The effects of ranitidine on pituitary-thyroid function.

Although several studies have examined the effects of cimetidine on pituitary-thyroid function, few have investigated ranitidine in this respect. We found no changes in thyroid-stimulating-hormone (TSH) or prolactin responses to TSH-releasing-hormone (TRH) in 10 patients with peptic ulcer disease given oral ranitidine. Serum total and free thyroxine (TT4 and FT4) concentrations declined slightly, whereas total and free triiodothyronine (TT3 and FT3) increased slightly following ranitidine. None of these changes achieved statistical significance. Both the ratio of TT4/TT3 and FT4/FT3, however, declined (P less than 0.05) following ranitidine. Thus ranitidine may have a minor influence on peripheral deiodination of thyroxine but has little effect on hormone production from the thyroid gland. The diagnostic value of biochemical tests of thyroid function is not seriously compromised in patients receiving ranitidine.     

The effect of morphine on pituitary-thyroid function in the rat

The administration of morphine (Mo) to adult male rats resulted in a decrease in body weight, thyroid weight and pituitary-thyroid-stimulating hormone (TSH) content and in increase in pituitary and adrenal weight. Serum TSH and goiter growth on propylthiouracil (PTU) challenge was normal. Stalk-median eminence (SME) TSH content was increased and net TSH synthesis as measured over 24 hr was augmented in Mo-treated rats. It is suggested that these endocrine changes may be mediated by Mo acting at a hypothalamic level to enhance TSH synthesis under certain experimental conditions.     

Central haemodynamic effects in man of intravenous d-alprenolol during rest and exercise

Summary The central haemodynamic reactions to the dextro isomer of alprenolol, and its interference with the responses to isoprenaline, have been studied by right heart catheterization in 6 healthy young males at rest, and in 5 of them during exercise. A total dose of 90 mg of dextro-alprenolol was infused at rest, and a further 50 mg during exercise 90 min later. The infusion produced no change in resting heart rate, cardiac output, systemic and pulmonary vascular resistance or systemic artery blood pressure either at rest or during exercise, but there was an increase in pulmonary artery diastolic pressure and right ventricular end-diastolic pressure, both at rest and probably during exercise. The haemodynamic responses to isoprenaline infusion were almost completely blocked immediately after dextro-alprenolol 90 mg, and 60 min later they were still much reduced. It is probable that the mode of action of dextro-alprenolol in the dose given was a combination of a -receptor blocking effect and a slight direct depression of myocardial contractility.     

Effect of nifedipine on plasma catecholamines in man at rest and during exercise

Summary Blood pressure, heart rate, and plasma catecholamine concentrations were measured in 9 normotensive volunteers during a randomized cross-over study of oral nifedipine (10 mg×5) and placebo; measurements were made at rest and during maximal anaerobic exercise. At rest nifedipine reduced blood pressure and increased heart rate and plasma noradrenaline, whereas plasma adrenaline did not change. During exercise, the blood pressure response was similar in nifedipine and placebo treated subjects; however, heart rate was significantly higher with nifedipine. Plasma noradrenaline increased more during exercise in nifedipine-treated subjects. By contrast, nifedipine inhibited the increase in plasma adrenaline induced by exercise.The results suggest that peripheral vasodilatation induced by nifedipine is responsible for increased sympathetic nerve activity, both at rest and during exercise, and that nifedipine inhibits adrenaline secretion in man.The data were presented in part at the Symposium: Calcium entry blockers and tissue protection, Rome, 1984     

矽肺患者运动时肺功能改变分析

目的　探讨矽肺患者、正常人运动试验高峰时肺功能的改变。方法　受试者作肺通气功能 ,测用力呼气量 (FVC)、第 1秒用力呼气量 (FEV1 ) ,计算 FEV1 % Pred(百分率 )、FEV1 / FVC和最大通气量 (MVV)。结果　矽肺组 FEV1 / FVC、MVV明显低于对照组 (5 7.1± 9.2 2 %、82 .90± 1 0 .30 % ;4 4 .80± 1 7.0 0 L/ min、92 .3± 1 2 .5 L/ min,P<0 .0 0 1 )。矽肺组运动试验高峰时潮气量 (pkvt)低于对照组 [(1 .0 6± 0 .4 1 ) l、(1 .5 3± 0 .36 ) l,P<0 .0 0 1 ],而呼吸率(pkfb)、死腔量与潮气之比 (pkvt/ vt)高于对照组 [(32 .2± 6 .6 4 ) / min、(2 8.3± 5 .38) / min;(0 .2 7± 0 .0 6 )、(0 .2 1±0 .0 5 ) ,pkvt]与 MVV呈正相关 (r=0 .71 ,P<0 .0 0 1 ) ,与 pkvd/ vt呈负相关 (r=- 0 .71 ,P<0 .0 0 1 )。结论　矽肺患者运动时浅快呼吸可增加耗氧量和呼吸肌疲劳 ,限制运动耐量     

The effects of beta-adrenoceptor blockade on breathing during progressive exercise in normal man.

1 We have studied the effects of single oral doses of 80 mg propranolol and 100 mg atenolol on breathing during progressive exercise in nine healthy men in a double-blind, placebo-controlled experiment. As judged by their effects on exercise heart rate significant levels of beta-adrenoceptor blockade were achieved. 2 At the two lower levels of work rate (50 watts and 100 watts) minute ventilation on atenolol was lower than on placebo while at the highest level of work (200 watts) minute ventilation was higher on atenolol than on placebo. The regression of VE atenolol on VE placebo was 1.28 which is significantly different from unity (P less than 0.001). The results with propranolol were more scattered and failed to reach the 5% level of significance. 3 Effects on the pattern of breathing are small but when minute ventilation is matched with placebo, atenolol results in larger tidal volumes and prolonged inspiratory and expiratory time. 4 These observations are discussed in relation to other work in the literature.     

Effect of ICI 118551 on bronchial beta-adrenoceptor function and exercise heart rate in normal man.

To determine whether the beta 2-selectivity of ICI 118551 extended to human airways, we measured bronchial beta-adrenoceptor blockade and the reduction in exercise heart rate in six normal subjects on different occasions after ingestion of ICI 118551 20 or 50 mg, propranolol 40 mg or placebo in random order. Bronchial beta-adrenoceptor blockade after each active drug was measured as the displacement of the airway dose-response curve to salbutamol and expressed as a dose ratio. Exercise heart rate was measured during the fifth minute of steady state exercise at 70% of the subject's maximum work load. The mean dose ratios for the salbutamol airway dose-response curves following ICI 118551 20 and 50 mg and propranolol 40 mg were 11, 55 and 48 respectively. The mean reductions in exercise heart rate for the three drugs were 0.6, 6.6 and 16.6% respectively. These results confirm that the beta 2-selectivity of ICI 118551 includes airway beta 2-adrenoceptors in man.     

The effect of oxprenolol dosage time on its pharmacokinetics and haemodynamic effects during exercise in man

Summary We have studied the effect of dosage time of oxprenolol (Trasicor^®) on its pharmacokinetics and pharmacodynamics in six healthy volunteers. The drug effects measured were heart rate and systolic blood pressure during exercise. Oxprenolol was taken orally at 08.00 h, 14.00 h, 20.00 h, and 02.00 h in randomized order, with 1 week between successive doses.There were differences in the pharmacokinetics of oxprenolol for the ratio between the apparent volume of distribution and systemic availability (P=0.04) and for elimination half-life (P=0.006). Both were lowest after administration at 14.00 h (163 (77) l and 1.2 (0.6) h; mean (SD)) and highest after administration at 02.00 h (229 (100) l, and 1.7 (0.6) h).The systolic blood pressure during exercise before oxprenolol did not vary with dosage time, but heart rate during exercise before intake was lowest before dosage time 08.00 h and highest before dosage time 20.00 h (P=0.03).The time-course of heart rate during exercise after oxprenolol was described by a model that incorporated the factors drug concentration and spontaneous diurnal variation. EC₅₀ and E_max did not vary between dosage times. The spontaneous diurnal variation in heart rate during exercise was unaffected by oxprenolol, leading to an apparently greater effect of oxprenolol during the night than during the day.     

边缘性碘缺乏地区孕妇及新生儿垂体——甲状腺轴功能研究

本研究旨在中国边缘性碘缺乏地区上海市孕妇及新生儿垂体－甲状腺轴功能。结果表明：（１）新生儿促甲状腺激素水平〈５ｍＩｕ／Ｌ者占６１．０％，〈１０ｍＩｕ／Ｌ者占２３．０％。孕妇ＴＳＨ水平〈５ｍＩｕ／Ｌ；者仅占５．５％，但新生儿及孕妇ＴＳＨ水平却呈平行改变。     

A study of the calcium carbimide-ethanol interaction in man

Summary In six male alcoholic volunteers, oral administration of calcium carbimide (0.7 mg/kg) before ingestion of ethanol (0.5 g/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia and increased pulse pressure, which was due mainly to decreased diastolic blood pressure. For these experimental conditions, calcium carbimide had a duration of action of at least 24 h to produce an interaction with ethanol. The order of intensity of the interaction with regard to the calcium carbimide pretreatment time interval was 4>812>24 h. Using the criterion of heart rate above 100 as indicative of the calcium carbimide-ethanol interaction, the onset was 0.13, 0.25, 0.25 and 0.38 h for the 4-, 8-, 12- and 24-h pretreatment experiments and the duration of the interaction was 1.6, 1.0, 1.0 and 0.12 h, respectively. There were positive linear correlations between acetaldehyde level and heart rate and between acetaldehyde level and pulse pressure. There was appreciable interindividual variability in the heart rate and blood pressure responses. Increased blood acetaldehyde level seemed to be required for the physiological changes to occur. Calcium carbimide pretreatment at the 4-h interval produced increased blood ethanol level for the last hour of the interaction and reduced the rate of ethanol metabolism.     

Clinical assessment of sympathetic function in man

Investigations are reviewed which are suitable for use in clinical situations in which lesions of the sympathetic nervous system are suspected. Particular attention is given to the problems of cardiovascular regulation as orthostatic hypotension is one of the commoner manifestations of sympathetic failure. Tests of the autonomic innervation of the eyes are also discussed. Tests of parasympathetic function are briefly described, as both parts of the autonomic nervous system may be affected by the same disease process.     

Some correlates of marihuana self-administration in man: A study of titration of intake as a function of drug potency

Previous research has suggested that psychosocial rather than strictly pharmacological factors may play a dominant role in the subjective response to socially relevant (i.e., low) doses of marihuana. The insensitivity of experienced marihuana users to pharmacological factors was studied in an ad lib self-administration situation. Subjects tested repeatedly with varying drug potencies were asked to smoke a sufficient amount to achieve a predefined subjective state of intoxication. Several indices of amount consumed suggested that effective titration of intake did not occur. Rather, subjects consumed more total THC the greater the potency of the material. Doses which produced a subjectively optimal high had significant behavioral and physiological effects. The results are consistent with the hypothesis that psychosocial variables may be more significant than pharmacological variables in determining the recreational intake of marihuana.     

Plasma levels and protein binding of phenytoin during exercise in man: the effect of elevated free fatty acids

Five healthy subjects performed submaximal physical exercise approximately 20 h after a single oral dose of phenytoin (5 mg/kg of the sodium salt). The plasma levels of free fatty acids (FFA) increased 2- to 3-fold in the post-exercise period. In spite of this, the degree of plasma binding of phenytoin and its total concentration in plasma were unaffected. Thus FFA at the levels reached (1.5-2.9 mEq/l), did not displace phenytoin from its binding sites on albumin. Furthermore, during the FFA peak the plasma protein binding of warfarin, as measured in vitro, did not decrease as compared to the pre-exercise period. These findings contrast to previous observations in rats and dogs, where FFA caused a considerable displacement of warfarin and phenytoin at relatively low FFA/albumin molar ratios.     

Effect of verapamil on left ventricular function at rest and during exercise in normal men

Verapamil is a calcium channel blocking agent used primarily for treatment of arrhythmias and coronary artery disease. It may also depress myocardial contractility. The purpose of this study was to assess the effect of verapamil on left ventricular function. Twelve normal men, 22-29 years of age, were studied at rest and during exercise, with and without verapamil, using first-pass radionuclide angiocardiography. Verapamil was administered by continuous intravenous infusion to produce steady-state blood levels of 106-123 ng/ml. The heart rate, ejection fraction, stroke volume index, and end-diastolic volume index were measured with and without the drug. Verapamil increased the mean resting heart rate from 74 to 78 beats/min (p = 0.001), decreased the mean stroke volume index from 48 to 42 ml/m2 (p = 0.01), and decreased the mean end-diastolic volume index from 77 to 71 ml/m2 (p less than 0.05). No changes in cardiac index, ejection fraction, end-systolic volume index, or peak systolic pressure/end-systolic volume ratio were observed at rest. No differences occurred in exercise hemodynamics. Thus verapamil at therapeutic dose levels did not significantly depress contractility or have other clinically important hemodynamic effects at rest or during exercise in normal subjects.     

A preliminary metabolic study of alpidem in rat and man

The metabolism of alpidem, a new anxiolytic agent in the chemical series of imidazopyridines, was investigated in rat and man. In both species the compound is extensively metabolised by three main routes of biotransformation: aromatic oxidation of the imidazopyridine ring; n-dealkylation; and/or aliphatic oxidation of the substituted amide side chains.     

Rate of phenytoin accumulation in man: A simulation study

Computer simulations were performed using a one-compartment open model with either first-order or zero-order input and either Michaelis-Menten or Michaelis-Menten and first-order elimination. Twelve theoretical cases constructed from various combinations of typical and atypical values for phenytoin pharmacokinetic parameters, V _max and K _m , were examined. In many cases, at least 90% of the eventual steady-state serum level would be achieved within 4 weeks when phenytoin was administered at an appropriate rate. In the case of a low-to-average V_max value and an average-to-high K_m value, an initial maintenance dose of 3–4 mg phenytoin sodium/kg/day would, within a few days, result in serum phenytoin levels above the usual therapeutic range. On the other hand, if V _max and K _m values were both low (3.8 mg/kg/day and 1.45 mg/liter, respectively), a very slow rate of accumulation would ensue. Thirty days after the start of 4 mg phenytoin sodium/kg/day, a serum level of about 16 g/ml would likely occur. The magnitude of continued accumulation beyond this level would be significantly influenced by the rate of renal elimination of unchanged phenytoin. It is recommended that, after initiation or adjustment of phenytoin therapy, serum phenytoin levels be monitored weekly for 3–4 weeks, then monthly for 2 additional months. Long-term follow-up should include serum phenytoin levels every 3– 6 months or as clinically indicated. Appreciation of the characteristics of phenytoin accumulation in relation to rate of administration and individual pharmacokinetic parameters is important for accurate interpretation of serum phenytoin levels and rational adjustment of dosage regimens.This work was supported in part by USPHS Grant AH16033.