Drug Safety
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The introduction of treatment with tretinoin (all-trans retinoic acid) and its combination with antineoplastic therapy has improved the outcome of acute promyelocytic leukaemia (APL). Retinoic acid syndrome is the major adverse effect of tretinoin and it occurs in about 25% of treated APL patients in the absence of prophylactic measures and is often fatal. ⋯ Adequate prophylaxis, based on the addition to tretinoin of dexamethasone and also, according to most authors, antineoplastic therapy (in case of rapidly increasing leucocyte counts) has decreased the incidence of retinoic acid syndrome to about 15%. Most importantly, these measures have reduced its mortality to about 1% of all treated patients.
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Systemic and localised adverse effects of local anaesthetic drugs usually occur because of excessive dosage, rapid absorption or inadvertent intravascular injection. Small children are more prone than adults to methaemoglobinaemia, and the combination of sulfonamides and prilocaine, even when correctly administered, should be avoided in this age group. The incidence of true allergy to local anaesthetics is rare. ⋯ Drugs inhibiting hepatic microsomal enzymes, such as cimetidine, may allow the accumulation of unexpectedly high (possibly toxic) blood concentrations of lidocaine. Reduction of hepatic blood flow by drugs or hypotension will decrease the hepatic clearance of amide local anaesthetics. Special caution must be exercised in patients taking digoxin, calcium antagonists and/or beta-blockers.
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Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen and others are the treatment of choice for mild to moderate pain. Because of the relative safety and efficacy of NSAIDs, many of the agents are now available in the US and in other parts of the world without a physician prescription. While these drugs are relatively well tolerated, adverse effects resulting from their use can occur. ⋯ Other postulated mechanisms of NSAID involvement in the development of necrotising fasciitis include an impairment of natural host defense mechanisms. A review of the medical literature for reports of possible NSAID-associated necrotising fasciitis revealed that the events were rare, but clinically significant. From the available evidence, a causal relationship between NSAIDs and necrotising fasciitis cannot be established.
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The worldwide expansion in the use of benzodiazepines has led to their frequent, and often inappropriate, use and to increase in their involvement in self-induced poisoning and iatrogenic overdosing. Flumazenil is a specific and competitive antagonist at the central benzodiazepine receptor, reversing all effects of benzodiazepine agonists without tranquillising or anticonvulsant actions. Incremental intravenous bolus injections of flumazenil 0.1 to 0.3 mg are the most effective and well tolerated in the diagnosis and treatment of pure benzodiazepine overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma. ⋯ Flumazenil per se does not induce adverse effects. Coma reversal by flumazenil may cause mild, short-lived reactions caused by sudden awakening. Withdrawal symptoms in long term benzodiazepine users and seizures in patients who have taken an overdose of TCA or carbamazepine and a benzodiazepine can occur with flumazenil; these symptoms are avoidable by utilising slow flumazenil dose titration.
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Ropivacaine is a new, long-acting local anaesthetic, prepared as a single enantiomer (the S form). Ropivacaine has a pKa of 8.07, a protein binding of approximately 94%, but a lower lipid solubility than bupivacaine. Extensive animal toxicological studies have shown a lower propensity for cardiotoxicity with ropivacaine than with bupivacaine. ⋯ In comparative studies of ropivacaine and bupivacaine, the 2 drugs appear to be associated with a similar incidence of similar types of adverse effects excluding cardiovascular and CNS toxicities which are lower with ropivacaine. In conclusion, ropivacaine is effective for pain relief during labour and in the postoperative period. Ropivacaine is associated with less cardiovascular and CNS toxicity than bupivacaine and provides a greater degree of dissociation between sensory and motor effects producing less intense motor blockade and more rapid recovery to full patient mobilisation.