Alpha-blocking drugs effects

Alpha-receptor-blocking drugs do not seem to be effective in the treatment of peripheral vascular occlusive disease characterized by morphologic changes that limit flow in the vessels. Occasionally, individuals with Raynaud s phenomenon and other conditions involving excessive reversible vasospasm in the peripheral circulation do benefit from prazosin or phenoxybenzamine, although calcium channel blockers may be preferable for most patients. 

Noncompetitive antagonists cause a nonparallel shift to the right and can be reversed only partially by increasing the dose of the agonist drug. Such antagonists appear to decrease both the potency and the efficacy of agonists. One example is phenoxybenzamine, which irreversibly blocks the effects of NE at alpha receptors by formation of a covalent bond. 

D. Toxicity and Interactions Sedation is common, especially with diphenhydramine, doxylamine, and promethazine. It is much less common with second-generation agents, which do not enter the CNS readily. Antimuscarinic effects such as dry mouth and blurred vision occur with some first-generation drugs in some patients. Alpha-blocking actions may cause orthostatic hypotension. 

Positive inotropic and chronotropic effects of catecholamines are not blocked by alpha blockers, but these drugs can block catecholamine induced cardiac arrhythmias. 

It is not clear, however, exactly how these drugs inhibit neurons involved in the polysynaptic pathways. There is preliminary evidence that one of these compounds (cyclobenzaprine) might block serotonin receptors on spinal interneurons, thereby decreasing the excitatory influence of serotonin on alpha motor neuron activity.50,55 Although this effect has been attributed to cyclobenzaprine in animals (rats), the effect of this drug and other muscle relaxants in humans remains to be determined. 

Labetalol [Normodyne, Trandate). Labetalol is a nonselective beta blocker. This drug appears to have some alpha-1-selective blocking effects. Labetalol is used primarily in the management of hypertension and, while usually given orally, may be injected intravenously in emergency hypertensive situations. 

Alpha-adrenergic antagonists are used primarily as antihypertensive drugs because of their ability to block vascular alpha-1 receptors. Beta-adrenergic antagonists (beta blockers) are administered primarily for their inhibitory effects on myocardial function and are used in the prevention and treatment of hypertension, angina pectoris, arrhythmias, and myocardial reinfarction. Many of the drugs introduced in this chapter are discussed further in chapters that deal with the specific clinical conditions (e.g., hypertension, asthma, and other disorders). 

Cilostazol is a PDE3 inhibitor and also is a drug with multiple mechanisms of action (23,24), some of which are directly platelet-related, and others of which exert their effects indirectly via endothelial cells (Figs, 4 and 5), As a PDE inhibitor, it increases the concentration of cyclic nucleotides within platelets and inhibits platelet aggregation in response to shear forces (via ADP) and a variety of agonists. Like other inhibitors of platelet activation, it blocks the expression and release of P-selectin, a key adhesion molecule on the membrane of platelet alpha granules that externalizes with activation, and plays an important role in the interactions between platelets, endothelial cells, and leukocytes, The effect of cilostazol on P-selectin expression appears to be additive to those of aspirin and clopidogrel (25). 

Prazosin (see structure in Figure 12.2), the prototypic drug in this class, decreases peripheral vascular resistance in arterioles and veins by blocking alpha receptors on vascular smooth muscle. It does not decrease cardiac output. Because of this effect, patients taking prazosin are more prone ( 50 percent) to postural hypotension, particularly following the first dose. In some cases, the hypotension is so severe that the patient may lose consciousness. In an attempt to compensate, the baroreceptors may produce an accompanying tachycardia. 

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