Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrate usage worldwide is on the increase as the indications for therapy expand. Present indications for nitrate therapy include chronic stable angina pectoris, unstable angina pectoris, complications of acute myocardial infarction, and 'unloading' therapy for acute and chronic congestive heart failure. Nitrates are also being used in the operating suite by anaesthesiologists to control systolic blood pressure during various surgical procedures. New nitrate delivery systems have recently become available which provide considerable dosing flexibility, further increasing the interest in this group of compounds. The dominant action of nitrates is a direct effect on vascular smooth muscle, producing vasodilation of the veins and arteries. These drugs decrease myocardial work by lowering systolic blood pressure, systemic vascular resistance, and reducing intracardiac dimensions. In addition, nitrates have a potent effect on cardiac preload as a result of systemic venodilatation. There is also some evidence that nitrates exert direct effects on the coronary circulation (vasodilatation of coronary arteries and coronary collateral vessels, and direct atherosclerotic stenosis dilatation). These actions may play a role in relieving myocardial ischaemia. Adverse sequelae of nitrate therapy are well known and serious adverse reactions are uncommon. Headache and dizziness are the most frequent side effects. Nitrate tolerance is a definite problem - present evidence indicates that long acting formulations, high doses, or frequent dosing regimens are particularly likely to induce vascular tolerance to nitrates. Consequently, provision of a nitrate-free interval has taken on increasing significance as a strategy to avoid tolerance. Nitrate delivery systems are numerous. Although availability varies from country to country, in most countries there are a wide variety of formulations of glyceryl trinitrate (nitroglycerin) available, including sublingual and oral tablets, oral spray, topical ointment as well as discs or patches for transdermal administration, a transmucosal tablet and an intravenous formulation. Similar formulations of isosorbide dinitrate, except buccal tablets, are available in some countries. Isosorbide 5-mononitrate, a potent metabolite of isosorbide dinitrate, is achieving increasing popularity as an antianginal drug. Optimum nitrate therapy requires a good understanding of the properties of the various formulations, particularly onset and duration of action and propensity to induce tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glyceryl trinitrate (nitroglycerin) and the organic nitrates. Choosing the method of administration. 311 8

Isosorbide-5-mononitrate (IS-5-MN) 5, 10, 20, 30, 40 and 50 mg were administered orally to 2 healthy male volunteers. The pharmacological effect was determined using digital pulse plethysmography and the orthostatic tilting test, and at the same time side effects were monitored. The threshold of oral activity of IS-5-MN was found to be 5 mg. The maximum response was reached with doses of 20-30 mg. The duration of action of this dose was approximately 8 h. Higher doses did not lead to any further increase, but rather to a decrease in the pharmacological response, while the side-effects, such as headaches, dizziness and nausea, became more prominent. In a randomized, double-blind, three-way cross-over study in 11 female volunteers IS-5-MN 30 mg proved to be more potent with respect to pharmacological activity than sustained released ISDN 20 mg (isosorbide dinitrate), whereas there was no difference in side-effects. Thus, it can be estimated that IS-5-MN 20 mg is approximately equivalent to 20 mg sustained released ISDN. IS-5-MN is rapidly absorbed after oral administration and the maximum concentration in serum was reached 1.2 +/- 0.2 h after doses of 10 to 50 mg. The pharmacokinetics showed dose-linearity. The compound was eliminated with an average half life of 4.04 +/- 0.16 h, which is appropriate for a reasonably prolonged duration of action without the need for a sustained release formulation.
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PMID:First data on effects and pharmacokinetics of isosorbide-5-mononitrate in normal man. 725 Jan 75