Abstract: Pharmacotherapy for hypertension. Rational pharmacotherapy of arterial hypertension Verapamil causes a decrease in lithium levels

Yu.A. Bunin
Russian Medical Academy of Postgraduate Education, Moscow

Classification, main reasons for development
and general principles of treatment of hypertensive crises
Despite intensive study of arterial hypertension (AH) and the presence of a number of national and international recommendations for its treatment, it is often difficult for practicing physicians of various specialties to decide when and how to begin treatment of patients with a significant increase in blood pressure, because there is no consensus on the issue about what kind of increase in blood pressure is a condition requiring emergency medical care. In addition, in Russia there is still no number of effective antihypertensive drugs for parenteral and oral use.
In international clinical practice, situations associated with severe hypertension (blood pressure from 180/110 mm Hg and above) are divided into three groups:
1) emergency conditions (hypertensive emergencies);
2) hypertensive urgencies;
3) stable, asymptomatic (little symptomatic) uncontrolled severe hypertension.
Emergency and emergency conditions are usually the result of a hypertensive crisis.
Emergency conditions in most cases include:
rapidly progressing or malignant hypertension;
diseases of the central nervous system:
hypertensive encephalopathy;
hemorrhagic stroke;
subarachnoid hemorrhage;
atherothrombotic cerebral infarction with very high hypertension;
diseases of the cardiovascular system:
acute aortic dissection;
acute left ventricular failure;
acute myocardial infarction or unstable angina;
kidney diseases:
acute glomerulonephritis;
renal crises due to collagenosis;
severe arterial hypertension after kidney transplantation;
increased concentration of catecholamines:
hypertensive crises with pheochromocytoma;
hypertensive crises (“rebound”) after sudden cessation of antihypertensive drugs;
the use of sympathomimetic drugs;
food or drug interactions with monoamine oxidase inhibitors*;
neurological disorders (autonomic dysfunction) in Guillain-Barre syndrome or after spinal cord injury;
preeclampsia/eclampsia;
surgical interventions:
severe arterial hypertension in patients requiring urgent surgery;
postoperative arterial hypertension;
postoperative bleeding in the area of ​​the vascular suture;
condition after coronary bypass surgery;
severe body burns;
severe nosebleeds.
A sudden, usually significant, increase in blood pressure (often systolic blood pressure (SBP) more than 220-230 mm Hg and/or diastolic blood pressure (DBP) more than 120-130 mm Hg) is accompanied by acute damage to target organs: cardiac -vascular system, brain, kidneys, eyes. This complicated hypertensive crisis is quite rare and requires a rapid but controlled reduction in blood pressure to a safe level (not necessarily to normal values), which is usually achieved by intravenous administration of drugs. Patients should be immediately hospitalized in specialized emergency departments that have trained personnel and modern equipment for dosed intravenous administration of drugs and dynamic, including invasive, monitoring of hemodynamics and the condition of target organs. The primary goal of treatment for most of them is to reduce mean blood pressure (MAP) by no more than 25% over a period of several minutes to one to two hours, depending on the patient's condition. You can then continue to lower your blood pressure to approximately 160/100 mmHg. Art. over the next two to six hours. An excessive drop in blood pressure should be avoided, as this can cause ischemia or even infarction of the target organ.
The term “urgent condition” (hypertensive urgency) is used for severe hypertension (according to some authors, not always a crisis course), which does not lead to rapid damage to target organs. If a hypertensive crisis is diagnosed in these patients, then it should be classified as an “uncomplicated” form. From a practical point of view, this means that lowering blood pressure can not be carried out as quickly as in a hypertensive emergency, but over several hours or one or two days and often using oral medications. It is likely that sometimes, when the risk of complications is high, treatment of emergency conditions should begin in the hospital (emergency department) and then continue on an outpatient basis.
Shayne P.H. and Pitts S.R. propose to include in the group of emergency conditions patients with a significant increase in blood pressure (diastolic blood pressure (DBP) more than 115-120 mm Hg) and a high risk of rapid progression of target organ damage, but without the development of acute damage. In their opinion, this group should primarily include patients who already have a history of target organ disease: incoming cerebrovascular accident or stroke, acute coronary syndrome, coronary artery disease, congestive heart failure, renal dysfunction, etc. These authors also classify high blood pressure in pregnant women, not accompanied by preeclampsia, as hypertensive urgency. We submit the opinion of Shayne P.H. and Pitts S.R. quite specific and worthy of attention from the point of view of its practical use.
Thus, the first two groups of conditions (hypertensive emergencies and hypertensive urgencies) require rapid intervention, while severe but stable and asymptomatic arterial hypertension requires timely (according to some authors, within a week) routine examination and selection of effective antihypertensive therapy.
Hypertensive crisis, considered as a condition characterized by a sudden, usually significant rise in blood pressure, which is accompanied by damage to vital organs or poses a real threat of damage to them, is the main clinical situation requiring urgent antihypertensive therapy. However, the need for emergency medical care in patients with arterial hypertension arises not only during its crisis, and the blood pressure level is not considered as the main criterion for diagnosing emergency conditions. The main reasons for the development of hypertensive crises are:
sudden increase in blood pressure in patients with chronic arterial hypertension;
sudden withdrawal of certain antihypertensive drugs;
parenchymal kidney diseases (acute glomerulonephritis, collagenosis);
renovascular arterial hypertension (atherosclerosis of the renal arteries, fibromuscular dysplasia, etc.);
pheochromocytoma, renin-secreting tumor, primary hyperaldosteronism (rare);
the use of tricyclic antidepressants (amitriptyline, clomipramine, imipramine, etc.), cocaine, amphetamines, sympathomimetics, cyclosporine, erythropoietins;
consumption of foods containing tyramine while using MAO inhibitors; taking glucocorticoids, non-steroidal anti-inflammatory drugs;
preeclampsia, eclampsia;
traumatic brain injury, ischemic stroke, brain tumor.
Hypertensive crises are more often recorded in elderly patients. Complicated hypertensive crises develop in less than 1-2% of patients. About 500 thousand such cases are registered annually in the USA. In most of them, the cause of hypertensive crises is ineffective treatment of essential hypertension (hypertension). However, according to some data, more than 20% of these patients have symptomatic (secondary) arterial hypertension. Among them, parenchymal kidney diseases, renovascular hypertension (most often (2/3 of all cases) is based on atherosclerosis of the renal arteries) and pheochromocytoma predominate, and primary aldosteronism (Conn's syndrome) is rare. Hypertensive crises may be caused by rapid discontinuation of antihypertensive medications (especially beta-blockers and central a-adrenergic agonists, such as clonidine), use of certain medications, or drug use.
Complaints, anamnesis, physical examination, supported by a number of laboratory and instrumental studies, determine the tactics of managing patients with acute hypertension syndrome (the need for hospitalization, the rate of blood pressure decrease, the choice and method of administration of an antihypertensive drug, etc.). The key to their successful treatment is differentiation between complicated and uncomplicated hypertensive crisis, identifying and, if possible, eliminating the cause of the hypertensive crisis and/or determining adequate treatment for the underlying disease that led to its development.
Physical examination should be aimed directly at looking for signs of target organ damage. Blood pressure should be measured in both arms (a significant difference in it may indicate, in particular, dissection of the aortic aneurysm) while lying and standing (if possible). The cardiovascular examination focuses primarily on identifying symptoms of heart failure (shortness of breath, wheezing in the lungs, galloping rhythm, etc.). A neurological examination determines the presence of disturbances of consciousness, cerebral or focal symptoms. Ophthalmoscopy allows you to detect changes in the fundus (hemorrhage, exudate, swelling of the optic nerve nipple, etc.).
Registration of an ECG, a general blood test, a study of the concentration of creatinine, urea in the blood plasma and a urine test are carried out in all patients with a hypertensive crisis. At the same time, chest radiography, echocardiography, CT, MRI are performed according to indications. In most cases, these studies are carried out simultaneously with the initiation of antihypertensive treatment.

Basic antihypertensive drugs
used to treat hypertensive crises
A fairly large number of drugs (parenteral and oral) (Tables 1 and 2) are used to treat hypertensive crises. The main requirements for them are: rapid onset of action and rapid manifestation of the maximum effect (preference is given to short-acting drugs), the ability to titrate the dose over a wide range, and a low frequency of severe side effects. If the cause of a hypertensive crisis is unknown, then empirical therapy is carried out, and in some cases specific treatment is used (acute coronary syndrome, pheochromocytoma, eclampsia, etc.). In the absence of hypertensive drugs for the treatment of hypertensive crises listed in table. 1, IV forms of other drugs can be used: calcium antagonists (verapamil, diltiazem, etc.), beta-blockers (for example, propranolol: IV bolus 2.5-10 mg over 3-5 minutes; IV infusion 3 mg/h). At the same time, the prescription of diuretics for hypertensive crises should not be routine, but should be carried out only for special indications (for example, pulmonary edema).
Sodium nitroprusside, which is an active arterial and venous nitrovasodilator, remains one of the main drugs for the relief of complicated hypertensive crises. When administered intravenously, it begins to act within a few seconds, and its effect disappears within three to five minutes after stopping the drug, which allows for good control of the decrease in blood pressure and minimizes the risk of hypotension.
The use of nitroglycerin is preferable to sodium nitroprusside in patients with arterial hypertension and coronary artery disease (unstable angina, coronary artery bypass surgery, myocardial infarction) due to the fact that it is known to have, along with antihypertensive, also a pronounced antianginal (anti-ischemic) effect. In patients with coronary artery disease, blood pressure should be carefully monitored because a significant decrease in blood pressure may increase myocardial ischemia. With prolonged continuous infusion (more than 24-48 hours), tolerance to nitroglycerin may develop.
Fenoldopam is a selective agonist of postsynaptic dopaminergic receptors, the use of which does not worsen renal perfusion, despite a decrease in systemic blood pressure. It can be used in most complicated hypertensive crises (a “rival” of sodium nitroprusside) and is an alternative to traditional antihypertensive drugs for the treatment of patients with renal failure.
Drugs that, according to many cardiologists, are an alternative to sodium nitroprusside in the treatment of complicated hypertensive crises (high efficiency and no risk of accumulation of toxic metabolites) include nicardipine (a dihydropyridine calcium antagonist), used as an intravenous infusion, and labetalol (a blocker b-adrenergic and a-adrenergic receptors), administered both IV bolus and IV drip (Table 1).
The use of labetalol leads to a combined blockade of a- and b-adrenergic receptors, a decrease in total peripheral vascular resistance (TPVR), without a negative effect on coronary, cerebral and renal blood flow. Therefore, it is effective and safe in many complicated hypertensive crises, including cases of exacerbation of coronary heart disease (unstable angina, myocardial infarction) and pathology of the central nervous system (hypertensive encephalopathy, acute cerebrovascular accident, etc.).
Similar to the use of sublingual captopril, IV enalaprilat has been used successfully for about 20 years to treat hypertensive crises. A number of studies have noted that its effectiveness (the severity of blood pressure reduction) correlates with the concentration of angiotensin II and renin activity in the blood plasma. Intravenous administration of enalaprilat does not cause serious adverse reactions. However, its use, like other angiotensin-converting enzyme inhibitors, is contraindicated in pregnant women. It should not be used in the acute period of MI.
The pharmacological properties of esmolol make it an “ideal b-blocker” for use in emergency situations because it has a rapid (within 60-120 seconds) and short-lasting (10-20 minutes) action. Esmolol is recommended to reduce high blood pressure in patients with acute myocardial ischemia, dissecting aortic aneurysm and arterial hypertension that occurs during surgery, during recovery from anesthesia and in the postoperative period.
Hydralazine has been used as an antihypertensive drug for over 40 years. The rather long duration (up to 8 hours or more) and the unpredictability of its antihypertensive effect create, according to some authors, significant difficulties in the use of this drug in patients with complicated hypertensive crises, including in the treatment of eclampsia. The use of hydralazine is contraindicated for lowering blood pressure in patients with coronary artery disease and aortic dissection.
Quite narrow indications for the treatment of severe hypertension have been defined for the use of phentolamine and trimethaphan, and diazoxide is falling out of use, although our limited clinical experience indicates its sufficient effectiveness and safety.
For the treatment of uncomplicated hypertensive crises, oral antihypertensive drugs are more often used (Table 2).
Nifedipine is not included in the table. 2, since the use of its usual dosage form (without sustained release), especially sublingual, for the relief of hypertensive crises is not recommended by most clinicians. There is quite convincing data on the possibility of developing severe complications when using nifedipine, which are associated with a rapid and significant decrease in blood pressure, leading to a deterioration in coronary and cerebral blood flow. Thus, it should not be prescribed for the treatment of hypertensive crises or used with great caution orally (5-10 mg). Nifedipine is clearly contraindicated in patients with hypertensive crisis and acute coronary syndrome, stroke, angina pectoris of functional class III-IV.

Features of treatment of certain types
emergency conditions for arterial
hypertension (complicated hypertensive crises)
Brief recommendations for pharmacotherapy of some emergency conditions in arterial hypertension are presented in Table. 3 and in the figure.

Ischemia or myocardial infarction
Since the goal of treatment for these patients is to stop or reduce myocardial ischemia, preference is given to the intravenous administration of nitroglycerin, which, along with a decrease in blood pressure (reduction in peripheral vascular resistance), causes dilatation of the large coronary arteries, reduces venous return to the heart (reduction of preload) and end-diastolic pressure LV. All this helps to improve myocardial perfusion. In patients with exacerbation of coronary artery disease and high arterial hypertension, in the absence of contraindications, it is possible to use labetalol, b-blockers (esmolol, etc.), as well as non-dihydropyridine calcium antagonists (verapamil, diltiazem). Sodium nitroprusside or fenoldopam are recommended only in cases of refractoriness to nitroglycerin, labetalol and b-blockers. It is not advisable to use drugs that cause reflex tachycardia (diazoxide, hydralazine, dihydropyridine calcium antagonists), which can lead to expansion of the zone of myocardial ischemia.

Pulmonary edema
Reduction of high blood pressure in patients with acute LV systolic dysfunction causing pulmonary edema should be carried out with vasodilators that reduce both pre- and afterload (sodium nitroprusside), in combination with loop diuretics. IV administration of nitroglycerin, enalaprilat (contraindicated in MI) and fenoldopam can also be effective.
Drugs that increase myocardial work (diazoxide, hydralazine) or worsen its contractile function (labetalol, b-blockers, calcium antagonists) should not be used in acute systolic heart failure.

Aortic dissection
This is the most dangerous acute disease of the aorta, which poses a significant threat to the patient’s life. In the United States, about 2,000 aortic dissections are reported annually, with a mortality rate of 3-4% of all sudden deaths from cardiovascular disease. The most common risk factor for aortic dissection is hypertension. Both the ascending and descending aorta can be affected.
Intravenous antihypertensive therapy should be started immediately in all patients with suspected aortic dissection (with the exception of patients with hypotension, of course). At the same time, the pain syndrome is stopped by intravenous administration of morphine. As a rule, it is recommended to reduce blood pressure more quickly than in other complicated hypertensive crises. Reduction of SBP to 100-120 mm Hg. Art. (or blood pressure up to 60-75 mm Hg) is achieved within a few minutes, provided there are no symptoms of organ hypoperfusion. The goal of pharmacotherapy is to reduce blood pressure, myocardial contractility (dp/dt), heart rate and, ultimately, aortic wall tension. Therefore, standard treatment includes a combination of a vasodilator (sodium nitroprusside) and a b-blocker (esmolol, propranolol, metoprolol, etc.).
Fenoldopam can be used instead of sodium nitroprusside. When there are contraindications for the use of b-blockers, it is advisable to prescribe intravenous administration of verapamil or diltiazem, which reduce blood pressure and myocardial contractility. Intravenous administration of the α- and β-adrenergic receptor antagonist labetalol is an alternative to the combination of a vasodilator and a β-blocker. The use of the ganglion blocker trimethaphan, which causes a decrease in both blood pressure and dp/dt, is also probably possible without b-blockers. At the same time, monotherapy with drugs that can increase tachycardia, cardiac output and aortic wall tension (hydralazine, diazoxide, dihydropyridine calcium antagonists) should not be carried out in these cases.
For dissection of the ascending aorta, emergency surgical treatment is indicated (aortic replacement and sometimes aortic valve replacement), and in patients with damage to the descending aorta, long-term medical treatment is possible.

Hypertensive encephalopathy
The stability of cerebral blood flow is maintained by the mechanism of autoregulation with changes in blood pressure in healthy individuals ranging from 60 to 120 mmHg. Art., and in patients with chronic hypertension - from 110 to 160 mm Hg. Art. . If systemic blood pressure exceeds the upper limit of autoregulation, then a significant increase in cerebral blood flow and the development of cerebral edema, which is the main cause of hypertensive encephalopathy, are possible.
The main symptoms of hypertensive encephalopathy are headache, nausea, vomiting, blurred vision, and lethargy. Impaired consciousness, convulsions are possible, and in the absence of adequate treatment, the development of cerebral hemorrhages, coma and death. During the examination, in addition, swelling of the optic nerve nipple is detected, combined or not combined with other manifestations of retinopathy. To confirm the diagnosis of hypertensive encephalopathy, it is necessary to exclude a number of diseases that have similar symptoms (stroke, subarachnoid hemorrhage, brain tumor, etc.). For this purpose, most patients are advised to undergo computed tomography or magnetic resonance imaging.
In case of hypertensive encephalopathy, it is necessary to quickly (approximately within an hour) reduce blood pressure (average blood pressure by 25% or DBP to 100-110 mm Hg) by intravenous administration of labetalol, sodium nitroprusside, nicardipine or fenoldopam.
The use of antihypertensive drugs that have a sedative effect (clonidine, methyldopa, reserpine) is contraindicated. After lowering blood pressure, the symptoms of hypertensive encephalopathy go away within a few hours.

Ischemic, hemorrhagic strokes
and subarachnoid hemorrhage
Current recommendations suggest withholding antihypertensive therapy for at least 10 days after the onset of ischemic stroke. The exception is patients in whom cerebrovascular accident is combined with acute heart failure, acute coronary syndrome, aortic dissection, or when their blood pressure exceeds 220/120 mmHg. Art. .
These recommendations are justified by the fact that in most people with ischemic stroke, high blood pressure, which is probably a protective reaction in these cases, decreases independently within a few days, and a decrease in blood pressure in the first hours and days of the disease can lead to a deterioration in blood flow in the peri-infarction area. zone and expansion of the focus of brain damage.
When it is necessary to lower blood pressure (BPMR by no more than 25% over several hours), it is currently recommended to use labetalol first rather than sodium nitroprusside, which, like other vasodilators (for example, nitroglycerin), should be a second-line drug due to the risk of increased intracranial pressure when using it (Kaplan N.M., 2003).
As with ischemic stroke, it is not recommended to reduce blood pressure in patients with subarachnoid hemorrhage (SAH), except in special cases when it is excessively elevated (more than 220/120 mmHg). As a number of studies have shown, antihypertensive therapy does not improve the course of the disease: reducing blood pressure during SAH, while reducing the risk of repeated hemorrhages, significantly increases the number of cases of cerebral infarction.
If a decision is made about the need to control blood pressure in patients with subarachnoid hemorrhage, one must remember the possibility of increased intracranial pressure when using sodium nitroprusside or nitroglycerin (although this is quite rare in the clinic), so preference is given to labetalol. It is advisable to prescribe nimodipine, which helps reduce the incidence of cerebral vascular spasm (which is characteristic of this disease) and therefore reduces the risk of cerebral ischemia.
Although the optimal tactics for controlling arterial hypertension in patients with hemorrhagic stroke is still unclear, most of them are recommended to gradually and carefully lower blood pressure if it is more than 180/105 mmHg. Art. (IV labetalol, sodium nitroprusside, etc., see Table 3). The goal of treatment is to maintain SBP between 140 and 160 mmHg. Art., carefully monitoring the patient’s condition to prevent an increase in neurological symptoms associated with a decrease in blood pressure and cerebral hypoperfusion.
In ischemic, hemorrhagic strokes and subarachnoid hemorrhage, as well as in hypertensive encephalopathy, the use of antihypertensive drugs that have a depressant effect on the central nervous system (clonidine, methyldopa, reserpine) is contraindicated.
Preeclampsia and eclampsia
Pregnant women with preeclampsia and eclampsia require hospitalization and bed rest. In case of treatment-resistant preeclampsia or development of eclampsia, immediate delivery is indicated. For a rapid but controlled reduction in blood pressure in these clinical situations, drugs that are safe and effective when administered parenterally are recommended: hydralazine, labetalol, nicardipine. Although hydralazine has traditionally been widely used in the treatment of preeclampsia and eclampsia, some experts prefer labetalol and nicardipine due to fewer adverse reactions and high effectiveness. Thus, a number of studies have shown that intravenous administration of labetalol at a dose of 1 mg/kg to women with hypertension in the last trimester of pregnancy did not affect uteroplacental blood flow and fetal heart rate, despite a significant decrease in blood pressure and heart rate in the mother.
At the same time, there is evidence that sodium nitroprusside may pose a certain danger to the fetus, so it should be a reserve drug and used during pregnancy only as a last resort. Trimethaphan and diuretics are not recommended for the treatment of preeclampsia and eclampsia - due to an increased risk of developing meconium ileus - since with preeclampsia there is almost always a decrease in uteroplacental blood flow. To prevent seizures, use magnesium sulfate: 4-6 g IV for 15-20 minutes, then a continuous IV infusion at a rate of 1-2 g/hour.

Postoperative hypertension
Arterial hypertension quite often, in 25-75% of cases, develops after surgery. It increases the number of complications in the postoperative period (bleeding from the area of ​​vascular sutures, myocardial ischemia, acute heart failure, etc.), and also has a negative impact on the prognosis. Severe postoperative hypertension is more often reported in patients whose blood pressure was poorly controlled before surgery. It is obvious that many patients in the postoperative period cannot take drugs orally for a certain time, and therefore they must use parenteral administration of antihypertensive drugs.
Before performing noncardiac surgery in patients with arterial hypertension, it is necessary to achieve a stable reduction in blood pressure. Most oral antihypertensive medications can be prescribed on the morning of surgery, with the exception of diuretics due to the risk of hypovolemia. Drugs whose use cannot be interrupted (for example, b-blockers) should be administered parenterally. In the days immediately after surgery, antihypertensive therapy selected before surgery continues.
After coronary artery bypass surgery, blood pressure increases in more than 33% of cases. Arterial hypertension, in the pathogenesis of which cardiac denervation and immunosuppressive therapy play a major role, is a frequent companion to heart transplantation.
The main drugs for lowering blood pressure in patients undergoing cardiac surgery are sodium nitroprusside, nitroglycerin, labetalol, b-blockers and calcium antagonists. There is evidence of the effective use of fenoldopam for this purpose, including after coronary artery bypass surgery. After heart surgery, it is not recommended to prescribe hydralazine and diazoxide, which, by causing tachycardia, increase the load on the myocardium.

Hypertensive crises caused by
increased sympathetic activity
nervous system
Pheochromocytoma in 85-90% of cases is a benign tumor of the adrenal medulla that produces catecholamines. In approximately 70% of cases, arterial hypertension with pheochromocytoma is of a crisis nature. Hypertensive crises are characterized by palpitations, headache, sweating, pale skin, and polyuria. Leukocytosis, eosinophilia, and hyperglycemia are often detected in the blood.
To relieve a hypertensive crisis in pheochromocytoma, 5-10 mg of phentolamine is administered intravenously (the use of b-blockers without a-blockers is contraindicated). Backup drugs may include sodium nitroprusside and labetalol. At the same time, according to some data, the use of labetalol for this purpose is inappropriate due to insufficient effectiveness or even an increase in blood pressure.
Sudden cessation of taking certain antihypertensive drugs that affect the activity of the sympathetic nervous system (clonidine, b-blockers) can also cause a significant increase in blood pressure (“rebound” hypertension) and the appearance of a number of other symptoms, such as tachycardia, cardiac arrhythmias, etc. d. Treatment of rebound hypertension consists of continuing interrupted antihypertensive therapy after rapidly lowering blood pressure with phentolamine, sodium nitroprusside, or labetalol. It must be remembered that the use of b-blockers in patients taking clonidine negatively affects the course of “rebound” hypertension.
Some other clinical situations also lead to a significant increase in adrenergic activity and the appearance of severe hypertension:
1) use of drugs with sympathomimetic activity (cocaine, amphetamines, phencyclidine, phenylpropanolamine, etc.);
2) interaction of monoamine oxidase inhibitors with foods containing tyramine (we talked about them earlier);
3) Guillain-Barre syndrome (inflammatory disease of the nervous system);
4) spinal cord damage.
When treating these arterial hypertension (as in patients with pheochromocytoma), monotherapy with b-blockers should be avoided, because inhibition of vasodilation associated with stimulation of b-adrenergic receptors leads to the elimination of the counterbalance of a-adrenergic vasoconstriction and a further increase in blood pressure. High blood pressure is reduced by intravenous administration of phentolamine, sodium nitroprusside, fenoldopam, labetalol. However, data on the effectiveness of the latter in these patients are contradictory and require clarification.

Kidney failure
For antihypertensive therapy in patients with renal failure, drugs are used that do not negatively affect renal blood flow and glomerular filtration: calcium antagonists, fenoldopam, labetalol, sodium nitroprusside, a-blockers. Diuretics (mostly loop diuretics and often in fairly high doses) are used only in the presence of hypervolemia. Thiazide diuretics are ineffective when the glomerular filtration rate is less than 30 ml/min. Since b-blockers can reduce renal blood flow, their use should be avoided in renal failure. Potassium-sparing diuretics are contraindicated in patients with this pathology, aggravated by hyperalemia. Dose adjustment of antihypertensive drugs excreted by the kidneys is necessary.
A number of controlled clinical studies have shown that fenoldopam infusion improves diuresis, natriuresis, and creatinine clearance compared to sodium nitroprusside. With the introduction of sodium nitroprusside to patients with renal insufficiency, the risk of intoxication with cyanide and thiocyanate increases (it is necessary to reduce the initial rate of administration of the drug and control their level in the blood plasma). In connection with the above, it is probably necessary to give preference to fenoldopam, rather than sodium nitroprusside, when emergency treatment of hypertension is required against the background of renal failure. Some patients may require emergency hemodialysis to control blood pressure. Bilateral nephrectomy followed by permanent hemodialysis or kidney transplantation is also used as a treatment option for drug-refractory hypertension.

Literature
1. Kaplan N.M. Management of hypertensive emergencies. Lancet. 1994; 344: 1335-1338.
2. Mansoor G.A. Frishman W.H. Comprehensive management of hypertensive emergencies and urgencies. Heart Dis. 2002; 4(6): 358-371.
3. Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure: the sixth report (JNCVI). Arch. Intern. Med. 1997; 157: 2413-2446.
4. Shayne P.H., Pitts S.R. Severely increased blood pressure in the emergency department. Ann. Emerg. Med. 2003; 41: 513-529.
5. Vaughan C.J., Delanty N. Hypertensive emergencies. Lancet. 2000; 354:414-417.
6. Varon J., Marik P.E. The diagnosis and management of hypertensive crises. Chest. 2000; 118: 214-227.
7. Houston M.C. Pathophysiology, clinical aspects, and treatment of hypertensive crises. Prog. Cardiovasc. Dis. 1989; 2: 99-148.
8. Elliot W.J. Hypertensive emergencies. Critical Car Clinics. 2001; 17:1-13.
9. Murphy M.B., Murray C., Shorten G.D. Fenoldopam: a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. N.Engl. J. Med. 2001; 345:1548-1551.
10. Di Pette D.J., Ferraro J.C., Evans R.R. et al. Enalapriat, an intravenous angiotensin-converting enzyme inhibitor, in hypertensive crises. Clin. Pharmacol. Ther. 1985; 38: 199-204.
11. Polosyants O.B., Vertkin A.L. Treatment of complicated hypertensive crisis at the prehospital stage. // Arterial hypertension. 2004. No. 10. P. 122-126.
12. Hirschl M.M., Binder M., Bur A. et al. Impact of the renin-angiotensin-aldosterone system on blood pressure response to intravenous enalapriat in patients with hypertensive crises. J.Hum. Hypertens. 1997; 11: 177-183.
13. Gray R.J., Bateman T.M., Czer L.S. et al. Comparison of esmolol and nitroprusside for acute post-cardiac surgical hypertension. Am. J. Cardiol. 1987; 59: 887-891.
14. Grossman E., Messerli F.H., Grodzicki T., Kowey P. Should a moratorium be placed on sublingual nifedipine capsules for hypertensive emergencies or pseudoemergencies? JAMA. 1996; 276: 1328-1331.
15. Gemici K., Baran I., Bakar M. et al. Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial Doppler ultrasonography during hypertensive crisis. Blood Press. 2003; 12:46-48.
16. Calhoun D.A., Oparil S. Treatment of hypertensive crises. New England Journal of Medicine. 1990; 323: 1177-1183.
17. Lay J., Antman E.M., Jimenez-Silva, Kupelnick B. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N.Engl. J. Med. 1992; 327:248.
18. O'Gara P.T. Recognition and management of patients with diseases of the aorta: aneurysms and dissection. In Braunwald E., Goldman L. (eds). Primary cardiology. Saunders company. 2003; p. 643-658.
19. Isselbacher E.M. Diseases of the aorta. In Braunwald E., Zipes D., Libby P. (eds). Heart disease. A textbook of cardiovascular medicine. Philadelphia: W.B. Saunders company. 2001, p. 1422-1456.
20. Adams H.P., Brott T.G., Crowell R.M. et al. Guidelines for the management of patients with acute ischemic stroke. Stroke. 1994; 25: 1901-1914.
21. Wijdicks E.F., Vermeulen M., Murray G. D. et al. The effects of treating hypertension following aneurysmal subarachnoid hemorrhage. Clin. Neurol. Neurosurg. 1990; 92: 111-115.
22. Broderick J.P., Adams H.P., Barsan W. et al. Guidelines for the management of spontaneous intracerebral hemorrhage. American heart association. Stroke. 1999; 30: 905-915.
23. Nylund L., Lunell N.O., Lewander R. et al. Labetalol for the treatment of hypertension in pregnancy. Acta Obst. Gynecol. Scand. 1984; Suppl 118:71–73.
24. Awad K., Ali P., Frishman W.H. et al. Pharmacologic approaches for the management of systemic hypertension in pregnancy. Heart Disease. 2000; 2: 124-132.
25. Blumenfeld J.D., Laragh J.H. Management of hypertensive crises: the scientific basis for treatment decisions. Am. J. Hypertens. 2001; 14: 1154-1167.
26. Murphy M.B., Murray C., Shorten G.D. Fenoldopam a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. N.Engl. J. Med. 2001; 345: 1548-1557.
27. Zazgornik J., Biesenbach G., Janko O. et al. Bilateral nephrectomy: the best, but often overlooked, treatment for refrectory hypertension in hemodialysis patients. Am. J. Hypertens. 1998; 11: 1364-1370.

Goals and objectives of antihypertensive therapy

§ The goal of treatment for patients with hypertension: to minimize the risk of cardiovascular morbidity and mortality. The main thing in achieving this goal is to reduce high blood pressure to target values, correct all modifiable risk factors (smoking, dyslipidemia, hyperglycemia, obesity) and adequate treatment of concomitant diseases (diabetes mellitus, etc.).

§ Target blood pressure in the general population of patients with hypertension< 140/90 мм рт.ст.

§ When hypertension is combined with diabetes mellitus and/or renal dysfunction (serum creatinine > 1.5 mg/dl, proteinuria, GFR<60 мл/мин) целевое АД < 130/80 мм рт.ст.

Algorithm for the management of patients with hypertension depending on the risk category

§ In high and very high risk groups, along with the implementation of a non-drug treatment program, drug therapy is recommended to be started immediately.

§ In groups of patients with average risk, it is permissible to monitor the patient with regular blood pressure monitoring and conduct a non-drug treatment program for 3-6 months before deciding to start drug therapy. Antihypertensive drugs are prescribed for sustained blood pressure > 140/90 mmHg.

§ Early, active drug therapy is indicated for patients with high normal blood pressure (130-139/85-89 mm Hg), who have diabetes mellitus, renal or heart failure, as well as those who have had a stroke or transient cerebrovascular accident.

Tactics for starting antihypertensive therapy

There are two possible strategies for initial treatment of hypertension: monotherapy and combination therapy (Fig. 4).

Rice. 4. Strategy for the treatment of hypertension

Rationale for choosing an antihypertensive drug to initiate treatment of arterial hypertension

Currently, seven classes of antihypertensive drugs are recommended for long-term treatment of hypertension:

§ thiazide and thiazide-like diuretics;

§ beta-blockers;

§ calcium antagonists;

§ ACE inhibitors;

§ angiotensin II receptor blockers;

§ imidazoline receptor agonists;

§ alpha-blockers.

Modern guidelines highlight the main indications for prescribing antihypertensive drugs, based on evidence-based medicine (Table 1).

Table 1. Indications for prescribing antihypertensive drugs

Drug class	Clinical situations in favor of use	Absolute contraindications	Relative contraindications
Thiazide diuretics	CHF ISAH AG in the elderly	Gout	Pregnancy Dyslipidemia
Loop diuretics	chronic renal failure chronic heart failure
Aldosterone antagonists	CHF After MI	Hyperkalemia CRF
Beta blockers	Angina pectoris After a MI CHF (starting with low doses) Pregnancy Tachyarrhythmias	AV block II-III stage. Bronchial asthma	Atherosclerosis of peripheral arteries IGT COPD Athletes and physically active individuals
Dihydropyridine calcium antagonists	ISAH hypertension in the elderly Angina pectoris Atherosclerosis of the carotid arteries Pregnancy		Tachyarrhythmias CHF
Non-dihydropyridine calcium antagonists	Angina pectoris Atherosclerosis of the carotid arteries Supraventricular tachycardia	AV block II-III c. CHF
ACEI	CHF LV dysfunction After MI Nephropathy Proteinuria
Angiotensin receptor blockers	Diabetic nephropathy in type 2 diabetes Diabetic MAU Proteinuria LVH Cough caused by ACE inhibitors	Pregnancy Hyperkalemia Bilateral renal artery stenosis
α1-blockers	Benign prostatic hyperplasia Dyslipidemia	Orthostatic hypotension	CHF
Imidazoline receptor agonists	Metabolic syndrome Diabetes mellitus		Severe CHF AV block II-III stage.

CHAPTER 3. HYPOTENSIVE DRUGS

Diuretics.

Diuretics are drugs whose direct effect on the kidneys leads to inhibition of sodium and water reabsorption and, consequently, to an increase in the volume of excreted fluid.

In accordance with the latest recommendations of the United States Joint National Committee on Hypertension Control (JNC VII, 2003) and additions to the recommendations of the World Health Organization and the International Society of Hypertension (WHO/IAS, 2003), diuretics as the initial therapy for hypertension should be prescribed to all patients with hypertension, with the exception of those who have contraindications.

Classification of diuretics

Diuretic drugs can be classified in different ways:

1) by chemical structure,

2) according to the mechanism of diuretic action,

3) by localization of action in the nephron.

According to the mechanism of action, the following groups of diuretics are distinguished:

§ carbonic anhydrase inhibitors;

§ osmotic diuretics;

§ increasing the release from the body mainly of Na +, K +, Cl - (loop diuretics);

§ increasing the release of Na +, Cl - from the body (thiazides and thiazide-like diuretics);

§ mineralocorticoid receptor antagonists;

§ renal epithelial sodium channel inhibitors (indirect aldosterone antagonists, potassium-sparing diuretics).

Most often, diuretics are divided into three groups depending on the site of their action in the nephron, which determines the severity of the natriuretic effect, expressed as a percentage of excreted sodium from the total amount of sodium filtered in the renal glomeruli.

§ Potent diuretics (i.e. causing excretion of more than 15-20% of filtered sodium):

Organic mercury compounds (not currently used in clinical practice);

Derivatives of sulfamonlanthranilic acid (furosemide, bumetanide, pyretanide, torasemide, etc.);

Derivatives of phenoxyacetic acid (ethacrynic acid, indacrinone, etc.).

§ Diuretics with a moderate natriuretic effect (i.e., causing the excretion of 5-10% of filtered sodium):

Benzothiadiazine derivatives (thiazides and hydrothiazides) - chlorothiazide, hydrochlorothiazide, bendroflumethiazide, polythiazide, cyclothiazide, etc.;

Heterocyclic compounds similar in the mechanism of tubular action to thiazide diuretics are chlorthalidone, metolazone, clopamide, indapamide, xipamide, etc.

§ Low-acting diuretics (i.e., those causing excretion of less than 5% of filtered sodium):

Potassium-sparing diuretics - amiloride, triamterene, spironolactone;

Carbonic anhydrase inhibitors - acetazolamide, etc. (not used in the treatment of arterial hypertension);

Osmotic diuretics - mannitol, urea, glycerin, etc. (not used in the treatment of arterial hypertension).

Thiazide, loop and potassium-sparing diuretics used in the treatment of hypertension are distinguished by the site of action at the level of the renal tubules.

§ Thiazide and thiazide-like diuretics suppress the reabsorption of sodium ions at the level of that part of the thick segment of the ascending limb of the loop of Henle, which is located in the renal cortex, as well as in the initial part of the distal tubules.

§ Loop diuretics affect the reabsorption of sodium ions in that part of the thick segment of the ascending limb of the loop of Henle, which is located in the renal medulla. In this section, the tubules are impermeable to water, but active transport of chlorine into the tubule cells occurs, which is accompanied by significant sodium reabsorption. It is the blockade of chlorine transport that leads to an increase in natriuresis and diuresis.

§ Potassium-sparing diuretics block the exchange of sodium ions for potassium ions at the level of the distal convoluted tubules and collecting ducts. This leads to potassium retention and suppression of sodium ion reabsorption.

The localization of the action of diuretics is shown in Figure 5.

H2O

Passive

Cl-

H2O

transport

ADG

Active

transport

Rice. 5. Localization of the action of diuretics.

Note: 1 – carbonic anhydrase inhibitors; 2 – osmotic diuretics; 3 – loop diuretics; 4 – thiazide and thiazide-like diuretics; 5 – potassium-sparing diuretics.

The effect of diuretics on renal hemodynamics and the excretion of major ions is shown in Table 2.

Table 2. Effect of diuretics on renal hemodynamics and excretion of major ions

Diuretics	KF	PC	Ion excretion
Na+	K+	Ca++	Mg++	Cl-	HCO3-
Carbonic anhydrase inhibitors	↓	#			#	#
Osmotic
Loop
Thiazides and thiazide-like	#	#			↓
Indirect aldosterone antagonists	#	#		↓	↓	↓		#
Direct aldosterone antagonists	#	#		↓	#	↓		#

Note: - increase; ↓ - decrease; # - lack of influence.

Pharmacokinetics of diuretics

Pharmacokinetic parameters of diuretics are presented in Table 3.

Table 3. Pharmacokinetic parameters of diuretics

Drugs	Dose, mg/day	DB, %	Elimination duration	Elimination routes
Thiazide and thiazide-like diuretics
Hydrochlorothiazide	12,5-50	60-80	6-18	kidneys
Chlorothiazide	250-500		6-12	kidneys
Indapamide	1,5-2,5		12-24	kidneys + liver
Xipamide	10-40		12-24	kidneys + liver
Metolazone	2,5-5	50-60	12-24	kidneys + liver
Chlorthalidone	12,5-50		24-72	kidneys + liver
Loop diuretics
Bumetanide	0,5-4	60-90	2-5	kidneys + liver
Torasemide	2,5-10	80-90	6-8	kidneys + liver
Furosemide	20-240	10-90	2-4	kidneys
Potassium-sparing diuretics
Amiloride	5-10		6-24	kidneys
Triamterene	50-150		8-12	kidneys + liver
Spironolactone	25-100		3-5 days	liver

Note: BD – bioavailability.

TDs are well absorbed from the gastrointestinal tract, so they are prescribed during or after meals, once in the morning or twice in the morning. During treatment, a diet rich in potassium and low in salt is recommended. Loop diuretics are strong diuretics that cause a quick, short-term effect. Their hypotensive effect is much less pronounced than that of thiazide drugs, increasing the dose is accompanied by dehydration. Prescribed in the morning on an empty stomach.

The mechanism of the hypotensive action of thiazide diuretics (TD)

Action TD in relation to blood pressure is divided into 3 phases: acute, subacute and chronic. The acute phase lasts 3-4 weeks, and the decrease in blood pressure occurs due to an increase in natriuresis, a decrease in the volume of extracellular fluid and BCC, and the associated decrease in CO. When a large amount of sodium is taken with food, the effectiveness of the treatment of TD may be low or completely absent.

In the future, within 2-3 weeks (subacute phase), after a decrease in CO, an increase in the activity of the RAS and SAS is noted. This neurohumoral activation causes a compensatory increase in BCC, which still remains somewhat reduced.

In the chronic phase of taking TD, a decrease in OPSS is observed. This process is associated with a change in the activation of SMC ion channels and a decrease in vascular tone.

Features of thiazide diuretics

1) Moderate natriuretic (and diuretic) effect and longer action than loop diuretics.

2) The greatest diuretic and hypotensive effect is achieved when prescribing relatively low doses of TD (12.5 - 25 mg of hydrochlorothiazide per day or equivalent doses of other thiazide diuretics). With a further increase in dose, the antihypertensive effect does not increase.

3) Reduced effect in patients with renal failure (serum creatinine level above 2.0 mg/dl; glomerular filtration rate less than 30 ml/min).

4) Reducing the excretion of calcium ions in the urine (calcium-sparing effect).

A number of diuretic drugs that differ in chemical structure from TD have pharmacological properties similar to them, which gives reason to call them thiazide-like diuretics. Indapamide occupies a special place in the group of thiazide-like diuretics. Indapamide differs from other thiazide and thiazide-like diuretics in that, along with a diuretic effect, it has a direct vasodilating effect on the systemic and renal arteries. Peripheral vasodilation is associated with the ability of the drug to inhibit the entry of calcium ions into the SMC and stimulate the synthesis of prostacyclin. Indapamide is known to cause reversal of LVH. The incidence of side effects with indapamide is lower than with other thiazide diuretics.

Two more drugs are close to indapamide - xipamide and metolazone. These drugs have a significant sodium and diuretic effect even in patients with severe renal insufficiency (glomerular filtration rate less than 30 ml / min).

Features of loop diuretics (LD)
1) Pronounced but short-term diuretic effect.

During the period of action of PD, the excretion of sodium ions in the urine increases significantly, but after the cessation of the diuretic effect of the drugs, the rate of excretion of sodium ions decreases to a level below the initial level. This phenomenon is called the “ricochet phenomenon” (or recoil). It is assumed that the basis of the “rebound phenomenon” is a sharp activation of the RAS and, possibly, other antinatriuretic neurohumoral systems in response to massive diuresis caused by PD. The existence of the “rebound phenomenon” explains why, when taken once daily, loop diuretics may not have a significant effect on the daily excretion of sodium ions. To achieve the removal of sodium ions from the body and achieve a hypotensive effect, short-acting PDs (furosemide and bumetanide) must be prescribed 2 times a day. Long-acting PDs (torsemide) do not have a rebound effect and are therefore more effective in the treatment of hypertension.

2) The diuretic effect increases significantly as the dose increases.

3) Maintaining effectiveness at a low glomerular filtration rate, which allows the use of PD for the treatment of hypertension in patients with renal failure.

4) Increased excretion of calcium ions in the urine.

5) Greater severity of adverse drug reactions.

Features of potassium-sparing diuretics (KD)

1) KDs prevent the loss of potassium in the urine, acting at the level of the distal convoluted tubules and collecting ducts as either a competitive antagonist of aldosterone (spironolactone) or direct inhibitors of the secretion of potassium ions (amiloride, triamterene).

2) Prescribed in combination with thiazide or loop diuretics as potassium-sparing drugs.

3) As monotherapy, spironolactone is used in the treatment of “idiopathic hyperaldosteronism”, when hypersecretion of aldosterone is caused by bilateral hyperplasia of the adrenal cortex.

4) Adverse drug reactions include: hyperkalemia, gynecomastia and impotence in men, menstrual irregularities and hirsutism in women.

Side effects of diuretics

1. Electrolyte disturbances:

§ hypokalemia, which can cause ventricular arrhythmias;

§ Hypomagnesemia.

2. Metabolic influences:

§ impaired carbohydrate tolerance,

§ increased blood levels of TG, LDL cholesterol,

§ hyperuricemia.

3. Sexual dysfunction:

§ impotence.

4. Effect on blood:

§ thrombocytopenia,

§ leukopenia.

5. Ototoxicity (loop diuretics).

Contraindications to the use of diuretics

§ gout,

§ Hypokalemia.

Interactions

Drug interactions involving beta blockers are presented in table. 4.

Table 4. Drug interactions involving diuretics

Pharmacotherapy of arterial hypertension, atherosclerosis

Lecture text

In recent years, there has been a steady increase in cardiovascular diseases and mortality from them throughout the world. The leading position among cardiovascular diseases is occupied by ischemic heart disease caused by atherosclerotic lesions of the coronary arteries. It is well known that lipid metabolism disorders—hyperlipidemia—play a key role in the pathogenesis of atherosclerosis. Hyperlipidemia (HLP) is a general term that reflects a pathological increase in plasma lipid levels. Human blood plasma lipids - triglycerides, phospholipids and cholesterol are in a protein-bound state, i.e. in the form of lipoproteins.

In the modern industrialized world, one of the most socially significant diseases is arterial hypertension (AH). Today, hypertension is the leading cause of death and disability and the main factor in the development of cardiovascular pathology. The importance of the problem of hypertension is increasing, which is associated with an increase in people's life expectancy and the high prevalence of risk factors for hypertension, such as obesity, low physical activity, and unbalanced nutrition. It is estimated that more than 1 billion people in the world have hypertension, and approximately 7.1 million deaths per year are associated with this pathology. Hypertension is an extremely common condition and annually leads to significant direct and indirect economic losses. The prevalence of hypertension increases with age: this pathology is diagnosed in half of people in the age group 60-69 years and already in 75% of patients aged 70 years and older.

Today, clear evidence has been obtained that uncontrolled hypertension can lead to serious consequences for humans, including damage to target organs - the heart, kidneys, brain, and retina. Hypertension is a major risk factor for coronary artery disease and the underlying atherosclerosis of coronary artery disease and significantly increases the risk of stroke. Considering the above facts, optimal antihypertensive therapy should not only reduce blood pressure, but also prevent complications associated with hypertension.

The World Health Organization has proposed that hypertension be considered a condition when blood pressure is 140/90 mmHg. and higher. There are primary (essential) hypertension or hypertension and secondary (symptomatic) hypertension, which occurs due to diseases of the kidneys, nervous system, infections, pathology of the endocrine system, etc. About 90% of all cases of hypertension occur in the primary, so-called hypertension, the leading symptom of which is is hypertension not associated with any known cause. 10% of all cases of hypertension are secondary (symptomatic) forms, which are caused by pathology of the kidneys and renal vessels, endocrine system, coarctation of the aorta and other reasons.

The central nervous system and, first of all, its sympathetic division, the RAAS system, the cardiovascular system and the kidneys take part in the regulation of blood pressure levels. Disturbances in these links can cause changes in blood pressure levels.

To date, public awareness of hypertension and its consequences remains unsatisfactory.

To control blood pressure, you need to:

Know about him...

Know how to deal with it...

Prevent the consequences of its increase.

It is important to remember that hypertension is not only an independent disease, but also one of the main risk factors for coronary heart disease. Patients with hypertension more often develop myocardial infarction, cerebral stroke and other complications.

An increase in blood pressure is promoted by a number of factors closely related to lifestyle and habits: unhealthy diet, smoking, lack of physical activity, psycho-emotional stress.

Hypertension develops more often in people who eat irrationally, abuse fatty and salty foods, alcohol, and are overweight. Stressful situations, and especially inadequate reactions to them on the part of people themselves, can also be classified as factors unfavorable to health. Normalizing weight, a sufficient level of adequate physical daily activity, giving up bad habits, and a balanced diet can lead to a decrease in blood pressure.

Despite the fact that a healthy lifestyle plays a certain role in the prevention and treatment of hypertension, the main role in the treatment of hypertension belongs to drug treatment, i.e. pharmacotherapy.

Send your good work in the knowledge base is simple. Use the form below

Students, graduate students, young scientists who use the knowledge base in their studies and work will be very grateful to you.

Posted on http://www.allbest.ru/

State autonomous educational institution

secondary vocational education of the Republic of Tatarstan

"Zelenodolsk Medical School"/technical school/

"Pharmacotherapy of hypertension"

The work was completed by a student

211 groups: Nasyrova Lucia

Head: Dusaeva R.G.

pharmacology teacher

Introduction

Hypertension (HD) is a disease of the cardiovascular system that develops as a result of primary dysfunction (neurosis) of higher vasoregulatory centers and subsequent neurohormonal and renal mechanisms, and is characterized by arterial hypertension, functional, and in severe stages - organic changes in the kidneys, heart, and central nervous system. In other words, hypertension is a neurosis of the centers that regulate blood pressure.

Hypertension is the most common disease in many regions of the world. In economically developed countries, an increase in blood pressure (BP) of more than 140/90 mm Hg. Art. is found in approximately 20-40% of the adult population, while in persons over 65 years of age, the detection rate of arterial hypertension (AH) exceeds 50%. In itself, an increase in blood pressure does not create an immediate threat to the life and health of patients, however, hypertension is one of the main risk factors for the development of coronary heart disease (CHD), cerebral stroke, as well as heart and (less often) renal failure. Thus, in patients with hypertension who have not reached 45 years of age, symptomatic hypertension relatively often (in 18-21.9% of cases) becomes the cause of stroke. With the help of regular therapy with antihypertensive drugs, it is possible to reduce mortality from cerebral stroke by 40-50% and from myocardial infarction by 15-20%.

This determined the relevance of this study, the topic of which is “Pharmacotherapy of hypertension.”

Purpose of the study- consider medications for pharmacotherapy of hypertension.

Tasks

· Familiarize yourself with the etiology, pathogenesis, prevention and treatment tactics of hypertension

· Study groups of drugs (Diuretics, ACE inhibitors, Beta blockers, non-selective beta blockers, vasodilators)

Choice of drugs

Depending on the degree of increase in diastolic ("lower") blood pressure, hypertension can be divided into mild (90-105 mmHg), moderate (106-114 mmHg) and severe (more than 115 mmHg). ). With mild hypertension, the use of antihypertensive drugs is not always necessary. Patients' compliance with recommendations to limit salt in the diet, reduce excess body weight, physical activity, quit smoking and other bad habits already leads to a decrease in blood pressure.

A good effect in labile, low hypertension gives the use of tranquilizers and sedatives, including decoctions and tinctures of valerian, motherwort, astragalus, peppermint.

The basic principle of the treatment of patients with hypertension is the sequential (stepwise) use of drugs of the main groups: diuretics, beta-blockers, calcium antagonists, vasodilators and ACE inhibitors.

Algorithm for individualization of antihypertensive therapy

Dihydropyridine calcium antagonists (nifedipine, amlodipine), as well as captopril (Capoten) and other ACE inhibitors are increasingly being used as first-stage antihypertensive drugs.

The choice of drugs of the second stage is made on the basis of their individual tolerability with the least number of side effects. The most successful combination of diuretics with beta-blockers (the latter, even when taken alone, can lower diastolic blood pressure below 90 mm Hg in 80% of patients with arterial hypertension and give the least number of adverse reactions).

Patients who cannot take beta-blockers are prescribed calcium antagonists or ACE inhibitors, less often peripheral vasodilators.

At the second stage, a combination of a beta-blocker and prazosin (or doxazosin), atenolol (or metoprolol) with nifedipine or other dihydropyridines is effective.

At the third stage, either captopril or methyldopa is added to the diuretics. A combination consisting of a diuretic, a beta-blocker and an alpha-blocker (prazosin or doxazosin) is effective.

Patients with diabetes and severe dyslipoproteinemia should not be prescribed diuretics and beta-blockers. Preference should be given to alpha-blockers, ACE inhibitors and calcium antagonists. adrenergic blocker, hypertensive vasoregulatory

For patients with bronchial asthma and broncho-obstructive pulmonary diseases, non-selective and large doses of selective beta-blockers are contraindicated, since their use causes broncho-obstruction phenomena.

For those suffering from angina, the first-line drugs are beta-blockers and calcium antagonists.

For those who have suffered a myocardial infarction, beta-blockers and ACE inhibitors are most recommended.

For hypertensive patients with heart failure, it is better to prescribe diuretics and ACE inhibitors. Beta blockers and calcium antagonists should not be used in this case.

For patients with cerebrovascular insufficiency, the first-line drugs should be calcium antagonists, which have a beneficial effect on cerebral circulation. Alpha blockers are not used in this case.

Patients with arterial hypertension and chronic renal failure should use ACE inhibitors, calcium antagonists and loop diuretics.

Diuretics are indicated for elderly patients.

For young people - beta-blockers.

Diuretics are medications that increase urine production by reducing the reabsorption of sodium and water. Diuresis is regulated by both intra- and extrarenal urinary mechanisms.

Intrarenal mechanisms include effects on epithelial cells of the renal tubules. This is exactly how modern diuretics work. Depending on the point of application and mechanism of action, diuretics are divided into loop or powerful, thiazide and potassium-sparing.

FUROSEMIDE. The diuretic effect of furosemide is dose dependent. The weak inhibitory effect of the drug on carbonic anhydrase of the renal tubules leads to the loss of bicarbonates and neutralizes metabolic alkalosis in parallel with the loss of sodium, the excretion of magnesium and calcium increases, which is used to correct hypercalcemia.

When administered intravenously, the effect of the drug begins after 15 minutes and lasts for b-^ hours, when taken orally - somewhat later.

Furosemide is prescribed at 40-120 mg/day. orally, intramuscularly or intravenously - up to 240 mg/day. When a large dose is administered intravenously, the rate is 4 mg/min.

ETHACRYNOIC ACID. The mechanism of action is similar to furosemide, but does not inhibit carbonic anhydrase. The effect of the drug after oral administration begins after 30 minutes, and after intravenous administration - after 15 minutes, maximum effect - after 1-2 hours, duration - from 3 to 8 hours, depending on the method of administration.

The average dose is 50-250 mg/day, less often - large doses. The drug is not administered intramuscularly due to its strong local irritant effect.

If you have hearing impairment, use with caution.

in furosemide. The daily dose is 1-3 mg.

Loop diuretics have a wide therapeutic range. Patients with hypokalemia should use with caution.

BUMETANIDE. The onset of action and its duration are the same as that of furosemide. The peculiarity of the drug is a more pronounced vasodilating effect than

Well absorbed from the gastrointestinal tract, maximum effect is after 30 minutes. 95-97% of the drug in the blood is bound to albumin, 30% is metabolized in the liver to form glucuronides, 70% is excreted through the kidneys in its pure form. T1/2 - 1.5 hours.

Tiazide diuretics and related compounds

The action of thiazide diuretics and related drugs is based on the blockade of sodium and chlorine countertransport through the luminar membrane of the initial segment of the distal convoluted tubules, where in healthy people up to 5-8% of filtered sodium is reabsorbed. As a result, the volume of plasma and extracellular fluid decreases, and cardiac output decreases.

Hydrochlorothiazide. Thiazide diuretic with moderate strength and medium duration of action. Increases the excretion of sodium, potassium, chlorine and water, without having a primary effect on the acid-base balance. The diuretic effect does not depend on acid-base imbalance. The drug potentiates the effect of reserpine.

Hydrochlorothiazide is well absorbed from the gastrointestinal tract. It accumulates in erythrocytes, where it is 3.5 times more abundant than in blood plasma. With a relatively short half-life, the duration of the hypotensive effect is 12-18 hours.

The diuretic effect occurs within 1-2 hours and lasts 6-12 hours. The drug is prescribed orally during or after meals at a dose of 25-100 mg/day. once in the morning or twice in the morning. Treatment can be intermittent and long-term. In more severe forms, hydrochlorothiazide is taken more often, and the dose often has to be increased. A diet rich in potassium and low in table salt is indicated.

During long-term treatment, it is necessary to strive to prescribe the minimum effective dose of the drug.

INDAPAMIDE is a diuretic antihypertensive agent. The drug should be taken before meals. The onset of action is 2 hours after administration, duration is 24-36 hours.

The drug is well absorbed when taken orally. In the blood, it binds 70-79% to plasma proteins, reversibly to erythrocytes. T1/2 - about 14 hours. Indopamide is intensively excreted unchanged, only 7% of the drug is in the form of metabolites.

Used in a dose of 2.5 mg 1 time per day, less often - in severe forms of arterial hypertension and edema syndrome - 2.5 mg 2 times a day.

CLOPAMIDE is a sulfonamide diuretic with moderate strength and duration of action. The diuretic effect occurs 1-3 hours after taking the drug and lasts 8-24 hours. The drug is prescribed 20-40 mg 1 time per day. Maintenance dose - 10-20 mg/day. every other day or every day.

The main side effects of diuretics: hypokalemia, heart rhythm disturbances, changes in carbohydrate tolerance.

Numerous studies have shown that the use of small doses of diuretics is as effective as large ones. At the same time, side effects such as hypokalemia, hyperlipidemia and arrhythmias are significantly reduced, and often not detected. In a recent multicenter study on the treatment and prevention of adverse outcomes in the elderly, low-dose diuretics produced a persistent hypotensive effect in more than half of the cases. However, it should be emphasized that when using small doses, it occurs more slowly - after 4 weeks. This can be achieved most quickly when taking indapamide.

Potassium-sparing diuretics

Potassium-sparing diuretics inhibit sodium reabsorption in the distal collecting duct, thereby promoting sodium and water excretion and retain potassium. Blood pressure decreases initially due to a decrease in the volume of plasma and extracellular fluid, as well as a decrease in cardiac output

Potassium-sparing diuretics are prescribed to combat or prevent hypokalemia and potentiate the action of other diuretics. Most often used in combination with hydrochlorothiazide.

AMILORIDE. The onset of the diuretic effect is after 2 hours, the maximum effect is after 6-10 hours, the duration of action is up to 24 hours. Amiloride is prescribed 5-10 mg per day once, the maximum dose is 20 mg/day. There are combination drugs - amiloride in combination with hydrochlorothiazide or furosemide.

SPIRONOLACTONE. It is not used alone without other diuretics in the treatment of arterial hypertension.

In older people, the metabolism of spironolactone is perverted, which is associated with a high incidence of side effects (gynecomastia).

Action - after 2-3 days, initial doses - 25-200 mg/day. for 2-4 doses. The maximum dose is 75-400 mg/day.

Side Effects: hyperkalemia, digestive disorders (most typical for spironolactone). With prolonged use of high doses, gynecomastia and central nervous system dysfunction may develop.

TRIAMTEREN.

The onset of action is after 1 hour, duration is 7-9 hours. Start with 25-100 mg/day. The usual dose is 50 mg/day. There are combination drugs - triamterene with hydrochlorothiazide (Triampur).

Absorbed quickly, but only 30-70%, about 67% binds to plasma proteins. The half-life is 5-7 hours, metabolized in the liver to form active metabolites. The predominant route of excretion is bile, partly through the kidneys.

When taking doses of triamperene above 50 mg/day. Possible nausea and epigastric pain, change in urine color and nephropathy.

Calcium antagonists

Calcium antagonists block the entry of calcium ions into the cell, reduce the conversion of phosphate-bound energy into mechanical work, thus reducing the ability of the myocardium to develop mechanical tension, reducing its contractility. The effect of these drugs on the wall of the coronary vessels leads to their expansion (antispastic effect) and an increase in coronary blood flow, and the effect on the peripheral arteries leads to systemic arteriolar dilatation, a decrease in peripheral resistance, systolic and diastolic blood pressure (hypotensive effect).

Calcium antagonists are different chemical compounds. One group includes papaverine derivatives (verapamil, tiapamil); in another, more numerous, dihydropyridine derivatives (nifedipine, isradipine, nimodipine, amlodipine, etc.). Diltiazem belongs to the benzothiazepine derivatives.

There are first and second generation calcium antagonists. First generation calcium antagonists include conventional (instant) tablets and capsules of nifedipine, verapamil and diltiazem. Second-generation calcium antagonists are represented by new dosage forms of nifedipine, verapamil and diltiazem and their new derivatives.

First generation calcium antagonists

NIFEDIPINE (tablets and capsules) is an active systemic arteriolar dilator that has only a slight negative inotropic effect and practically no antiarrhythmic properties. As a result of the expansion of peripheral arteries, blood pressure decreases, which causes a slight reflex increase in heart rate.

Nifedipine is completely metabolized in the liver and excreted in the urine exclusively in the form of inactive metabolites. Interindividual differences in the rate of absorption are determined by the intense first-pass effect through the liver. When taken orally, the drug is completely absorbed.

The onset of action of the drug is after 30-60 minutes. The hemodynamic effect lasts 4-6 hours (average 6.5 hours). Chewing the tablets speeds up its action. When applied sublingually, the effect occurs within 5-10 minutes, reaching a maximum after 15-45 minutes, which is important for relieving a hypertensive crisis. Apply 5-10 mg 3-4 times a day.

Side Effects: tachycardia, facial redness, feeling of heat, swelling of the feet (in a third of patients).

VERAPAMIL. It belongs to the derivatives of phenylalkylamines, has not only a vasodilating, but also a pronounced negative inotropic effect, reduces heart rate, and has antiarrhythmic properties. Blood pressure under the influence of the drug in usual doses (40-80 mg) decreases slightly.

When administered intravenously, the maximum hypotensive effect occurs after 5 minutes. When taking the drug orally, the effect begins after 1-2 hours and coincides with the maximum concentration in the blood.

The effect after oral administration begins within an hour, reaches a maximum after 2 hours and lasts up to 6 hours.

The drug is initially prescribed orally at a dose of 80-120 mg 3-4 times a day, then gradually can be increased to a maximum of 720 mg/day.

Side effects: bradycardia, impaired atrioventricular and intraventricular conduction, worsening heart failure.

DILTIAZEM. The drug is used for various forms of arterial hypertension. In terms of pharmacological effect, it occupies an intermediate position between nifedipine and verapamil.

Diltiazem inhibits sinus node function and atrioventricular conduction to a lesser extent than verapamil, and reduces blood pressure less than nifedipine.

Prescribe 90-120 mg 3-4 times a day.

Verapamil, diltiazem and nifedipine should not be used for cardiogenic shock, heart failure; diltiazem and verpa mil should not be used for sick sinus syndrome, impaired atrioventricular conduction, or bradycardia.

Second generation calcium antagonists

Represented by new dosage forms of nifedipine, verapamil, diltiazem and their new derivatives.

A distinctive feature is a highly specific effect on individual organs and vascular beds, a more powerful effect than that of conventional tablets and capsules, and fewer side effects.

New dosage forms are slow release tablets (SR, SL, retard) and continuous release.

When ingesting NIFEDIPINE tablets WITH BIPHASE RELEASE, consisting of two components (5 mg are absorbed quickly, and the remaining 15 mg within 8 hours), their onset of action occurs after 10-15 minutes, and its duration is 21 hours. Orally, a single dose of 20 mg is prescribed.

NIFEDIPINE RETARD - TIMED-RELEASE tablets begin their action after 60 minutes and last for 12 hours. They are prescribed 10-20 mg 2 times a day.

NIFEDIPINE CONTINUOUS RELEASE is a specially developed therapeutic system that provides a slow, controlled rate of release of the drug while maintaining its level in the blood plasma for 30 hours after administration.

The daily dose of nifedipine continuous release corresponds to the daily dose of the drug in capsule (60 or 90 mg) and is taken once a day for arterial hypertension and angina pectoris at rest and at rest. When elderly people take slow-release drugs, T1/2 also increases by 1.5 times, so they should take them in reduced doses.

Side effects from nifedipine continuous release occur half as often (6% of patients) as when prescribing other dosage forms (12%).

Verapamil sustained release preparations(slow release, retard, isoptin SR) also have some advantages compared to conventional tablets. Thus, from isoptin SR (retard) tablets, verapamil is released 100% in 7 hours, and from retard capsules 80% of the drug is mobilized in 12 hours. This achieves an increase in the duration of the effect and maintaining a constant therapeutic concentration in the blood. However, the advantage over regular verapamil tablets is not so great, since during long-term treatment, especially in the elderly, regular tablets are prescribed 2 times.

In patients with arterial hypertension, slow-release verapamil preparations have a hypotensive effect at a dose of 120 mg 2 times or 240 mg 3 times a day or at a dose of 240-480 mg once.

AMLODIPINE is a second generation calcium antagonist.

The greatest effect is achieved in patients with mild and moderate hypertension.

For patients with arterial hypertension, the dose of the drug should be 2.5-10 mg once a day.

In elderly and senile people, the clearance of the drug decreases, which requires a dose reduction.

A change in the pharmacokinetics of amlodipine was revealed in patients with liver cirrhosis, which dictates the need to adjust their daily dose.

Kidney disease does not affect the pharmacokinetics of the drug.

Side Effects: rare - swelling of the feet, redness of the face.

ISRADIPIN. For arterial hypertension, the drug is prescribed from 5 to 20 mg. Typically, a dose of 5-7.5 mg is effective in 70-80% of patients with arterial hypertension. Hypotensive effect -7-9 hours.

After 2 weeks, side effects typical of dihydropyridine appear - swelling of the feet, redness of the face.

Contraindications to the use of calcium antagonists

Nifedipine should not be prescribed for initial hypotension, sick sinus syndrome, or pregnancy. Verapamil is contraindicated in cases of atrioventricular conduction disorders, sick sinus syndrome, severe heart failure and arterial hypotension.

With the appearance of edema of the legs, it is necessary to reduce the dose of nifedipine or prescribe diuretics. Often, edema disappears without changing therapy when the patient's physical activity is limited.

Cases of overdose of calcium antagonists are not yet known.

Side effects. Side effects common to calcium antagonists associated with peripheral vasodilation are hyperemia of the skin of the face and neck, arterial hypotension, and constipation.

When taking nifedipine, tachycardia and swelling of the legs and feet are possible, not associated with heart failure.

Due to the cardiodepressive action, verapamil can cause bradycardia, atrioventricular blockade and, in rare cases (when using large doses), atrioventricular dissociation.

Beta blockers

Beta-adrenergic receptor blockers are widely used in the treatment of a number of therapeutic, primarily cardiovascular diseases. The main indications for the appointment of this group of drugs: angina pectoris, arterial hypertension and heart rhythm disturbances.

There are non-selective beta-blockers that block beta-1- and beta-2-adrenergic receptors (propranolol, sotalol, nadolol, oxprenolol, pindolol), and selective ones that have predominantly beta-1-in inhibitory activity (metoprolol, atenolol).

When using non-selective (and selective in high doses) beta-blockers, bronchospasm and hyperglycemia may occur due to blockade of beta-2-adrenergic receptors.

For practical use, the following pharmacological features of beta-blockers are important: cardioselectivity, the presence of sympathomimetic activity, quinidine-like action and duration of effect.

When taken orally, beta-blockers reduce blood pressure for several hours, but a stable hypotensive effect occurs only after 2-3 weeks.

Non-selective beta- adrenergic blockers

PROPRANOLOL is a non-selective beta-blocker without its own sympathomimetic activity with a short duration of action.

Propranolol is prescribed orally, starting with small doses - 10-20 mg, gradually - especially for older people and if heart failure is suspected - over 2-3 days, bringing the daily dose to an effective dose (160-180-240 mg). Given the short half-life of the drug, to achieve a constant therapeutic concentration it is necessary to take propranolol 4-5 times a day.

PINDOLOL is a non-selective beta-blocker with sympathomimetic activity.

The drug causes a less pronounced negative inotropic effect at rest than propranolol. It has a weaker effect on beta-2 adrenergic receptors than other non-selective beta-blockers and is therefore safer for bronchospasm and diabetes mellitus. The hypotensive effect of pindolol is lower than that of propranolol: the onset of action is after a week, and the maximum effect is after 4-6 weeks.

Pindolol is well absorbed when taken orally. It is characterized by high bioavailability. The half-life is 3-6 hours, the beta-blocking effect lasts for 8 hours.

Pindolol is used 5 mg 3 times a day, and in severe cases 10 mg 3 times a day. If necessary, the drug can be administered intravenously in a dose of 0.4 mg; the maximum dose for intravenous administration is 1-2 mg. Non-selective beta-blockers are compatible with diuretics, antiadrenergic drugs, methyldopa, reserpine, barbiturates, digitalis.

WITHelectivebeta blockers

METOPROLOL is a selective beta-blocker.

The hypotensive effect of metoprolol occurs quickly: systolic pressure decreases after 15 minutes, maximum after 2 hours and the effect lasts 6 hours. Diastolic pressure decreases steadily after several weeks of regular use of the drug.

Metoprolol is prescribed for arterial hypertension and angina at a dose of 50-100 mg/day, although doses of 150-450 mg/day are also used for treatment.

ATENOLOL is a selective beta-blocker that does not have its own sympathomimetic and membrane-stabilizing activity. In the treatment of arterial hypertension it can be used both in monotherapy and in combination with other antihypertensive drugs.

Masks the clinical manifestations of thyrotoxicosis. For arterial hypertension, the initial dose is 50 mg once a day for two to three weeks. If necessary, the dose is increased to 100 mg once a day.

Contraindications for use: beta-blockers should not be used in cases of severe bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), severe obstructive respiratory failure, bronchial asthma, asthmatic bronchitis, sick sinus syndrome, disorders of atrioventricular conduction.

Relative contraindications: peptic ulcer of the stomach and duodenum, diabetes mellitus in the stage of decompensation, peripheral circulatory disorders, severe circulatory failure (with initial manifestations, beta-blockers can be prescribed in combination with diuretics, cardiac glycosides and nitrates), pregnancy.

Interaction of beta-blockers with otherGimi medicinalPreparations:

When beta-blockers are co-administered with reserpine or clonidine, increased bradycardia is observed.

Intravenous anesthesia agents increase the negative inotropic, hypotensive and bronchospastic effects of beta-blockers, which in some cases requires discontinuation of the drug during surgical treatment.

Diuretics may increase the toxicity of beta-blockers and their side effects (bronchospasm, heart failure).

Cardiac glycosides can potentiate the occurrence of bradyarrhythmias and cardiac conduction disorders.

Anticoagulants and corticosteroids enhance the antiarrhythmic effect of beta-blockers.

The beta blockers themselves eliminate some of the side effects of peripheral vasodilators (in particular, tachycardia) and increase the antiarrhythmic activity of quinidine.

Side effects. When treated with beta-blockers, bradycardia, arterial hypotension, increased left ventricular failure, exacerbation of bronchial asthma, atrioventricular block of varying degrees, increased Raynaud's syndrome and intermittent claudication (due to changes in peripheral arterial blood flow), hyperlipidemia, impaired carbohydrate tolerance, and, in rare cases, may be observed. sexual dysfunction.

When taking them, drowsiness, dizziness, decreased reaction speed, weakness, and depression are possible.

ACE inhibitors

This group of drugs includes drugs that block the conversion of the inactive peptide, angiotensin I, into the active compound, angiotensin II.

ACE (angiotensin-converting enzyme) inhibitors have a hypotensive effect with little effect on cardiac output, heart rate and glomerular filtration rate.

ACE inhibitors lead to a decrease in peripheral arterial resistance in patients with arterial hypertension with increased or normal cardiac output. The degree of blood pressure reduction is the same in the supine and standing positions and does not change when moving to a vertical position. However, patients with volume-dependent hypertension may experience an orthostatic reaction.

The hypotensive effect of ACE inhibitors is due to the suppression of the renin-angiotensin-aldosterone system (RAS) and the prevention of the degradation of bradykinin, which causes the main relaxation of vascular smooth muscles, promotes the production of vasodilating prostanoids and the release of one or more relaxing factors from the endothelium.

CAPTOPRIL. The effect of a single dose occurs after 15-60 minutes, the maximum effect - after 60-90 minutes. Its duration depends on the dose and is 6-12 hours. Several weeks of continuous use are required for the full therapeutic effect to develop.

After oral administration of therapeutic doses, captopril is rapidly absorbed and reaches peak concentrations within an hour. Food reduces absorption by 30-40°/o, so it should be given an hour before meals. The half-life is less than 3 hours. In the presence of chronic renal failure, a dose reduction is required when the creatinine clearance is 10-12 ml/min.

In patients with congestive circulatory failure due to the risk of hypotension, the initial dose is prescribed 6.25 or 12.5 mg 3 times a day.

ENALAPRIL. The onset of action is within an hour, maximum after 4-6 hours, duration - up to 24 hours.

Patients with heart failure should start with 2.5 mg. It takes several weeks for the full therapeutic effect to develop.

Contraindications to the use of ACE inhibitors:

angioedema, including after the use of any ACE inhibitor, as well as pregnancy, should be immediately canceled after its establishment.

The risk of complications when using ACE inhibitors increases with autoimmune diseases, especially systemic lupus erythematosus, scleroderma, and bone marrow depression.

In the presence of renal failure, dose adjustment is required.

Liver dysfunction (for captopril, enalapril) reduces the metabolism of drugs.

Complications and side effects of ACE inhibitors. Rarely, hepatotoxicity (cholestasis and hepatonecrosis) occurs.

Cough (non-productive, persistent) occurs during the first week, in paroxysms, leading to vomiting. It goes away a few days after stopping the drug.

The interaction of ACE inhibitors with alcohol, diuretics, and other antihypertensive drugs leads to a significant total hypotensive effect both with constant combination and with the first dose, causing orthostatic hypotension between the first and fifth hours after administration. To prevent it, it is recommended to discontinue antihypertensive drugs and diuretics 2-3 days before prescribing ACE inhibitors.

Nonsteroidal anti-inflammatory drugs interact competitively with ACE inhibitors, reducing the hypotensive effect of the latter.

Potassium-sparing and potassium-replacing drugs contribute to the development of hyperkalemia.

Estrogens, due to fluid retention, can reduce the hypotensive effect of ACE inhibitors.

Combined treatment with ACE inhibitors and lithium preparations leads to an increase in lithium concentrations and lithium intoxication, especially with simultaneous use of diuretics.

Sympathomimetics can competitively reduce the hypotensive effect of ACE inhibitors.

Tetracyclines and antacids may reduce the absorption of some ACE inhibitors.

Vasodilators

Arteriolar and mixed vasodilators are used to treat patients with arterial hypertension. The first group of drugs includes diazoxide, the second - sodium nitroprusside, nitroglycerin. Conventionally, alpha-blockers (prazosin and doxazosin) can be classified as mixed vasodilators.

Arteriolar vasodilators reduce total peripheral resistance by acting directly on arterioles. The capacity of the venous vessels does not change. Due to the dilation of arterioles, cardiac output, heart rate and the force of myocardial contractions increase.

SODIUM NITROPRUSSIDE is an arteriolar and venous vasodilator. The drug reduces peripheral resistance (action on arterioles) and increases venous capacity (action on veins), thus reducing post- and preload on the heart.

The hypotensive effect of sodium nitroprusside is accompanied by an increase in heart rate without an increase in cardiac output

Sodium nitroprusside is prescribed intravenously. Its hypotensive effect develops in the first 1-5 minutes and stops 10-15 minutes after the end of administration.

The initial dose of the drug is 0.5-1.5 mcg/kg-min, then it is increased by 5-10 mcg/kg-min every 5 minutes until the desired effect is achieved. Sodium nitroprusside (50 mg) must be diluted in 500 or 250 ml of a 5% dextrose solution before administration.

DOXAZOSIN. It is a long-acting alpha-1 adrenergic receptor antagonist and is structurally close to prazosin. Blockade of alpha-1 adrenergic receptors in peripheral vessels leads to vasodilation. A decrease in peripheral vascular resistance causes a decrease in mean blood pressure both at rest and during exercise.

The bioavailability of doxazosin is 62-69%, peak concentration in the blood is 1.7-3.6 hours after oral administration. Apply from 1 to 16 mg once a day, and the “first dose effect” is not pronounced. In combination therapy in resistant patients, the effectiveness of doxazosin increases when combined with nifedipine, amlodipine, atenolol, captopril, enalapril and chlorthalidone.

Side effects: dizziness, nausea, headache.

Other medicines

This group of drugs, which act primarily on the central mechanisms regulating blood pressure, includes rauwolfia drugs (reserpine and raunatin), clonidine and methyldopa.

RAUWOLFIA PREPARATIONS (reserpine, raunatin). Their action is reduced to a direct blocking effect on sympathetic nervous activity. Causes sodium and water retention.

The hypotensive effect develops slowly - over several weeks. Even with mild forms of hypertension, a decrease in pressure is observed in only 1/4 of patients. The hypotensive effect is enhanced when combined with diuretics.

Side effects: depressive states are most common, especially in elderly and senile people. Drowsiness, nasal congestion and weight gain are observed in 5-15% of cases. In addition, reserpine causes ulcerative lesions of the gastrointestinal tract, impotence, bronchospasm, arrhythmias and edema.

clonidine. Refers to stimulants of adrenergic receptors of central action. Due to stimulation of central alpha-adrenergic receptors, sympathetic activation from the vasomotor center of the central nervous system is inhibited, which leads to a decrease in cardiac output, heart rate and peripheral vascular resistance. In addition, it blocks the release of norepinephrine and reduces the level of catecholamines in the blood plasma. May retain sodium and water. When taken orally, the effect is within 30-60 minutes, when applied under the tongue - after 10-15 minutes and lasts 2-4, less often - 6 hours.

At the end of the action, stimulation of the sympathoadrenal system occurs, and accordingly a sharp increase in blood pressure is possible. There are special transdermal forms of clonidine that have an effect one day after applying the patch, lasting up to 7 days.

Side effects: dry mouth, drowsiness, impotence. If the drug is abruptly discontinued, hypertensive crisis, tachycardia, sweating, and anxiety are observed. The drug potentiates the effect of alcohol, sedatives and depressants.

METHYLDOPA. The mechanism of action is similar to clonidine. Use 250 mg 3-4 times a day (up to 1500 mg/day). The drug accumulates in the body. The hypotensive effect is enhanced when combined with diuretics.

With long-term treatment, after 1.5-3 months, addiction to the drug occurs and its effectiveness decreases. In chronic renal failure, the dose of methyldopa should be reduced.

Side effects: autoimmune myocarditis, anemia, hepatitis. Methyldopa is potentially hepatotoxic. In addition, drowsiness is noted. dry mouth, galactorrhea, impotence.

Hypertensive crisis

Increases in blood pressure, accompanied by symptoms of a hypertensive crisis, require immediate therapeutic intervention.

A rapid increase in diastolic pressure (up to 120 mm Hg or more) creates a real threat of the development of encephalopathy. In this case, it is necessary to quickly eliminate peripheral vasoconstriction, hypervolemia and cerebral symptoms (convulsions, vomiting, agitation, etc.).

The first choice in these situations is: fast-acting vasodilators - nitroprusside, diazoxide (hyperstat); ganglion blockers (arfonad, pentamine); diuretics (furosemide, ethacrynic acid).

Nitroprusside and arfonade are usually administered to seriously ill patients in intensive care units with careful monitoring of blood pressure levels, since a slight overdose of drugs can cause collapse.

SODIUM NITROPRUSSIDE is a direct-acting arterial and venous vasodilator. It is used for almost all forms of hypertensive crises. It reduces blood pressure quickly, its dose is easy to adjust during infusion, and the effect stops within 5 minutes after the end of administration.

Sodium nitroprusside is administered intravenously (50 mg in 250 ml of 5% glucose solution starting at 0.5 μg/kg/min (approximately 10 ml/hour). As a rule, an injection rate of 1-3 μg/kg/min is sufficient , maximum - 10 mcg/kg/min.

The hypotensive effect during treatment with sodium nitroprusside is more pronounced in those taking other antihypertensive drugs. Monitoring the patient during the infusion requires special care, since a sharp drop in blood pressure is possible.

Infusion of the drug lasting more than 24 hours, its use in high doses, and renal failure contribute to the accumulation of thiocyanate, a toxic metabolite of nitroprusside. Its effect can be manifested by tinnitus, blurred visual images, and delirium.

NITROGLYCERIN in the form of a continuous intravenous infusion can be used in cases where the use of sodium nitroprusside has relative contraindications: for example, in severe ischemic heart disease, severe liver or renal failure. The initial rate of administration is 5-10 mcg/min; subsequently, the dose is gradually increased under the control of blood pressure, if necessary - up to 200 mcg/min or even more (depending on the clinical effect).

Nitroglycerin is preferable for moderate hypertension in patients with acute coronary insufficiency or after coronary artery bypass surgery, as it improves gas exchange in the lungs and collateral coronary blood flow.

Nitroglycerin is more potent than nitroprusside in reducing preload rather than afterload. It should not be prescribed for myocardial infarction of lower localization with spread to the right ventricle, since the condition of such patients largely depends on the magnitude of preload, which determines the ability to maintain sufficient cardiac output.

DIAZOXIDE, HYDRALAZINE, AMINAZINE and THREE METAFAN are currently used quite rarely for hypertensive crises.

Intramuscular hydralazine is used to treat preeclampsia. In this case, to further reduce blood pressure and prevent salt and water retention in the body, it is often necessary to administer furosemide into a vein.

Indications for intravenous drip or jet administration of chlorpromazine are strictly individual, since the effect of this drug is not always controllable: it can depress the respiratory center, cause tachycardia and an excessive drop in blood pressure, and in case of cerebral vascular atherosclerosis, increase disturbances in intracerebral blood circulation.

Pharmacotherapy of complicated hypertensive crisis

To eliminate cramps and increase diuresis, a SOLUTION OF MAGNESIUM SULPHATE is slowly administered intramuscularly or intravenously. The drug is indicated for eclampsia in pregnant women. However, in large doses it can depress the respiratory center. In this case, the antidote is a 10% calcium chloride solution (10 ml IV).

If there is a threat of hemorrhage in the brain, intravenous administration of DIBAZOL (5.0-10 ml of 0.5% solution) may be useful. However, even in large doses, dibazole cannot be considered as the leading treatment for hypertensive crises, since its hypotensive effect in many cases is clearly insufficient.

The same can be said about injections of PAPAVERINE HYDROCHLORIDE, NO-SHPA and other substances that have an antispasmodic effect, but have little effect on systemic blood pressure.

In case of a hypertensive crisis, accompanied by pulmonary edema or occurring against the background of congestive heart failure, fast-acting drugs that reduce both post- and preload (nitroprusside, pentamine) are indicated.

In case of pulmonary edema and congestive heart failure, antihypertensive drugs that increase the load on the heart or reduce cardiac output are contraindicated - hydralazine, diazoxide, clonidine, alpha-blockers.

Treatment of hypertensive crisis due to renal failure is aimed at reducing hypervolemia and vasoconstriction. Preference is given to drugs that increase renal blood flow - hydralazine, dopegite.

The same drugs are also used to treat high blood pressure in pregnant women (hydralazine, dopegit, furosemide).

A decrease in blood pressure during dissecting aortic aneurysm as an urgent situation is carried out with fast-acting drugs - nitroprusside or arfonade. Vasodilators - diazoxide and hydralazine, which increase the load on the heart, are contraindicated in this situation.

Antihypertensive drugs for oral administration

They are successfully used for the treatment of hypertensive crises in cases where a moderately rapid, non-emergency reduction in blood pressure is necessary, especially in an outpatient setting and more often in uncomplicated hypertensive crises.

NIFEDIPINE sublingually is used for hypertensive crises that require gradual normalization of blood pressure. Its action begins within the first 30 minutes after administration.

There is information about the occurrence of myocardial ischemia when taking nifedipine sublingually, which requires caution in patients with coronary artery disease or if the ECG shows signs of severe hypertrophy of the left ventricle of the heart.

The capsule with nifedipine (10 mg) is chewed or broken and dissolved. The duration of action of nifedipine taken sublingually is 4-5 hours. At this time, you can begin treatment with agents that have a longer effect.

Side effects of nifedipine include hot flashes and orthostatic hypotension.

CLONIDINE is prescribed at 0.2 mg for the first dose, then 0.1 mg every hour until a total dose of 0.7 mg or a decrease in blood pressure of at least 20 mm Hg. Art.

Blood pressure is measured every 15 minutes for the first hour, every 30 minutes for the second hour, and every hour thereafter.

After 6 hours, an additional diuretic is prescribed, and the intervals between doses of clonidine are increased to 8 hours. With this regimen, a pronounced sedative effect may be observed.

CAPTOPRIL (Capoten) is also used to relieve hypertensive crisis. Take 6.5-50 mg orally. The action begins after 15 minutes and lasts 4-6 hours.

Mixed adrenergic blocker - LABETALOL is prescribed 200-400 mg orally. The action begins after 30-60 minutes and lasts about 8 hours.

So, a patient with hypertension cannot:

Eat salty, spicy, fatty foods.

Gain extra pounds.

Abuse alcohol, especially combining libations with taking medications.

Work at night, sleep less than 7 hours.

Be nervous about trifles.

Lead a sedentary lifestyle.

Skip or stop taking medications prescribed by your doctor.

Try on yourself medicines that “helped” your neighbor (brother, matchmaker, etc.).

A patient with hypertension needs:

Quit smoking.

Limit salt intake. Herbal seasonings will help make dishes less bland.

Eat more greens, fruits, foods rich in potassium, and do not get carried away with protein foods.

Eat regularly, especially if you are taking medications at the same time as eating.

Try to lose extra pounds.

Be able to switch gears and not get hung up on troubles.

Move more. Walking, swimming, and therapeutic exercises are especially useful.

Measure your blood pressure regularly.

· In the initial stage of hypertension, the increase in blood pressure is usually not persistent and can be relatively easily normalized with the help of herbal medicine. The following fees are recommended for this:

Valerian root and rhizomes, motherwort herb five-lobed, caraway fruits, blood-red hawthorn flowers - 15 g each, mistletoe leaves and Baikal skullcap rhizomes - 20 g each.

Pour a tablespoon of the mixture with a glass of boiling water, leave for 1-2 hours, strain, squeeze, add boiled water to a volume of 200 ml. Take l^^ glasses warm 3-4 times a day before meals. The course of treatment is a month.

Motherwort and marsh grass - 3 parts each, wild rosemary herb - 1-2, kidney tea - 1 part.

Pour 5 g of the mixture into 300 ml of boiling water, boil for 5 minutes, then leave in a warm place or in a thermos for 4 hours. Take 100 ml 3 times a day before meals. The course of treatment is 1/2-2 months.

Hawthorn flowers, white birch leaves, horsetail grass - 1 part each, marsh grass - 2 parts.

Pour 10 g of the mixture into 500 ml of water, boil, leave for 5-6 hours, then strain. Take 100 ml 2-3 times a day. The course of treatment is a month.

Some vegetables, fruits and berries have a hypotensive effect, which allows you to combine business with pleasure.

Here are some recipes.

LINGONBERRY JUICE OR BERRIES take 200 g 2-3 times a day. Course - 10 days.

FERMENTED VISCELAIN BERRIES WITH SUGAR take 2-3 tablespoons 2-3 times a day for 3 weeks.

BEET JUICE, containing many vitamins and mineral salts, is recommended to take a tablespoon 3 times a day for 2-3 weeks.

If you do not find one or two medicinal plants from the listed recipes, you can prepare decoctions and infusions without them.

Conclusion

Hypertension, like any chronic progressive disease, is easier to prevent than to treat. Therefore, the prevention of hypertension, especially for people with a family history, is an urgent task. A correct lifestyle and regular monitoring by a cardiologist help delay or mitigate the manifestations of hypertension, and often even prevent its development altogether.

First of all, anyone whose blood pressure is within the high or borderline normal range should think about hypertension, especially for young people and adolescents. In this case, regular examination by a cardiologist at least once a year will largely protect the patient from unexpected development of arterial hypertension.

Everyone needs to have information about cases of hypertension in the family, especially among close relatives. These data will help to predict with a high degree of probability whether a person is at risk for hypertension.

A person who may develop arterial hypertension, as a preventive measure, needs to reconsider the usual way of life and make the necessary amendments to it. This concerns increasing physical activity, which should not be excessive. Regular outdoor activities are especially good, especially those that, in addition to the nervous system, also strengthen the heart muscle: running, walking, swimming, skiing.

The diet should be complete and varied, including vegetables and fruits, as well as cereals, lean meats, and fish. Large amounts of table salt are not good for anyone, and for people with the possibility of developing hypertension, it is truly a “white death”. You should also not get carried away with alcoholic beverages and tobacco products.

A healthy lifestyle, a calm and supportive atmosphere in the family and at work, regular preventive examinations with a cardiologist - this is the entire prevention of hypertension and cardiovascular diseases.

Literature

1. Gogin, E. E. Arterial hypertension [Text] / E. E. Gogin, A. I. Senenko, E. I. Tyurin. - M.: VMedA, 2009. - 412 p.

2. Hypertension and secondary arterial hypertension [Text] / Ed. M. S. Kushakovsky. - M.: Medicine, 1982.

3. Kapkan, M. Arterial hypertension [Text] / M. Kapkan. - M., 1998.

4. Cardiology: a guide for doctors [Text] / Ed. R. G. Oganova, I. G. Fomina. - M.: Medicine, 2004.

5. Makolkin V.I. Internal diseases [Text]: 4th ed., revised. and additional / V. I. Makolkin, S. I. Ovcharenko. - M.: Medicine, 1999. - 592 p.

6. Mukhin N. A. Propaedeutics of internal diseases [Text] / N. A. Mukhin, V. S. Moiseev. - M., 2008.

7. Prevention, diagnosis and treatment of primary arterial hypertension [Text]: Report of the WHO expert committee // Combating arterial hypertension - Geneva, 1999, p. 862.

8. Prevention, diagnosis and treatment of primary arterial hypertension in the Russian Federation [Text] // Russian Medical Journal, 2000, volume 8, no. 8, p. 318-349.

Posted on Allbest.ru

...

Similar documents

Pathogenesis and general characteristics of hypertension - one of the chronic diseases of the cardiovascular system. "Target organs" for hypertension, complications of the disease. Methods of diagnosis and treatment directions for hypertension.

abstract, added 11/10/2013


Primary prevention of hypertension, modifiable risk factors. Target organ damage and complications of hypertension. Organization of preventive measures for hypertension at a health school, curriculum and development of classes.

course work, added 06/07/2016


The concept and causes of the development of hypertension. Classification and clinical picture of hypertension. Risk factors in patients. Diagnosis of patients with hypertension. Analysis and evaluation of patient study results.

course work, added 04/22/2016


Etiology and main pathological aspects of arterial hypertension as a persistent increase in blood pressure. Classification, prevention and treatment of hypotension. Study of the level of compliance in the treatment of patients with hypertension.

course work, added 07/06/2015


Clinical signs of hypertension, its classification according to a number of signs. Risk factors for the disease. Causes of hypertensive crises. Treatment of hypertension, prevention of complications. Nursing activities in hypertension.

course work, added 06/02/2015


Treatment and prevention of hypertension. Primary and secondary arterial hypertension. Etiology of hypertension, provoking and contributing factors of its development. Information that leads the nurse to suspect a medical emergency.

presentation, added 04/14/2014


Symptoms, causes and factors contributing to the development of rheumatism, heart disease, hypertension, coronary heart disease, chronic heart failure. Organization of care and prevention for diseases of the cardiovascular system.

presentation, added 02/11/2014


Hypertension (arterial hypertension) is a chronic disease that affects various systems of the body. Types of hypertension, its main symptoms. Etiology, provoking and contributing factors in the development of the disease. Methods of diagnosis and treatment.

presentation, added 03/07/2013


Diagnosis and treatment of hypertension and angina pectoris. Upon admission, the patient complained of slight dizziness and pressing pain in the left half of the chest. Objective condition, examination data. Selection of antihypertensive therapy.

medical history, added 09/05/2013


Psychological aspects, concept, factors and causes of development, classification and clinical picture of the manifestation of hypertension. Features of patients, personality reaction to illness. Basic principles of psychocorrection of personality in hypertension.