Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety and tolerability of lacidipine was assessed in a volunteer population, and its pharmacodynamic and pharmacokinetic profiles evaluated. In normotensive subjects, single oral doses of 3-5 mg of lacidipine produced a dose-related fall in peripheral vascular resistance. This was accompanied by reflex-mediated increases in heart rate and cardiac output to maintain blood pressure. Adverse events were those typically related to the vasodilatory action of lacidipine, such as flushing and headache. A 4-mg dose of lacidipine elicited a cardiovascular response equivalent to that with 10 mg of nifedipine, given as a single oral dose. Lacidipine did not affect sinoatrial or atrioventricular conduction in the healthy subjects studied. Two specialized electrophysiologic studies in patients confirmed that lacidipine does not affect pacemaker tissue and that it exhibits relative selectivity for the vascular smooth muscle. Lacidipine is eliminated primarily by hepatic metabolism, and extensive first-pass loss occurs after oral dosing. Absolute bioavailability is less than 10%. The systemic availability of lacidipine was increased in healthy elderly subjects and in patients with impaired hepatic function, but not in patients with impaired renal function.
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PMID:Clinical pharmacology of lacidipine. 172 14

Lacidipine is an orally administered calcium channel blocker of the dihydropyridine class, which shows selectivity for vascular smooth muscle over cardiac tissue and has a long duration of action. In studies using ambulatory blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the morning reduced blood pressure over 24 hours, with the reductions being greater during the day than at night in some studies. 77 to 87% of patients with mild to moderate hypertension had their blood pressure controlled by treatment with lacidipine 2 to 8 mg/day for 1 to 4 months in dose-finding studies. When administered once daily, lacidipine 4 to 6 mg was equivalent in antihypertensive efficacy to hydrochlorothiazide 25 to 50 mg/day, atenolol 50 to 100 mg/day, and the prototype calcium channel blocker nifedipine 20 to 40 mg twice daily (sustained-release formulation). The adverse effects of lacidipine are those common to other dihydropyridine calcium channel blockers, and include headache, flushing, ankle oedema, dizziness and palpitations. The long term effects of lacidipine on cardiovascular morbidity and mortality, and possible additional clinical benefits in terms of its antiatherosclerotic effects, are under investigation; the outcome of these studies will be important in defining the future role of this agent in the treatment of hypertension. Thus, available evidence suggests lacidipine provides a further alternative to the dihydropyridine calcium channel blockers currently available for the treatment of essential hypertension.
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PMID:Lacidipine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of hypertension. 752 28

GUIDELINES ON DRUG SAFETY: Recent European Union draft guidelines for the safety evaluation of drugs intended for long-term use state that during drug development the safety profile of the new compound should be assessed over a period of time consistent with intended usage. This is in reasonable agreement with guidelines prepared by other regulatory authorities. CLINICAL DRUG DEVELOPMENT: Satisfactory preclinical data on a new compound are used to obtain authorization for human testing from the National Committees on Safety of Medicines. Clinical trials are performed in four phases, ranging from phase I studies performed on healthy volunteers (n = 20-50) to postmarketing (phase IV) studies. The latter are of great importance as they cover large patient populations (n = 2000 to > or = 10,000) and allow detection of rare adverse drug reactions. ADVERSE DRUG REACTIONS: Type B reactions are serious, unpredictable reactions to a drug that necessitate treatment withdrawal. Type A reactions are dose-dependent, and represent the majority of adverse reactions. They are often managed by dose reduction rather than drug withdrawal. ADVERSE REACTIONS TO ANTIHYPERTENSIVE AGENTS: Examples of type B adverse reactions to antihypertensives are the cutaneous and ocular reactions to practolol, and angioneurotic oedema associated with angiotensin converting enzyme inhibitors. Lacidipine, a second-generation calcium antagonist, is an example of a modern antihypertensive agent with a favourable safety profile. The adverse reactions associated with lacidipine are mild to moderate and of the A type, the major ones being those typical of calcium antagonists (headache, flushing and pedal oedema due to vasodilation.
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PMID:Assessing the safety profile of a new antihypertensive agent. 882 81