Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dilevalol, the RR-stereoisomer of labetalol, is a non-cardioselective beta-adrenoceptor antagonist with substantial partial beta 2-agonist and negligible alpha 1-blocking activity. Reduction in blood pressure during dilevalol administration is associated with peripheral vasodilatation, and heart rate remains essentially unchanged. Following oral administration, dilevalol is completely absorbed. Once-daily administration is possible, due to a long elimination half-life. Large well-controlled trials reveal that dilevalol is equivalent in antihypertensive efficacy to metoprolol, the ACE inhibitors captopril and enalapril, and the calcium antagonist nifedipine. Smaller noncomparative and comparative trials demonstrate the blood pressure-lowering effects of dilevalol and suggest an efficacy at least equivalent to that of the 'pure' beta-blockers atenolol and propranolol and the alpha 1-blockers urapidil and doxazosin. Dilevalol appears to be well tolerated, the most frequent adverse effects being dizziness, headache and diarrhoea in only about 7% of patients each. Unlike alpha 1-blockers and labetalol, dilevalol is not commonly associated with orthostatic hypotension. Thus, data suggest that dilevalol, with its distinctive pharmacological profile, is likely to be a useful addition to the options currently available for treating patients with mild to moderate essential hypertension.
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PMID:Dilevalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension. 218 2

The efficacy and safety of enalapril and its effects on the quality of life were evaluated in 1017 Puerto Rican patients with uncomplicated mild to moderate essential hypertension. Enalapril was administered for 4 weeks in an open label, noncomparative study. Initially, patients received enalapril 5 mg and the dosage was titrated upwards, according to response, to a maximum of 20 mg/day. The goal of therapy was to achieve a diastolic blood pressure (DBP) less than 90 mm Hg. The study included 468 male and 545 female patients (mean age 52.6 +/- 11.9 years). A subgroup of 294 elderly patients was also evaluated (mean age 65.9 +/- 6.1 years). Mean blood pressure decreased from 157/99 mm Hg to 138/84 mm Hg (p less than 0.0001) in 966 patients who received enalapril as monotherapy. Mean blood pressure decreased from 164/99 mm Hg to 143/85 mm Hg (p less than 0.0001) in the elderly patients. After 4 weeks of enalapril monotherapy, 67% of the patients had a DBP less than 90 mm Hg. Enalapril was very well tolerated. Headache and dizziness were the most frequently reported side effects. Among the patients who completed a quality of life questionnaire, more than 70% reported feeling the same or better and less than 2% reported feeling worse after enalapril therapy. In conclusion, enalapril seems to be an excellent alternative as initial therapy in young and elderly Puerto Rican hypertensive patients.
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PMID:A cooperative study to evaluate the efficacy and safety of enalapril in Puerto Rican patients with mild to moderate hypertension. 218 27

Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs.
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PMID:Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 219 68

Recently there has been extensive development of orally active angiotensin converting enzyme (ACE) inhibitors in addition to those already marketed, for example, captopril, enalapril, lisinopril and ramipril. It was initially thought that ACE inhibitors were likely to be most useful as antihypertensive agents in conditions in which circulating renin and angiotensin II were elevated. However, it is now clear that they can also lower arterial pressure when plasma renin is not high. In addition, they have beneficial effects in cardiac failure. Thus, captopril, enalapril, lisinopril and ramipril can be used in the treatment of mild to moderate hypertension either alone or in conjunction with diuretics or calcium antagonists. Broadly speaking, efficacy appears to be similar to that of beta-blockers or diuretics. Unfortunately, however, there are no long term studies comparing one ACE inhibitor with another or with other classes of antihypertensive agents. Furthermore, there are no prognostic studies which show that use of ACE inhibitors reduces morbidity or mortality in hypertension. Many new ACE inhibitors are undergoing clinical assessment, including alacepril, cilazapril, fosenopril, perindopril, quinapril and ramipril. The drugs vary, in that some exist in the active form whereas others are prodrugs which are converted to the active agent following absorption. In addition they each possess one of several ligands, for example, carboxyl, phosphinyl or sulfhydryl groups, and so vary in their affinity for ACE. Although many of these agents are renally excreted, a small number are metabolised via the liver (e.g. quinapril and spirapril) and this may prove advantageous in the presence of renal impairment. In common with captopril and enalapril, the new ACE inhibitors inhibit the renin-angiotensin system and initial results suggest that they are effective in lowering blood pressure in essential hypertension. Furthermore, they reduce systemic vascular resistance in the absence of a reflex tachycardia. There are a number of adverse effects which are attributable to the pharmacological mechanism of the ACE inhibitors as a group; these include hypotension, particularly in patients with high renin levels, prior diuretic use, renal impairment or in the elderly. Additional adverse effects may relate to chemical structure. The high incidence of adverse effects noted in early studies related to excess dosage and to the presence of a sulfhydryl group, which the more recently developed ACE inhibitors lack. The adverse effects most commonly reported with established and new ACE inhibitors include headache and fatigue, cough, skin rashes, hypotension and diarrhoea. As a group, ACE inhibitors have an acceptable but not negligible adverse effect burden.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin converting enzyme inhibitors and moderate hypertension. 222 19

We assessed the efficacy of long-acting nifedipine as monotherapy in 52 patients with mild to moderate essential hypertension in a randomized, controlled crossover study. Good blood pressure control was achieved in 34 of 40 patients (85%) receiving nifedipine (mean daily dose, 52 mg in 2 divided doses) compared with 23 of 40 patients (58%) receiving metoprolol (mean daily dose, 155 mg in 2 divided doses). After treatment for 4 weeks, the mean blood pressures with nifedipine (149.7 +/- 16.6/88.7 +/- 11.1 mm of mercury) and metoprolol administration (163.9 +/- 23.3/94.2 +/- 10.2 mm of mercury) were significantly lower than with placebo (176.7 +/- 17.3/100.9 +/- 7.1 mm of mercury) (P less than .05). The mean systolic pressure during nifedipine treatment was 14.2 mm of mercury lower (95% confidence interval [CI], 3.9 to 24.5 mm of mercury) and mean diastolic pressure 5.5 mm of mercury (95% CI, 0.3 to 10.7 mm of mercury) lower than with metoprolol therapy. Both drugs were reasonably well tolerated, and intolerance requiring withdrawal was encountered in 3 of 45 (7%) patients receiving nifedipine, compared with 1 of 45 (2%) of those taking metoprolol and placebo, respectively. Adverse effects of nifedipine, most of which were transient, included palpitations, headache, facial flushing, and ankle edema. Long-acting nifedipine is a promising agent when given alone for mild to moderate hypertension and can be safely administered in clinical practice.
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PMID:Long-acting nifedipine versus metoprolol as monotherapy for essential hypertension. A randomized, controlled crossover study. 240 30

In this study of 10 patients with essential hypertension inadequately controlled by standard beta-blocker-diuretic combination therapy, the addition of 5 mg of MDL-899, a peripheral arteriolar vasodilator, resulted in significant reductions in blood pressure, both supine and standing, which was maximal 4-8 h after dosing, with no additional orthostatic component. There were associated small rises in heart rate but no evidence of significant activation of the sympathetic or renin-angiotensin systems. Six patients continued for 4 weeks receiving MDL-899 twice daily with significant improvement in their blood pressure control--from a mean of 182/95 to 146/77 mm Hg (supine) and from 161/93 to 138/79 mm Hg (erect). These six patients experienced no significant side effects, but four patients were unable to proceed with the study as a result of adverse effects, particularly headache, following the first few doses. It seems likely that these side effects are dose related. In a combined drug regimen, MDL-899 is an effective vasodilator drug that significantly improved the blood pressure control of patients with essential hypertension.
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PMID:Clinical evaluation of the vasodilator MDL-899 in patients with essential hypertension. 241 6

Nicardipine, a new calcium antagonist, was tested in a 14-week double-blind trial including 15 outpatients with uncomplicated essential hypertension. They were randomly assigned to nicardipine (20-30 mg three times daily) or placebo as first-step treatment. When necessary but always after a minimum of 4 weeks, pindolol (15 mg/day) was combined with nicardipine or placebo. At the end of step 1 (85 +/- 6 days with nicardipine vs. 58 +/- 6 days with placebo, p less than 0.01), nicardipine induced larger drops in supine systolic and diastolic blood pressure (SBP and DBP) than the placebo (21 +/- 2.5 vs 1.4 +/- 3 mm Hg, p less than 0.001, and 13 +/- 2 vs. 3.5 +/- 1.5 mm Hg, p less than 0.001, respectively). In the nicardipine group (n = 57), 53% of patients had controlled blood pressure (SBP less than 160 mm Hg and DBP less than 95 mm Hg) versus 17% in the placebo group (n = 47), p less than 0.001. There was no significant correlation between the decrease in blood pressure and the age of patients. The most common side effects in the nicardipine group were flushes (12%), headache (8%), ankle edema (5%), and asthenia (4%). When blood pressure was not brought under control and pindolol was prescribed as the second-step treatment, the nicardipine group (n = 52) displayed larger drops in SBP and DBP than the placebo group (n = 40) (27 +/- 5 vs. 15 +/- 3 mm Hg, p less than 0.01, and 18 +/- 1 vs. 9 +/- 2 mm Hg, p less than 0.001, respectively). These results show that a calcium antagonist is useful for first-step treatment of hypertension.
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PMID:First-step treatment of mild to moderate uncomplicated essential hypertension by a new calcium antagonist: nicardipine. 241 2

Thirty-two adult Nigerians with mild-to-moderate essential hypertension were included in a double-blind placebo-controlled trial matching nifedipine 20 mg twice daily with placebo for 6 weeks. Nifedipine caused very significant reductions of both systolic and diastolic blood pressures in all patients. Blood pressure fell from a mean of 181.3 (SE 3.9)/114.7 (SE 2.4) to 122.8 (SE 1.9)/79.4 (SE 1.6). Mean arterial pressure fell from a mean of 136.75 (SE -2.2) to 94.19 (SE -1.39). Polyuria was a common side effect in six of the 16 patients who received nifedipine. One additional patient developed transient occipital headache. Nifedipine monotherapy would appear to be an effective first-line drug in the management of essential hypertension in adult blacks.
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PMID:Monotherapy with nifedipine for essential hypertension in adult blacks. 242 59

In the Swiss Ketanserin Study the antihypertensive efficacy and tolerability of ketanserin (given in 20 or 40 mg doses twice daily) was investigated, after a placebo run-in phase, as monotherapy (n = 68) as well as in combination with either atenolol (100 mg/day) (n = 30) or the potassium-sparing diuretic hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day) (n = 26) in 124 patients with essential hypertension, aged 41 to 82 years. With the addition of ketanserin, diastolic blood pressure fell by 8 +/- 8, 8 +/- 8, and 7 +/- 9 (+/- SD) mm Hg, respectively (p less than 0.05 for all) in the three treatment groups; heart rate remained unchanged or fell slightly. Ketanserin had no effect on body weight, or biochemical variables, including total serum cholesterol and triglycerides, with the exception of a minor increase in apolipoprotein B. Using a patient self-assessment questionnaire (30 items), the addition of ketanserin was associated with a reduction of most of the symptoms encountered in the placebo phase, including sleep disturbances, general feeling of weakness, headaches, nervousness, and fatigue, but there was a tendency toward increases in stuffy nose and dry mouth. In patients older than 60 years, the antihypertensive efficacy of ketanserin was greater, with 59% achieving a diastolic pressure less than or equal to 95 mm Hg versus 45% in the younger patients. This age trend also emerged when ketanserin was combined with either atenolol or the diuretic.
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PMID:Antihypertensive efficacy of ketanserin alone or in combination with a beta-blocker or a diuretic: the Swiss Ketanserin Study. 244 58

From a hemodynamic point of view, the calcium antagonists represent an interesting way of treating hypertension, because they reduce total peripheral resistance without compromising cardiac output. Blood flow is also maintained during muscular exercise. Verapamil and diltiazem induce slight reduction in heart rate, but this is compensated by increase in stroke volume. Verapamil and diltiazem also prolong atrioventricular conduction time, in contrast to the dihydropyridines. Most clinical data are available for verapamil, diltiazem, and nifedipine. In patients with mild-to-moderate hypertension, these compounds seem as effective as diuretics and beta-blockers. They do not induce disturbances in glucose metabolism, serum uric acid, or serum potassium, and unwanted disturbances in blood lipids have not been described. The dihydropyridines may safely be combined with beta-blockers, but the combination of either verapamil or diltiazem with a beta-blocker should be avoided (because of the high risk of bradycardia). The calcium antagonists seem particularly useful in patients with the combination of hypertension and angina pectoris or peripheral vascular diseases or chronic obstructive lung diseases or diabetes. They are also effective in hypertensive crises. They may also be tried as a first line drug in patients with mild and moderate essential hypertension, particularly when diuretics or beta-blockers are contraindicated. Temporary side effects due to vasodilatation (headache, flushing, and palpitations) are seen frequently, particularly on the dihydropyridines. Edema is the most frequent serious side effect of the dihydropyridines, and constipation is most common with verapamil. At this point, few long-term data are available and it is not known whether the calcium antagonists will give better or worse results, with respect to morbidity and mortality, than the beta-blockers, diuretics, or other more recent antihypertensive agents.
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PMID:Clinical use of calcium antagonists in hypertension: update 1986. 245 35


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