H[2] receptor activity; effect in isolated rabbit heart

Histamine can stimulate the heart by directly interacting with cardiac histamine receptors. In the present study we have investigated the H[2] receptor activity in isolated rabbit heart. Cimetidine, a specific H[2] receptor antagonist was used. The isolated heart was mounted in langendroff apparatus. The heart was perfused at a constant pressure with oxygenated Ringer's Locke solution. H[2] receptor antagonist produces negative inotropic effect in the presence of histamine. This indicates that H[2] receptors are present in rabbit heart, and plays a role in mediation of positive inotropic effect produced through CAMP by histamine

Adrenaline; the effects in presence of beta blocker in isolated mammalian heart

There is no doubt that the effects of the catecholamines of the heart are mainly due to the stimulation of beta-adrenoceptors but in the mid 1960' s the first evidence was presented that a-adrenoceptors mediating positive inotrpoism exists also in the myocardium beside well established beta -adrenoceptors. In our observation adrenaline shows a positive inotropic response. The response of adrenaline in presence of metoprolol [beta1blocker] showed negative inotropic effect

Effect metformin on urinary VMA levels in type II diabetic subjects

The purpose of this study was to observe the effect of metformin on 24-hours urinary VMA levels in newly diagnosed untreated type 2 diabetic subjects. The study consisted of four weeks for each participant with weekly follow up visits. Samples were collected at 0800-0900 hours after over night fast. Study was conducted in the Department of Pharmacology and Therapeutics, BMSI, JPMC, Karachi. Total duration of study was six months. Fifteen newly diagnosed untreated type 2 diabetics, with fasting plasma glucose levels >/= 126 mg/dl on two occasions and/or postprandial glucose levels >/= 200 mg/dl were enrolled in the study. Patients with concurrent illness or diabetic complications were excluded. Metformin was started from 500 mg/day and titrated at weekly intervals according to glycaemic control and the subjects tolerance to the drug. A 24-hour urinary VMA was assessed at day - 0 [before metformin therapy] and day - 28 [4 weeks after metformin therapy] by using VMA reagent kit of Biosystems Spain on Spectronic -21 spectrophotometer USA. Metformin caused highly significant [P < 0.001] reduction in mean fasting plasma glucose from 233.33 +/- 15.62 mg /dl on day-0 to 151.53 +/- 6.02 mg/dl on day - 28, and a significant [P < 0.01] decrease in 24 - hour urinary VMA levels from 5.18 + 0.50 mg / 24 hours on day-0 to 3.32 + 0.28 mg / 24 hours on day-28. Our results indicate that metformin causes highly significant reduction in fasting plasma glucose and a significant decrease in 24 - hour urinary VMA levels in newly diagnosed untreated type 2 diabetic subjects

Role of verapamil in acute opioid abstinence syndrome

To determine the effectiveness of calcium channel blocker, verapamil in the treatment of acute opioid withdrawal syndrome in patients with chronic dependence on opioid. A clinical study. The study was conducted at Psychological Medicine ward, Civil Hospital Karachi from January 1998 to April 1998. A total of twenty [20] patients were admitted for ten [10] days in hospital. No treatment was given during the first two days of admission after abrupt termination of opioid to observe the acute opioid withdrawal signs and symptoms. Then the verapamil was given orally to each patient in a 40mg dose thrice daily from day 3 to day 10 of admission. The intensity of signs and symptoms was recorded by using subjective and objective opiate withdrawal questionnaire. Urine analysis for opioids was done on day 1, 5 and 10 of admission. Verapamil significantly decreased the intensity of signs and symptoms of acute opioid withdrawal from day 4 to day 10 of admission. Urine analyses for opioids were positive on day 1 while zero on day 10. Verapamil was found to be safe and effective for the treatment of signs and symptoms of acute opioid withdrawal in in-door patients without any significant side effect

comparative study of kinetic parameters of alprazolam in hepatic and renal insufficient patients

To compare the kinetic parameters of Alprazolam in both hepatic and renal insufficient patients. Jinnah Postgradute Medical Institute, Karachi. Blood samples were collected from three groups of the patients after giving tablet Alprazolam [0.25 mg B.D] for 21 days. These samples were then analyzed for kinetic parameters i.e. Plasma half life, clearance, plasma concentration and volume of distribution. The parameters included plasma concentration of Alprazolam, clearance [cl], serum alkaline phosphate, serum bilirubin and serum glutamate pyruvate transaminase. Patients were divided into three groups i.e. 1] control, 2] suffering from renal insufficiency, 3] suffering from hepatic insufficiency. On day seven and day twenty one, in the same group [both renal], plasma conc. and t 1/2 increased while Vd and cl decreased. On the other hand in the same group [both hepatic], on day 7 and 21, plasma conc. and t 1/2 increased while Vd and cI decreased. When comparative study done on day 7 and 21 in opposite groups [renal vs hepatic], plasma conc., Vd and t 1/2 increased while cI decreased. In hepatic insufficiency, the doses of Alprazolam [benzodiazepines] should be reduced but in renal insufficiency doses should be reduced in only severe forms of renal dysfunction

Snakebite: identification, prevalence and management

Bites from venomous and non-venomous snakes occur throughout the world, but are particularly important in tropical and subtropical regions, where the large number of snake species and the rural lifestyle of the population can lead to significant morbidity and mortality. To determining the goals for reducing the morbidity and mortality as we have tried to explore the every aspect of the incidence. Jinnah Postgraduate Medical Center, Karachi. Clinical confirmation of snakebite with envenoming was by identification of the dead snake brought by victims and by clinical signs and symptoms such as paralysis [krait and cobra] and rapid progressive local edema with active bleeding [viper]. Whole blood clotting test is a simple, rapid and reliable test of coagulopathy. It is also of use in assessing the effectiveness of ASV and is of crucial importance for controlling administration of expensive ASV in relation to restoration of blood coagulability. 130 [57.27%] patients were bitten from cobra and krait whereas 63 [27.76%] individuals were suffered from viper bites. 6 [2.64%] cases were victimized by sea snakes while 28 cases were bitten by some other species labeled as non venomous variety [Graph II]. These 28 cases did not have any signs of systemic envenoming. Among all snakebite victims 33[14.54%] developed complications like severe bleeding, jaundice, acute renal failure, intracranial bleed and respiratory failure. 25 [11.01%] deaths were ensue while remaining 202 were completely recovered. It was observed that Cobra, Krait, Russell's viper commonly called Dabois whereas saw scaled viper locally called as Lundi or Jalebi are responsible for practically all the snakes bite cases. As venom secretion is greater in the months of May to September the incidences of snakebite cases are higher in these months

Evaluation of suspected chronic pesticide poisoning among residents near agriculture fields

The present study was performed to evaluate the incidence of organophosphorus toxicity among agrarian and non agrarian subjects residing near agriculture fields. The location of this study was Nawakot village, Multan. From the cotton producing area of Multan, 225 volunteers [farmers] including 103 females and 122 males were selected. Children <12 years of age constitute 15% of the population. A total of 100 volunteers [non agrarians] from Multan city were taken as control. Blood [4 ml] was drawn from the volunteers to test the level of acetylcholine estrase [Ach E] in plasma. The blood samples were then analysed at the laboratory of National Poison Control Center [NPCC]. Organo-phosphate [OP] and carbamates [CM] both act to block Ach E hydrolysis, necessary for synaptic response in the CNS. Acute illnesses were seen in 6 [2.67%], children [group 1]. They had fever and signs of pulmonary infections. Generalised weakness was found in 9 males and 13 females. Paraesthesia was found in 11 volunteers of group IV. Blood sampling test revealed that 6 volunteers [2.67%] had plasma Ach E below 5300 IU/ml [< 50% reduction], whereas 4 volunteers had Ach E level between 5300 - 5500 IU/ml [< 45% reduction], 81 volunteers fall in group "c", and 126 individuals had an Ach E reduction of at least 25% and 8 volunteers had the serum cholinesterase level above 10000 IU/ml. None of volunteers had the value above 11000 IU whereas plasma Ach E level of control population was between 11500 - 13500 IU/ml. Medical tests of the level of Ach E in plasma suggest that the overall incidence of poisoning from exposure to OP and CM is quite high, and appears to be consistent with the results from other studies in other developing countries

Role of 5HT in the modification of intestinal motility, in vitro study

To determine with the mechanism of action involved in the therapeutic potential of serotonin and its blocker on gastrointestinal motility. The standard method was used for obtaining the longitudinal and circular muscles strip of rabbit ileum for in vitro studies. Each muscle strip was exposed to serotonin and its blocker and the result obtained was recorded on polygraph apparatus. The effects were recorded in vice versa fashion i.e. agonist v/s antagonist and antagonist v/s agonist on longitudinal and circular muscle strip separately. Serotonin had depressant effect on the force of contraction. On addition of antagonist in the presence of agonist, the effects were increased. Longitudinal muscle showed more pronounced effect i.e. 52.7% with methysergide in comparison to circular muscle, which was 15.6%. Circular muscle showed reduction in the force of contraction with serotonin, which was increased on addition of antagonist, but still below the level of base line contraction. Serotonin when given from external source in vitro, decreased the force, however, there was minimal increase in the rate of contraction. Hence, serotonin decreases the intestinal motility giving an impression of having antispasmodic effect. The results of this study can be utilized in the development of new drug related to G.I. motility mediated through 5HT receptors

Half life of Alprazolam in hepatic insufficient patients

Alprazolam is a triazolobenzodiazepine which is primarily metabolized by the liver. To see its half life in hepatic insufficient patients tab. Alprazolam in a dose of 0.25 mg, B.D. was given orally to 15 such patients and 5 normal subjects taken as control. Drug was given for a period of 21 days to both groups. Blood samples were drawn at day 7 and 21. There was no remarkable change in half life on day 7 and 21, among control group. Same results were seen among hepatic group on both days but half life increased to about double on day 7 and 21, when compared to control ones. Thus, it was concluded that in hepatic insufficient patients, half life increases significantly due to alteration in hepatic biotransformation mechanism