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Adverse drug reaction sjk
- 1. Presented by- Ms.S.J.Kamble Department ofPharmacology Ashokrao Mane College of Pharmacy, Peth Vadgaon
- 2. Definition Any noxious or unintended effect of drug which occurs at doses normally used in man for prophylaxis, diagnosis and treatment of disease 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.
- 3. Adverse drug event (ADE): • Any untoward medical occurrence that may present during treatment with a medicine, but which does not necessarily have a causal relationship with the treatment.
- 4. SEVERITY OF ADRs Minor – no therapy, antidote or prolongation of hospitalization is required Moderate – requires change in drug therapy, specific treatment or prolongs hospital stay by atleast one day Severe – potentially life-threatening, causes permanent damage or requires intensive medical treatment Lethal – directly or indirectly contributes to death of the patient
- 5. Reasons Medication errors- Self medication - OTC drugs- over use or misuse of drug Excess pharmacological action Overprescribing drugs to patients- Potent medicaments Inadequate monitoring of the patient- Digitalis, diuretics, corticosteroids Misused – adverse effects or death Sudden withdrawal of drugs- Steroidal drugs or hormones Stopped by decreasing the dose
- 6. Difference in bioavailability- Number of brands & formulations of same drugs available Difference- Bioavailability Formation of toxicity Drug interactions- Drug-drug interaction Drug-food interaction Inactivation or change in ADME Use of potent drugs- Narrow therapeutic index Digoxin,Phenytoin, Cyclosporine, Carbamazepine
- 7. Patient Factors- Age Disease state- Renal dysfunction, Hepatic damage Discontinuation of therapy
- 8. MANIFESTATIONS OF ADRs GIT – nausea, vomiting, constipation, diarrhea, gastric mucosal erosion & ulceration with bleeding HEMATOPOIETIC – bone marrow depression ORGAN TOXICITIES – hepatotoxicity, nephrotoxicity, cardiac toxicity, ototoxicity, ocular toxicity, CNS toxicity, endocrine & infertility, dermatological toxicity OTHERS – mask taste & smell.
- 9. Classification Predictable ADR (Type A) 1. Excessive pharmacological effect (A) 2. Secondary pharmacological effect (A & C) 3. Rebound effect on discontinuation(E) Unpredictable ADR (Type B) 1. Allergic reactions & anaphylaxis(B) 2. Idiosyncracy(B) 3. Genetically determined effects(D)
- 10. TYPES OF ADVERSE DRUG REACTIONS Type A(augmented/predictable)-Side effect,Toxic effect, poisoning, Secondary effect, intolerance Type B (bizarre/non-predictable)-Drug allergy/ idosyncrasy Type C (chronic use)-Drug dependance, organ damage Type D (delayed effect)-Mutagenicity,Carcinogenicity, teratogenicity Type E (end of use/abrupt withdrawal)-Withdrawl reactions Others-Photosensitivity, Drug induced diseases
- 11. Type A Type B Type C Type D Type E Others Side effects Allergic reactions Drug dependence Teratogenicity Withdrawal reactions Iatrogenic Secondary effects Idiosyncrasy Cumulative toxicity Mutagenicity Photosensitive reactions Toxic effects Organ damage Carcinogenicity Masking of diseases Poisoning Immuno suppression Exacerbation of disease Intolerance
- 12. Type A (augmented) Type B (bizarre) • Due to extension of pharmacological action • Immunological/ genetic basis • Predictable • Mostly not predictable • Quantitative (dose dependent) • Qualitative (dose dependent) • High incidence but low mortality • Low incidence but high mortality • Dose reduction is needed • Drugs has to be discontinued • Examples: dryness of mouth & • Anaphylactic reaction due to blurring of vision due to penicillin G; hemolysis with atropine; hypoglycemia with primaquine glibenclamide
- 13. Type Areactions • Side effect • Toxic effect and drug toxicity or poisoning • Secondary effect • Intolerance
- 14. SIDE EFFECTS • Unwanted & unavoidable PD effects at therapeutic doses • It may be same as therapeutic effect (atropine, GTN) • It may be a different facet of action (promethazine, estrogen) • May be therapeutic in one context but side effect in another context (codeine) • Discovery based on side effects (sulfonamides)
- 15. SECONDARY EFFECTS • Indirect consequences of a primary action of a drug • Examples : suppression of bacterial flora by tetracyclines leads to superinfections • Corticosteroids weaken host defence mechanisms so that latent TB gets activated. • At average dose of drug- several pharmacological effects •Antihistaminic drugs- anti-allergic (skin rashes, cough & cold)- can also cause Drowsiness, CNS depressant activity
- 16. TOXIC EFFECTS • Result from excessive pharmacological action of the drug due to over dosage (absolute/relative) or prolonged use. • Manifestations are predictable & dose related • Functional alteration (atropine), drug induced tissue damage (paracetamol), extension of therapeutic effect (barbiturates, heparin), additional action of a drug (morphine, streptomycin) Most common cause of ADR Dose- excessive CNS depressants, cardiotonics, hypoglycemic agents At average dose they can produce, 1. Kidney disease patients 2. Age of patients- Neonates, infants, elderly
- 17. POISONING • Poisoning - harmful effects of a chemical on biological system • Result from large doses (it is the dose which distinguishes a drug from a poison) • Management protocol
- 18. INTOLERANCE • It is the appearance of characteristic toxic effects of a drug in an individual at therapeutic doses. • Indicates low threshold of the individual to the action of the drug • Eg. Chloroquine (vomiting & abdominal pain), triflupromazine (muscular dystonias), carbamazepine (ataxia)
- 19. Type B reactions • Drug allergy / allergic reactions • Idiosyncratic reactions (pharmacogenomics) Hypersensitivity Allergy- Adverse response to foreign substances resulting from previous exposure to that substance Small proportion of population Features- Not expected pharmacological effect Time interval- initial exposure to drug & development of allergy Reoccurs- small quantity of drug
- 20. IDIOSYNCRASY • Genetically determined abnormal reaction to a chemical • total absence or reduced activity of some enzyme ( eg. G6PD deficiency – primaquine, salicylates, sulfonamides - hemolysis • Examples: barbiturates (excitement & mental confusion), chloramphenicol (aplastic anemia)
- 21. Idiosyncracy Effect Drug Aplastic anemia Chloramphenicol Uterine cancer Oestrogens Kidney cancer Pelvis cancer Analgesic induced nephropathy Asthma Quinidine Excitement & mental confusion Barbiturates Phocomelia Thalidomide
- 22. Immunologically mediated reaction producing symptoms which are unrelated to the pharmacodynamic profile of the drug.
- 23. TYPES OF ALLERGIC REACTIONS • Type 1 (anaphylactic reactions) • Type 2 (cytolytic reactions) • Type 3 (arthus reaction) • Type 4 (delayed hypersensitivity reaction)
- 24. Allergic reaction Causative Drugs Anaphylaxis Penicillin, Anaesthetics, Iodine containing compounds Skin rashes Sulphonamide, Penicillin, barbiturates Haemolytic anemia Sulphonamide, Penicillin Hepatitis Tetracycline, Acetaminophen, Methyldopa Leucopenia Sulphonamide Thrombocytopenia Digoxin, Quinidine, Thiazides
- 25. TYPE C REACTIONS • Drug dependence • Organ damage • Cumulative toxicity • Immunosuppression
- 26. DRUG DEPENDENCE • Drugs for personal satisfaction is accorded a higher priority than other basic needs, oftenin the face of known risks tohealth. • Psychological (reinforcement) & physical dependence • Drug abuse, addiction &habituation
- 27. • Psychological –individual believes that optimal state of well being is achieved only through action of drug (emotionally distressed if drugis not taken – compulsive drug use) • Physical –altered physiological state produced by repeated administration of a drug, necessitates continuous presence of drug to maintain physiological equilibrium (discontinuation – withdrawal syndrome) – neuroadaptation
- 28. • Drug abuse –use of a drug by self medication (deviates from the approved medical and social pattern) – continuous, occasional • Drug addiction – compulsive drug use/ overwhelming involvement, • Drug habituation – less intense involvement with drug, withdrawal produces only mild discomfort
- 29. Type D reaction • Mutagenicity and carcinogenicity • Teratogenicity
- 30. MUTAGENICITY & CARCINOGENICITY • Drug cause genetic defects and cancer respectively. • Oxidation of drug - produce reactive intermediates – affect genes and cause structural changes in chromosomes – covalent interaction with DNA – induce mutations.
- 31. TERATOGENICITY • Fetal abnormalities when given to pregnant mothers • Affect fetus at 3 stages: 1. Fertilization & implantation – conception to 17days – failure 2. Organogenesis – 18 to 55 days – most vulnerable (deformities) 3. Growth & development – 56 days onwards – developmental & functional abnormalities.
- 32. Teratogenicity – Teratos – monster, genicity - generation Somatic cells of embryo- defects in organ system Teratogen - drugs- abnormalities in the development of embryo that are compatible with pre-natal life Observable post- natally Dose- lower Foetal hepatic enzymes function- minimum
- 33. DRUG EFFECT Thalidomide Phocomelia, heart defects, gut atresia Warfarin Saddle nose, retarded growth, defects of limbs, eyes and CNS Corticosteroids Cleft palate and congenital cataract Androgens Masculinisation in female Oestrogens Testicular atrophy in males Ethanol Fetal alcohol syndrome Valproate Neural tube defects Phenytoin Cleft lip/palate, microcephaly, mental retardation Aminoglycosides Deafness
- 35. Genetic condition Drugs causing toxicity Glucose-6-phosphate dehydrogenase deficiency Antimalerial, Quinidine Glaucoma Corticosteroids Porphyria Barbiturates Methaemoglobinemia Salicylates
- 36. TYPE E (withdrawal reaction) • Acute adrenal insufficiency – corticosteroids • Rebound hypertension – clonidine • Worsening of angina pectoris –beta blockers • Seizures – antiepileptics Continuous use of drugs- tolerance Sudden withdrawal- produce severe adverse effects Rebound hypertension- withdrawal of hypotensive drugs Increase in frequency of seizures- withdrawal of an antiepileptic
- 37. PHOTOSENSITIVITY • Cutaneous reaction resulting from druginduced sensitization of the skin to UVradiation • phototoxic (tetracyclines, nalidixic acid, fluoroquinolones) - short wavelengths (290-320nm) – shorter duration after exposure ends • photoallergic (sulfonamides, sulfonylureas, chloroquine) –longer wavelengths (320-400nm) – persist long after exposure –lesion extend beyond exposed areas.
- 38. Drug Induced Diseases Drugs used to cure one disease may induce another disease condition to various organs of the body Drug induced Liver diseases Drug induced Renal diseases Drug induced Haematological disorder Drug induced Gastrointestinal disorder Drug induced Dermatological disorder Drug induced Ocular disorder Drug induced Ototoxicity
- 39. Drug induced Liver diseases Liver- metabolism & excretion of drugs Drugs causing direct liver damage- Chemical structure Predictable Dose dependent Eg- Isoniazide, Methotrexate, Tetracycline, Acetaminophen, Aspirin Drugs causing liver damage through host hypersensitivity Allergic reactions- Skin rashes, fever, Eosinophilia Unpredictable Dose independent Eg-Phenytoin, Sulfonamides, MAO inhibitors, TCA, Methyldopa
- 40. Drug induced Renal diseases Excreted through urine Most of kidney cells- exposed to higher conc.of drug Renal Disease Causative Drugs Acute Renal Failure NSAID’s, Quinine Kidney stone Sulphonamides Diabetes insipidus Sulfonylurea's, Lithium Renal ischemia Methysergid Interstitial nephritis NSAID’s, Penicillin, Ampicillin,Cephalosporin
- 41. Drug induced Haematological disorder Affects normal functioning of blood cells Abnormality in cell numbers & functioning of bone marrow Adverse effect Description Causative Drugs Aplastic anemia Destruction of red bone marrow Salicylates, Chloramphenicol, Phenylbutazone, Phenytoin Megaloblastic anaemia Vit.B12 and folic acid deficiency, leads to increase in abnormal RBC 5-flurouracil Haemolytic anaemia Occurs due to genetic abnormality, lifespan shortens Methyldopa, Levodopa, mefenamic acid, streptomycin Agranulocytosis Destruction of Leucocytes Anti-TB drugs, Sulfonylurea Thrombocyto- penia Aspirin, Penicillin, Rifampin, Sulphonamides, Phenylbutazone
- 42. Drug induced Gastrointestinal disorder ADR Causative Drugs Nausea & Vomiting All orally administered drugs Dysgensia Levodopa, Metronidazole Gastric Ulcer All NSAID’s Constipation Morphine, Vinca alkaloids Diarrhoea Antibiotics
- 43. Drug induced Ototoxicity Vestibular toxicity- Impairment of body balance Cochlear toxicity- Permanent hearing loss Eg- Aminoglycosides- Streptomycin, Gentamycin, Amikacin Most toxic- permanent damage Diuretics-Furosemide,
- 44. Role of Pharmacist in ADR monitoring Literature review Patient history Drug level studies Therapeutic decision making
- 45. PHARMACOVIGILANCE • “Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problems.” • Usefulness – educate doctors, official regulation of drug use, reduction in drug-related harm to patients, rationale use of medicines.
- 46. Activities involved in pharmacovigilance • Post marketing surveillance & other methods of ADR monitoring • Dissemination of ADR data – drug alerts, medical letters, advisories sent by FDA • Changes in labelling of medications
- 47. Governing bodies of Pharmacovigilance • Uppsala Monitoring Committee (Sweden) – international collaborating centre • Central Drugs Standard Control Organization (CDSCO) – India • Assess causality (Naranjo algorithm) and severity (modified Hartwig scale
- 49. PREVENTION OF ADVERSE EFFECTS Avoid inappropriate use of drugs Use appropriate dose, route & frequency of drug administration Previous history of drug interactions, allergic diseases Rule out drug interactions Adopt correct administration technique Carry out appropriate laboratory monitoring