ADVERSE DRUG REACTION POWER POINT PRESENTATION FOR UNDERGRADUATE STUDENTS

PHARMACOLOGY AND TOXICOLOGY

1. Dr. Ravi Mundugaru Ph.D. Assistant Professor Dept. of Pharmacology Adichunchanagiri Institute of Medical Sciences, BG Nagar Adverse Drug Reactions

2. Adverse drug reactions Any noxious change which is suspected to be due to a drug , occurs at doses normally used in man , requires treatment or decrease in dose or indicates caution in the future use of the same drug. It may develop promptly/ prolonged medication/ even after stoppage .

3. Severity of adverse drug reactions Minor: No therapy or antidote or prolongation of hospitalisation requires. Moderate: Require change in drug therapy, uses of specific treatment or prolongation of hospitalisation. Severe: Potential life threatening, causes permanent damage or requires intensive medical treatment. lethal: Directly or indirectly contributes to death of the patient.

4. PHARMACODYNAMIC EFFECTS Desirable/ beneficial undesirable/ADRs Expected UDE Un Expected UDE Side effects hypersensitivity Secondary effects Genetically determined Toxicity idiosyncratic

5. Expected undesirable effects 1. Side effects : Even observed with therapeutic doses e.g.: Dicyclomine –Antispasmodic– dryness of mouth Promethazine — Anti allergic ---( Sedation ) Antacid – Antiulcer activity- ( Epigastric distress )

6. 2. Secondary effects: Indirect consequence of the main PD action e.g.: development of super infection in Tetracycline use Glucocorticoids- reinfection of dormant TB

7. 3. Toxicity : Exaggerated form of side effects Occur due to over dose or after prolonged use of the drug 1.PD:e.g.: Bleeding due to high dose of heparin 2.PK:e.g .:Crystaluria— S ulfonamide ppt. in acidic urine Poisoning : Paracetamol poisoning, opioid, sedative drugs due to homicidal , suicidal tendencies

8. Diazepam poisoning

9. Unexpected undesirable effects Either immunological mediated P harmaco genetically idiosyncratic reaction

10. Drug allergy/ hypersensitivity reactions: Previous exposure to the drug when re-exposed to sensitized individual Type I / anaphylactic : IgE mediated AG- AB reaction on mast cells Develops within min. lasts 2-3 hr.

11. NSAIDS, β - Lactam antibiotics, Proton pump inhibitors

12. Type II / accelerated : IgG and IgM mediated compliment activation- release of inflammatory mediators Occurs within 72 hrs of drug administration. Lupus erythematous, thrombocytopenia, aplastic anemia, hemolysis organ damage….. Chloramphenicol, Phenylbutazone, antithyroid drugs, Sulfonamides

13. Type III / delayed allergic : It occurs after 72 hrs but within 1-2 weeks Circulating IgG mediated AG-AB reactions – precipitate over vascular compartments Steven Johnson syndrome, rashes, serum sickness, erythema multiforme , myocarditis, arthritis.

14. Steven Johnson Syndrome Lamotrigine , Sulfonamides, Cotrimaxazole , Sulfasalazine

15. Type IV / cell mediated: Develops > 12hrs. Antigen specific receptors are developed on T lymphocytes. T-lymphocyte produces lymphokines which attracts granulocyte and initiates inflammatory changes. Phototoxicity , contact dermatitis, rashes and fever etc.

16. Contact dermatitis – type IV allergic reactions Penicillin, Neomycin, Sulfonamides

17. Idiosyncratic drug reaction: These are some times harmful/fatal e.g.: Malignant hyperthermia– halothane, Succinylcholine, and neuroleptics Aplastic anaemia – low dose of Chloramphenicol Aspirin- -- late onset of asthma Thiazide-- - erectile dysfunction Barbiturates causing CNS exitment and mental confusion Quinine causing asthma , abdominal cramps and angioedema

18. DRUG DEPENDENCE It is a state in which use of drugs for personal satisfaction is accorded a higher priority than other basic needs, often in the face of known risk to health. E.g. :- Opioids , Alcohol , Barbiturates , Amphetamine. Two types:- Psychological dependence:- there is an intense desire to continue taking the drug as patient feels his well being depends upon the drug. Physical dependence:- Repeated drug use produces physiological changes in the body, which makes continuous presence of the drug in the body necessary to maintain normal function Abrupt stoppage of the drug results – ‘withdrawal syndrome’

19. Principles of treatment of drug dependence:- 1.Hospitalization . 2.Substitution therapy:- Methadone/ buprenorphine for morphine addiction. 3.Aversion therapy:- Disulphiram – for alcohol 4.Blockade therapy:- Naltrexone – opioid dep. 5.General measures:- Maintain nutrition, family support and rehabilitation.

20. TERATOGENICITY:- Capacity of drug to cause foetal abnormalities when administered to pregnant mother. Thalidomide disaster (1958-61)- phocomelia

21. Drug can affect foetus at 3 stages:- 1.Fertilization and implantation:- conception 17 days- failure of pregnancy 2.Organogenesis:- 18 to 55 days of gestation 3.Growth and development- 56 days onwards

22. HUMAN TERATOZENIC DRUGS Phenytoin-

23. Warfarin- depressed nose, eye and hand defects, growth retardation. Valproate sod.:- spina bifida and neural tube defects.

24. Alcohol:- Tetracyclines:- Lithium :- foetal goiter

25. Photosensitivity Phototoxic Ex: erythema , edema, vascular eruption Photo allergic - Drugs and dug metabolites induces cell mediated immune response which on exposure to UV-A produces exzematous contact dermatitis.

26. Mutagenicity and carcinogenicity Drugs having capacity to cause genetic defects Anti cancer drugs Radioisotopes Estrogen Tobaco etc

27. Drug induced disease Iatrogenic disease (Physician induced diseases) Ex: Peptic ulcer from NSAIDs

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