Pharmacokinetic drug interactions with gastrointestinal motility modifying agents.

Drugs may affect gastrointestinal motility and, therefore, absorption of other concomitantly administered drugs. Gastrointestinal prokinetic agents increase the rate of gastric emptying and also upper intestinal motility. These effects would be expected to increase the initial rate of absorption of orally administered drugs, but reduce total bioavailability of the agents. Metoclopramide has been shown to increase the rate of absorption of several classes of drug, reflected by reduced time taken to achieve maximal plasma concentration (tmax) and increased maximal plasma concentration (Cmax). However, the effect of these agents on the area under the plasma concentration-time curve from zero to infinity (AUC0-infinity), when measured, is not consistent. Cisapride and domperidone appear to have similar effects, but there are relatively less data available regarding these products. Opioids may delay gastric emptying considerably, an effect which will often have significant clinical and therapeutic implications. Most of the data confirming this observation concern oral analgesics, but the effect should be considered when prescribing any oral medication. Drugs with anticholinergic or sympathomimetic activity are likely to have a similar effect and this is confirmed, in the main, by the limited data available. Although many effects reported in the literature are of limited clinical importance, they may be significant when prescribing a drug with a narrow therapeutic index, especially if it is absorbed poorly.

Inhibition by halothane of potassium-stimulated acetylcholine release from rat cortical slices.

1. Cholinergic neurones in the basal forebrain are linked to cortical activation and arousal. 2. The present study was designed to examine the hypothesis that clinically relevant doses of halothane (0.1 to 5%) would significantly reduce depolarization-evoked acetylcholine (ACh) release from rat cortical slices. 3. ACh release was measured from rat cortical slices by a chemiluminescent technique. 4. Depolarization-evoked ACh release was inhibited significantly by halothane with an IC50 of 0.38%. This value equates to 0.3 MAC (the minimum alveolar concentration at which no movement occurs to a standard surgical stimulus in 50% of subjects) for the rat. 5. The potent effect of halothane on ACh release suggests that this mechanism may be a target for the action of volatile anaesthetic agents. This in vitro effect on ACh release is consistent with effects of halothane reported in vivo.

Postal survey on the long-term use of neuromuscular block in the intensive care.

OBJECTIVE: To assess the long-term use of neuromuscular blocking (NMB) agents in intensive care, especially with reference to the potential problems of the long-term use of NMB drugs in the intensive care unit (ICU). METHOD: A postal survey questionnaire was sent to 409 ICUs in Great Britain. RESULTS: Two hundred thirty-eight completed questionnaires were returned and analysed. Most ICUs were anaesthetist-led (85.8%) with only five ICUs being staffed by full-time intensivists. Facilitation of mechanical ventilation and increased intracranial pressure were the main indications for the prolonged use of neuromuscular blockade. Atracurium and vecuronium (83%) were administered most commonly by bolus alone (13.8%), bolus followed by continuous infusion (23.9%) or continuous infusion only (60.9%). The most frequently cited criteria for the use of either vecuronium or stracurium were their pharmacokinetics and haemodynamic stability. Neuromuscular block was most commonly monitored clinically (91.7%), with only 8.3% of the responders using a peripheral nerve stimulator. All responders indicated the concomitant use of sedatives (propofol/midazolam alone or in combination in 89.4% of responders) and/or opioids (morphine, fentanyl or alfentanil in 74.8% of respondents) with muscle relaxants. CONCLUSION: Most responders agreed that while neuromuscular block in the ICU population may provide advantages, it cannot be considered benign. Indeed, a great majority consider that NMB agents should be used only as a last option and -for as short a period as possible.

Acid aspiration prophylaxis in 202 obstetric anaesthetic units in the UK.

A postal survey of obstetric anaesthetic units in the UK was conducted by questionnaire to gain information about current acid aspiration prophylaxis. Information regarding the delivery rate and the caesarean section rate under regional techniques was also requested. Replies were received from 202 obstetric anaesthetic units in the UK, a 75% response rate. The results are compared to similar surveys carried out in 1984 and 1988. Sodium citrate and the H(2) antagonist ranitidine remain the drugs most commonly used for acid aspiration prophylaxis. However, the number of departments carrying out routine prophylaxis for patients in active labour has fallen from 75% in 1988 to 57% in the current survey.

Anaesthetic implications of aortic stent surgery.

We present a case of abdominal aortic aneurysm repair using a new technique of aortic stenting and discuss the anaesthetic technique used and the perioperative advantages of the technique.

Choline acetyltransferase activity of rat synaptosomes is sensitive to enflurane, but not halothane or isoflurane.

We have examined the activity of choline acetyltransferase (ChAT) in rat cortical synaptosomes in the presence of three volatile anaesthetic agents: enflurane, halothane and isoflurane. The Michaelis constant Km, for choline was reduced significantly (P = 0.012) in the presence of 6.5% enflurane (3 rat MAC) compared with control samples exposed to carrier air only, while maximum reaction velocity (Vmax) remained unaltered. The reduction in Km was also significant at enflurane concentrations of 4.4% (2 rat MAC) (P = 0.043) and 2.2% (1 rat MAC) (P = 0.043). Halothane 3% (2.5 rat MAC) and 4.5% isoflurane (3 rat MAC) had no effect on either kinetic property. If present in vivo, an enflurane-induced alteration in acetylcholine metabolism, through modified ChAT, may contribute to the convulsive properties of this anaesthetic.

Volatile anesthetic agents inhibit choline uptake into rat synaptosomes.

BACKGROUND: Acetylcholine is an excitatory neurotransmitter associated with the maintenance of consciousness. Choline uptake is the rate-limiting step in acetylcholine synthesis and may be a target for the action of volatile anesthetic agents. METHODS: [Methyl-3H]choline uptake was investigated using rat cortical synaptosomes. The preparation was exposed to air, as control, or equipotent partial pressures (2.4 rat MAC) of enflurane, halothane or isoflurane. In addition, the dose-response relation for halothane on [methyl-3H]choline uptake was studied. RESULTS: The maximum rate of uptake was reduced significantly by 24% in the presence of enflurane (5.5%, 2.4 rat MAC) and isoflurane (3.5%, 2.4 rat MAC) and by 38% in the presence of halothane (3%, 2.4 rat MAC) with no change in Michaelis constant in the presence of each agent. A linear relation between the inhibition of [methyl-3H]choline uptake and the concentration of halothane was observed up to 3% halothane above which there was no further inhibition. The concentration of halothane resulting in half-maximum inhibition of total choline uptake was 1.5%. CONCLUSIONS: Noncompetitive inhibition of [methyl-3H]choline uptake by volatile anesthetic agents has been demonstrated in the in vitro synaptosome preparation. If present in vivo reduction in anesthetic-sensitive choline uptake may reduce the presynaptic availability of acetylcholine and hence contribute to the process of anesthesia.