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Biomedical subjects

R L Parsons

Publications and source records attributed to R L Parsons.

At least 127 records · Page 7Linked to original sources

Absorption of propranolol and practolol in Coeliac disease.

Plasma concentrations of propranolol and practolol were measured in patients with coeliac disease and normal subjects. The mean plasma propranolol concentration in the coeliac patients was higher throughout the period of study, the differences being significant at one, six, and eight hours. The plasma concentration profile of practolol in the coeliacs followed a similar pattern but lagged behind that of the normal subjects. A possible reason for these differences is an alteration in the rate of drug diffusion across the atrophic mucosa of the upper jejunum in coeliac disease. Analysis of the results of the propranolol study suggests that an increase in the rate of absorption combined with saturation of first pass extraction may account for the increased plasma concentrations of unchanged propranolol found in coeliac disease. These abnormalities of drug absorption do not appear to be related to the duration of treatment with a gluten free diet.

Adult↗

The effect of age on plasma levels of propranolol and practolol in man.

1. Plasma levels of propranolol and practolol were measured in groups of elderly and young subjects, after the oral administration of propranolol (40 mg) and practolol (200 mg) on separate occasions. 2. At all sampling times the mean plasma propranolol level in the group of elderly subjects was substantially greater than the corresponding level in the group of young subjects, there being a significant difference between the two, and a fourfold difference in the mean peak levels. 3. After practolol, there was no significant difference between the mean plasma concentrations of the drug in the two groups for the first 2 hours. Subsequently, the mean plasma levels in the group of elderly subjects were somewhat higher than the corresponding levels in the young group, the differences between the two reaching significance. 4. It is suggested that there is a need to substantially reduce the dose of propranolol given to elderly patients. With practolol, however, no reduction is necessary providing renal function is normal for the patient's age.

Administration, Oral↗

The effects of tetraphenylboron on neuromuscular transmission in the frog.

1 The effect of tetraphenylboron (TPB) were studied on the frog sciatic nerve-sartorius muscle preparation. 2 TPB (0.01-1 mM) blocked indirectly elicited twitches of the preparation. 3 TPB (0.01-0.1 mM) produced no depolarization but lowered membrane resistance. TPB increased miniature endplate potential (m.e.p.p.) frequency, the rate of rise of the endplate potential (e.p.p.), and slowed the rate of rise and rate of fall of the muscle action potential. 4 In Mg2+ solutions the quantal content of e.p.ps was initially increased by TPB (0.01 mM). This was followed by a decrease of e.p.p. and m.e.p.p. amplitudes, accompanied by a lack of e.p.p. failures. 5 Larger concentrations of TPB (0.1 mM) produced an increase in e.p.p. amplitude followed by the sudden abolition of e.p.ps. This effect was associated with abolition of the nerve terminal spike. 6 TPB (0.1 mM) exhibited no postjunctional blocking action. 7 The results indicate that TPB acts prejunctionally, initially causing an increased release of acetylcholine. Subsequently, transmitter output is reduced by a reduction of quantal size.

Action Potentials↗

The effects of tetraphenylboron on spontaneous transmitter release at the frog neuromuscular junction.

1 The effects of tetraphenylboron (TPB) on spontaneous transmitter release were studied in the frog sartorius muscle preparation. 2 TPB (0.001-1 mM) produced a time-dependent increase in miniature endplate potential (m.e.p.p.) activity that was not sustained. TPB (0.1 mM) produced similar effects on m.e.p.p. frequency in normal Ringer solutions, in the absence of Ca2+ or Cl- and in the presence of excess Ca2+ and of tetrodotoxin. The effect of TPB (0.01 mM) was reduced but not abolished in the absence of Ca2+. 3 As m.e.p.p. frequency fell from its peak level in TPB (0.04 mM) m.e.p.p. amplitude was reduced. The reduction of m.e.p.p. amplitude was not prevented by choline (30-300 muM). 4 When m.e.p.p. activity fell below the noise level in the presence of TPB (0.1 mM), lanthanum (0.5 mM) was ineffective in promoting measurable m.e.p.p. activity. 5 The effects of TPB were slowly reversible by washing. 6 The results indicate that TPB acts to reduce the nerve terminal stores of acetylcholine, probably by a combination of rapid release and concomitant inhibition of transmitter storage.

Action Potentials↗

The interaction between caffeine and calcium in the desensitization of muscle postjunctional membrane receptors.

The interaction between caffeine and calcium on the rate of desensitization of muscle postjunctional membrane (PJM) receptors during the sustained application of 0.27 mM carbamylcholine (CARB) has been studied in vitro on the sartorius muscle of the frog. The rate of PJM repolarization with CARB added to the solution bathing the muscle or the recovery of the effective transmembrane resistance (EMR) during the microperfusion of CARB directly onto the end-plate region of individual fibers was used as an index of the rate of desensitization. Caffeine (1.5 mM) increased the rate of PJM repolarization with bulk application of CARB in a 1.8 or 10 mM calcium Ringer solution but had no effect on PJM repolarization in a calcium-deficient, 4 mM magnesium Ringer solution. For EMR measurements the preparation was rendered mechanically quiescent by repeated challenges with isotonic KCl during an exposure of several hours to a calcium-free, 4 mM magnesium-1 mM EGTA Ringer solution. In these fibers, the microperfusion of 0.27 mM CARB together with 1.8 mM calcium plus 1.5 mM caffeine significantly increased the rate of EMR recovery above that observed in the absence of caffeine. Raising the calcium concentration to 10 mM had a similar effect; however, no additional increase was noted by the inclusion of 1.5 mM caffeine. It is suggested that the major role of caffeine in PJM desensitization is to increase the calcium permeability of the surface membrane. The transmembrane movement of calcium and the consequent intracellular accumulation of calcium is seen as a critical factor in controlling the rate of PJM desensitization.

Animals↗