Pharmacology_Adverse Drug Reactions

Adverse Drug Reactions: 

Adverse Drug Reactions ADR Adverse Drug Effects

ADR: 

ADR 2 Any ‘ UNDESIRABLE ’ or ‘ UNINTENDED ’ effect of Drug Administration

WHO: 

WHO Any response to a drug which is noxious and unintended , and which occurs at doses normally used in man for prophylaxis , diagnosis or therapy of disease, or for modification of physiological functions. 3

Does not include….: 

Does not include…. Therapeutic failure Overdose Drug abuse Errors in drug administration 4

Thalidomide Tragedy: 

Thalidomide Tragedy 5

Thalidomide babies: 

Thalidomide babies 6

Slide 7: 

Thalidomide first appeared in Germany in October 1957. Prescribed as sedative to pregnant women for ‘Morning Sickness’. Test conducted only in Rodents. Rodents metabolize thalidomide in different way. Tests on monkeys & rabbits produced same effects as humans. 7

Sample size needed to detect ADR: 

Sample size needed to detect ADR Incidence of ADR No. of pts. to be observed to detect 1, 2 or 3 cases of ADR 1 2 3 1 in 100 300 480 650 1 in 200 600 960 1300 1 in 1000 3000 4800 6500 1 in 2000 6000 9600 13000 1 in 10,000 30000 48000 65000 8

Everything below the sun including the sun can cause adverse effect: 

Everything below the sun including the sun can cause adverse effect 9

Adverse Drug Reaction: 

Adverse Drug Reaction 10

Categories of ADR’s: 

Categories of ADR’s 11

Type of ADR’s: 

Type of ADR’s 12

Type of ADR’s: 

Type of ADR’s 13

Severity of ADR’s: 

Severity of ADR’s 14

Adverse Drug Effects: 

Adverse Drug Effects 15

Toxic Effect: 

Toxic Effect Excessive Pharmacological activity Overdose E.g.: Coma by barbiturates Resp. failure with morphine Gentamicin causes Nephrotoxicity 16

Side Effects: 

Side Effects Unwanted effects at therapeutic dose Effect Beneficial Harmful E.g. Antihistamines Atropine 17

Secondary Effect: 

Secondary Effect Indirect effect of the primary action of the drug E.g. Suprainfections Oral candidiasis with ICS 18

Drug Poisoning: 

Drug Poisoning Large doses Affects vital funcitons Management Prevent further exposure to drug Removal of drug from body Supportive measures Hydration Blood pressure Respiration Euglycemia 19

Drug Intolerance: 

Drug Intolerance Toxic effects at therapeutic doses Low threshold of individuals to drug E.g. Chlorpromazine – Extrapyramidal symptoms Carbamazepine - Ataxia 20

Idiosyncrasy: 

Idiosyncrasy Abnormal behavior / action Genetic basis E.g.: Chloramphenicol – Aplastic anemia Barbiturates - Excitement 21

Terratogenecity: 

Terratogenecity Prenatal exposure - Fetal abnormality Irreversible effects Effects: Abortion Deformities – Thalidomide, Phenytoin Hampered growth – NSAID’s Pregnancy Category: A B C D X 22

Mutagenecity & Carcinogenecity: 

Mutagenecity & Carcinogenecity Carcinogenecity Induce cancers Radiation Estrogens Tobacco/Nicotine Mutagenecity Structural changes in chromosomes 23

Drug Hypersensitivity: 

Drug Hypersensitivity Immune mediated drug reactions Antigen antibody reactions Cell mediated reactions Cross allergy Reversible ??? Types Type-I (Immediate hypersensitivity) Type-II (Cytotoxic) Type-III (Immune complex) Type-IV (Delayed hypersensitivity) 24

Type I: Immediate Hypersensitivity: 

Type I: Immediate Hypersensitivity Analphylaxis Ag – Ab ( IgE ) reaction Release of mediators from Mast cells Histamine 5-HT Leukotrienes Prostaglandins PAF 25

Type II: Cytotoxic: 

Type II: Cytotoxic Antibodies bind to drug + tissue IgG , IgM Ag- Ab reaction on cells Complement activation E.g. Thrombocytopenia SLE 26

Type III: Immune Complex Reactions: 

Type III: Immune Complex Reactions Arthus type reactions Circulating antibodies Ag- Ab complexes bind to endothelium and activate Complement Inflammatory response E.g. SJ Syndrome Serum sickness 27

Type IV: Delayed Hypersensitivity: 

Type IV: Delayed Hypersensitivity Sensitization of T-lymphocytes (receptors for Ag) Lymphokines Inflammatory response E.g. Contact dermatitis Rash 28

Photosensitivity: 

Photosensitivity 29

Drug Dependence: 

Drug Dependence 30

Drug Dependence: 

Drug Dependence 31

Drug Withdrawal: 

Drug Withdrawal Dependence producing drugs Rebound phenomenon E.g.: Corticosteroids Beta adrenergic blockers Phenobarbitone 32

Iatrogenic Diseases: 

Iatrogenic Diseases Drug induced diseases Physician induced diseases Functional disturbances even after drug is removed from body E.g.: Hepatitis – Erythromycin, INH Parkinsonism – Phenothioazines Peptic ulcer – Corticosteroids / NSAID’s 33

NATIONAL PHARMACOVIGILANCE PROGRAM (NPP): 

NATIONAL PHARMACOVIGILANCE PROGRAM (NPP) MOHFW, Govt. of India

Definition: 

Definition Pharmacovigilance is defined as the detection, assessment and prevention of adverse drug reactions in humans.

Broad Objectives of NPP: 

Broad Objectives of NPP To foster the culture of adverse event (AE) notification & reporting. To establish a viable & broad – based adverse drug reaction (ADR) monitoring programme in India.

Objectives of NPP: 

Objectives of NPP To create an ADR database for the Indian population. To create awareness of ADR monitoring among clinicians. To ensure optimum safety of drug products in Indian market.

Aims of NPP: 

Aims of NPP Improve patient care and safety in relation to use of medicine. Improve public health & safety in relation to use of medicines. Promote understanding, and educate about Adverse Event (AE) reporting.

Preventing ADR’s: 

Preventing ADR’s 39

Prevention of ADR: 

Prevention of ADR Never use any drug unless there is good indication. If the patient is pregnant do not use the drug unless the need is imperative. Allergy and idiosyncrasy are important causes of ADRs. Ask if the patient had previous reactions. Ask if the patient is already taking other drugs including self medication

Preventing ADRs …: 

Preventing ADRs … Age, hepatic and renal disease may impair clearance of drugs so smaller doses may be needed. Genetic factors may also predispose to certain ADRs Prescribe as few drugs as possible and give clear instructions Where possible use familiar drugs. With new drugs be particularly alert for ADRs and unexpected event. If serious ADRs are liable to occur warn the patient

Slide 42: 

Warfarin, Insulin and Digoxin are the most Dangerous drugs in the elderly. Do we believe that?

Thank You: 

Thank You Questions?