The Pharmacokinetics of Long Acting Propranolol

McAinsh, J; Baber, N.; Taylor, Douglas S.; Young, James F.; Smith, Brandon; Zacharias, Farouk

doi:10.1016/b978-0-08-023768-8.51049-5

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“…A peripheral bolus (0.5 mg/kg) of P was followed by portal infusion (8.0 pg/kg per min). H3-Propranolol (H3-P) was given as a peripheral bolus (2 pCi/kg) and infusion (12.1 nCi/kg per rnin) as was DPH (7. Previous studies have shown that long-acting propranolol (LA) produces lower mean peak concentrations of propranolol in plasma and has a longer mean time to peak than conventional (CP) propranolol (McAinsh et al, 1978). We have investigated the pharmacokinetics of both propranolol (P) and 4-hydroxypropranolol(4HP) in ten healthy subjects and report the results after 4 days of treatment with either 320 mg/day of LA or CP.…”

Section: Interaction Betweenmentioning

confidence: 99%

Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

1982

Clin Exp Pharmacol Physiol

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Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a n active compound found in many peppers, is believed to reduce the effectiveness of some cutaneous stimuli by impairing the function of sensory nerves, particularly those containing substance P. In the present work, an indirect immunohistochemical method has been used to localize substance P-like immunoreactivity in nerves associated with the cardiovascular system in the guinea-pig. It was found that reactive nerves were present throughout the system. The larger arteries, the pericardium, cardiac valves and the vena cava near the heart were all densely supplied. In general, the numbers of positive nerves decreased as smaller vessels were approached.Guinea-pigs were injected subcutaneously with capsaicin (Sigma). The drug was administered in a carrier made up of 50% ethanol and 50% Tween 80. For long-term effects to be examined, the injections were given in increasing doses (25, 50, 100, 200 and 400 mg/kg on five successive days) and the animals taken at from 2 to 61 days after the final injection. Guinea-pigs were also examined at from 2 h to 10 days after a single injection of capsaicin (50 mg/kg). At 2 h the intensity of reaction of fibres was slightly reduced. This reduction in intensity continued up to 24 h. At 12 h many swollen, distorted axons were seen; their appearance was similar to axons after axotomy or chemical toxins. At 24 h very few fibres with substance P-like immunoreactivity were detected. In the longer term experiments, depletion of substance P was found to persist up to 61 days.These results suggest that substance P fibres in the cardiovascular system are sensory. The presence and distribution of neuropeptides inthe autonomic ganglia which supply pelvic viscera in the guinea-pig. M. Costa, J. B. Furness, D. Mayor and R. Papka (introduced by P. Me fin), The distribution of substance P, vasoactive intestinal polypeptide (VIP), enkephalin and somatostatin immunoreactivity in the anterior and posterior pelvic plexuses was investigated by using an immunohistochemical technique applied to whole mounts. In all the small ganglia present along the hypogastric nerve and in the pelvic plexuses substance P immunoreactive fibres formed both a loose network throughout the ganglia and some well defined baskets around 0305-1870/82/0800-0389 $02.00 0 1982 Blackwell Scientific Publications 389Abstracts ganglion cell bodies. In the ganglia of these plexuses a significant proportion of nerve cell bodies showed substance P immunoreactivity. Following treatment with capsaicin the immunoreactivity of the loose ganglionic network and of a large proportion of nerve fibres in the nerve bundles of the plexus and of the hypogastric ganglia disappeared while the substance P immunoreactive ganglion cells and the pericellular baskets were not affected. Numerous ganglion cells in these plexuses showed VIP immunoreactivity and in the ganglia varicose nerve fibres formed pericellular baskets around non-immunoreactive ganglion cells. Large numbers of immunoreactive fibres were als...

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Section: Interaction Betweenmentioning

confidence: 99%

Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

1982

Clin Exp Pharmacol Physiol

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The Pharmacokinetics of Long Acting Propranolol

Cited by 1 publication

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Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists

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