ADVERSE DRUG REACTIONS- BPHARM SECOND YEAR STUDENTS

Adverse drug reactions type with example.

1. ADVERSE DRUG REACTIONS Ms.Fathimath raihana Assistant professor P a college of pharmacy

2. Adverse drug reaction is defined as any response to a drug that is noxious, unintended and that occurs at doses used in man for prophylaxis, diagnosis or therapy. Types TYPE A TYPE B TYPE C TYPE D TYPE E Augmented Bizarre Chronic Delayed End of use

3. TYPE A Side effects Secondary effects Toxic effects TYPE B Allergic reactions ( Immunologically mediated ) Idiosyncratic reactions ( Genetically mediated ) Type I Anaphylaxis Eg : Penicillin Lignocaine Type II Cytolytic reactions Eg : Anemia due to phenytoin Type III Arthus reactions Eg : Sulfonamides Type IV Delayed hypersenstivity Eg : Penicillins

4. TYPE A : Predictable or Augmented reactions. These are predictable reactions related to the pharmacological effects of the drug. They are dose-related, quantitative adverse effects. For eg : Insulin induced hypogylcemia Warfarin induced bleeding They are reversible by dose reduction or stopping the dose.

5. They are classified into three : Side effects : Unwanted effects of a drug that are an extension of the pharmacological effects and are seen with the therapeutic dose. Eg : Insulin - hypoglycaemia Furosemide - hypokalemia Secondary effects : I ndirect consequences of a primary drug action. Eg : Superinfection - by broad spectrum antibiotics. Toxic effects : Seen with higher doses of drug and can be serious. Eg : Morphine – respiratory depression.

6. TYPE B : Bizarre reactions. They are unrelated to the pharmacological effects of the drug. Hence, unpredictable. They may be : Idiosyncratic – Genetically mediated Allergy – Immunologically mediated Idiosyncrasy : It is a genetically determined abnormal reaction to a drug. Eg : Primaquine and sulphonamides – haemolysis in patients with G6PD deficiency. Chloramphenicol – agranulocytosis Barbiturates - excitement

7. Allergy : They are immunologically mediated reactions which are not related to the therapeutic effects of the drug. The drug or its metabolite act as antigen to induce antibody. Types and mechanism : Type I hypersensitivity – Anaphylactic reactions : ( Immediate ) It is rapidly occurring reactions. Itching, urticaria , hay fever, asthma , anaphylactic shock. Ig E mediated.

8. Exposure to certain drugs ( Penicillins , aspirin, lignocaine) Production of Ig-E antibodies – fix to mast cells On re-exposure to the same drug Ag-Ab reaction occurs on the mast cell surface Release of mediators ( Histamine, 5-HT, Prostaglandins, leukotrienes, Platelet Activating Factor )

9. ii. Type II hypersensitivity : Cytotoxic reactions: They are IgG and IgM mediated. Drug binds to a protein. Together they act as an antigen. Induce the formation of antibodies. Antibody react with cell-bound antigen. Activation of complement system. Destruction of cells or Cytolysis. ( Thrombocytopenia, aplastic anemia , agranulocytosis ) Eg : Mismatched blood transfusions Haemolytic anemia by quinine, quinidine

10. iii. Type III hypersensitivity : Arthus reactions. Antigen binds to circulating antibodies. Complexes are deposited on the blood vessel. Initiates inflammatory response. Results in vasculitis. Eg : Serum sickness ( Fever, urticarial, joint pain ) – P enicillins , Sulphonamides Steven-Johnson syndrome – Sulphonamides

11. iv. Type IV hypersensitivity : Cell mediated or Delayed Mediated by T-lymphocytes and macrophages. The antigen reacts with receptors on T-lymphocytes Produce lymphokines Local allergic reaction Eg : Contact dermatitis – local anaesthetics, penicillins .

12. TYPE C : Continuous or chronic use. It occurs due to prolonged use of drugs. Both duration and dose of drug influence this type of ADR. Eg : Chloroquine - retinopathy Analgesic - nephropathy

13. TYPE D : Delayed effects. It occur after stopping a treatment . May be after years also. Eg : Leukaemia after treatment of Hodgkin’s lymphoma. Teratogenic effects

14. TYPE E : End of use. This occur due to sudden discontinuation of a drug after prolonged use. Eg : Angina – A fter sudden withdrawal of atenolol Withdrawal syndrome – Opioids

15. Prevention of drug allergies : It is important to check family history. If allergy is present, avoid the drug. For drugs known to cause allergy – sensitivity test should be done. Eg s for drugs causing allergy : Penicillins Sulphonamides Quinolones Cephalosporins Anaesthetics

16. Other ADRs : Drug intolerance : It is the inability of a person to tolerate a drug even in the therapeutic doses and is unpredictable. Eg : Streptomycin – vestibular dysfunction. Iatrogenic diseases : ( Physician induced ) These are drug-induced diseases. Even after the drug is withdrawn, its toxic effect is there. Eg : Isoniazid - hepatitis Chemotherapy – hair loss

17. Drug dependence : Drugs that influence the behaviour and mood are often misused to obtain pleasurable effects. Eg : Alcohol, barbiturates Teratogenecity : It is the ability of a drug to cause foetal abnormalities . Eg : Thalidomide - phocomelia Carcinogenicity and mutagenicity : It is the ability of a drug to cause cancers and genetic abnormalities. Eg : Radioactive isotopes Genotoxicity : It is the ability of a drug to cause genetic abnormalities and these could be inherited to next generations. Eg : Nitrosamines

18. Hepatotoxicity : It is the ability of a drug to cause hepatic toxicity . They may be : Dose dependent Non-dose dependent Fatty liver Chronic active hepatitis Cholestasis – Flow of bile from liver stops - jaundice.