Sympatholytics 3-Blockers

P-Sympatholytics are antagonists of norepiphephrine and epinephrine at p-adrenoceptors they lack affinity for a-receptors. 

P-Blockers also serve to lower cardiac rate (sinus tachycardia, p. 134) and elevated blood pressure due to high cardiac output (p. 312). The mechanism underlying their antihypertensive action via reduction of peripheral resistance is unclear. 

Applied topically to the eye, p-blockers are used in the management of glaucoma they lower production of aqueous humor without affecting its drainage. 

Undesired effects. The hazards of treatment with p-blockers become apparent particularly when continuous activation of p-receptors is needed in order to maintain the function of an organ. 

Congestive heart failure In myocardial insufficiency, the heart depends on a tonic sympathetic drive to maintain adequate cardiac output. Sympathetic activation gives rise to an increase in heart rate and systolic muscle tension, enabling cardiac output to be restored to a level comparable to that in a healthy subject. When sympathetic drive is eliminated during p-receptor blockade, stroke volume and cardiac rate decline, a latent myocardial insufficiency is unmasked, and overt insufficiency is exacerbated (A). 

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Nevertheless, this method was successfully applied by Gulyaeva et al. for the log P and log D determination of 15 P-sympatholytic drugs [56]. Another study by Welerowicz and Buszewski compared the HpophiHcity values of P-blockers obtained with a column made of a monoHthic-silica Cjg with a conventional porous silica particles Cjg as reference material [27]. A modified method was used for evaluating logP with two main differences (i) logfeg was considered rather than retention times, and (ii) benzene and butyl-benzene were used as calibration compounds. 

The basic structure shared by most 3-sympatholytics is the side chain of 3-sympathomimetics (cf isoproterenol with the p-blockers propranolol, pindolol, atenolol). As a rule, this basic structure is linked to an aromatic nucleus by a methylene and oxygen bridge. The side chain C-atom bearing the hydroxyl group forms the chiral center. With some exceptions (e.g., timolol, penbuto-lol), all p-sympatholytics are brought as racemates into the market (p. 62). 

Some p-sympatholytics possess higher affinity for cardiac Pi-receptors than for P2-receptors and thus display cardioselectivity (e.g., metoprolol, ace-butolol, bisoprolol). None of these blockers is sufficiently selective to per-Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Antihypertensive drugs can be divided into eight classes based on the mechanism of action diuretics, )3-adrenoblockers, centrally acting sympatholytics, peripherally acting sympatholytics, calcium channel blockers, myotropic hypotensive drugs, angiotensin-con-verting enzyme inhibitors, and calcium channel activators. 

To circumvent problems, encourage patient compliance, avoid excessive doses, avoid combining sympatholytics and -blockers, and maintain antihypertensive medication in surgical patients. When discontinuing medication, taper the dose slowly, one drug at a time use special caution in patients with coronary artery or cerebrovascular disease. 

Central-acting sympatholytics (e.g., clonidine and methyldopa) Peripheral-acting sympatholytics (e.g., guanadrel) p-blockers Thiazides Anticholinergics Antidepressants... 

The antiarrythmic drug amiodarone inhibits reserpine binding in a concentration-dependent manner and has a sympatholytic, anti-adrenergic effect in the heart, inhibiting the uptake of norepinephrine (Haikerwal et al., 1999). Blockers of VMAT and L-type calcium channels have also been reported to exert reciprocal inhibitory actions (Mahata et al., 1996). 

The chemical structure of p-blockers also determines their pharmacokinetic properties. Except for hydrophilic representatives (atenolol), p-sympatholytics are completely absorbed from the intestines and subsequently undergo presystemic elimination to a major extent (A). 

From the influence of the autonomic nervous system it follows that all sympatholytic or sympathomimetic and parasympatholytic or parasympathomimetic drugs can produce corresponding effects on cardiac performance. These possibilities are exploited therapeutically for instance, p-blockers for suppressing excessive sympathetic drive (p. 96) ipratropium for treating sinus bradycardia (p. 108). An unwanted activation of the sympathetic system can result from anxiety, pain, and other emotional stress. In these cases, the heart can be protected from harmful stimulation by psychopharmaceuticals such as benzodiazepines (diazepam and others important in myocardial infarction). 

Synonyms Parasympatholytics Cholinergic blockers Sympatholytics Antispasmodics... 

The parasympathetic branch of the autonomic nervous system (see 15.1 The Nervous System) depresses a response using adrenergic blockers (sympatholytics) that block the norepinephrine response at the adrenergic receptor sites (see Table 15.2). 

Diuretic with beta-blocker, added calcium blocker, ACE inhibitor or alpha blocker, or centrally acting sympatholytic... 

Centrally Acting Sympatholytics (adrenergic blockers) clonidine HC1 (Catapres), methyldopa (Aldomet)... 

Adrenergic Neuron Blockers (peripherally acting sympatholytics) Guanethidine monosulfate (Ismelin), reserpine (Serpasil)... 

Calcium-entry blocker Central sympatholytic Angiotensin-converting enzyme inhibitor... 

Blockers, Clonidine, Methyldopa Sinus bradycardia, AV block Sympatholytic Isoproterenol Temporary pacing ... 

MDL 899 (26) is a direct acting arteriolar vasodilator in man, but coadministration of a beta-blocker is necessary to prevent reflex-related side effects. A clinical study with cadralazlne (ISF 2469, 27) shows this compound similar to hydralazine with fewer side effects. Two other vasodilators, budralazine (28) and pinacidil (29) may owe some of their activity to calcium channel blockade.Anthranilamlde (WIN 48,049) lowers blood pressure in monkeys without accompanying tachycardia. This compound acts primarily as a direct vasodilator but also has sympatholytic and dopaminergic activities. Compounds and 32 also lower blood pres-... 

Step 2 Diuretic with beta blocker, sympatholytics... 

If blood pressure does not decrease, the patient is given a diuretic with a beta-blocker or a second drug is added such as a calcium chaimel blocker, ACE inhibitor, alpha blocker, or centrally acting sympatholytic. 

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