Adverse Drug Reactions (ADR)

Adverse Drug Reactions (ADR)

Content

• Side effects and toxic effects

• Classification of Adverse Drug Reactions

• Hypersensitivity reactions

• Factors modifying drug effects

Intended Learning Outcomes

At the end of this lecture, student will be able to 

• Differentiate between side effects and toxic effects

• Classify Adverse Drug Reactions

• Describe hypersensitivity reactions

• Explain the factors modifying drug effects

Adverse Drug Reactions

• Any response to a drug i.e. Noxious, unintended

• Occurs at doses used for prophylaxis, diagnosis, therapy

• Excludes drug overdose, abuse, therapeutic errors

• Drug tolerance – close to ADR

Administration of drugs may result into:

• Side effects: dryness of mouth with atropine

• Untoward effects

– Resistant staphylococcal diarrhea with tetracycline therapy

• Toxic effects: 

– Respiratory depression with morphine

• Allergic/ idiosyncratic reactions

– Salicylates – hemolysis (G6PD deficiency)

 

 

 

 

ADR Types

Type A

•Augmented

Type B

•Bizarre

Type C

•Chronic

Type D

•Delayed

Type E

•End of dose

Immunity

1. Innate immune system

• Mast cells, epithelial cells, NK cells, Macrophages,

Dendritic cells, N, B, E

• Destroy withoput prior exposure

2. Adaptive immune system

• Cell mediated immunity ( T cells)

• Humoral immunity (B lymphocytes)

Hypersensitivity

• Type I (Immediate hypersensitivity)

– Ag + Reaginic Ab – degranulation of mast cells & basophils

– Anaphylaxis 

• Type II (Cytotoxic reaction)

– Ag + Ab – destruction by lysis or phagocytosis

– Chloramphenicol – Autoimmune hemolysis

• Type III (Immune complex mediated)

– Ag + Ab – form immune complexes

– Serum sickness

• Type IV (Cell mediated/ delayed hypersensitivity)

– Ag contact T lymphocyte

– Contact dermatitis by chemicals, dust, chlamydia

Manifestations of ADR

• GIT

• Hemopoietic

• Hepatocellular

• Cardiac

• Renal

• Taste and smell

• Ocular

• Ototoxicty

• Dermal

• Electroloyte disturbances

• Endocrine disturbances

• Behavioral and CNS

• Carcinogenesis

• Teratogenicity

• Exacerbation of disease

• Iatrogenic disease

• Immunosupression

• ADR – abrupt withdrawl

Factors Modifying Drug Effects

• Body weight

• Age

• Pregnancy and lactation

• Diet, tobacco, alcohol & environment

• Route of administration

• Psychological factors

• Genetic factors

• Metabolic disturbances

• Presence of disease

• Cumulation

• Other drugs and chemicals

• Synergism / Antagonism

• Drug tolerance

• Drug dependence

Summary

• Administration of drug may result into side effects, untoward effects, toxic effects, allergic/ idiosyncratic reactions

• ADR types:

– Augmented

– Bizarre

– Chronic

– Delayed

– End of dose

• Various factors modify drug effects: Metabolic disturbances, Presence of disease, Cumulation, Other drugs and chemicals

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