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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The antihypertensive effect of a new vasodilating drug, pinacidil, was compared with prazosin in a randomized, open study in general practice including 131 patients with a sitting diastolic blood pressure (DBP) between 100-115 mmHg. At inclusion 108 patients were untreated and the remaining patients were on treatment with thiazide diuretics and/or beta-blockers. The aim was to reduce the sitting DBP to less than or equal to 95 mmHg, which was achieved in 85% of the patients treated with pinacidil and in 77% of the patients treated with prazosin (NS). In the responding patients the reductions were (mean +/- SD) 16 +/- 7 mmHg (p less than 0.001) and 13 +/- 6 mmHg (p less than 0.001) in the pinacidil group (n = 60) and the prazosin group (n = 46), respectively (p less than 0.10). During 5 months of maintenance therapy no statistically significant differences in blood pressures between the two treatment groups were present. Side-effects were typical of vasodilator therapy, i.e. headache, dizziness, tachycardia and edema, leading to discontinuation of therapy in 10 patients in each treatment group. Heart rate (HR) was increased with pinacidil and unchanged with prazosin. Edema was frequently seen with pinacidil and dizziness with prazosin. Because of edema a thiazide diuretic was given to nine patients in the pinacidil group and two patients in the prazosin group. No clinically significant changes in ECG and biochemical variables were observed. In conclusion, the study has demonstrated that pinacidil is as effective an antihypertensive agent as prazosin. Pinacidil may be used as monotherapy. However, the study suggests that pinacidil should be used as add-on therapy to thiazide diuretics.
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PMID:The antihypertensive effect of pinacidil versus prazosin in mild to moderate hypertensive patients seen in general practice. 318 83

Forty-three patients with mild essential hypertension were randomized into two double-blind studies: pinacidil vs. placebo or pinacidil vs. hydralazine. Pinacidil (62 +/- 18 mg/day) decreased office systolic and diastolic blood pressures from 145 to 137 mm Hg and from 98 to 89 mm Hg, respectively, after 6 weeks of therapy. Similarly, hydralazine (128 +/- 28 mg/day) reduced supine systolic blood pressure from 140 to 134 mm Hg and supine diastolic blood pressure from 93 mm Hg to 84 mm Hg. Significant tachycardia was not noted with either drug. Ambulatory blood pressure was monitored for 24 h during the placebo-washout and efficacy phases with both pinacidil and hydralazine. Mean 24-h blood pressure was 128 systolic and 81 diastolic with pinacidil and 121 systolic and 76 diastolic with hydralazine. Reduction in awake hypertensive diastolic blood pressure was significant for both pinacidil and hydralazine. Normal sleep diastolic blood pressure was not reduced by pinacidil but was reduced by hydralazine. Side-effects with both drugs included edema, headache, and palpitations. These data demonstrate that pinacidil is as effective an antihypertensive agent as hydralazine.
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PMID:Antihypertensive efficacy of pinacidil--automatic ambulatory blood pressure monitoring. 380 13

Pinacidil, a new cyanoguanidine derivative, is an antihypertensive agent with arteriolar vasodilating properties, which acts on precapillary resistance vessels. A trial was carried out in 30 patients with essential hypertension WHO I-II. The treatment period was divided into three phases. Hydrochlorothiazide (HCTZ) and amiloride were administered for 4 weeks in Phase 1 and supine and standing blood pressure decreased significantly. During Phase 2 pinacidil was added to HCTZ/amiloride for the following 3 months. A further significant reduction in blood pressure was obtained. In the next period of treatment (Phase 3) patients were divided into two groups. For 1 month Group A (15 patients) received pinacidil alone and Group B (15 patients) received HCTZ/amiloride. Conventional laboratory blood tests in all patients remained unchanged during treatment. Reported side effects during Phase 2 were headache (2 patients), dizziness (3 patients), palpitations (2 patients) and ankle oedema (2 patients). Plasma renin activity was slightly increased at the end both of Phases 1 and 2. Plasma catecholamines were increased but not significantly at the end of Phase 2 as compared to Phase 1. The results indicate that pinacidil is effective in lowering blood pressure in mild to moderate essential hypertension.
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PMID:Effect of pinacidil on blood pressure, plasma catecholamines and plasma renin activity in essential hypertension. 389 69

Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or beta-receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell by 44/25 mmHg and 37/24 mmHg respectively over the study period of 12 weeks. Side-effects such as dizziness, headache, facial flushing and mild oedema were experienced by 10 patients during the study, all of which were mild and transient and did not require withdrawal from pinacidil therapy. Pinacidil is an effective and well tolerated agent in the treatment of essential hypertension.
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PMID:Pinacidil, a new vasodilator, in the treatment of mild to moderate essential hypertension. 400 40

Pinacidil is a new and potent vasodilator, which has recently been used in the treatment of various forms of hypertension. In this study pharmacokinetic parameters were determined following administration of intravenous (0.2 mg/kg) and capsule (12.5 mg) formulations of pinacidil to twelve healthy volunteers. The serum half-life (t1/2) and volume of distribution (Vd) of pinacidil were 2.04 +/- 0.40 h and 1.4 +/- 0.4 l/kg respectively, while the elimination rate constant (k el) was 0.34 +/- 0.07 h-1. The mean bioavailability of pinacidil (capsule formulation) was 57% +/- 16 S.D. Mild side-effects such as dizziness, headache and fatigue were noted in two volunteers following intravenous administration of pinacidil, while no side-effects were reported with the oral formulation.
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PMID:Pharmacokinetics and bioavailability of pinacidil capsules in human volunteers. 400 51