Pharmacological properties of extracts from the stem bark of Syzygium guineense on the ileum and heart of laboratory rodents.

A methanol extract of Syzygium guineense bark inhibited intrinsic contractions of rabbit isolated ileum. The inhibition, at bath concentrations of 0.5 - 2.0 mg/ml, was dose-related but non-linear. It produced sustained hypotension in anaesthetized rats. A dose of 5 ug lowered systolic, diastolic and mean blood pressure by 16%, 22% and 17%, respectively below the pre-drug levels. Maximum effect was obtained at a dose of 40 ug when the systolic, diastolic and mean blood pressures fell by 23%, 36% and 28%, respectively below the pre-drug levels. The greater fall in blood pressure was in diastolic than systolic blood pressure. The extract caused a weaker but similar effect to isoprenaline on rabbit isolated heart. While the effect on rabbit isolated ileum supports the folkloric use of the plant as an antispasmodic, further work is required to confirm and categorize the observed pharmacological activities.

Pharmacological Properties of Extracts from the Stem Bark of Syzgium guineense on the Ileum and Heart of Laboratory Rodents

A methanol extract of Syzygium guineense bark inhibited intrinsic contractions of rabbit isolated ileum. The inhibition; at bath concentrations of 0.5 - 2.0 mg/ml; was dose-related but non-linear. It produced sustained hypotension in anaesthetized rats. A dose of 5 ug lowered systolic; diastolic and mean blood pressure by 16; 22and 17; respectively below the pre-drug levels. Maximum effect was obtained at a dose of 40 ug when the systolic; diastolic and mean blood pressures fell by 23; 36and 28; respectively below the pre-drug levels. The greater fall in blood pressure was in diastolic than systolic blood pressure. The extract caused a weaker but similar effect to isoprenaline on rabbit isolated heart. While the effect on rabbit isolated ileum supports the folkloric use of the plant as an antispasmodic; further work is required to confirm and categorize the observed pharmacological activities

Changes in haemodynamics and plasma catecholamine concentrations after field block for inguinal herniorrhaphy using lignocaine with adrenaline.

Haemodynamic changes and plasma catecholamine concentrations were measured in 12 patients aged 24 to 87 years after performance of a field block for elective repair of inguinal or femoral hernia. The local anaesthetic used comprised a mixture of lignocaine 0.5% with adrenaline 1:200,000; the dose of lignocaine administered varied from 3.8 mg/kg to 4.9 mg/kg. Plasma adrenaline increased by 326% and plasma noradrenaline by 75% at 10 minutes after completion of the block. Mean heart rate increased from 75 to 94 beats/minute after 20 minutes, whilst there were no obvious changes in systolic and diastolic arterial pressures. Potentially serious arrhythmias developed in two patients, thought to be related to the peak plasma concentrations of adrenaline produced. It is recommended that the dose of adrenaline used as described for this block should be reduced.

Hypertensive and catecholamine response to tracheal intubation in patients with pregnancy-induced hypertension.

The pressor and catecholamine responses to laryngoscopy and intubation were studied in nine patients with pregnancy-induced hypertension (PIH) and in eight normotensive controls. Five of the PIH patients had received oral labetalol as antihypertensive therapy. Mean arterial pressure (MAP) increased significantly from the pre-induction value in all groups 1 min after intubation, and also at 3 min in those with PIH who had not received labetalol. Arterial pressure was significantly greater in both PIH groups than in the control group at all times. However, the percentage increase in MAP on intubation was significantly less in the labetalol treated group than in either the untreated or the control groups. There were no significant differences between the groups in plasma concentrations of either noradrenaline or adrenaline; noradrenaline concentration increased significantly after intubation only in the control group. Labetalol appears to confer some protection against the pressor response to intubation in parturients with PIH.

Postoperative absorption of controlled-release morphine sulphate. A study in patients given no parenteral opioids.

The absorption of morphine sulphate in a controlled-release formulation was studied in 12 patients who had undergone unilateral inguinal hernia repair under a light general anaesthetic and ilio-inguinal block. Serum morphine concentrations were measured serially and gastric emptying was assessed by measurement of paracetamol absorption. Three patients had delayed gastric emptying and impaired morphine absorption in the immediate postoperative period. Four hours later, there was a significant reduction in gastric emptying in eight patients who had normal paracetamol and morphine absorption in the immediate postoperative period.

Effects of beta-adrenoceptor antagonism on the cardiovascular and catecholamine responses to tracheal intubation.

The catecholamine and cardiovascular responses to laryngoscopy and tracheal intubation were studied in 20 patients who underwent elective gynaecological surgery and who were allocated randomly to receive either practolol 10 mg or saline intravenously prior to induction of anaesthesia. Anaesthesia was induced with fentanyl and thiopentone; atracurium was administered and the lungs were ventilated artificially with 67% nitrous oxide in oxygen. Tracheal intubation was performed when muscle relaxation was adequate. Arterial pressure, heart rate, plasma noradrenaline and adrenaline concentrations were measured before and after tracheal intubation. A significant increase in catecholamine concentrations occurred in both groups in response to tracheal intubation but the magnitude of the increase in adrenaline was greater in the practolol group. There were no significant differences in arterial pressure or heart rate changes between the groups. We conclude that pretreatment with practolol is of no value in the attenuation of the hypertensive response to direct laryngoscopy and tracheal intubation in previously normotensive patients.

Plasma catecholamine concentrations--changes after infiltration with local anaesthetic solutions and adrenaline during bat-ear surgery.

Plasma catecholamine concentrations were measured in 12 patients who had bilateral bat-ear surgery following infiltration of each ear with 2 ml 2% lignocaine with adrenaline 1:100,000. Venous blood samples were withdrawn before and at set intervals after infiltration. Plasma adrenaline concentration increased from 0.8 pmol/ml to a peak of 2.2 pmol/ml at 2 minutes after infiltration; this is an increase of 175%. There was no significant change in plasma noradrenaline concentration.

The pharmacokinetics of oral and intravenous nalbuphine in healthy volunteers.

The pharmacokinetics of nalbuphine were studied in 10 healthy volunteers on two separate occasions following administration by either the intravenous (20 mg) or oral (60 mg) route. After administration, serum concentrations of nalbuphine were measured for 12 h using a high pressure liquid chromatography assay, and pharmacokinetic parameters were derived using a three compartment model. After i.v. administration, elimination half-life was 222 (111-460) min (mean and range) and total body clearance was 1.5 (0.8-2.3) 1 min-1.Cmax after oral administration was 21.4 (6.0-36.2) ng ml-1 and tmax was 46.6 (15.3-89.0) min. Bioavailability of the oral preparation was 11.8 (6.1-20.1)%.

Effects of alfentanil on the pressor and catecholamine responses to tracheal intubation.

The effects of alfentanil (given during induction of anaesthesia) on the haemodynamic and catecholamine responses to tracheal intubation were studied in 44 adult patients who received alfentanil 10 micrograms kg-1 or 40 micrograms kg-1, or saline placebo. Alfentanil 10 micrograms kg-1 and 40 micrograms kg-1 prevented any increase in heart rate and arterial pressure after tracheal intubation. Alfentanil 40 micrograms kg-1 produced profound hypotension and bradycardia. The use of alfentanil in both doses was associated with a decrease in plasma adrenaline concentrations after tracheal intubation.

Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation.

The catecholamine and cardiovascular responses to laryngoscopy alone have been compared with those following laryngoscopy and intubation in 24 patients allocated randomly to each group. Following induction with fentanyl and thiopentone, atracurium was administered and artificial ventilation undertaken via a face mask for 2 min with 67% nitrous oxide in oxygen. Following laryngoscopy, the vocal cords were visualized for 10 s. In one group of patients, ventilation was then re-instituted via a face mask, while in the second group the trachea was intubated during the 10-s period and ventilation of the lungs maintained. Arterial pressure, heart rate and plasma noradrenaline and adrenaline concentrations were measured before and after induction and at 1, 3 and 5 min after laryngoscopy. There were significant and similar increases in arterial pressure and circulating catecholamine concentrations following laryngoscopy with or without intubation. Intubation, however, was associated with significant increases in heart rate which did not occur in the laryngoscopy-only group.

Effect of topical lignocaine on the sympathoadrenal responses to tracheal intubation.

The catecholamine and cardiovascular responses to laryngoscopy and tracheal intubation have been studied in 30 patients undergoing elective gynaecological surgery, allocated randomly to one of three groups: group 1 received 4% lignocaine 160 mg using a Forrester Spray; group 2 received 4% lignocaine 160 mg by "Laryng-o-jet"; group 3 received an equal volume of saline administered by Forrester Spray. In all three groups, there were similar and statistically significant increases in mean arterial pressure and plasma adrenaline and noradrenaline concentrations 1 min after intubation, with diminution of these responses by 5 min after intubation. There were no differences between the three groups at any stage, which suggests that topical anaesthesia of the mucosa of the upper airway, as performed conventionally, is ineffective as a means of ameliorating the pressor and catecholamine responses to routine laryngoscopy and intubation.

Effect of halothane on cardiovascular and plasma catecholamine responses to tracheal intubation.

The catecholamine and cardiovascular responses to intubation were investigated during halothane anaesthesia. Thirty patients were allocated randomly to two groups. Following induction of anaesthesia and muscle relaxation, group 1 was ventilated with 70% nitrous oxide in oxygen before intubation; group 2 received 1% halothane in addition. After intubation, both groups received 0.5% halothane. Arterial pressure and heart rate, and plasma noradrenaline and adrenaline concentrations were measured throughout the induction sequence. In group 1 intubation was associated with increases (from pre-induction values) in systolic arterial pressure of 13% and diastolic arterial pressure of 35%, although the plasma concentrations of noradrenaline did not alter significantly. In group 2, although there was a pressor response to intubation, no overall change in systolic arterial pressure and only a 13% increase in diastolic arterial pressure occurred when compared with pre-induction values. This response was associated with a 78% increase in the noradrenaline concentration; the adrenaline concentration did not alter significantly.

Absorption of controlled release morphine sulphate in the immediate postoperative period.

The absorption of morphine sulphate, given orally as a controlled release preparation, was studied in 10 patients who had undergone peripheral vascular surgery with a standard opioid-based general anaesthetic technique. Serum morphine concentrations were measured (high pressure liquid chromatography) every 2 h for the first 16 h after surgery and the results were strongly suggestive of a decrease in the rate of absorption of morphine in this situation.

Changes in plasma catecholamine concentrations following infiltration with large volumes of local anaesthetic solution containing adrenaline.

Plasma catecholamine concentrations have been measured in nine patients undergoing rhinoplasty following infiltration to the facial area of 21 ml of 0.5% lignocaine with adrenaline 1:200,000 and in seven patients undergoing brachial plexus blockade with 40 ml of 0.5% lignocaine, 0.25% bupivacaine and adrenaline 1:200,000. In the rhinoplasty group there was a 566% increase in plasma adrenaline concentration 2 min after cessation of infiltration, whilst in the brachial plexus group a 112% increase in the plasma concentration of adrenaline occurred at 10 min after completion of the block. There was no change in plasma noradrenaline concentration in either group. It is concluded that the so-called safe dose of adrenaline (1.0 microgram kg-1 during halothane anaesthesia) is meaningless unless the site of administration is specified.

Measurement of plasma catecholamine concentrations. An assessment of anxiety.

This study was designed to assess the value of measurement of plasma catecholamine concentrations as an objective index of anxiety. A preliminary study was undertaken on 11 healthy volunteers (medically qualified), to determine if venous cannulation per se produced any change in plasma catecholamine concentrations. There were no changes in plasma catecholamine concentrations in the 2 h following insertion of an i.v. cannula, suggesting that venous cannulation did not induce a measurable stress response. A second study was performed on 48 surgical patients who were asked to rate their perceived anxiety on a linear analogue scale immediately before premedication and immediately before induction of anaesthesia. Venous blood was obtained at the same time as these ratings. There were no significant changes in perceived anxiety or plasma noradrenaline concentrations following premedication. However, compared with values before premedication, there was a mean percentage increase in plasma adrenaline concentration of 40% before induction of anaesthesia. A significant correlation was shown between mean percentage change in Linear Analogue Anxiety Score and mean percentage change in plasma adrenaline concentrations (r = 0.32).

Pharmacokinetics of single-dose i.v. morphine in normal volunteers and patients with end-stage renal failure.

Morphine 0.125 mg kg-1 was administered i.v. to 11 normal subjects and nine patients with chronic renal failure requiring regular haemodialysis. Plasma morphine concentrations were measured using high pressure liquid chromatography (HPLC). Although there was considerable individual variation in both groups, mean plasma concentrations of morphine were significantly higher in the patients with renal failure for 15 min after administration. The decay of plasma concentration fitted a three-compartment mamillary pharmacokinetic model in all subjects. Derived values (mean +/- SEM) of T 1/2 alpha, volume of distribution of the second compartment (V2), total volume of distribution at steady state (Vss) and transfer rate constant from the first to the second compartment (k12), were significantly different between groups. Mean values of terminal elimination half-life (T 1/2 gamma) and total body clearance were similar in the two groups. It was concluded that elimination of unchanged morphine is not impaired significantly in patients with chronic renal failure, although accumulation of morphine-3-glucuronide probably occurs. Although the pharmacological effect of morphine is not related temporally to plasma morphine concentrations, the higher values in patients with renal failure may be implicated in their increased sensitivity to the drug.

Plasma catecholamine concentrations. The effects of infiltration with local analgesics and vasoconstrictors during nasal operations.

Plasma catecholamine concentrations were measured in 19 patients allocated randomly to receive submucous infiltration with 4 ml of either 0.5% lignocaine with adrenaline 1:200 000 or prilocaine 0.5% with octapressin 0.03 iu per ml. Venous blood samples were obtained before and at 2, 5, and 10 minutes following infiltration. Plasma adrenaline increased from 0.35 to 1.72 p mol/ml at 2 minutes infiltration with the former solution whilst there was little change in plasma noradrenaline concentration. No similar peak in adrenaline concentration occurred after infiltration with prilocaine/ octapressin solutions but with both solutions there was a small increase in plasma noradrenaline and adrenaline concentrations 10 minutes after infiltration, at the time of surgical stimulation.

Plasma catecholamine responses to tracheal intubation.

Plasma adrenaline and noradrenaline concentrations were measured in 24 patients during the induction of anaesthesia and the subsequent tracheal intubation. The patients received either suxamethonium 1 mg kg-1 or pancuronium 0.1 mg kg-1 to facilitate tracheal intubation. Mean arterial pressure (MAP) increased in both groups following laryngoscopy and tracheal intubation and there were concomitant increases in the plasma catecholamine concentrations, the changes being more marked in the suxamethonium group. There was a significant correlation between MAP and plasma catecholamine concentrations in the suxamethonium group. Measurement of plasma catecholamine concentrations in samples obtained simultaneously from central venous, peripheral venous and arterial sites were in broad agreement; the greatest changes occurred in central venous samples.

Catecholamine responses during anaesthesia for phaeochromocytoma.

Plasma catecholamine concentrations were measured, at frequent intervals, in a 40-yr-old female patient undergoing resection of a phaeochromocytoma under enflurane anaesthesia. Measurements before operation revealed that the tumour secreted predominantly noradrenaline and during surgery the plasma concentration of the hormone increased markedly (180 pmol ml-1; normal range 1.5-3.0 pmol ml-1). Plasma adrenaline concentrations increased markedly only at endotracheal intubation and in the period immediately after operation.