Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rilmenidine is an oxazoline derivative with antihypertensive activity which was developed to enhance the dissociation between the hypotensive and adverse effect profile of centrally acting agents. Experimental studies have indicated that rilmenidine is selective for both alpha 2-adrenoceptors (v alpha 1) and newly discovered nonadrenergic imidazoline receptors in the brain and in the periphery. In experimental studies, rilmenidine differs from clonidine in that it is more selective for imidazoline receptors than for alpha 2-adrenoceptors; at equihypotensive doses, rilmenidine causes less bradycardia and reduction in cardiac output, less sedation, and little or no antinociceptive action compared to clonidine. The hypotensive effects of rilmenidine are antagonised by idazoxan and yohimbine, but idazoxan (imidazoline structure) is six times more potent than yohimbine (a selective alpha 2-antagonist). In isolated renal proximal tubule cells, where imidazoline binding has also been shown, rilmenidine inhibits reabsorption of sodium. Clinical studies comparing 1 mg rilmenidine with placebo demonstrated significant reductions in blood pressure (BP) (61% rilmenidine v 23% placebo normalized to 160/90 mm Hg). The reduction in BP was not associated with classical alpha 2 side effects such as dry mouth or daytime drowsiness. Compared with clonidine (0.15 to 0.3 mg), equihypotensive doses of rilmenidine (1 to 2 mg) induced two to three times less dry mouth, daytime drowsiness, and constipation; no orthostatic hypotension was reported. Methyldopa (0.5 to 1 mg) v rilmenidine (1 to 2 mg) indicated a comparable reduction of BP with significantly less weakness, drowsiness, orthostatic dizziness, and dry mouth on rilmenidine; there was no evidence of the "clonidine withdrawal syndrome" on drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distinctive features of rilmenidine possibly related to its selectivity for imidazoline receptors. 135 Jul 32

1 Methyldopa has a short plasma half-life, but longer duration of antihypertensive effect. A single bedtime dose of methyldopa has been recommended to improve compliance and decrease side effects. 2 This double-blind crossover study was designed to determine the duration of antihypertensive effect of methyldopa by comparing hourly supine and standing blood pressures, throughout the day during placebo, single morning dose, and single evening dose methyldopa therapy in 10 patients. The major side effects, drowsiness and dry mouth were assessed by visual analogue scale. Exercise blood pressures were measured 6, 12, 18 and 24 h after the dose. 3 The antihypertensive effect of methyldopa peaked after 6-9 h and declined thereafter with a half-life of approximately 10 h. Little antihypertensive effect remained 24-26 h after the dose. The time course of the reduction in blood pressure during exercise and of the major side effects paralleled the antihypertensive effects. 4 The results suggest that the duration of antihypertensive effect of methyldopa is long enough to permit twice daily dosing, but that single daily dosing cannot be recommended for most patients. The study illustrates the importance of knowing the time of the last methyldopa dose when assessing blood pressure measurements in patients taking the drug.
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PMID:Duration of effect of single daily dose methyldopa therapy. 709 15

A case of methyldopa overdose, confirmed by quantitative blood analysis, is presented. The clinical manifestations were coma, hypothermia, hypotension, bradycardia, and dry mouth. This combination of clinical findings, previously considered characteristic of phenothiazines or tricyclic antidepressants poisoning, should also raise the suspicion of methyldopa overdose. Methyldopa is a commonly used antihypertensive agent. Surprisingly, reports on overdose are exceedingly rare [1, 2]. We have recently treated a case of methyldopa overdose in which the presenting signs resembled those of psychotropic drug poisoning.
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PMID:Methyldopa poisoning. 717 95

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