug may show cross reactivity
 Same drug can cause different allergic reactions in
different individuals

12. TYPES OF HYPERSENSITIVITY
REACTIONS
 TYPE 1 HYPERSENSITIVITY REACTION
1. Ig E MEDIATED
2. On re exposure, antigen-antibody reaction take
place on mast cell surface, release of histamine ,PG,
5-HT ,LT
3. Urticaria, angio oedema, broncho constriction ,
anaphylactic shock

13. TYPES OF HYPERSENSITIVITY REACTIONS
 TYPE 2 HYPERSENSITIVITY REACTION ( CYTOLYTIC
RXNS)
1. Drug and component of host cell act as antigen
2. Ig G and Ig M mediated
3. Antigen-antibody reaction take place on the surface
of these cells , leads to complement activation and
hence cell lysis
4. Thrombocytopenia , hemolysis , SLE
5. Occurs within 72 hours of re exposure

14. TYPES OF HYPERSENSITIVITY REACTIONS
 TYPE 3 HYPERSENSITIVITY REACTIONS
1. Ag and Ab are circulating
2. IgG mediated
3. Antigen –antibody complexes are formed
4. Deposited on vascular endothelium , activation of
complement ,immune response
5. Eg: serum sickness, steven johnson syndrome

15. TYPES OF HYPERSENSITIVITY REACTIONS
 TYPE 4 HYPERSENSITIVITY REACTION (DELAYED
HYPERSENSITIVITY)
1. Sensitized T lymphocytes with receptors for antige
2. On exposure to antigen they produce mediators
3. Local /tissue allergic reactions
4. Eg: contact dermatitis

16. TREATMENT OF DRUG ALLERGY
 Offending drug must be stopped immediately
 Treatment for anaphylaxis
 Recliningposition, high flow oxygen
 Inj Adrenaline0.5mg (0.5ml of 1/1000 IM)
 H1 AntihistaminicsIMor slow IV
 Inj Hydrocortisone100 -200mg IV

17. GENETICALLY MEDIATED ABNORMAL RESPONSE
TO A DRUG
 Drug responses in some individual may be markedly
different from the effect usually observed
Eg1:
Presence of atypical Psuedocholine estrase – Prolongation of
action of succinylcholine
Succinylcholine apnoea → Respiratory failure
Eg2:
Acetylator Status
Slow acetylators – neurotoxicity with INH
Fast acetylators- Hepatotoxicity with INH

18. IDIOSYNCRATIC REACTIONS
 Harmful and sometimes fatal reactions that occur in a
small minority of individuals
Cause is not well understood
Eg: Malignant Hyperthermia with halothane
Aplastic anemia with single dose chloramphenicol

19. TYPE C ADRs (CHRONIC EFFECTS)
 These are associated with prolonged use of a drug
Eg: Cushing syndrome after chronic use of
prednisolone
Eg: Analgesic nephropathy with aspirin

20. TYPE D ADRs (DELAY DEFECTS)
 These occur remotely ie years after treatment, or
effects appearing in their children who didn’t receive
the treatment
Eg: Secondary cancers in patients treated for blood
cancer
Eg: Teratogenic effects

21. TYPE E ADRs (End –of – treatment Effects)
 These occur when a drug is suddenly discontinued
Eg: Rebound hypertension after abrupt withdrawal of
propranolol
Eg: adrenocortical insufficiency after sudden stopping of
prednisolone

22. TYPE F ADRs (Failure of a Drug to Produce desired
effect)
 Failure of drug to produce the desired therapeutic
effect in some people due to genetic variability

23. ORGAN TOXICITIES
 HEPATOTOXICITY
 Direct (predictable)
hepatocellular damage
eg: Paracetamol Metabolites tetracyclines
 Cholestatic jaundice (unpredictable)
eg: Chlorpromazine erythromycin
 Unpredictable hepatitis like reaction
eg: INH, rifampicin, halothane

24. MAJOR ORGAN TOXICITIES
Phenacetin Analgesicnephropathy
Aminoglycosideantibiotics,
iodinated x-ray contrast media
Tubularnecrosis
Gold salts, penicillamine Nephrotic syndrome
Lithium Carbonate, demeclocycline Nephrogenicdiabetes insipdus
Acetazolamide,calcium salts Nephrolithiasis
Methicillin, hydralazin Interstitial nephritis, SLE
NEPHROTOXICITY

25. ORGAN TOXICITES
Primaquine nitrofurantoin Nalidixic Acid Hemolytic anemia in G-6PD deficiency
Sulphonamides sulphones, methotrexate Megaloblastic Anemia
Nitrate and nitrate sulphones Methemoglobinemia
Sodium valporate co-trimoxazole Thrombocytopenia
Chloramphenicol,Phenylbutazone,
Carbemazepine
Pancytopeniaand aplastic anemia
Chloramphenicol,thiouracil,derivatives
used as antithyroid drugs, sulphones
Agranulocytosis
HEMATOLOGICAL TOXOCITY

26. ENDOCRINE AND METABOLIC DISORDERS
Lithium Carbonate prolongeduse of
iodine-containing expectorants
Disorders of thyroid funciton
Spironolactonedigitalis Gynecomastia
Antipsychotic phenothiazines,
methyldopa
Galactorrhea-amenorrheasysndrome
Lithium, phenothiazines, methyldopa,
clonidine
Impotence in males
Probenecid, frusemide ethambutol Hyperuricemia
Oral cotraceptivesthiazide and loop
diuretics
Hyperglycemia

27. ELECTROLYTE IMBALANCE
Hypernatremia Mineralocorticoids,
glucocorticoids
Hyperkalemia Spironolactone, ACE
INHIBITORS
Hypokalemia Loop diuretics

28. DERMATOLOGICAL TOXICITY
Dimethylchlortetacycline, nalidixic acid,
sulfonamides
Photodermatits
Long-acting sulfonamides, sulfones,
ethosuximide
Stevens- johnson syndrome
Heparincyclophosphamideand other
cytotoxicdrugs
Alopecia
Oral contraceptives androgens
sulfonamides, sulfones, penicillins
Acne Urticaria
Busulfan, chloroquineoral contraceptives Hyperpigmentation
Chloroquine, chloropromazine Lichenoidskin eruptions
Sulfonamides, salicylates Fixed drug Eruptions
Ampicillin, Allopurinol Nonspecific skinrashes

29. NEUROLOGICAL DISORDERS
Haloperidol, metoclopramide Parkinsonismand other
extrapyramidaldisorders
Nalidixic acid, lignocaine, theophyline Convulsions
Nitroglycerine hydralazine Headache
Corticosteroids, tetracyclines, oral
contraceptives
Pseudotumor cerebri
(intracranialhypertension)
Ether Exacebationof preexisting
myesthenia
INH vincristine, clioquinol PeripheralNeuropathy

30. PSYCHIATRIC DISORDERS
Reserpine, methyldopa Depression
L-dopa, amphetamine Hypomaniaor Mania (Excited
reaction)
Amphetaminecorticosteroids Schizophrenia-likestate(or
paranoid reaction)
Bromocriptine, Propranolol Hallucinatory States
Atropine, digitalis glycosides, amantadine Delirious state
Amphetamine, L-dopa, bromocriptine Insomnia

31. DISORDERS OF THE GASTROINTESTINAL TRACT
Aspirin, corticosteroids Peptic ulcerationor
gastrichaemorrhage
Valporate Clindamycin, broad spectrum
antibiotics
Pancreatitis
Pseudomembranous colitis
Opioids ferrous sulphate, tricyclic
antidepressants
Constipation

32. CARDIOVASCULAR DISORDERS
Daunorubicin,doxorubicin Cardiomyopathy
Carbenoxolone, steroids, propranolol Exacerbationof congestive
cardiac failure
Thyroidhormones, cardiac glycosides Carida arrhythmias
Clonidinewithdrawal, oralcontraceptives,
corticosteroids
Hypertension
Propranolol withdrawal, ∝ adrenoceptor
blockers
Exacerbationof angina
Ergot Alkaloids Raynaud’s phenomenon
vasospasm, gangrene

33. MUSCULOSKELETAL DISORDERS
Corticosteroidsclofibrate Myopathy
Phenytoin,
Phenobarbitone
Osteomalacia
Heparin, glucocorticoids
Buserelin
Osteoporosis

34. OCULAR DISORDERS
Hyperbaric oxygencorticosteroids Cataract
Antipsychotic phenothiazines,
chloroquine
Retinopathy
Digoxin, ethambutol Aletrations in colour vision
Chloroquine, indomethacin Corneal opacities
Ethambutolpenicillamine Optic neuritis

35. Pharmacovigilance
 The Detection, Understanding, Assessment and
Prevention of ADRs
 For patient safety
 Pharmacovigilance Programme of India launched in
2010
 All ADRs should be notified to the respective ADR
monitoring Centre, from where it is sent to PvPI and
then to the International Drug Monitoring Centre,
WHO.

36. Important Questions
 Define ADR
 Describe the typres of ADRs with examples
 Management of ADRs/Drug Allergy
 Pharmacovigilance

37. THANK YOU