Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A trial of methyldopa in hypertension was conducted in 60 patients for a mean time of 9.4 months. Initially, four different dosages of methyldopa were studied and blood pressure was significantly lowered in the supine and standing positions. Standing blood pressure was significantly reduced more than supine. An average of 5.2 visits passed before maintenance blood pressure was obtained. There was no significent evidence of deterioration during the duration of this study. Side effects were mild. Only two patients voluntarily requested discontinuance of this study. Tolerance to the drug occurred and approximately 50 per cent of the patients no longer had a significant blood pressure reduction to methyldopa alone by the end of the study. Methyldopa appears to be a significant addition to the drug therapy of hypertension.
 ...
PMID:The long-term effectiveness of methyldopa in hypertension. 590 53

Methyldopa, clonidine, and a more recently developed drug, guanabenz, have similar antihypertensive mechanisms, predominantly suppression of central sympathetic outflow by alpha 2-receptor agonism and consequent reduction in peripheral sympathetic activity. Recent studies clearly demonstrate an important role of the sympathetic nervous system in the control of sodium excretion. Therefore, the interrelationships between the use of central alpha-adrenergic agonists as antihypertensive agents and their influence on renal handling of sodium are important. Certain problems accompany the use of the older centrally acting drugs as monotherapy. As a response to the hypotensive effects of these drugs, certain renal adaptations take place which presumably are homeostatic attempts to restore blood pressure and plasma volume to baseline, but which lead to a positive sodium balance, antihypertensive tolerance and occasionally the development of overt edema. The high incidence of tolerance has led most physicians to use diuretics on a routine basis, superimposing the side effects of diuretics and compromising compliance. The potential natriuretic properties of guanabenz appear to counter-balance the sodium retaining side effects commonly seen with other centrally acting and vasodilating antihypertensive drugs. This property, therefore, makes this agent a scientifically interesting and potentially useful therapeutic drug for the therapy of high blood pressure.
 ...
PMID:Natriuretic and water diuretic effects of central alpha 2-adrenoceptor agonists. 608 25

Overall, the worldwide experience on enalapril to date is very encouraging. The drug produces good to excellent responses in 54 to 66 percent of patients with essential hypertension and is at least as effective as either diuretics or beta blockers. The effects of enalapril compared with those of diuretics confirm that patients more dependent upon the renin-angiotensin system respond better. When hydrochlorothiazide is administered concomitantly with enalapril, almost all patients respond, with good long-term maintenance. In patients with severe hypertension, Blocadren or Aldomet may be added in addition to hydrochlorothiazide and will produce additional benefit. Enalapril attenuates the adverse metabolic effects of hydrochlorothiazide, particularly hypokalemia. Overall, although the efficacy of enalapril and that of captopril are similar, enalapril is better tolerated and does not appear to be associated with any significant occurrence of captopril-type side effects, particularly the skin rash and loss of taste. As expected, enalapril and other converting inhibitors may be associated with azotemia in patients with bilateral renovascular hypertension.
 ...
PMID:Enalapril worldwide experience. 608 56

Clonidine (Catapres, Catapresan), guanfacine (Estulic), and methyldopa (Aldomet) are the prototypes of centrally acting antihypertensive drugs. Clonidine and guanfacine are lipophilic drugs that readily penetrate into the brain, where they stimulate alpha-adrenergic receptors in the pontomedullary region. The stimulation of these central alpha-adrenergic receptors has been shown to activate an inhibiting neuron, which causes a reduction of peripheral sympathetic tone and a subsequent fall in arterial blood pressure and heart rate. Both a centrally initiated reduction of vagus reflex activity and the activation of presynaptic alpha 2-adrenergic blocking agents in the heart may contribute to the bradycardia. Studies indicate that methyldopa also penetrates into the brain, where it is converted into alpha-methylnorepinephrine. This amine may stimulate the same central alpha-adrenergic receptors as those activated by clonidine, which will result in a hypotensive effect. Possibly, alpha-methyldopamine might also play a role. Accordingly, the modes of action of clonidine and alpha-methyldopa probably are very similar at a basic level. The central adrenergic receptors probably are located postsynaptically. Their receptor demand corresponds more closely to that of the alpha 2-subtype. Central alpha 1-adrenergic receptors might possibly play a part in the modulation of vagally induced baroreflex bradycardia. A discussion on the pharmacological basis of the side effects of the centrally acting antihypertensives has been limited to those adverse reactions that are somehow related to alpha-adrenergic receptors. Sedation, a common side effect, appears to be mediated by central alpha 2-adrenergic receptors, at least in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:The hypotensive activity and side effects of methyldopa, clonidine, and guanfacine. 609 46

alpha-Methyldopa acts through a metabolite in the central nervous system. Of the three metabolites most prominently considered as potential mediators of alpha-methyldopa hypotension--alpha-methyldopamine, alpha-methylnorepinephrine (MNE), and alpha-methylepinephrine (ME)--ME is the most potent depressor agent following intravenous infusion into rats, following injection into the lateral ventricle, and following injection into the solitary tract nucleus (NTS). The depressor effect of ME in the NTS is attenuated as effectively by timolol as by yohimbine, while the combination of both timolol and yohimbine completely abolishes the pharmacological activity of ME in the NTS. ME is approximately eightfold more potent than MNE in the NTS and also has a greater susceptibility to timolol attenuation.
Hypertension
PMID:Antihypertensive metabolites of alpha-methyldopa. 609 49

Once the diagnosis of chronic hypertension in pregnancy has been made, many centers in the United States treat moderate to severe cases of chronic hypertension pharmacologically, hoping to delay or obviate the onset of superimposed preeclampsia and to improve perinatal outcome. Methyldopa, which is most often used, is the only antihypertensive drug for which there is no evidence of adverse effects in long-term follow-up studies of fetuses exposed to it. Newer beta-blocker drugs such as atenolol and labetalol are receiving much attention abroad. These newer drugs have fewer maternal side effects and, as yet, no adverse effects on fetuses have been seen. Clinical trials of labetalol will soon start in the United States.
 ...
PMID:Management of the pregnant patient with chronic hypertension. 613 51

There are few studies of hypertension in Sudan. In this report, 124 patients attending a newly established hypertension clinic are studied, most of whom were taking irregular treatment initially. Seventy-three (59%) had a strong family history of hypertension. There was a very low incidence of cigarette smoking (13.7%), and alcohol consumption (4.8%). As with blacks in the U.K. and the U.S.A., the commonest complications were cerebrovascular accidents and congestive cardiac failure. Most of the patients had moderately elevated blood pressures on the first visit, which fell significantly after 3 and 6 months of clinic attendance. Methyldopa and thiazides were the commonest drugs used, but a small pilot survey demonstrated that beta-blockers were effective. The high cost and poor availability of drugs contribute to poor compliance in these patients.
 ...
PMID:A blood pressure clinic in a developing country. 613 97

This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central alpha-adrenergic blood pressure regulating mechanisms. Fundamental principles Arterial baro- and chemoreceptor signals reach the nucleus of the tractus solitarius (NTS) via vagal and glossopharyngeal afferents. The NTS communicates with sympathetic preganglionic neurons in the spinal cord via centers and tracts in the medulla, pons, and hypothalamus that include an alpha-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-1 epinephrine cells of the medulla, B-1 and B-3 serotonin cells of the medulla, and A-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded by linked or single genes. New methods of purifying and locating alpha- and beta-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic alpha 2-receptors in a brain stem inhibitory network, which down-regulates these receptors. Alpha 1-receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. Alpha 2-receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although alpha-methylnorepinephrine is probably the principal metabolite of methyldopa, alpha-methylepinephrine and alpha-methyldopamine may also contribute. The site of action usually is identified as the NTS. Possible roles for the descending tracts were suggested. Clinical pharmacology Methyldopa, clonidine, guanfacine, and related drugs lower blood pressure principally by CNS mechanisms but peripheral actions may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:In summary: satellite symposium on central alpha-adrenergic blood pressure regulating mechanisms. 615 4

The effects on blood lipids and uric acid of six different antihypertensive drugs used alone, and of five different combinations of two antihypertensive drugs, are reported here. Prazosin significantly lowered serum low density lipoprotein and very low density lipoprotein (LDL + VLDL) cholesterol and total triglycerides while maintaining high density lipoprotein (HDL) levels. Atenolol lowered LDL + VLDL cholesterol slightly. Both pindolol and hydrochlorothiazide (HCTZ) were neutral, while oxprenolol increased total triglycerides. Propranolol lowered HDL cholesterol and increased total triglycerides and uric acid. The combination of prazosin plus pindolol has a direct favorable lipid profile, while the combination of propranolol plus HCTZ lowered HDL cholesterol and increased total triglycerides. The combination of propranolol plus prazosin lowered HDL cholesterol, but to a lesser degree than propranolol alone, which suggests that prazosin was not able to completely counteract the negative effects of propranolol on HDL. Methyldopa plus HCTZ, and HCTZ plus amiloride were neutral with regard to effects on blood lipids. It is suggested that the metabolic effects of antihypertensive drugs could be of special importance in the long-term treatment of mild hypertension.
 ...
PMID:Antihypertensive drugs and blood lipids: the Oslo study. 617 60

Trophic adrenergic influences may in part potentiate the pressure dependent development of structural cardiovascular changes in hypertension. Regression of such changes by antihypertensive treatment should therefore be most successful if adrenergic blocking drugs are used. In the present study spontaneously hypertensive rats (SHR) received either alpha-methyldopa, metoprolol, felodipine, a new vasodilating Ca2+-antagonist, or metoprolol and felodipine in combination for 10 weeks. Their left ventricles were weighed and resistance vessel design was analysed using a haemodynamic technique. Arterial pressure (MAP) was equally reduced by metoprolol and felodipine. Despite their different modes of action cardiovascular design was also equally affected. The combined regimen reduced average MAP more than either drug alone. It also caused more pronounced regression of cardiovascular structural changes. Methyldopa lowered MAP less than either metoprolol or felodipine and had only modest effects on cardiovascular design. Thus, the extent of MAP reduction, regardless of which therapeutic regimen is used to induce it, determines the extent of regression of structural cardiovascular changes during antihypertensive treatment.
 ...
PMID:Regression of structural cardiovascular changes by antihypertensive therapy in spontaneously hypertensive rats. 624 24


<< Previous 1 2 3 4 5 6 7 Next >>