Nonselective receptor antagonist

Propranolol and other nonselective receptor antagonists inhibit the vasodilation caused by isoproterenol and augment the pressor response to Epi. This action is significant in patients with pheochromocytoma, in whom [ receptor antagonists should be used only after adequate a receptor blockade has been established. This sequence avoids uncompensated a receptor-mediated vasoconstriction caused by catecholamines secreted by the tumor. 

Phenylephrine (90) is a selective receptor agonist (+)-niguldipine (91) is a selective antagonist for the receptor. Pra2osin (92) and 5-methylurapidil (93) are nonselective a -receptor antagonists. CEC can differentiate receptors from the other receptors. Pra2osin has low and high affinity for and receptors, respectively. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Endothelins are a family of vasoactive peptides secreted by endothelial cells. The three major endothelin peptides are all composed of 21 amino acids. Endothelins are the most potent vasoconstrictors known. Contraction of vascular smooth muscle in response to endothelin is associated with an increase in intracellular calcium. Increases in endothelin levels have been reported in patients with vasospastic, hypoxic, and ischemic diseases. The two identified isoforms of endothelin receptors have differing affinity for the three endothelin peptides. Selective and nonselective endothelin receptor antagonists are in development for potential use in the treatment of hypertension and other disorders associated with increased vascular resistance. 

Atropine Nonselective competitive antagonist at all muscarinic receptors in CNS and periphery Blocks muscarinic excess at exocrine glands, heart, smooth muscle Mandatory antidote for severe cholinesterase inhibitor poisoning Intravenous infusion until antimuscarinic signs appear continue as long as necessary Toxicity Insignificant as long as AChE inhibition continues... 

Local anesthetic action, also known as "membrane-stabilizing" action, is a prominent effect of several 3 blockers (Table 10-2). This action is the result of typical local anesthetic blockade of sodium channels (see Chapter 26) and can be demonstrated experimentally in isolated neurons, heart muscle, and skeletal muscle membrane. However, it is unlikely that this effect is important after systemic administration of these drugs, since the concentration in plasma usually achieved by these routes is too low for the anesthetic effects to be evident. These membrane-stabilizing 3 blockers are not used topically on the eye, where local anesthesia of the cornea would be highly undesirable. Sotalol is a nonselective 3-receptor antagonist that lacks local anesthetic action but has marked class III antiarrhythmic effects, reflecting potassium channel blockade (see Chapter 14). 

Nadolol is noteworthy for its very long duration of action its spectrum of action is similar to that of timolol. Timolol is a nonselective agent with no local anesthetic activity. It has excellent ocular hypotensive effects when administered topically in the eye. Levobunolol (nonselective) and betaxolol (E -selective) are also used for topical ophthalmic application in glaucoma the latter drug may be less likely to induce bronchoconstriction than nonselective antagonists. Carteolol is a nonselective 13-receptor antagonist. 

Carvedilol, medroxalol, and bucindolol are nonselective 3-receptor antagonists with some capacity to block 04-adrenergic receptors. Carvedilol antagonizes the actions of catecholamines more potently at 3 receptors than at a. receptors. 

The endothelin system can be blocked with receptor antagonists and drugs that block endothelin-converting enzyme. Endothelin or ETB receptors can be blocked selectively, or both can be blocked with nonselective - antagonists. 

Bosentan is a nonselective receptor blocker. It is active orally, and blocks both the initial transient depressor (ETB) and the prolonged pressor ( ) responses to intravenous endothelin. Many orally active endothelin receptor antagonists with increased selectivity have been developed and are available for research use. Examples include the selective antagonists sitaxsentan and ambrisentan. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

When nonselective beta blockers are used, some antagonism of beta-2 receptors also occurs.2,31 The antagonism of beta-2 receptors on bronchiole smooth muscle often leads to some degree of bronchoconstric-tion and an increase in airway resistance. Although this event is usually not a problem in individuals with normal pulmonary function, patients with respiratory problems such as asthma, bronchitis, and emphysema may be adversely affected by nonselective beta antagonists. In these patients, one of the beta-1-selective drugs should be administered. 

Blockade of the 2 receptors in bronchial smooth muscle may lead to an increase in airway resistance, particularly in patients with asthma. Betai-receptor antagonists such as metoprolol or atenolol may have some advantage over nonselective antagonists when blockade of Bi receptors in the heart is desired and -receptor blockade is undesirable. However, no currently available i-selective antagonist is sufficiently specific to completely avoid interactions with 62 adrenoceptors. Consequently, these drugs should generally be avoided in patients with asthma. On the other hand, some patients with chronic obstructive pulmonary disease (COPD) may tolerate these drugs quite well. 

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