Epidemiology Predisposing
Causes
Types
Factors
Classification
Drugs
causing ADRs
Recognition & Detection Establishment of Cause-effect relationship Management of ADRs Evaluation for ADRs during drug development Strategies for prevention of ADRs
Response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiologic function Excludes therapeutic failures, overdose, drug abuse, noncompliance, and medication errors
A major cause of morbidity and mortality Most common iatrogenic illness, complicating 5 to 15 % of therapeutic drug courses Account for 5% of acute medical emergencies 3 to 6 % of all hospitalizations are due to an ADR 10 to 20 % of hospitalized patients suffer from an ADR 4th to 6th leading cause of death among hospitalized patients* 30 to 60 % are preventable
Age (children and elderly) Female gender Polypharmacy Multiple co-morbid conditions Inappropriate medication prescribing, use, or monitoring Renal insufficiency
Liver disease Alcoholism HIV infection Herpes infection Prior history of ADRs Extent (dose) and duration of exposure Genetic predisposition
Inappropriate
use of drugs Inadequately monitored use Drug-drug interactions Self-medication Inadequately evaluated and irrational drugs
Type A: Augmented
Dose-related effects Normal pharmacological effect of the drug Often predictable Toxic effect or side effect Examples:
postural hypotension in a patient on antihypertensive medication digoxin toxicity hypoglycemia with anti-diabetics hypokalemia with diuretics heart block with propranolol dry mouth with anticholinergics
Type B: Bizzare
Effects related to abnormal interaction between
patient and drug Non-dose related Unrelated to normal pharmacodynamics of the drug Generally unpredictable, have genetic basis
Idiosyncratic / Allergic e.g. malignant hyperthermia Immunological e.g. rash associated with Penicillin use
Type D: Delayed
Delayed effect
Type E: End-of-use
Withdrawal
Addisonian crisis after steroid withdrawal Angina pectoris after stopping -blockers
Mild Does not affect patients day-to-day activity Moderate Affects patients day-to-day activity to some extent Severe Adversely affects patients day-to-day activity
Non-serious Serious o Death / Results in death o Life-threatening o Require hospitalization / Prolongation of existing hospitalization o Cause permanent disability o Cause congenital anomalies o Require intervention to prevent any of the above
Cardiovascular drugs
Hypoglycemics Antihypertensives
NSAID/Analgesics
Diagnostic agents CNS drugs
Hypoglycemics
Antihypertensives NSAID/Analgesics
Diagnostic agents
CNS drugs*
The possibility of an ADR must be considered when an unexpected event occurs in a patient taking a drug, for which there is no obvious cause
Subjective report:
Patient complaint
Objective report:
Direct observation of event Abnormal findings
Type A reactions: Reduction in dose or withdrawal of medication altogether Type B reactions: Uncommon, unpredictable, high morbidity & mortality First step: immediate withdrawal If mild: no further intervention If moderate to severe: antihistamines + steroids + adrenaline Type C and D reactions: Irreversible/partially reversible by withdrawal by the time it is detected Type E reactions: Re-introduction and more gradual withdrawal
Availability of safe and quality drugs Rational use of drugs Individualization of therapy (p-drug concept) Continued Medical Education It is an absolute obligation on doctors to use only those drugs about which they have troubled to inform themselves Role of Health Authorities