Clin Pharmacokinet
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Rapacuronium is an aminosteroidal nondepolarising neuromuscular blocking agent (NMBA). Its neuromuscular blocking effects have a different time course to those of most currently available agents. It also has lower potency than many of the other NMBAs. ⋯ Because it gives rapid onset in a dose consistent with brief duration of action, it was hoped that rapacuronium might be a suitable alternative to suxamethonium. It does not have the problems associated with suxamethonium, but its use is associated with bronchospasm, the incidence of which is dose-related. Rapacuronium has been withdrawn from sale because of this adverse effect, and its future availability is uncertain.
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Although epilepsy affects men and women equally, there are many women's health issues in epilepsy, especially for women of childbearing age. These issues, which include menstrual cycle influences on seizure activity (catamenial epilepsy), interactions of contraceptives with antiepileptic drugs (AEDs), pharmacokinetic changes during pregnancy, teratogenicity and the safety of breastfeeding, challenge both the woman with epilepsy and the many healthcare providers involved in her care. Although the information in the literature on women's issues in epilepsy has grown steeply in recent years, there are many examples showing that much work is yet to be done. ⋯ AED dosage adjustments may be necessary during pregnancy and should be based on clinical symptoms, not entirely on serum drug concentrations. Many groups have turned their attention to women's issues in epilepsy and have developed clinical practice guidelines. Although the future holds promise in this area, many questions and the need for progress remain.
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Sepsis and septic shock are accompanied by profound changes in the organism that may alter both the pharmacokinetics and the pharmacodynamics of drugs. This review elaborates on the mechanisms by which sepsis-induced pathophysiological changes may influence pharmacological processes. Drug absorption following intramuscular, subcutaneous, transdermal and oral administration may be reduced due to a decreased perfusion of muscles, skin and splanchnic organs. ⋯ Changes in drug effect during septic conditions may theoretically result from changes in pharmacodynamics due to changes in the affinity of the receptor for the drug or alterations in the intrinsic activity at the receptor. The lack of valid pharmacological studies in patients with sepsis and septic shock makes drug administration in these patients a difficult challenge. The patient's underlying pathophysiological condition may guide individual dosage selection, which may be guided by measuring plasma concentration or drug effect.
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Review
Impact of stereoselectivity on the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs.
Many antiarrhythmic drugs introduced into the market during the past three decades have a chiral centre in their structure and are marketed as racemates. Most of these agents, including disopyramide, encainide, flecainide, mexiletine, propafenone and tocainide, belong to class I antiarrhythmics, whereas verapamil is a class IV antiarrhythmic agent. Except for encainide and flecainide, there is substantial stereoselectivity in one or more of the pharmacological actions of chiral antiarrhythmics, with the activity of enantiomers differing by as much as 100-fold or more for some of these drugs. ⋯ Similarly, there is no stereoselectivity in the renal clearance of tocainide, a drug that undergoes tubular reabsorption in addition to glomerular filtration. Overall, substantial stereoselectivity has been observed in both the pharmacokinetics and pharmacodynamics of chiral antiarrhythmic agents. Because the effects of these drugs are related to their plasma concentrations, this information is of special clinical relevance.
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The blood-brain barrier (BBB) is a gate that controls the influx and efflux of a wide variety of substances and consequently restricts the delivery of drugs into the central nervous system (CNS). Brain tumours may disrupt the function of this barrier locally and nonhomogeneously. Therefore, the delivery of drugs to brain tumours has long been a controversial subject. ⋯ Systemic toxicity remains the limiting factor for most methods that use intravascular delivery. This review evaluates the strategies used to increase drug delivery in view of current knowledge of drug pharmacokinetics and its relevance to clinical studies of chemosensitive brain tumours. The main focus is on primary CNS lymphoma, as it is a chemosensitive brain tumour and its management routinely utilises specialised strategies to enhance drug delivery to the affected CNS compartments.