Smooth muscle relaxants, direct

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

A special guanylate cyclase receptor can be found in the nitric oxide (NO) signaling pathway. The activation of the sequence of events in that pathway results in smooth muscle relaxation. This pathway is directly linked to other cascades by receiving a Ca2+ signal and utilizing calmodulin (CaM) as transmitter protein. 

Sildenafil was developed. However, there are different types of PDEs (nine are known today). As discussed previously, a potent drug has to be specific. Sildenafil inhibits PDE-5, which is absent in the kidney, although sildenafil s effect on smooth muscle relaxation was confirmed. The direction of the drug changed to treating angina instead, as sildenafil relaxes the vascular muscle of the heart. 

Pharmacology These agents are synthetic adrenocortical steroids with basic glucocorticoid actions and effects. Glucocorticoids may decrease number and activity of inflammatory cells, enhance effect of beta-adrenergic drugs on cyclic AMP production, inhibit bronchoconstrictor mechanisms, or produce direct smooth muscle relaxation. Inhaler use provides effective local steroid activity with minimal systemic effect. 

Nonselective antimuscarinic drugs have been employed in the therapy of peptic ulcers (see Chapter 40) because they can reduce gastric acid secretion they also have been used as adjunctive therapy in the treatment of irritable bowel syndrome. Antimuscarinic drugs can decrease the pain associated with postprandial spasm of intestinal smooth muscle by blocking contractile responses to ACh. Some of the agents used for this disorder have only antimuscarinic activity (e.g., propantheline), while other drugs have additional properties that contribute to their antispasmodic action. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic concentrations primarily have a direct smooth muscle relaxant effect with little antimuscarinic action. 

Direct vasodilators reduce pressure by dilating resistance vessels (arteries) by vascular smooth muscle relaxation (e.g., Ca + channel blockers such as verapamil (4.133) or nifedipine (5.151) vasodilators such as dihydralazine (5.152))... 

It has got antispasmodic with direct smooth muscle relaxant action. It is used in morning and motion sickness. 

A combination of phentolamine with the nonspecific smooth muscle relaxant papaverine, when injected directly into the penis, may cause erections in men with sexual dysfunction. Long-term administration may result in fibrotic reactions. Systemic absorption may lead to orthostatic hypotension priapism may require direct treatment with an -adrenoceptor agonist such as phenylephrine. Alternative therapies for erectile dysfunction include prostaglandins (see Chapter 18), sildenafil and other cGMP phosphodiesterase inhibitors (see Chapter 12), and apomorphine. 

Ethanol is a vasodilator, probably as a result of both CNS effects (depression of the vasomotor center) and direct smooth muscle relaxation caused by its metabolite, acetaldehyde. In cases of severe overdose, hypothermia—caused by vasodilation—may be marked in cold environments. Ethanol also relaxes the uterus and—before the introduction of more effective and safer uterine relaxants (eg, calcium channel antagonists)—was used intravenously for the suppression of premature labor. 

The general properties of the methylxanthines (theophylline, caffeine) are discussed elsewhere (see p. 194). Their mild diuretic action probably depends in part on smooth muscle relaxation in the afferent arteriolar bed increasing renal blood flow, and in part on a direct inhibitory effect on salt reabsorption in the proximal tubule. Their uses in medicine depend on other properties. 

Antispasmodics (see below) are given for abdominal pain, although there is little objective evidence for their efficacy from controlled clinical trials. The generation of evidence is complicated by the variable nature of IBS symptoms, the patients who suffer from them, and the high rate of placebo response in this condition. There are two main classes of antispasmodic, the antimuscarinic drugs and drugs which are direct smooth muscle relaxants. 

Alverine and peppermint oil also have direct smooth muscle relaxing activity. 

Vasodilators have a number of different mechanisms of action. Some are smooth muscle relaxants that act directly on the blood vessels, e.g. glyceryl trinitate, hydralazine, isosorbide dinitrate, pentaerythritol tetranitrate, sodium nitroprusside and other nitrite and nitrate drugs, which are thought to mimic the actions of the endogenous mediator nitric oxide, which relaxes smooth muscle through elevation of cGMP (see nitrergic stimulants). 

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