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

The incidence of both systolic and diastolic hypertension is increased in elderly patients, therefore antihypertensive drugs are commonly used in this population. In addition to changes in blood pressure, the aging process also causes numerous changes in other physiological parameters, resulting in altered pharmacokinetic and pharmacodynamic responses to the drugs. The dosage regimens for thiazide diuretics and amiloride must be individually titrated in the elderly patient, since the elimination of these agents decreases concurrently with decreased renal function, as indicated by compromised creatinine clearance. The initial doses of the calcium antagonists should be decreased in elderly patients, since representative compounds from all 3 chemically heterogeneous classes have been shown to have decreased clearance in these patients which appears to be primarily due to the status of hepatic function in the patient. However, with verapamil, the dosage should be further decreased in association with compromised renal function. The dosage of the angiotensin converting enzyme (ACE) inhibitors should be adjusted according to renal function rather than age. Lisinopril, which is primarily eliminated unchanged, is usually given in lower doses in the elderly, and doses of both captopril and enalapril may need to be reduced, depending on renal function. While there is no need to adjust the dosage regimen for the alpha-adrenoceptor blocking drugs (prazosin, terazosin), caution should be used with the beta-adrenergic blockers, particularly the hydrophilic agents, since they are renally eliminated. Labetalol may be a suitable alternative beta-blocker for the elderly patient, since its pharmacodynamic properties of decreased systemic vascular resistance without changes in heart rate or stroke volume are preferential for the elderly patient, and its pharmacokinetics are relatively unchanged in this population. Drugs that act primarily through the central nervous system, such as clonidine, methyldopa and guanfacine, require smaller doses in the presence of renal dysfunction. In contrast, guanabenz is metabolised primarily by the liver, so it would appear to be useful in elderly patients with renal dysfunction despite the lack of studies in this population. Guanadrel, an adrenergic neuron blocking drug, also requires a dosage reduction in patients with impaired renal function. In addition to the pharmacokinetic changes that occur in the elderly patient, pharmacodynamic changes may also be anticipated due to receptor modifications. Older patients have a decrease in beta-receptor sensitivity, while alpha-receptor sensitivity does not change. When designing the dosage regimen for a senior patient with hypertension, the combination of all these variables must be considered.
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PMID:Antihypertensive therapy in the aged patient. Clinical pharmacokinetic considerations. 168 70

Guanadrel sulphate is an orally active peripheral sympathetic inhibitor (adrenergic neuron-blocking drug). In comparative studies, guanadrel was comparable in efficacy with guanethidine or methyldopa in mild to moderately severe hypertension, although generally it caused fewer central nervous system side effects than methyldopa and less orthostatic dizziness and diarrhoea than guanethidine. However, its efficacy in patients whose blood pressure remains inadequately controlled by other drugs (except diuretics alone) has yet to be adequately demonstrated. Guanadrel has a rapid onset of action and a half-life of about 10 hours, thus dose titration can be achieved more rapidly than with guanethidine, and twice daily administration is appropriate. Generally, guanadrel has been well tolerated, withdrawal of treatment due to adverse effects seldom being necessary. Thus, guanadrel appears to be a suitable alternative to methyldopa for the treatment of mild to moderately severe hypertension not controlled adequately by diuretics alone.
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PMID:Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension. 389 42

In a two-year study of 547 hypertensive patients receiving diuretics, the addition of guanadrel sulfate or methyldopa reduced elevated blood pressure to a similar degree and provided good control in 70% of the patients. Guanadrel-treated patients experienced less frequent and less severe drowsiness than methyldopa-treated patients. The frequency of morning orthostatic faintness was low and similar in both treatment groups. Guanadrel produced no tissue toxicity. Guanadrel sulfate, a postganglionic sympathetic inhibitor, is nearly free of central nervous system side effects and is recommended over methyldopa for step 2 therapy when diuretics alone fail to control mild or moderate hypertension.
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PMID:Guanadrel sulfate compared with methyldopa for mild and moderate hypertension. 676 33

Guanadrel sulfate, a new adrenergic neuron inhibitor similar to guanethidine sulfate, was tested on 199 outpatients by 11 investigators. The patients had mild, moderate, or severe hypertension as determined by diastolic blood pressures of 95 to 105, 106 to 114, and 115 to 120 mm Hg, respectively. Guanadrel was found to be an effective antihypertensive agent for all levels of hypertension. Since guanadrel has a short onset of action and a short offset of action, which prevents many of the side effects of guanathidine, the dosage could be adjusted rapidly and safely. At low doses side effects are infrequent. There was no organ toxicity and no CNS effect. Guanadrel should be an effective step II or step III drug for treatment of hypertension.
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PMID:Guanadrel. A new antihypertensive drug. 720 75