Adrenergic blockade

Only non-selective p-blockers reduce bleeding complications in patients with known varices. Blockade of P, receptors reduces cardiac output and splanchnic blood flow. 02-Adrenergic blockade prevents p2-receptor-mediated splanchnic vasodilation while allowing unopposed a-adrenergic effects this enhances vasoconstriction of both the systemic and splanchnic vascular beds. The combination of P, and P2 effects makes the non-selective p-blockers preferable to car-dioselective agents in treating portal hypertension.1,36,41... 

Thiadiazoles have proven of some utility as aromatic nuclei for medicinal agents. For example, the previous volume detailed the preparation of a series of "azolamide" diuretic agents based on this class of heterocycle. It is thus of note that the 1,2,5-thiadiazole ring provides the nucleus for a clinically useful agent for treatment of hypertension which operates by an entirely different mechanism, p-adrenergic blockade. In its preparation, reaction of the amide-nitrile 211 with sulfur monochloride leads directly to the substituted thiadiazole 212. ... 

Quinazolines containing an electron-rich carbocyclic ring have been associated with smooth muscle relaxant activity. The mechanism of action (phosphodiesterase inhibition, a- adrenergic blockade) and organ selectivity (bronchi, vascular smooth muscle) vary greatly with substitution on the heterocyclic ring. 

The answer is c. (Hardman, pp 233—235.) The chief danger of therapy with p-adrenergie blocking agents, such as nadolol and propranolol, is associated with the blockade itself, p-adrenergic blockade results in an increase in airway resistance that can be fatal in asthmatic patients. Hypersensitivity reactions such as rash, fever, and purpura are rare and necessitate discontinuation of therapy... 

Tolerance to this effect usually occurs within 2 to 3 months. Reducing the dose or changing to an antipsychotic with less a-adrenergic blockade may also help. 

Amitriptyline, doxepin, and nortriptyline are effective, but side effects include anticholinergic effects, adrenergic blockade, and cardiac conduction prolongation. 

Trazodone, 25 to 100 mg, is often used for insomnia induced by selective serotonin reuptake inhibitors or bupropion. Side effects include serotonin syndrome (when used with other serotonergic drugs), oversedation, a-adrenergic blockade, dizziness, and rarely priapism. 

Yancy, C.W., et al., "Race and the Response to Adrenergic Blockade with Carvedilol in Patients with Chronic Heart Failure," N. Engl.. Med., 344, 1358-1365 (2001). 

In a study of the mechanism whereby BordeteUa pertussis vaccine increased acute ozone toxicity in rats, Thompson ascribed the effects to /3-adrenergic blockade, and not to an immune-mediated response. It was further noted that both atropine and reserpine reduced mortality, whidi suggested that the acute lethal effects of ozone were due to shock and circulatory collapse, rather than pulmonary edema. 

Pharmacology Bretylium tosylate inhibits norepinephrine release by depressing adrenergic nerve terminal excitability, inducing a chemical sympathectomy-like state. Bretylium blocks the release of norepinephrine in response to neuron stimulation. Peripheral adrenergic blockade causes orthostatic hypotension but has less effect on supine blood pressure. It has a positive inotropic effect on the myocardium. Pharmacokinetics Peak plasma concentration and peak hypotensive effects are seen within 1 hour of IM administration. However, suppression of premature ventricular beats is not maximal until 6 to 9 hours after dosing, when mean plasma concentration declines to less than 50% of peak level. Antifibrillatory effects occur within minutes of an IV injection. Suppression of ventricular tachycardia and other ventricular arrhythmias develops more slowly, usually 20 minutes to 2 hours after parenteral administration. 

Diabetes/Hypoglycemia -adrenergic blockade may blunt premonitory signs and symptoms (eg, tachycardia, blood pressure changes) of acute hypoglycemia. Nonselective -blockers may potentiate insulin-induced hypoglycemia. 

Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel JP (1998) Clinical effects of P-adrenergic blockade in chronic heart failure a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation 98 1184-1191 Liggett SB (1999) Molecular and genetic basis of p2 a

receptor function. J Allergy Clin Immunol 104 S42-S46... 

Altered homeostasis in older persons can lead to important and common adverse drug effects the less robust homeostatic milieu may be stressed by drugs, causing adverse effects. Examples include orthostatic hypotension due to antihypertensives and other agents that cause a-adrenergic blockade (e.g. terazosin, doxazosin, tricyclic antidepressants and phenothiazines) in those with barorecep-tor dysfunction. Diuretics can cause hyponatraemia or hypokalaemia in older patients, whereas ACE inhibitors and NSAIDs can cause hyperkalaemia. 

Alvarez C, Blade C, Cartana J. 1993. 2"Adrenergic blockade prevents hyperglycemia and hepatic glutathione depletion in nickel-injected rats. Toxicol Appl Pharm 121 112-117. 

The effects of P-adrenergic blockade on the consolidation of traumatic memories has been an area of special interest for the treatment of posttraumatic stress disorder (PTSD), and recently the first randomized controlled study on the effects of propranolol in the prevention of PTSD was published. Pittmann and coworkers (2002) could demonstrate that propranolol may reduce PTSD... 

Mechanism of Action An antihypertensive that produces long-lasting noncompetitive alpha-adrenergic blockade of postganglionic synapses in exocrine glands and smooth muscles. Relaxes urethra and increases opening of the bladder. Therapeutic Effect Controls hypertension. 

Currenfly available (3-blockers appear to be equally effective cardioselective or combined a- and (3-adrenergic blockade are less likely to cause undesirable effects and may be preferred... 

Antipsychotic agents may have several cardiovascular effects. Medication-induced hypotension is generally more problematic with lower-potency neuroleptics than with other antipsychotics and appears to be mediated through tti-adrenergic blockade. Besides increases in heart rate that may be the result of hypotension, antipsychotics with appreciable anticholinergic effects (see Clinical Implications, below) can lead to tachycardia (Gutgesell et ah, 1999). 

The antiarrhythmic action is due to cardiac adrenergic blockade. It decreases the slope of phase 4 depolarization and automaticity in SA node, Purkinje fibres and other ectopic foci. It also prolongs the effective refractory period of AV node and impedes AV conduction. ECG shows prolonged PR interval. It is useful in sinus tachycardia, atrial and nodal extrasystoles. It is also useful in sympathetically mediated arrhythmias in pheochromocytoma and halothane anaesthesia. 

Gold LA, Merimee TJ, Misbin RI. Propranolol and hypoglycemia the effects of beta-adrenergic blockade on glucose and alanine levels during fasting. J Clin Pharmacol 1980 20(l) 50-8. 

Frishman WH, Kowalski M, Nagnur S, Warshafsky S, Sica D. Cardiovascular considerations in using topical, oral, and intravenous drugs for the treatment of glaucoma and ocular hypertension focus on beta-adrenergic blockade. Heart Dis 2001 3(6) 386-97. 

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