Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Labetalol is a combined alpha- and beta-adrenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. Labetalol is more potent at beta that at alpha 1 adrenoceptors in man; the ratio of beta-alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration. Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first-pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half-life of the drug is approximately 6 hours. Unlike conventional beta-adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta-blockers, labetalol may influence the renin-angiotensin-aldosterone system and respiratory function. Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta-blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease. The most troublesome side effect of labetalol therapy is posture-related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta-adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.
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PMID:Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. 631 May 29

Thirty-two patients with primary hypertension were studied in a double-blind cross-over comparison between the cardioselective beta 1-blocking agent atenolol and the combined alpha- and beta-blocking agent labetalol. The doses used were atenolol 50--150 mg twice daily and labetalol 200--600 mg twice daily. Both drugs effectively reduced blood pressure and heart rate. Dose increments every second week resulted in a higher proportion of patients with normal blood pressure (les than or equal to 150/90 mm Hg) with both drugs. Labetalol was somewhat more effective in lowering upright blood pressure while atenolol caused a more pronounced heart-rate reduction. Both agents decreased plasma renin activity and urinary aldosterone excretion. Scalp tingling on labetalol (2 patients) and cold fingers with atenolol (1 patient) caused withdrawal of the drugs. Cold fingers were reported in another four patients during treatment with atenolol and in one when on labetalol. Tiredness and postural symptoms were more common during intake of labetalol.
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PMID:Antihypertensive and metabolic effects of increasing doses of atenolol and labetalol. A comparative study in primary hypertension. 676 Jun 79

The effects of labetalol, an alpha- and beta-adrenoceptor blocking drug, on blood pressure, heart rate, plasma renin activity (PRA) and plasma aldosterone were studied in 17 adult patients with essential hypertension. Following a total dose of 1 g labetalol administered over a 48-hour period, there was a rapid and significant fall in systolic and diastolic BP averaging 16,5 +/- 7,9%/14,8 +/- 7,5% respectively supine, 18,7 +/- 8,3%/17,8 +/- 7,2% standing and 23,9 +/- 7,1%/16,8 +/- 10,3% after moderate exercise; 24 hours after labetalol was discontinued, the BP had gone up but was still below pretreatment values. Bradycardia remained slight throughout. During treatment a significant decrease in PRA (mean : 45%) was observed in all patients and found to correlate in standing position with changes in standing and post-exercise mean arterial pressure. There was no significant changes in plasma aldosterone. Side-effects were mild and limited to tingling of the scalp in 5 patients. No clinical symptoms of postural hypotension were recorded.
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PMID:[Essential arterial hypertension. Effects of labetalol on blood pressure and renin-angiotensin system (author's transl)]. 700 49

A 44-year old female was admitted to our hospital for evaluation of uncontrolled hypertension. She received renal transplantation 3 months ago and suffered from a tingling sensation and weakness on both hands. Laboratory findings (low serum potassium, low plasma renin activity and elevated plasma aldosterone level) was consistent with primary aldosteronism. Through the postural study for plasma aldosterone and the adrenal CT finding we diagnosed this case as adrenal adenoma, which was confirmed by surgical removal. A retrospective review of medical records showed that characteristic findings in primary aldosteronism (hypokalemia and low plasma renin activity) were masked by renal failure and became evident after successful renal transplantation. It was suggested that impaired urinary potassium excretion and excess release of renin from the ischemic kidney masked the characteristic findings of primary aldosteronism. To our knowledge, this is the first report documenting the change of renin-angiotensin-aldosterone system after renal transplantation in a case of coexistence of primary aldosteronism and chronic renal failure.
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PMID:Primary aldosteronism detected after renal transplantation. 797 85

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect induced by a variety of chemotherapeutic agents. Symptoms are mainly sensory: pain, tingling, numbness, and temperature sensitivity. They may require the tapering of chemotherapy regimens or even their cessation; thus, the prevention/treatment of CIPN is critical to increase effectiveness of cancer treatment. However, CIPN management is mainly based on conventional neuropathic pain treatments, with poor clinical efficacy. Therefore, significant effort is made to identify new pharmacological targets to prevent/treat CIPN. Animal modeling is a key component in predicting human response to drugs and in understanding the pathophysiological mechanisms underlying CIPN. In fact, studies performed in rodents highlighted several pharmacological targets to treat/prevent CIPN. This review provides updated information about ongoing clinical trials testing drugs for the management of CIPN and presents some of their proof-of-concept studies conducted in rodent models. The presented drugs target oxidative stress, renin-angiotensin system, glutamatergic neurotransmission, sphingolipid metabolism, neuronal uptake transporters, nicotinamide adenine dinucleotide metabolism, endocannabinoid system, transient receptor potential channels, and serotoninergic receptors. As some clinical trials focus on the effect of the drugs on pain, others evaluate their efficacy by assessing general neuropathy. Moreover, based on studies conducted in rodent models, it remains unclear if some of the tested drugs act in an antinociceptive fashion or have neuroprotective properties. Thus, further investigations are needed to understand their mechanism of action, as well as a global standardization of the methods used to assess efficacy of new therapeutic strategies in the treatment of CIPN.
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PMID:An overview of ongoing clinical trials assessing pharmacological therapeutic strategies to manage chemotherapy-induced peripheral neuropathy, based on preclinical studies in rodent models. 3310 19