Vasodilator, coadministration

Alcohol can affect the metabolism of trichloroethylene. This is noted in both toxicity and pharmacokinetic studies. In toxicity studies, simultaneous exposure to ethanol and trichloroethylene increased the concentration of trichloroethylene in the blood and breath of male volunteers (Stewart et al. 1974c). These people also showed "degreaser s flush"—a transient vasodilation of superficial skin vessels. In rats, depressant effects in the central nervous system are exacerbated by coadministration of ethanol and trichloroethylene (Utesch et al. 1981). 

Angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors not only cause vasodilation (1 TPR), but also inhibit the aldosterone response to net sodium loss. Normally, aldosterone, which enhances reabsorption of sodium in the kidney, would oppose diuretic-induced sodium loss. Therefore, coadministration of ACE inhibitors would enhance the efficacy of diuretic drugs. 

For severely hypertensive patients, clonidine has been used in combination with a diuretic, a vasodilator, and a -blocker. Some care must be taken, however, because the coadministration of clonidine and a p-blocker may cause excessive sedation. Clonidine is especially useful in patients with renal failure, since its duration of... 

Nitrovasodilators see Chapter 31) produce vasodilation by NO-dependent elevation of cychc GMP in vascular smooth muscle. The pharmacologic effects of sildenafil, tadalafil, and vardenafil result from inhibition of the type 5 cyclic nucleotide phosphodiesterase (PDE5) that hydrolyzes cyclic GMP to 5 GMP in the vasculature. Thus, coadministration of an NO donor e.g., nitroglycerin) with a PDE5 inhibitor can cause potentially catastrophic hypotension. 

MDL 899 (26) is a direct acting arteriolar vasodilator in man, but coadministration of a beta-blocker is necessary to prevent reflex-related side effects. A clinical study with cadralazlne (ISF 2469, 27) shows this compound similar to hydralazine with fewer side effects. Two other vasodilators, budralazine (28) and pinacidil (29) may owe some of their activity to calcium channel blockade.Anthranilamlde (WIN 48,049) lowers blood pressure in monkeys without accompanying tachycardia. This compound acts primarily as a direct vasodilator but also has sympatholytic and dopaminergic activities. Compounds and 32 also lower blood pres-... 

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