摘要:

Ranitidine is a new histamine H2‐receptor antagonist that includes a furan ring structure, whereas other H2‐receptor antagonists include an imidazole ring. It is more potent than cimetidine in inhibiting gastric acid secretion and lacks cimetidine's anti‐androgenic and hepatic microsomal enzyme inhibiting effects. In the recommended dosage of 150 mg twice daily, ranitidine is as effective as cimetidine in healing duodenal and gastric ulcers and has the advantages of less frequent dosing and fewer side effects. Ranitidine appears to be the drug of choice in the treatment of the Zollinger‐Ellison syndrome because of its increased potency and lesser effect on endocrine function compared to cim

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03248.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03250.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03251.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Labetalol is a combined alpha‐ and beta‐adenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective competitive antagonist at beta‐adrenoceptors and a competitive antagonist of postsynaptic alpha1‐adrenoceptors. Labetalol is more potent at beta than at alpha1adrenoceptors 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

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03252.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03253.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03254.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03256.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Guanadrel sulfate is structurally and pharmacologically similar to guanethidine but has different pharmacokinetic properties. The drug produces peripheral postganglionic sympathetic blockade as a consequence of interference with neuronal release of norepinephrine and displacement of norepinephrine from storage vesicles. Animal studies using large multiples of human antihypertensive doses suggest a low order of human toxicity. Clinical studies have failed to reveal any major effect on hematologic, hepatic or renal function. The effect on serum lipids and plasma renin is unknown. The drug is well absorbed after oral administration. Peak plasma levels in humans occur 1.5–2 hours after a administration. Protein binding is less than 20%. Data from animal studies and clinical trials demonstrating a lack of central nervous system side effects indicate that little if any drug enters the central nervous system. The drug is partially metabolized by the liver, but nearly 50% of an orally administered dose appears unchanged in the urine. The mean elimination half‐life is approximately 12 hours.The onset of antihypertensive action after oral administration of guanadrel to humans is 30–120 minutes (mean 77 minutes). The offset of drug action after a single oral dose ranges between 4–14 hours (mean 9 hours). The hypotensive response to guanadrel in hypertensive subjects is the result of a decline in systemic vascular resistance with an impairment of the normal sympathetic reflexes in the erect position. Guanadrel causes a reduction in renal blood flow and glomerular filtration rate in the erect position. Open label clinical trials of antihypertensive efficacy indicate that guanadrel is effective in 60 and 70% of patients in the supine and erect positions, respectively. In comparative clinical trials, guanadrel appears to be as effective as guanethidine or methyldopa in reducing blood pressure in persons with mild to moderately severe hypertension; mean doses ranged from 56–162 mg/day. In other studies, investigators have used doses of 5–600 mg daily. The maximum recommended dosage is 400 mg/day. Side effects reported with guanadrel administration are those that would be predicted for a postganglionic sympathetic inhibitor that does not enter the central nervous system. Sexual dysfunction, orthostatic dizziness and diarrhea occur with the drug but do not seem to be as frequent or as severe as with guanethidine administration. In a comparison of guanadrel to methyldopa, methyldopa caused more complaints of drowsiness, and drowsiness scores of methyldopa patients remained higher than those of guanadrel patients even after two years of therapy. The drug has received approval as a step 2 antihypertensive agent in the United States. The available data suggest that it will serve as a reasonable alternative to other step 2 antihy

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03257.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03258.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1983.tb03260.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY