Sympathetic blocker

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

Increased antihypertensive and hypotensive effects with diuretics, sympathetic blockers. Inaeased serum potassium with potassium-sparing diuretics. Decreased antihypertensive effects with indomethacin. 

As we have had occasion to note more than a few times previously, the guanidine function forms the basis of a family of hypotensive agents active by reason of their activity as blockers of the peripheral sympathetic system. Condensation of tetra-hydroisoquinoline with the S-methyl ether of thiourea affords the antihypertensive drug debrisoquin (135). ... 

Compounds which act as antagonists at the receptors for beta sympathetic transmitters (beta blockers) have gained very wide acceptance as antihypertensive agents. It was found subsequent to their introduction that there are two populations of beta receptors the beta-1 receptors are richest in the cardiovascular system whereas beta-2 receptors are mostly found in the bronchi. Lack of receptor-type specificity led to bronchial spasm in some asthmatic individuals on ingestion of the earlier beta blockers. Much of the work outlined below had as its goal the preparation of agents which showed selectivity for beta-1 receptors. 

Hydralazine 4-8 hour Up to 30 minute 5-40 mg prn dosing Headache, tachycardia, lupus like syndrome, potential nephrotoxicity Often given with beta-blocker to counter reflex sympathetic drive, may increase ICP... 

This peripheral activity may be a rational basis for the use of systemic local anaesthetics in neuropathic states since ectopic activity in damaged nerves has been shown to be highly sensitive to systemic sodium channel blockers. This too is probably part of the basis for the analgesic effects of established effective anti-convulsants that block sodium channels such as carbamazepine, although central actions are important and may even predominate. The precise actions of excitability blockers therefore remains hazy as does any clear basis for the effectiveness of antidepressants and other adrenergic agents in the treatment of neuropathic pain as both central and peripheral actions, including sympathetic effects are possible. 

In randomized, controlled, clinical trials, calcium channel blockers were as effective as p-blockers at preventing ischemic symptoms. Calcium channel blockers are recommended as initial treatment in IHD when /3-blockers are contraindicated or not tolerated. In addition, CCBs may be used in combination with /3-blockers when initial treatment is unsuccessful. However, the combination of a (1-blocker with either verapamil or diltiazem should be used with extreme caution since all of these drugs decrease AV nodal conduction, increasing the risk for severe bradycardia or AV block when used together. If combination therapy is warranted, a long-acting dihydropyridine CCB is preferred. (3-Blockers will prevent reflex increases in sympathetic tone and heart rate with the use of calcium channel blockers with potent vasodilatory effects. 

Current data suggest little benefit on clinical outcomes beyond symptom relief for calcium channel blockers in the setting of ACS.43 Moreover, the use of first-generation shortacting dihydropyridines, such as nifedipine, should be avoided because they appear to worsen outcomes through their negative inotropic effects, induction of reflex sympathetic activation, tachycardia, and increased myocardial ischemia.43 Therefore, calcium channel blockers should be avoided in the acute management of MI unless there is a clear symptomatic need or a contraindication to p-blockers. 

Vasovagal syncope has traditionally been treated successfully with oral /L blockers (e.g., metoprolol) to inhibit the sympathetic surge that causes... 

Hirst Yes, I have. I have stimulated the sympathetic changes with physiological frequencies of stimulation, loaded the animals with benextramine, an irreversible a blocker, and I can see no changes in the neuronal responses although the responses to circulating catecholamines are abolished. 

The relevance of either the experimentally demonstrated central hypotensive action of the 3-blockers, or their ability to antagonise sympathetically mediated renin release remains to be proven. While it is still possible that the mechanism of the anti-hypertensive action of the 3-blocking drugs could contain both a central and a renin-inhibitary component, the clinical evidence would appear to rule against the possibility of either being a major component of the mode-of-action. 

Historically, the first effective pharmacologic agents for lowering the blood pressure were the ganglionic blockers. At the level of the ganglia, these compounds block both sympathetic and parasympathetic transmission. The decrease in parasympathetic function is responsible for urinary retention, for the failure to develop an erection in the male patient and for the paralytic ileus. 

The inhibition of sympathetic tone to the venous system (capacitance vessels) results in increased pooling of blood in the venous vascular bed with consequent decreased venous return to the heart and decreased cardiac output. This phenomenon is more pronounced in upright positions because of the effect of gravity. The hemodynamic effects of ganglionic blockers include decreases in cardiac output, renal blood flow, cerebral blood flow and orthostatic hypotension(20,21). 

Beta-adrenoceptor blockers block the sympathetic system antagonising the effect on the lungs, resulting in bronchoconstriction. Non-steroidal anti-inflammatory drugs inhibit prostaglandin synthesis, which may lead to bronchoconstriction. 

An anti-hypertensive sympathetic neurone blocker debrisoquine 27... 

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