157 - Adverse Drug Reactions Flashcards
Risk factors for adverse drug reactions 1 2 3 4
• History of a previous ADR • Pharmacodynamics: – Target selectivity – Target distribution • Pharmacokinetics: – Impairment of the organs of excretion (hepatic or renal dysfunction) – Extremes of age – Polypharmacy • Drug-interactions
Examples of drugs with a low therapeutic index 1 2 3 4 5
- Anticoagulants
- Cardiac glycosides
- Anticonvulsants
- Lithium
- Hypoglycaemics
Dose-dependent adverse drug reactions
1
2
3
Side Effects
Overdose Effects
Idiosyncratic Effects
Non-dose-dependent adverse drug reactions
Hypersensitivity
Features of side-effects
1
2
3
- Occur at therapeutic levels
- Frequent, non-deleterious, predictable
- On-target action but target at multiple sites
Example of a side effect from on-target action, at a site different to the one intended
Beta-adrenoceptor agonists/antagonists affect the heart and airways
Examples of on target side effects
1
2
3
1) Aspirin - desired response is analgesia, can have gastric bleeding
2) Beta-adrenoceptor antagonists - desired response is hypertension treatment, can exacerbate asthma
3) Adrenaline - desired effect is to localise anaesthetic solutions, but can cause cardiac excitability
Examples of drugs that have on-target side effects from action at multiple sites
1
2
1) Beta adrenoceptor agonists/antagonists
2) Muscarinic receptor antagonists
Examples of drugs with off-target action, leading to side-effects
1) Tricyclics (from poor selectivity)
2) Antihistamines (from metabolism, EG terfenadine)
Terfenadine
1
2
–Histamine H1 receptor antagonist for seasonal allergic rhinitis
–Almost 0% bioavailability
•Converted to active metabolite fexofenadine by P450 enzyme, CYP-34A.
When can Terfenadine be dangerous?
1
2
3
•Grapefruit juice –Contains dihydroxybergammotin that inhibits CYP-34A. •Terfenadine + Grapefruit juice –Life-threatening ventricular arrythmia –Terfenadine becomes bioavailable •Also inhibits K+ channels
Example of two drugs that inhibit CYP450 enzymes
Erythromycin, ketoconazole
Example of a drug that stimulates CYP450 enzymes
Dexamethasone
Overdose 1 2 3 4 5 6
- Occur when drug accumulates in the plasma
- Drugs with low therapeutic index
- ‘Infrequent’ side effects of other drugs
- Wrong dose
- Underlying problem (metabolism/excretion) patient history
- Drug interaction
Example of a fatal drug overdose
Atropine - delirium, coma, death
