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
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
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