Peripheral sympatholytics

Drugs of this class are now rarely used, mainly due to the emergence of new, better tolerated drugs. Two drugs, guanethidine (Ismelin) and guanadrel (Gilorel) , however, are very effective and inhibit the activity of the sympathetic nervous system, blocking the release of norepinephrine from the secretory granules.

Guanethidine, reserpine, and rauwolfia alkaloids were widely used in the 1950s and 1960s to treat hypertension, demonstrating a good hypotensive effect, dose-dependent. Combinations of these drugs with diuretics were especially successful in antihypertensive treatment. However, the need to use large dosages, the frequency and severity of side effects (diarrhea, disorders of sexual function, nasal congestion, drowsiness, depression, orthostatic hypotension) have limited their use. Currently there are no studies on the use of these agents in patients with diabetes mellitus and arterial hypertension.

Central-adrenostimulators have an unusual mechanism of action. By stimulating central 2 receptors in the vasomotor centers of the brain, they increase the inhibitory activity of neurons and reduce sympathetic transmission from the central nervous system, as a result of which hemodynamic changes occur: a decrease in peripheral resistance, a slight decrease in cardiac output, a decrease in blood pressure. The drugs in this series include methyldopa (Aldomet, Dopegit), clonidine (Clomellin, Hemiton), guanfacine (Tenex, Estulic). These drugs are effective in 35% -50% of patients, but the rejection of therapy due to side effects occurs in 20% -30% of patients. Undesirable effects include drowsiness, sedation, dry mouth, disorders of sexual function; weakness, headaches, dizziness, depression.

Methyldopa can cause various autoimmune diseases; when used in 5% -10% of patients, liver damage occurs, accompanied by an increase in liver enzymes and hyperthermia; 35% -40% show a Coombs positive reaction.

Currently there is a form of clonidine for percutaneous administration in the form of drug-impregnated skin stickers, replaced once a week (provide a daily dose of 0.1, 0.2 or 0.3 mg). This form of the drug is as effective as oral ingestion, but it gives less side reactions. In 30% of patients, skin irritation occurs at the site of the stickers.

The use of drugs of this class practically gave way to new, better tolerated agents, but still in some situations possible indications are created for their use, for example, in patients with diabetes mellitus resistant to therapy with ACE inhibitors or BAR in combination with a diuretic .

1-blockers. Currently, three selective рен 1-blockers are used: doxazosin (Kardura), prazozin (Minipress), terazosin (Chitrin) . The action of these drugs is due to the blocking of postsynaptic 1 receptors in the smooth muscle vascular wall, which inhibits the capture of catecholamines in the vessel wall. Vasoconstriction stops and vasodilation occurs.

Although it was shown that  1-blockers reduce diastolic blood pressure as effectively as drugs of other groups, systolic blood pressure is not sufficiently reduced in their application. In addition, side effects, such as orthostatic hypotension, tachycardia, dizziness, disorders of the gastrointestinal tract, limit the use of  1-ad blocking agents as drugs of the 1st and even 2nd row.

These side effects are less pronounced in the long-acting drug doxazosin. Moreover, some studies have demonstrated that the use of doxazosin may have a beneficial effect on lipid levels, reducing cholesterol levels and increasing HDL to a greater extent than some other drugs. In addition, there is evidence that these drugs reduce plasma insulin levels and improve glucose tolerance. Due to these possible benefits,  1 – adrenergic blockers in combination with drugs of other groups can be used in patients with various metabolic disorders.

Direct vasodilators , hydralazine (Apresolin) and minoxidil (Loniten) , act directly on the smooth muscle vascular wall, and have been used to treat hypertension for many decades. As a result of the dilation of arterioles, peripheral resistance and blood pressure are reduced, baroreceptors are stimulated; heart rate and catecholamine release increases. This leads to sodium retention and an increase in OTC. Because of this, direct vasodilators can be used as antihypertensive agents only temporarily. Side effects: tachycardia, fluid retention, flushing, headaches, and, in the case of minoxidil, excessive hair growth on the face and body, also leave little room for using direct vasodilators as the main antihypertensive drugs. However, in the case of the ineffectiveness of all other drugs, in hypertensive crises or in malignant arterial hypertension,direct vasodilators have indications for use.

local_offerevent_note June 15, 2019

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