Clonidine in the treatment of arterial hypertension. Diuretics in the treatment of hypertension
The drugs of predominantly central action of the clonidine group (hemiton, clopheline) are widely used for the treatment of arterial hypertension. They act on the brain and through adrenoreactive systems. In the initial phase of the effect, central action predominates with heart rate reduction, fall of MI, sometimes with rise of PS. Then stimulation of alpha-adrenoreceptors causes vasodilation. There is a marked inhibitory effect on CNS, sleep deepens, BP decreases. Because of these qualities, the drugs are liked by the patients, especially by those who take them at night.
When administered intravenously or sublingually, clonidine rapidly lowers BP, very useful in crises. At the same time, rapid BP lowering is associated with a drop in cardiac output. At the same time, clonidine has a number of undesirable side effects. When taken repeatedly during the day, it causes drowsiness, decreased ability to work, lethargy, and depression. After using the drug for several hours, sharp dryness in the mouth is observed. It may cause orthostatic hypotension. Due to renin activation, diuresis decreases in patients.
Clonidine causes hypoglycemia, which should be considered in diabetes mellitus and brain disorders. Particularly unfavorable is the phenomenon of "ricochet" in the form of a sharp rise in BP upon drug withdrawal. It should also be taken into account that the period of dose effect is shortened during prolonged use of clonidine. The result is that the patients start to have crises, forcing them to increase sharply the frequency of drug intake up to 6-8 times a day. We recommend to use it sublingually and intravenously only in crises. Stopping the drug after prolonged use may cause complications.
A group of drugs of purely peripheral action (hydralazine) is used to treat arterial hypertension. However, their use in moderate doses as monotherapy is insufficient, in large doses - causes significant side effects often accompanied by the development of autoimmune reactions. The drugs are used in combination with other medications - reserpine, methyldopa. In the presence of severe angina, hydrolazine is dangerous, because it causes, in connection with coronarodilatation, the "stealing" syndrome. No negative metabolic effects of the drug have been observed.
The group of first-line antihypertensive agents today includes diuretics. The most effective of them for long-term treatment are thiazide diuretics of moderate power. They include hypothiazide, hygroton (oxodolin), clopamide (brinaldix).
The hypotensive effect of diuretics is of a complex nature. At the beginning, their use leads to an increased excretion through the kidneys.of water and sodium ions, which results in a drop in the volume of extracellular fluid and MI. This is an immediate effect that sets in quickly. At this time, at high doses (more than 55 mg of hypothiazide per day), hypotensive reactions, orthostatic insufficiency, and tachycardia may be observed. In addition to decreased BP and MI, a drop in blood calcium and sodium is noted. Subsequently (if there is no overdose), ME and mineral composition of blood normalize, and BP steadily decreases.
In this main phase of the hypotensive effect, the main effect of diuretics also affects the state of cellular metabolism, especially smooth muscle cells. Their calcium (Ca++) and sodium (Na+) content decreases. Such shifts lead to decreased sensitivity to angiotensin II, to norepinephrine, reduced intensity of synthesis of the "actomyosin + calcium" complex, without which myocyte contraction is impossible. The onset of vasodilation is promoted by a simultaneous decrease in prostaglandin synthesis. Thus, diuretics lead to a steady decrease of peripheral vascular resistance due to vasodilation.
Patients with low and normal plasma renin levels (so-called "volume-dependent" forms of AH) are particularly sensitive to diuretic treatment. If the blood renin level cannot be investigated in the clinic, these patients are recognized by the sensitivity to the sodium content of the food, as well as by the effectiveness of diuretic treatment. Diuretics have their own significant side effects. Decreased tone of not only arteries but also veins can lead to orthostatic hypotension even when treated with moderate doses. Of the entire group of diuretics, only brinaldix does not have this effect. The most well-known side effect in the clinic is the development of hypokalemia, which leads to a number of disorders - general weakness, seizures, gastric-intestinal disorders, arrhythmias. Therefore, during treatment with diuretics it is necessary to compensate for potassium losses. In addition, prolonged use of diuretics reveals a tendency to hyponatremia and increasing levels of uric acid and low-density lipoproteins in blood.
Diuretics also contribute to hyperglycemia, making it difficult to treat diabetic patients.
Author: Arkady Lvovich Vertkin, Doctor of Medicine, Professor