Simultaneous use of two analgesics of different modes of action is rational, but two drugs of the same class/mechanism of action are unlikely to benefit unless there is a difference in emphasis, e.g. analgesia and anti-inflammatory action (paracetamol plus aspirin), or in duration of action; a patient taking an NSAID with a long duration, e.g. naproxen (used once or twice a day), is benefited by an additional drug of shorter duration for an acute exacerbation, e.g. ibuprofen, paracetamol.
A low-efficacy opioid can reduce the effectiveness of a high-efficacy opioid by successfully competing with the latter for receptors. Partial agonist (agonist/antagonist) opioids, e.g. pentazocine, will also antagonise the action of other opioids, e.g. heroin, and may even induce the withdrawal syndrome in dependent subjects.
FIXED-RATIO (COMPOUND) COMBINATIONS
Large numbers of these are offered particularly to bridge the efficacy gap between paracetamol and morphine. Doctors should consider the formulae of these preparations before using them. Caffeine has been shown to enhance the analgesic effect of aspirin and of paracetamol and to accelerate the onset of effect, but at least 30 mg and probably 60 mg are needed (a cup of coffee averages about 80 mg and of tea averages about 30 mg).
Tablets containing paracetamol (325 mg) plus dextropropoxyphene (32.5 mg) (co-proxamol, Distal-gesic), in a dose of 1-2 tablets, provide an effective dose of both drugs and have been extremely
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