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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twentysix women with pregnancy-induced hypertension have been randomly treated with either labetalol or Aldomet. A more satisfactory control of blood pressure was obtained with labetalol with minimal side-effects. After two weeks of treatment with labetalol renal function had significantly improved with a markedly lower incidence of proteinuria. More patients went into spontaneous labour following labetalol than following Aldomet; the Bishop score was also higher in this group. No adverse effects attributable to labetalol were noted in the baby either ante- or post-natally.
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PMID:Comparison of the alpha and beta blocking drug, labetalol, and methyl dopa in the treatment of moderate and severe pregnancy-induced hypertension. 742 66

Aromatic alpha-amino-alpha-methyl acids and alpha-hydrazino-alpha-methyl acids are known aromatic amino acid decarboxylase inhibitors. Specific derivatives such as 2-amino-2-methyl-3-(3,4- dihydroxyphenyl)propanoate, Aldomet, and 2-hydrazino-2-methyl-3-(3,4- dihydroxyphenyl)propanoate, Lodosyn, have been developed as therapeutic agents to treat hypertension and Parkinson's disease, respectively. We recently reported a method for the kinetic resolution of the racemic esters of such compounds using a crude preparation of a novel enzyme catalyst from the yeast Candida lipolytica (Yee, C.; Blythe, T.A., McNabb, T.J.; Walts, A.E. J. Org. Chem. 1992, 57, 3525-3527). Here we report the purification and initial characterization of the active enzyme component, an enzyme given the name Candida lipolytica ester hydrolase (CLEH). CLEH was purified to > 95% homogeneity by chromatography on Matrex Blue B resin. The enzyme was found to be a glycoprotein with M(r) = 80,000-300,000. In addition to esterolytic activity, the enzyme was found to catalyze the hydrolysis of amides, anilides and peptides. Sequence analysis of internal peptides of CLEH revealed striking homology to a number of enzymes belonging to the group of serine carboxypeptidases (E.C. 3.4.16.1). One peptide aligned with the canonical serine carboxypeptidase active site sequence, GESYAG. Based on the structural relationship of CLEH to serine carboxypeptidases, three representative serine carboxypeptidases were evaluated for their utility in resolving racemic alpha-tertiary ester substrates and compared with the activity of CLEH. All enzymes revealed similarly high activity and enantioselectivity towards the alpha-hydrazino-alpha-methyl ester precursor of the Parkinson-drug Carbidopa. However, differences in enantioselectivity were observed with other alpha-tertiary-substituted ester substrates. Serine carboxypeptidase-catalyzed ester resolutions thus offer a new route to many sterically hindered homochiral alpha-amino, alpha-hydrazino and alpha-hydroxy carboxylic acids.
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PMID:Enzymes for the resolution of alpha-tertiary-substituted carboxylic acid esters. 785 60

Hypertension in pregnancy remains a major cause of maternal and fetal morbidity and mortality. It is a late manifestation of a multifactorial, multisystem disease, initiated very early in pregnancy, the features of which suggest an inadequate maternal response to pregnancy. There is a genetic susceptibility to pre-eclampsia. Endothelial cell dysfunction in response to an unknown factor(s) may evoke some of the hormonal anomalies. In established severe disease there is volume contraction, reduced cardiac output, enhanced vascular reactivity, platelet exhaustion and disseminated intravascular coagulation in addition to the hypertension. Delivery is associated with resolution of the hypertension. Pharmacological treatment is most suitable for early-onset, severe disease when an attempt to delay delivery is indicated. Methyldopa or beta-blockers and/or vasodilators may be used. ACE inhibitors are contra-indicated. Low-dose aspirin may be useful in prophylaxis.
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PMID:Pre-eclampsia--the 'disease of theories'. 791 88

The LOMIR-MCT-IL study was designed to investigate the effects of different antihypertensive drugs on the quality of life (QoL) of men with mild-to-moderate hypertension. This report focuses on the subgroup of patients treated with the combination of the angiotensin converting enzyme (ACE) inhibitor captopril and the calcium antagonist isradipine. The LOMIR-MCT-IL was a double-blind multicenter, placebo-controlled, one-year follow-up study in which 368 hypertensive men, aged 40-65 years, were randomly allocated to receive either isradipine, methyldopa or placebo at three titration levels. If diastolic blood pressure (DBP) remained > 90 mmHg, captopril was added openly. The QoL evaluation introduced a qualitative self-structured subjective measure in addition to prestructured quantitative measures. The quality of life was assessed at baseline, after 6 months and at the end of the study. Methyldopa normalized DBP in 50% of patients when given as monotherapy and an additional 34% with the addition of captopril (84% total). With placebo, 36% normalized DBP and another 39% on addition of captopril (75% total) and, with isradipine, 64% normalized DBP and an additional 26% with added captopril (90% total). Assessment of QoL showed that both the placebo and the isradipine+captopril groups showed significant improvement in semantic memory after antihypertensive treatment. The isradipine+captopril group showed a clear tendency towards lower depression scores, better quality of sleep, better subjective evaluation of QoL and a more positive evaluation of personal life events in comparison to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does the combination of ACE inhibitor and calcium antagonist control hypertension and improve quality of life? The LOMIR-MCT-IL study experience. 820 97

Traditional centrally acting antihypertensives have been associated with a high incidence of adverse effects and are no longer recommended as first-line therapy. The newer imidazoline receptor agonists must overcome this reputation if they are to gain recognition as potential first-line agents for hypertension. Methyldopa, a centrally acting alpha(2)-agonist, is characterized by a number of serious adverse reactions that limit its use. Although unpredictable idiosyncratic or hypersensitivity reactions are uncommon, these include hepatitis, myocarditis, and hemolytic anaemia. Less serious problems such as abnormal liver function tests, positive Coombs test, drug-induced fever, and pancreatitis also occur. Central side effects include drowsiness, fatigue, lethargy, sedation, depression, psychotic reactions, nasal stuffiness, impotence, and exacerbation of Parkinsonism. In hypertensive men, methyldopa is less well tolerated than either captopril or propranolol, and up to 20% of patients discontinue therapy because of adverse effects. Clonidine acts primarily as an alpha(2)-agonist but also acts as an agonist at imidazoline receptors in the rostroventrolateral medulla. It is equipotent to most other antihypertensives but is considerably less well-tolerated in comparative trials. The principal adverse effects of clonidine are drowsiness, sedation, lethargy and dry mouth. Reserpine acts primarily by depleting central catecholamine neurotransmitter stores. It was very extensively used in early hypertension trials, but its central side effects of sedation, nasal stuffiness, and severe depression are now considered so undesirable that the drug is seldom prescribed. The imidazoline (I1) agonists moxonidine and rilmenidine act selectively and have very little central alpha(2)-agonist activity. In comparative studies against placebo and other reference antihypertensives, the only adverse effect consistently associated with these drugs was dry mouth (approximate placebo-corrected incidence 10%). Sedation was not pronounced. Withdrawal syndromes are complex pathophysiologic processes and occur with a variety of antihypertensive drugs. Cessation of therapy with clonidine and, to a lesser extent, methyldopa may result in a severe withdrawal syndrome characterized by restlessness, sweating, anxiety, tremor, palpitations, and headache. There may be a rapid rise in blood pressure, often with a true "rebound" to higher than pretreatment levels. Plasma and urinary catecholamine levels are increased, and fatalities have been reported. It is important to stress that such a syndrome has not been recorded, in animal or human studies, with either moxonidine or rilmenidine.
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PMID:Aspects of tolerability of centrally acting antihypertensive drugs. 887 99

QuestionQuite a few of my pregnant patients have hypertensive disorders. What is the threshold for treating hypertension during pregnancy? Which of the various antihypertensive agents are considered safe during pregnancy?AnswerPharmacologic therapy could benefit mother and baby when diastolic pressure exceeds 110 mm Hg. Preeclampsia must be followed closely. Methyldopa (eg, Aldomet) and hydralazine (eg, Apresoline) are still the drugs of choice during pregnancy, although the safety and efficacy of calcium channel blockers and Beta-blockers appear well established.
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PMID:Therapeutic approach to hypertension during pregnancy. 964 May 15

Stimulating cardiac beta 1-adrenoceptors with oxyfedrine causes dilatation of coronary vessels and positive inotropic effects on the myocardium. beta 1-adrenergic agonists increase coronary blood flow in nonstenotic and stenotic vessels. The main indication for the use of the phosphodiesterase inhibitors pamrinone, mirinone, enoximone and piroximone is acute treatment of severe congestive heart failure. Theophylline is indicated for the treatment of asthma, chronic obstructive pulmonary disease, apnea in preterm infants ans sleep apnea syndrome. Severe arterial occlusive disease associated with atherosclerosis can be beneficially affected by elcosanoids. These drugs must be administered parenterally and have a half-life of only a few minutes. Sublingual or buccal preparations of nitrates are the only prompt method (within 1 or 2 min) of terminating anginal pain, except for biting nifedipine capsules. The short half-life (about 2.5 min) of nitroglycerin (glyceryl trinitrate) makes long term therapy impossible. Tolerance is a problem encountered with longer-acting nitric oxide donors. Knowledge of the pharmacokinetic properties of vasodilating drugs can prevent a too sudden and severe blood pressure decrease in patients with chronic hypertension. In considering the administration of a second dose, or another drug, the time necessary for the initially administered drug to reach maximal efficacy should be taken into account. In hypertensive emergencies urapidil, sodium nitroprusside, nitroglycerin, hydralazine and phentolamine are the drugs of choice, with the addition of beta-blockers during catecholamine crisis or dissecting aortic aneurysm. Childhood hypertension is most often treated with angiotensin-converting enzyme (ACE) inhibitors or calcium antagonists, primarily nifedipine. Because of the teratogenic risk involved with ACE inhibitors, extreme caution must be exercised when prescribing for adolescent females. The propagation of health benefits to breast-fed infants, combined with more women delaying pregnancy until their fourth decade, has entailed an increase in the need for hypertension management during lactation. Low dose hydrochlorothiazide, propranolol, nifedipine and enalapril or captopril do not pose enough of a risk of preclude breastfeeding in this group. The most frequently used antihypertensive agents during pregnancy are methyldopa, labetalol and calcium channel antagonists. Methyldopa and beta-blockers are the drugs of choice for treating mild to moderate hypertension. Prazosin and hydralazine are used to treat moderate to severe hypertension and hydralazine, urapidil or labetalol are used to treat hypertensive emergencies. The use of overly aggressive antihypertensive therapy during pregnancy should be avoided so that adequate uteroplacental blood flow is maintained. Methyldopa is the only drug accepted for use during the first trimester of pregnancy.
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PMID:Clinical pharmacokinetics of vasodilators. Part II. 967 32

Hypertension is found among 1 to 6% of young women. Treatment aims to decrease cardiovascular risk, the magnitude of which is less dependent on the absolute level of blood pressure (BP) than on associated cardiovascular risk factors, hypertension-related target organ damage and/or concomitant disease. Lifestyle modifications are recommended for all hypertensive individuals. The threshold of BP at which antihypertensive therapy should be initiated is based on absolute cardiovascular risk. Most young women are at low risk and not in need of antihypertensive therapy. All antihypertensive agents appear to be equally efficacious; choice depends on personal preference, social circumstances and an agent's effect on cardiovascular risk factors, target organ damage and/or concomitant disease. Although most agents are appropriate for, and tolerated well by, young women, another consideration remains that of pregnancy, 50% of which are unplanned. A clinician must be aware of a woman's method of contraception and the potential of an antihypertensive agent to cause birth defects following inadvertent exposure in early pregnancy. Conversely, if an oral contraceptive is effective and well tolerated, but the woman's BP becomes mildly elevated, continuing the contraceptive and initiating antihypertensive treatment may not be contraindicated, especially if the ability to plan pregnancy is important (e.g. in type 1 diabetes mellitus). No commonly used antihypertensive is known to be teratogenic, although ACE inhibitors and angiotensin receptor antagonists should be discontinued, and any antihypertensive drugs should be continued in pregnancy only if anticipated benefits outweigh potential reproductive risk(s). The hypertensive disorders of pregnancy complicate 5 to 10% of pregnancies and are a leading cause of maternal and perinatal mortality and morbidity. Treatment aims to improve pregnancy outcome. There is consensus that severe maternal hypertension (systolic BP > or = 170mm Hg and/or diastolic BP > or = 110mm Hg) should be treated immediately to avoid maternal stroke, death and, possibly, eclampsia. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated: the risks of transient severe hypertension, antenatal hospitalisation, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by therapy, but intrauterine fetal growth may also be impaired, particularly by atenolol. Methyldopa and other beta-blockers have been used most extensively. Reporting bias and the uncertainty of outcomes as defined warrant cautious interpretation of these findings and preclude treatment recommendations.
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PMID:Treating hypertension in women of child-bearing age and during pregnancy. 1136 52

Fifty per cent of pregnancies are unplanned, and 1-6% of young women have pre-existing hypertension. However, no commonly used antihypertensive agent is known to be teratogenic. ACE inhibitors (and angiotensin-receptor antagonists) should be discontinued due to fetotoxicity. Five to 10% of pregnant women have hypertension, of which pre-existing hypertension is but one type. There is consensus that severe maternal hypertension (blood pressure >or=170/110 mmHg) should be treated to minimize the risk of acute cerebrovascular complications. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus that mild-to-moderate hypertension in pregnancy should be treated. Clinical trials indicate that transient severe hypertension, antenatal hospitalization, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by normalizing blood pressure, but intrauterine fetal growth restriction may be increased. Methodological problems with published trials warrant cautious interpretation of these findings. Methyldopa and beta-blockers have been used most extensively, although atenolol may impair fetal growth in particular and should be avoided.
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PMID:Drugs in pregnancy. Antihypertensives. 1180 May 27

Effective therapy (Rx) in primary hypertension (PH) for 50 years, has featured sympathetic nervous system (SNS) mechanisms. Ganglionic blockers and reserpine were pre-eminent in the 1940s (mydriasis, ileus, impotence, peptic ulcer). Guanethidine, and in the 1960s clonidine and methyldopa, were step II agents to thiazide Rx in the 1950s. Reserpine depletes brain (depression) and peripheral (PPH) noradrenaline (NA) storage sites, guanethidine depleted NA storage via blockade of reuptake. Venomotor sympathoplegia resulted in postural hypertension. An analogue, metaiodobenzyguandine is used in diagnosis and Rx of pheochromocytoma. Clonidine lowers both central and PPH neuronal NA release via both stimulation of alpha agonist adrenoreceptors (sedation) and specific imadazoline binding sites (IBS). Methyldopa lowers pressure via PPH induced NA release (retrograde ejaculation) and via alphamethyl NA on central alpha-2 receptors (depression). The alpha-2 and alpha-2 receptor antagonists (alphaRA) cause reflex tachycardia and first-dose hypotension. Recently a two-fold incidence of congestive heart failure after alphaRA in treated primary hypertensives question their role in PH. The beta RA, with or absent alphaRA, remain premier since the 1970s due to mortality benefit in systolic dysfunction and post myocardial infarction, certifying the role of the SNS in the pathogenesis and sequelae and Rx of PH. The future includes beta RA, specific IBS agents, angiotensin (AII) RA with avid presynaptic AII affinity and vasopeptidase inhibitiors that raise peptides and suppress SNS.
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PMID:Sympatholytic therapy in primary hypertension: a user friendly role for the future. 1198 8


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