Adverse drug reactions Flashcards
What is the epidiemology of adverse drug reaction (ADR)?
7% incidence of serious ADR
7% of all hospital admission
30% should be avoidable-large NHS burden
Describe categories to classify ADR?
Onset, severity, type
WHat are the different ADR onsets?
Acute-within 1h-anaphylaxis
Sub-acute-1/24h
Latent
WHat are the different ADR severity?
Mild-no need to do antyhing
Moderate-need to change something
Severe-threatning/disability-prolong hospitalisation
can cause congenital anomalies–require intervention
What are the 5 types of ADR types?
Type A-extension of pharma effect-predictable and dose dependent (like a B-blokcer causing bronchoconstriction, atenolol and heart block) –cause 2/3rds of ADRs
digoxin is an exemple of a drug as you give you get predictable increase (linear) of ADR
Paracetamol tho, under a certain dose is pretty safe, but above a certain dose-very very sharp increase
Type B-idiosyncratic (happen in some people/other), immunologic (allergy)
Rare, unpredictable
eg: Chloramphenical (abx)-cause plastic aneamia (BM failure), ACEi -angioedema
many serious ADRs are totally unexpected
Type C-associated with long term use-involves dose accumulation (eg: metotrexate cause liver fibrosis)
Type D-delayed-can be dose independent eg: carcinigenecity, teratogenecity
Type E-end of dose-Withdrawal (opiates, cortico)/Rebound (stop drug and end up worse than before-steroids)/adaptive (neuroleptics (tranquilisers)
eg: clonidine-lower BP-but when u stop, BP even higher than before drug
What are the 4 types of allergy?
Type I-immediate -igE
Type II-cyotoxic Ab IgG/M
Type III-serum sickness-IgG/M
Type IV-delayed hypersensitivity-Tcell
What are pseudoallergies?
Not allergies-no immune response BUT pharma reaction
NSAIDs can cause bronchospasm-stop bronchodilation because stop prostaglandins but not production of leukotriens
ACE inhbitors-cough/angioedma–stop bradykinin production
What are the 5 most common causes of ADR?
Abx Antineoplastics Anticoagulatns CVD drugs Hypoglycemics AntiHypertensiov
mainyl not that toxic (except anti-cancer) but the amount of people that have them is so high-get a lot of reaction
What are the 2 forms of ADR detetction?
Subjective patient report
Objective report-observe event (anaphylaxic)
Abnromal findings-blood tests, etc
-> but because so rare, you have low chance to actually detect any ADR-rare events arent identified before marketing of drug
What is the yellow card scheme?
Dr report any suspected ADR that patients have had
Established drug-only very serious ones
black triangle/newer drugs-report all
voluntary scheme
What are the 3 ways that drugs can interact with one another? What 3 effects can that produce?
Pharmacodynamic-related to drugs effect in body (some receptor occupancy, etc)
pHarmakokinetic (abs, distrib, metabolism
Pharmaceutical-interacting outside body, like in IV
Can be additive, syngerstic, or antagnoistic
Abx-synergetic
Additive-aclhol and benzodiazepine
=> often intentional,
What are the 4 most important ways drugs can interact in a pharmatokinetic sense?
Alteration in absorption-chelation-compounds combine in gut and cant be absorbed (eg: some Abx and iron)
protein binding effects-drug displacing other drugs on plasma protein bound drugs-not as important as initially though
changes in drug metabolism-overcrowding of phase1/2 metabolism-accumulation of active metabolites/ metabolites. sometimes single p450 isozyme, sometimes multiple (to pick up flack of others if one is full)– inhbition of P450 (cimetidine, Erythromycin, ketoconazole, grapefruit juice)
Also CYP450 INDUCERS-rifamicin, carbamezapine, St John Worts-work too well and drug not acting
or alteration in elimination-in renal tubule
sometimes deliberate-probenecid stop penicilin excretion
Lithium and thiazide-lithium increase Na loss and K accumulation-too much
