Drug idiosyncrasy

Drug idiosyncrasy

1. DRUG IDIOSYNCRASY Dr.Nafeeya Department of Forensic Medicine & Toxicology

2. Categories Classification idiosyncrasy Monitoring & Detection Reporting Prevention Forensic aspects Overview

3. Categories Side effects Secondary effects Toxic effects Intolerance Idiosyncrasy Drug allergy Photosensitivity Drug dependence Drug withdrawal reactions Teratogenicity Mutagenicity and Carcinogenicity Drug induced diseases (Iatrogenic disorders) Iatrogenic, Idiosyncrasy, Idiopathic, Intolerance

4. Classification of Adverse Drug Reactions Depending upon- Type of reaction: Type A Type B Type C Type D Type E Type F Onset of event : Acute (<60 minutes) Sub-acute (1-24 hrs) Latent (>2 days) Severity: Minor, Moderate, Severe, Lethal ADRs.

5. Types of Adverse Drug Reactions Augmented(dose related) Bizarre (Non-Dose Related) Chronic (Dose Related and Time Related) Delayed (Time Related) End of Use (Withdrawal) Failure (Unexpected Failure of Therapy)

6. B izzare (Non-Dose Related) Features Uncommon Not related to the pharmacologic action of the drug Unpredictable High mortality Example Immunologic reactions: anaphylaxis to penicillin Idiosyncratic reactions: malignant hyperthermia with general anesthetics Management Withhold and avoid in future Idosyncrazy

7. Classification of ADRs-Depending on Severity Minor ADRs : No therapy, antidote or prolongation of hospitalization is required. • Moderate ADRs : Requires change in drug therapy, specific treatment or prolongs hospital stay by atleast 1 day. • Severe ADRs : Potentially life threatening, causes permanent damage or requires intensive medical treatment. • Lethal: Directly or indirectly contributes to death of the patient.

8. Drug idiosyncrasy" refers to untold reactions to drugs that occur in a small fraction of patients and have no obvious relationship to dose or duration of therapy . Definition

9. DRUG IDIOSYNCRAZY It is genetically determined abnormal response to a drug. The drug interacts with some unique feature of the individual, not found in majority of subjects, and produces the uncharacteristic reaction . Example :- Chloramphenicol produces non dose-related serious aplastic anaemia in rare individuals. Barbiturates cause excitement and mental confusion in some individuals. Quinine causes cramps ,asthma ,diarrhoea, vascular collapse. Primaquine causes acute haemolytic anaemia.

10. Idiosyncratic drug reaction-Causes Genetic abnormality Deficiency of enzyme in the body Abnormal receptor activity Drug interaction with unique features

11. Genetic abnormality The occurrence of an idiosyncratic reactions is dependent on the interaction between multiple genes and environmental factors

12. Common Pharmacogenetics Polymorphism

13. Deficiency of enzyme in the body Pseudocholinesterase deficiency Glucose 6 phosphate dehydrogenase deficiency Succinylcholine or Mivacurium Quinine, aspirin ,NSAID, sulfa drugs,

14. Abnormal receptor activity Activated receptors directly or indirectly regulate cell. Receptors are macromolecules involved in chemical signaling between chemical processes . Ligand gated ion channel G-protein coupled receptor Enzyme linked Nuclear receptors

15. Drug interaction with unique features Mechanism : Pharmaceutical interaction Pharmacokinetics interaction Pharmacodynamics interaction

16. Alcohol idiosyncratic reaction unusual condition that occurs when a small amount of alcohol produces intoxication that results in Aggression, Impaired consciousness, Prolonged sleep, Transient hallucinations, Illusions, and Delusions.

17. Detection of ADRs Pre- Marketing Studies Post– Marketing Surveillance Spontaneous adverse reaction reporting Epidemiological methods Case Control Studies Cohort Studies

18. PRE- MARKETING STUDIES Animal Models Risk information ,acute toxicity & which organs are affected . Safety test 3 phases of clinical trails Consequences

19. POST- MARKETING STUDIES

20. These methods are used to verify the link between drug exposure and an adverse outcome. Two epidemiological methods most commonly used are: Cohort Studies Case Control Studies Epidemiological studies Advantage: Reveals unsuspected ADRs Advantage: Can be analysed quickly as number of patients analysed is small.

21. Patient initials, Age at onset of reaction, Reaction term(s), Date of onset of reaction, Suspected medication(s) reporter information. Mandatory field for suspected ADR reporting form.

22. • • More rational Prescribing Better communication Consider risk factors for ADRs Patient counseling Better monitoring of treatment 70% ADRs are potentially avoidable Preventing ADR

23. Medical maloccurrence In some cases inspite of good medical attention and care ,an individual fail to respond properly or may suffer from adverse reactions of the drug . The injured person cannot get compensation Doctor was careful in selection of the drugs and has taken appropriate measures to overcome this effects.

24. Therapeutic misadventure Mischance or accident or disaster ,in which individuals may be injuried or died due to some unintentional act of doctor or hospital . 3 types-therapeutic ,diagnostic , experimental It is known that many of the therapeutic procedure cause death to patient ,the doctor is not directly responsible for the harm. Radiological procedure(contrast) cause fatal adverse reactions

25. Contributory negligence In this condition patient is also responsible for the injury suffered by him.As such doctor is not the direct , cause of the injury suffered by the patient. Failure to give proper history , cooperation,refusal to treatment ,against doctors advice .

26. References: Goodnman & gilmans phamacological basis of therapeutics 13 th edition K.D Tripathi –Essential of pharmacology -6 th edition Lippincott illustrated review –Pharmacology -6 th edition Bardalae principles of forensic medicicne & toxicology. Anil Aggrawal textbook of forensic medicine and toxicology Narayana reddy text book of forensic medicin e and toxicology

27. If you suspect an ADR do not assume someone else will report it……