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
Example of a drug that causes pathological damage on overdose
Paracetamol
Example of a drug with immunosuppressive effects in overdose
Corticosteroids
Example of a drug that leads to dysrhythmia in overdose
Digoxin (used to treat heart failure)
Idiosyncratic drug effects 1 2 3 4 5
- Infrequent
- Qualitatively abnormal response
- Dose-dependent
- Genetically determined
- Alteration in metabolism
Example of a drug with idiosyncratic effects
Codeine.
Slowed metabolism by CYP2D6 to morphine (decreasing CYP2D6 increases rate of metabolism of codeine to morphine)
Example of a drug that is altered in metabolism, leading to a idiosyncratic effects.
Suxamethonium (a nicotinic ACh inhibitor, used as a muscle relaxant).
Pseudocholinesterase degrades suxamethonium. If pseudocholinesterase is absent or deficient, then suxamethonium has greater effect than expected.
Examples of drugs that stimulate a type I hypersensitivity 1 2 3 4
Penicillins, lignocaine, atropine, aspirin
Examples of drugs that stimulate a type II hypersensitivity
1
2
3
Sulphonamides, Penicillins.
Halothane - liver damage
Examples of drugs that can stimulate a type IV hypersensitivity
1
2
3
- Penicillins
- Mercury, latex
Examples of drugs that can stimulate a type III hypersensitivity
Antivenoms, antisera (serum sickness)
Side effects of atropine
- anti-Salivation Lacrimation Urination Defecation
* context specific
Overdose effects of atropine
Blurred vision, difficulty swallowing, sedation,death.
Idiosyncratic effects of atropine
Slowed metabolism
Hypersensitivity reactions to atropine
“Red eye” Type I allergic response.
From use of atropine as a topical agent to dilate the pupil.
What counters the reactive intermediate generated by paracetamol in the liver?
Glutathione
When does paracetamol begin damaging the liver?
When the concentration is high enough that glutathione is overwhelmed in the liver, cause damage to hepatocytes
How can someone be sensitised to antibiotics that they’ve never been prescribed?
Widespread antibiotic use in the food chain
Halothane
An old general anaesthetic
