ADVERSE DRUG REACTIONS

I. Statistics 5% allergic 6-10% from drug allergy 3% hospital administration due to ADR 28% preventable Drugs associated: 29% analgesic; 10% sedative; 9% antibiotic; 7% antipsychotic PGH: 35% antibiotic; 34% anti-TB; 10% anticonvulsant; 10% ASA/NSAID II. Definition ADR - 4th leading cause of death (Apr. 14, 1998-Drug Reaction Kill an Estimate of 100000 a Year) - any response to a drug which is noxious and unintended and which occur at doses used in man for prophylaxis, diagnosis and therapy ADE: adverse drug experience -undesirable effect whether harmless, results from medication administered in a dosage normally given -it becomes an ADR when it is reported and subsequently evaluated to be secondary to drug usage ADR: undesirable, unintentional, suspected but not necessary proved, develop as a consequence of therapy or other procedures III. Reasons - Failure to take the correct dosage at correct time - Overdosing - Allergies to chemical components of the medication - Combining with alcohol (enzyme enhancer) - Taking other drug/preparation that interact with medication - Taking a medicine that was prescribed for someone else

IV. Causes a. Pharmaceutical cause -decreasing particle size/ changing excipients b. Pharmacokinetic cause -diazepam -aminoglycosides c. Pharmacodynamic cause- alter physiological effect -increase sensitivity of target organ in the body to the drug

V. Factors affecting ADRs a. Patient-Related - age, sex, genetic influences, concurrent diseases(renal, liver), previous ADR, compliance with dosing regimen, total number of medications, miscellaneous(diet, smoking, environmental) b. Drug-Related - dose, duration, inherent toxicity, pharmacokinetics, pharmacodynamics

VI. Classifications of ADRs Type A- Augmented a. Activity of the Drug (pharmacological) 1. Extension Effects- predictable, dose related response - prevention: adjustment of dosage regimen e.g. benzodiazepines- sedation (diazepam) furosemide- water and electrolyte imbalance heparin/warfarin- spontaneous bleeding (clopidogrel, clostazol, ASA) insulin- hypoglycaemia; sugar control 2. Adverse Effects -predictable, dose-dependent reaction unrelated to goal of therapy -produced by same drug-receptor interaction responsible for therapeutic effect, differing only in tissue/organ affected e.g. INH, Rif, PZA- hepatotoxicity Streptomycin- ototoxicity, nephrotoxicity Captopril- cough Simvastatin- rhabdomylosis Nitrates- HA Propanolol- bronchial asthma Tetracycline- hypoplasia of teeth Type B- Bizarre -aBnormal effect -unrelated from drugs known pharmacological action Characterisitics: -no normal dose-response curve (penicillin hypersensitivity- anaphylaxis) -rxn disappear on discontinuation of drug -recognized as immunological rxn -undetachable during conventional testing -little/ no relation to usual phacological effect of drug -delay between exposure to the drug and occurrence of the subsequent adverse reaction e.g. -Hypersensitivity reaction -Stevens-Johnsons Syndrome: chloramphenicol, aminoglycosides -Hemolytic Anemia: aminoglycosides, clinadmycin Type C- Continuous -long term effect are usually relatedto dose and duration of treatment e.g. -Ethambutol: eye -NSAID Type D- Delayed -Carcinogenesis -Teratogenesis: baby e.g. -Thalidomide: N&V -Vitamin A Type E- Ending of Use Use: withdrawal syndromes e.g. -benzodiazepine- rebound insomnia, agitation -clonidine: rebound HTN -corticosteroids: acute adrenal insufficiency -opioids: narcotic withdrawal

Type F- Failure of Efficacy -counterfeit drugs -underdosing -not for illness

ADR Reporting Why? -prevent drug-induced human suffering -avoid financial risk associated with unexpected risk *RA 3720, MC 5 s. 1994 *Report from Participating Hospital, Private practitioner, Manufacturer/Trade Outlet, Clinical Investigator, Regulatory Authorities, International Agency NADRAC *Case: -Fill form -Hospital Therapeutic Committee -NADRAC 1. Fill red alert card 2. Complete ADR Report Form 3. Submit to Central Block Pharmacy 4. PTC In report card of ADR: -brand name -manufacturer (if generic) -lot/batch no. *in duplicate *all are confidential

Ten Commandments to Reduce ADR 1. Critically review the total condition of patient. Be particularly careful when you prescribe to child, elderly, seriously ill, pregnant, & with renal, cardiac, or hepatic condition. 2. Use as few drugs as possible. Balance the seriousness of possible rxn against beneficial effect of each drug being considered. 3. Know well the drug. Compare efficacy and safety of each medication that appear to be worthy of consideration for the patient. 4. Dont change too readily from drugs that you know to the drugs you dont know. If you wish to change, know the drug. 5. Dont hesitate to use textbook and other reference providing info on drug rxn and interaction. 6. Be careful when prescribing drug known to exhibit a large variety of rxn and interactions. 7. Be aware of interaction with certain food, alcohol, and even household chemicals. 8. Regularly make an inventory of the drugs your patient is receiving. 9. Review patient regularly for all drugs used especially those bought without prescription. 10. If patient shows signs ans symptoms not clearly explains by course of illness, think of ADR.

DRUG INFORMATION SERVICE

I. Definition -access, evaluation, selection, & organization of drug literature for the use of health professional, patient, and public -involve interpretation & application of drug information to patient care problem II. Drug Literature -primary -secondary

-tertiary *basis to optimize the use of drug in patient Why needed? -vast drug literature -increasing drug therapy problem -growth of clinical pharmacy practice Functions: -support clinical service -pharmacy & therapeutics activities -publications -education -drug usage evaluation -investigational drug control -coordination of reporting program -poison information

III. DIS Process 1. Determine the primary question. -ask clarifying question -restate the question -ask when & whom to contact when answer become available *Types: -ADR&ADE -drug administration(dosage, compatibility, stability) -indication & therapeutic use -product specific concern -dosing -drug interactions -pharmacology & toxicology -miscellaneous: availability, foreign drugs, identification, calculations, pharmacokinetics 2. Develop an appropriate strategy. -match question w/ source -determine if question if for approved, investigation or unapproved drug -identify appropriate search keywords, terms, synonyms -be flexible in searching 3. Choose source of information. *oral *written/printed -primary: original article research/case reports in journal, presentations, & proceedings -secondary: abstracting & indexing services -tertiary: textbook, compendia, full text databases & review articles 4. Assessing printed sources of information. *Biomedical Journals: Lancet, BMJ, AIM, ArIM, JOAMA, AJHP, CP&T *Computerized Databases: Micromedex, IDIS, Medscape, Mayo Family Pharmacy, nlm.nih.gov. uspharmacist.com *Specific Sources: Pharmacotherapy, Pediatric Dosing, Generic Drug Information, Pharmacology, Patient Counseling, Interpretation of Lab Results, Dosage Calculations, Geriatric Dosing, AHFS Drug Information, Handbook on Injectable Drugs 5. Critical Appraisal of information source. *Textbook & Literature Review: date of publication, authorship, agreement with other sources *Original Research: abstract, basic research design, setting, participants, outcome measures, results

Basic Research Design: -randomized controlled trial, nonrandomized concurrent cohort study, nonrandomized historical cohort study, historical case control, case series w/out control, expert opinion 6. Formulating a response. -summary/evidence, recommendation 7. Communication of response. -oral, written 8. Documentation & Follow-up *Documentation: drug information, record, source *Follow-up: outcomes of recommendation

HOW DO WE START? 1. Build up your resources. 2. Be systematic in answering drug information questions. 3. Develop good search strategy. 4. Update yourself regularly. A pharmacist is a good provider of drug information regardless of the area of practice!