Haloperidol is one of 20 'essential' medications in palliative care. Its use is widespread in palliative care patients. The pharmacology of haloperidol is complex and the extent and severity of some of its adverse effects, particularly extrapyramidal adverse effects (EPS), may be related to the route of administration. Indications for the use of haloperidol in palliative care are nausea and vomiting and delirium. Adverse effects include EPS and QT prolongation. Sedation is not a common adverse effect of haloperidol. It is important that palliative care practitioners have a comprehensive understanding of the indications, doses, adverse effects and pharmacology of haloperidol. This review is intended to address these issues.
Opioids, defined as drugs that stimulate opioid receptors, are primarily used in the treatment of moderate to severe pain. They induce central nervous system (CNS) adverse effects which can be divided into three groups. The first group includes effects that lower the level of consciousness-sedation, drowsiness and sleep disturbance. The second group affects the thinking process and the ability to react-cognitive impairment, psychomotor impairment, delirium, hallucinations, dreams and nightmares. The third group is of the direct toxic effects of opioids on neurons and includes myoclonus (perhaps), hyperalgesia and tolerance. This review addresses the incidence, possible mechanisms, and treatment of each of these groups of opioid-induced adverse effects.
AimsThe aims of the study were a) to determine if there is evidence of saturable protein binding of cefazolin in plasma across the range of concentrations achieved clinically (between patient variability) and b) to investigate whether saturable protein binding is also evident from trough and peak concentrations in the same patient (within patient variability).
MethodsUnbound and total plasma concentrations were measured in patients who were treated with cefazolin intravenously by continuous infusion or intermittent injection. In study (i) single random samples were taken from one series of patients. In study (ii) paired samples (troughs and peaks) were taken from a second series of patients.
ResultsThirty-one patients were included in study (i). Linear regression analysis of the percentage unbound vs. unbound plasma concentrations revealed a slope significantly different from zero, suggesting saturable protein binding. Mean values for percentage unbound ranged from 9% at low concentrations (8.5 mg l -1 ) to 51% at high concentrations (140 mg l -1 ). Twelve patients were investigated in study (ii). Values for protein binding ranged from 85% at low concentrations (2.7 mg l -1 ) to 52% at high concentrations (200.3 mg l -1 ). The percentage unbound was significantly higher (P < 0.0001) at high (peak) concentrations than at lower (trough) concentrations, confirming saturable protein binding.
ConclusionsThe protein binding of cefazolin is saturable in vivo in humans, both between and within patients.
Opioids, defined as drugs that stimulate opioid receptors, are primarily used in the treatment of moderate to severe pain. They induce central nervous system (CNS) adverse effects which can be divided into three groups. The first group includes effects that lower the level of consciousness-sedation, drowsiness and sleep disturbance. The second group affects the thinking process and the ability to react-cognitive impairment, psychomotor impairment, delirium, hallucinations, dreams and nightmares. The third group is of the direct toxic effects of opioids on neurons and includes myoclonus (perhaps), hyperalgesia and tolerance. This review addresses the incidence, possible mechanisms, and treatment of each of these groups of opioid-induced adverse effects.
Significant temperature-dependent degradation of benzylpenicillin occurs during continuous home iv antibiotic programme infusions, which could result in loss of efficacy.
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