Biomedical subjects

I Ramzan

Publications and source records attributed to I Ramzan.

At least 19 recordsLinked to original sources

PubMed1998

A novel substance associated with gallamine-induced myoclonus.

If gallamine or d-tubocurarine gains access to the central nervous system it produces a myoclonus, a synchronized jerking of many skeletal muscles. Each jerk is accompanied by a slow wave in the inferior olive. The jerking continues for 24 h or more after the gallamine or d-tubocurarine can no longer be detected in the CSF. We report here that a novel substance appears in the CSF and persists for a long period of time, possibly as long as the twitching. This substance is not corticotrophin-releasing factor (CRF) nor does CRF or harmaline (a substance causing a tremor by an action on the inferior olive) lead to the appearance of the novel substance. At present the nature of this substance is not known.

Animals↗

PubMed1998

Droperidol elimination after cardiopulmonary bypass surgery.

A high-dose (0.75 to 2.8 mg/kg) pharmacokinetic study of droperidol was undertaken in patients during the recovery phase after cardiac surgery involving hypothermic cardiopulmonary bypass (CPB). The elimination half-life of droperidol in these patients, determined from concentration-time data obtained after CPB, was significantly prolonged relative to previously reported mean values in younger surgical patients not undergoing CPB and receiving lower doses of the drug (0.05-0.20 mg/kg). On stratification of the patients by droperidol dose, there was an inverse correlation between the size of the dose and the elimination half-life of droperidol: mean half-life decreased as mean dose increased. This difference in elimination half-life was not related to the duration of the CPB procedure, or the total anesthetic time, both of which were not significantly different between the patient groups receiving the three different doses of droperidol. The magnitude or duration of hypothermia after CPB did not differ between the three patient groups. The differences in half-lives are more likely due to the clinical condition of the patients, such that the patients who received the higher doses of droperidol were also judged clinically to be less ill and thus eliminated droperidol more efficiently. This hypothesis, however, could not be supported due to the small number of patients studied. The results obtained in this study indicate that droperidol elimination is significantly prolonged after high-dose administration to elderly patients undergoing hypothermic CPB procedures during cardiac surgery.

Adjuvants, Anesthesia↗

PubMed1998

Administration of a crystalloid fluid preload does not prevent the decrease in arterial blood pressure after induction of anaesthesia with propofol and fentanyl.

Anaesthesia was induced in 58 women (ASA I or II) undergoing elective gynaecological procedures, using propofol 2.5 mg kg-1 and fentanyl 1.5 micrograms kg-1. Patients were allocated to receive 20 ml kg-1 of crystalloid fluid preload over 20 min or to receive no fluids before induction of anaesthesia. A significant decrease in systolic arterial pressure (< 75% of baseline value) occurred in both the fluid-loaded and the control groups, and was similar in both groups. Administration of a fluid preload did not attenuate the decrease in systolic arterial pressure after induction of anaesthesia with propofol and fentanyl.

Adult↗

PubMed1997

Determination of propofol in rat whole blood and plasma by high-performance liquid chromatography.

A simple, accurate and sensitive high-performance liquid chromatographic method was developed for the determination of propofol, an intravenous anaesthetic agent, in rat whole blood or plasma samples. The method is based on precipitation of the protein in the biological fluid sample and direct injection of the supernatant into an HPLC system involving a C18 reversed-phase column using a methanol-water (70:30) mobile phase delivered at 1 ml/min. Propofol and the internal standard (4-tert.-octylphenol) were quantified using a fluorescence detector set at 276 nm (excitation) and 310 nm (emission). The analyte and internal standard had retention times of 6.3 and 10.5 min, respectively. The limit of quantification for propofol was 50 ng/ml using 100 microl of whole blood or plasma sample. Calibration curves were linear (r2=0.99) over a 1-10 microg/ml concentration range and intra- and inter-day precision were between 4-11%. The assay was applied to the determination of propofol whole blood pharmacokinetics and propofol whole blood to plasma distribution ratios in rats.

Anesthetics, Intravenous↗

PubMed1997

In vitro neuromuscular effects of valproic acid.

The contribution of the anticonvulsant agent, valproic acid, to the interaction between neuromuscular blockers and anticonvulsants remains unclear. Therefore, this study was undertaken to examine the acute neuromuscular effects of valproic acid and its potential for interaction with neuromuscular blocking drugs. Phrenic nerve-hemidiaphragm preparations from rats were mounted in modified Krebs buffer, maintained at 37 degrees C and aerated with a 5% carbon dioxide-95% oxygen gas mixture. Phrenic nerves were stimulated with 0.1 Hz supramaximal pulses of 0.2-ms duration and the elicited tension of the hemidiaphragm was recorded in seven preparations in the presence of valproic acid 100, 500 and 1000 mumol litre-1. In another six preparations, neuromuscular transmission was blocked completely with the non-depolarizing blocker tubocurarine 3 mumol litre-1 and the hemidiaphragm muscle was stimulated directly (2 Hz and 2 ms duration). The effect of the anticholinesterase drug, neostigmine, on an established block induced by valproic acid 1000 mumol litre-1 was also evaluated in five phrenic nerve stimulated preparations. The effect of valproic acid 100, 500 or 1000 mumol litre-1 on suxamethonium- or atracurium-induced neuromuscular block was also evaluated. Valproic acid produced a mean of 29.7 (SEM 1.7)% and 24.7 (1.7) % block of indirectly or directly elicited muscle twitches. The concentration of valproic acid that caused half maximal paralysis did not differ between indirect (460 (59) mumol litre-1) and direct (329 (35) mumol litre-1) stimulation. Neostigmine 1-3 mumol litre-1 failed to significantly alter the block of 19.8% induced by valproic acid 1000 mumol litre-1. Valproic acid 100, 500 or 1000 mumol litre-1 did not alter the concentrations of suxamethonium or atracurium needed to produce paralysis. These findings suggest that valproic acid does not produce significant block at the rat neuromuscular junction. The partial block that is produced is caused predominantly by a direct inhibitory effect on the muscle itself.

Animals↗

PubMed1997

Acute in vitro neuromuscular effects of carbamazepine and carbamazepine-10,11-epoxide.

We examined the acute neuromuscular effects of the anticonvulsant, carbamazepine, and its major metabolite, carbamazepine-10,11-epoxide, using the in vitro rat phrenic nerve-hemidiaphragm muscle preparation. Carbamazepine produced 8.8% +/- 2.2% (n = 12) neuromuscular paralysis as its concentration was increased from 1 to 50 microg/mL (4.2-210 microM). In contrast, carbamazepine-10,11-epoxide produced maximum paralysis of 65% +/- 8% (n = 10) in the concentration range 1-100 microg/mL (4-400 microM) and the concentration required to produce half this paralysis was 36 +/- 7 microg/mL (144 +/- 28 microM). Carbamazepine 10 microg/mL (42 microM) shifted the response-concentration curve for both a depolarizing (succinylcholine) and a nondepolarizing (atracurium) neuromuscular blocker, reducing their concentrations required for 50% paralysis by approximately 30%. In contrast, the metabolite, which was a more potent neuromuscular blocker by itself, failed to alter either succinylcholine or atracurium effect. These results concur with previous clinical reports where anticonvulsants have acutely reduced neuromuscular blocker dose requirements.

Animals↗

PubMed1996

Determinants of acute regional toxicity following isolated limb perfusion for melanoma.

Hyperthermic isolated limb perfusion (ILP) with melphalan is well established as an effective form of treatment for recurrent melanoma confined to an extremity. High drug concentrations in the limb are readily achieved, without systemic side-effects. However, regional toxicity can lead to considerable morbidity and functional disturbance. This study was undertaken to evaluate factors which might contribute to acute regional toxicity following ILP. Melphalan concentrations in limb blood samples taken at regular intervals during 135 ILPs were measured by HPLC, allowing peak melphalan concentration and area under the curve (AUC) for each procedure to be determined. Acute regional toxicity associated with ILP was found to be significantly correlated with limb tissue temperatures > 40 degrees C, peak melphalan concentration and melphalan AUC, in decreasing order, but was not correlated with tourniquet time. Further studies are required to directly assess melphalan uptake by tumour tissue, and to relate this to both limb toxicity and tumour response.

Antineoplastic Agents, Alkylating↗

PubMed1994

Pharmacokinetics of fluconazole in cats after intravenous and oral administration.

Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13.8 [2.6] hours) was similar to that observed after oral dosing (12.4 [3.0] hours). The plasma clearances (intravenous 0.9 [0.1], oral 0.9 [0.2] ml min-1 kg-1) and the volumes of distribution at steady state (intravenous 1.1 [0.1], oral 1.0 [0.1] litre kg-1) were also similar after the two routes of dosing. The peak plasma concentration was reached 2.6 hours after oral dosing and the drug was completely bioavailable (1.09 [0.05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre-1.

Administration, Oral↗

PubMed1994

In-vitro interaction between H2 antagonists and vecuronium.

The interaction between histamine H2 antagonists and the neuromuscular blocking drug vecuronium was investigated in the rat phrenic nerve-hemidiaphragm preparation. Cimetidine alone, in the concentration range 800-4000 microM produced between 14 and 74% neuromuscular paralysis with an EC50 (mean +/- s.e.) of 2900 +/- 100 microM. Ranitidine augmented the indirectly-evoked muscle response at concentrations between 30 and 160 microM but at higher concentrations, between 300 and 1800 microM, produced neuromuscular paralysis. Famotidine produced negligible and statistically insignificant (0-5%) neuromuscular paralysis at concentrations between 0.3 and 300 microM. Cimetidine (800 microM) shifted the neuromuscular concentration-effect curve of vecuronium to the left in a parallel manner, while ranitidine (160 microM) shifted it to the right. The potentiation ratio was 1.90 +/- 0.14 for cimetidine and 0.62 +/- 0.05 for ranitidine. Famotidine (30 microM) did not alter the response to vecuronium. These data indicate that higher than clinically relevant concentrations of cimetidine and ranitidine produce neuromuscular paralysis and may potentiate the action of vecuronium. Low concentrations of ranitidine may antagonize the action of vecuronium. Famotidine, in contrast, lacks significant neuromuscular effects.

Animals↗

PubMed1994

Omeprazole potentiates atracurium and succinylcholine paralysis in vivo in rats.

We examined the effect of proton pump inhibitor omeprazole on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintained at about 50% with intravenous (i.v.) bolus and infusion regimens of either atracurium or succinylcholine. Omeprazole, 0.5, 1, and 10 mg/kg i.v., was then administered at 10-min intervals while the infusion of the neuromuscular blocker was continued. Omeprazole at all three doses increased the steady-state neuromuscular paralysis produced with either atracurium (pre-omeprazole versus final post-omeprazole paralysis; mean +/- SE, n = 6, 53.0% +/- 2.3% vs 80.0% +/- 5.3%) or succinylcholine (50.8% +/- 1.5% vs 86.4% +/- 5.1%). Omeprazole, 0.5, 1.0, and 10 mg/kg i.v., given directly and without any neuromuscular blocker, produced approximately 5% depression of the muscle twitch response. Omeprazole, i.v. at human therapeutic doses, alters neuromuscular function and enhances the action of both atracurium and succinylcholine in vivo in rats.

Animals↗

PubMed1993

Interaction between succinylcholine and ranitidine in rats.

The hypothesis that the histamine H2 receptor blocker ranitidine potentiates neuromuscular paralysis during anaesthesia was tested in vivo in urethane anaesthetised and mechanically ventilated rats. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 48.5% (+/- 2.5 SEM) tibialis anterior muscle paralysis in 14 rats. Ranitidine 2.5, 5, 10, or 20 mg.kg-1 iv, was then administered into groups of three or five rats. Ranitidine produced an immediate potentiation of neuromuscular paralysis followed by a transient reversal and then a continued steady-state potentiation. Peak potentiation occurred within 20 (+/- 3.3) sec and was maintained in all the rats to steady-state. Peak reversal was evident 70 (+/- 8.1) sec after ranitidine administration. There was an excellent relationship (r2 = 0.98, P < 0.001) between peak potentiation and serum ranitidine concentration with 50% potentiation occurring at 25.8 (+/- 1.1) micrograms.ml-1. There was a weak relationship (r2 = 0.39, P < 0.05) between peak reversal and serum ranitidine but potentiation at steady-state was not correlated to serum ranitidine concentration (r2 = 0.19, P > 0.05). These results show that ranitidine alters the neuromuscular action of succinylcholine in rats in a similar manner to cimetidine.

Anesthesia, Intravenous↗

PubMed1993

Pain sensitivity in dietary-induced obese rats.

Previous literature indicates possible interrelationships between the endogenous opioids or endorphins, pain response, and obesity or eating behaviour. The pain response was, therefore, examined in a rat model of obesity induced by palatable food high in unsaturated fats. Pellet-fed control and energy-dense obese and nonobese rats were tested for latency of response to a thermal stimulus using the tail flick test. Obese rats exhibited a statistically significant increase in tail flick latency compared to controls. In addition, the observed latencies were significantly correlated to the body weight of the rats (r = 0.52, p < 0.01). These data suggest that dietary-induced obese rats are similar to obese humans in being less sensitive to painful stimuli, consistent with an increase in endogenous opioids in obesity.

Animals↗

PubMed1993

Ranitidine reverses gallamine paralysis in rats.

The effect of ranitidine on gallamine-induced depression of twitch tension was evaluated in urethane-anaesthetized and mechanically ventilated male Sprague-Dawley rats. Gallamine was administered as an intravenous (IV) bolus and constant rate infusion in 15 rats to maintain 89 +/- 7% (SE) depression of twitch tension induced by electrical stimulation of a sciatic nerve. Ranitidine, IV at either 0.5, 1, 2.5, 5, or 10 mg/kg, was then administered into groups of three rats. Ranitidine produced an immediate dose- and serum concentration-dependent reversal (antagonism) of the twitch tension depression induced with gallamine. The reversal was observed within approximately 30 s and was maintained for 3-26 (12 +/- 2) min. The dose of ranitidine that produced 50% reversal was 2.9 +/- 0.1 mg/kg, and this reversal was associated with a ranitidine serum concentration of 5.2 +/- 0.3 micrograms/mL. Ranitidine administered alone (and without gallamine) did not alter twitch tension at either 2.5 or 20 mg/kg. In addition, ranitidine did not alter either the gallamine neuromuscular blocking concentration in serum or the serum clearance of gallamine. Ranitidine reverses the neuromuscular action of gallamine, and this effect of ranitidine is not due to a pharmacokinetic interaction between ranitidine and gallamine.

Animals↗

PubMed1993

Interaction between famotidine and neuromuscular blockers: an in vivo study in rats.

The effect of histamine 2-antagonist famotidine on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs was examined in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintained at about 50% with intravenous bolus and infusion regimens of either atracurium, gallamine, succinylcholine, or decamethonium. Famotidine, 0.1, 1, and 4 mg/kg, intravenously, were then administered at 5-min intervals as the infusion of the neuromuscular blocker was continued. Famotidine at any of these three doses failed to alter the steady state neuromuscular paralysis produced with either atracurium (prefamotidine versus final postfamotidine paralysis (mean +/- SE depression of twitch tension, n = 6, 49.8 +/- 2.8 vs 51.5 +/- 2.6%), gallamine (47.8 +/- 1.6 vs 47.6 +/- 3.0%), succinylcholine (49.2 +/- 1.8 vs 49.4 +/- 2.0%), or decamethonium (50.3 +/- 2.1 vs 51.5 +/- 2.0%). Intravenous famotidine at human therapeutic doses, fails to alter neuromuscular function in vivo in rats.

Animals↗

PubMed1992

Myoclonus in the decerebrate cat produced by gallamine.

After intravenous infusion maintaining a neuromuscular blocking concentration very little gallamine enters the cerebrospinal fluid (CSF) of the intact anesthetized cat even after several days. After a similar intravenous infusion in the decerebrate cat gallamine enters the CSF slowly over 4 days eventually reaching a concentration similar to that in the plasma. This procedure is accompanied by very strong twitching in many muscles and the occurrence of slow waves in the inferior olive in synchrony with the twitches. A large dose (4 mg) of gallamine triethiodide injected directly into the cisterna magna of an intact anesthetized cat produced twitching within 1 min and slow waves in the inferior olive in good synchrony with the twitches; the effects lasted at least 43 h. Injection of a quantity of gallamine triethiodide (about 130 micrograms) sufficient to mimic the concentration in the CSF obtained after 3-4 days of neuromuscular block in the decerebrate cat (50-120 micrograms/ml gallamine) had extremely weak effects lasting for at most 1 h. However, this weak effect is probably due to the anesthetic because injection of a similar quantity into an (unanesthetized) decerebrate cat at any time after decerebration had strong effects. After intracisternal injection of gallamine the concentration in the CSF reaches very low levels within 12 h but twitching and activity in the inferior olive persists for 1-2 days. The reasons for this prolonged action are now being investigated. The effects of gallamine are compared with the condition of reticular reflex myoclonus.

Animals↗

PubMed1992

Interaction between succinylcholine and cimetidine in rats.

The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine.

Anesthesia, Intravenous↗

PubMed1992

Influence of cimetidine on gallamine-induced neuromuscular paralysis in rats.

1. The effect of cimetidine on gallamine-induced neuromuscular paralysis was evaluated in urethane-anaesthetized and mechanically ventilated rats. 2. Intravenous cimetidine (between 3.2 and 100 mg/kg) produced an immediate and sustained potentiation of gallamine-induced neuromuscular paralysis. 3. Intravenous calcium (0.35 mmol/kg) completely reversed the cimetidine-induced potentiation of gallamine's effect. 4. Cimetidine alone did not produce neuromuscular paralysis. 5. Cimetidine did not alter either the serum concentration or the total serum clearance of gallamine. 6. Cimetidine thus potentiates the action of gallamine via a pharmacodynamic and not a pharmacokinetic mechanism.

Animals↗

PubMed1991

High-performance liquid chromatographic assay for laudanosine in biological fluids and tissue for neurotoxic studies in rats.

A procedure for the determination of laudanosine, the central nervous system active metabolite of the neuromuscular blocking drug atracurium, in serum, cerebrospinal fluid and brain is described. The method uses a readily available internal standard, ethavrine, and a single-step protein precipitation with acetonitrile followed by high-performance liquid chromatographic separation with ultraviolet detection. Norlaudanosine, the major metabolite of laudanosine, can also be quantified. Linearity of detector response was obtained between 1 and 25 micrograms/ml or micrograms/g and the method is suitable for determining neurotoxic concentrations of laudanosine in experimental animals.

Animals↗