Physiological pharmacokinetics and pharmacodynamics of (+/-)-verapamil in female rats

Tissue distribution and pharmacodynamics of verapamil were evaluated during steady state intravenous (i.v.) infusion and after single dose intraperitoneal (i.p.) drug administration to female Sprague-Dawley rats. In one group of rats, verapamil was infused to a steady state concentration at which time animals were killed. Verapamil-induced decreases in mean arterial pressure (MAP) were monitored during infusion and correlated with concomitantly obtained plasma verapamil concentrations. Tissue (lung, liver, renal medulla, renal cortex, cardiac muscle, skeletal muscle, perirenal fat, brain stem, cerebral cortex, and cerebellum) and plasma samples were obtained immediately after animals were killed and verapamil and norverapamil concentrations determined. Another group of rats, after receiving i.p. verapamil, were killed at 1, 3, 5, 19, and 24 h. Elimination from each tissue evaluated was described by a first order process. Elimination half-life of verapamil was similar among plasma and tissues evaluated (1.5 to 2.2 h). The per cent verapamil not bound to plasma proteins was concentration-independent and similar between rats receiving i.p. (mean +/- S.D.) (2.28 +/- 0.72 per cent) and i.v. (2.08 +/- 0.03 per cent) verapamil. MAP and verapamil concentration in plasma (r = 0.75; p less than 0.01) and cardiac muscle (r = -0.82; p less than 0.01) were inversely correlated in a highly significant fashion during both i.v. and i.p. drug administrations. The tissue-to-plasma distribution ratio for verapamil and norverapamil was similar among animals receiving i.p. verapamil at all points of sampling, suggesting distribution equilibrium had been achieved. After steady state i.v. infusion, both verapamil and norverapamil tissue: plasma concentration ratios were greater than after i.p. administration. Higher tissue: plasma verapamil concentration ratios after i.v. administration than after i.p. administration suggest either only a pseudoequilibrium is attained after i.p. administration or that determinants of tissue distribution of racemic verapamil differ with different routes of drug administration. In these studies, MAP provided a reasonable pharmacodynamic marker for verapamil tissue and plasma concentrations.     

Characteristics and motives of women choosing elective induction of labour

Personal characteristics of healthy term pregnant women who chose elective induction or spontaneous onset of labour and the motives for their choice were assessed. Almost 50% of 237 women with uncomplicated pregnancies opted for elective induction when offered the opportunity. These women appeared to have had more complaints during their pregnancy and menstrual periods, more complications in their obstetrical history and to be more anxious about their labour than women who chose a spontaneous onset of labour. Predominant motives were a feeling of safety and the desire to shorten the duration of pregnancy. These characteristics and motives seem to reflect a lack of trust in physical reproductive functions. It is concluded that in evaluating effects of elective induction of labour, pre-existing differences between women who choose elective induction and women who opt for a spontaneous onset must be taken into account.     

The effects of caffeine on various body systems: a review

Caffeine is the most widely consumed drug in Western society. The intake of caffeine-containing beverages in many adults and children often reaches levels that can induce pharmacological effects. Ninety-nine percent of ingested caffeine is absorbed and distributed to all tissues and organs. The effects of caffeine intake differ greatly according to acute or chronic intake, level of intake, and the development of tolerance. Caffeine administered acutely to non-users or recent abstainers can induce hypertension, arrhythmias, altered myocardial function, increased plasma catecholamine levels, plasma renin activity, serum cholesterol levels, increased production of urine, gastric acid secretion, and alterations in mood and sleep patterns. Tolerance to chronic caffeine intake develops in most individuals, with the cessation of its effects on the renal system, the cardiovascular system, the gastrointestinal system and, to some extent, the central nervous system. Moderate caffeine consumers probably need to have little concern for the effect of caffeine intake on their health if their other life-style habits are also moderate.     

The expression and perception of facial emotion in brain-damaged patients

This study examined the expression and perception of facial emotion in patients with unilateral cerebrovascular pathology. Subjects were 12 right brain-damaged (RBD), 15 left brain-damaged (LBD) aphasic, and 16 normal control (NC) right-handed males. Expressions were elicited during posed and spontaneous conditions. Both positive and negative emotions were studied. RBDs were significantly impaired, relative to LBDs and NCs, in expressing and perceiving facial emotion. There were no group differences as a function of condition, but there were differences as a function of emotional valence. Qualitative performance differences also were observed. There was no evidence that the ability to produce a particular emotion was related to the ability to identify the same emotion. Overall, these findings support the notion that the right cerebral hemisphere is dominant for expressing and perceiving facial emotion.     

Short and middle latency vestibular evoked responses to acceleration in man.

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000 degrees/sec 2 and with a rise time of 1-2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200-2000 Hz; average of 1024 trials), had amplitudes of about 0.5 microV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30-300 Hz; N = 128 trials), with larger amplitudes (about 15 microV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths.(ABSTRACT TRUNCATED AT 250 WORDS)