Medications used to treat hypertension

If the systolic blood pressure remains at a level above 140 mm Hg. Art. Or diastolic blood pressure above 90 mm Hg. Art. 6 months after lifestyle changes, the treatment of hypertension involves the appointment of antihypertensive drugs. The use of medications along with lifestyle changes is shown to all patients with prehypertension or with a combination of arterial hypertension with diabetes, kidney disease, target organ damage or cardiovascular risk factors, as well as those patients whose BP numbers are> 160/100 mm gt; Art. Signs of hypertensive crisis require immediate reduction in blood pressure by using parenteral diuretics.

Most patients with hypertension at the beginning of treatment are prescribed one drug (usually a thiazide diuretic). Depending on the characteristics of the patient, the presence of concomitant pathology, at the beginning of treatment you can prescribe drugs of other groups or add them to the diuretic. Low-dose acetylsalicylic acid (81 1 mg once a day) demonstrated reduced risk of heart disease in patients with arterial hypertension and recommended by good tolerability and absence of contraindications ¹.

Some high-pressure tablets are contraindicated in certain diseases (for example, a-adrenoblockers in bronchial asthma) or are prescribed for a particular disease (eg, b-blockers or calcium channel blockers in angina pectoris, ACE inhibitors in diabetes mellitus or proteinuria). In the case of a single drug, men of the Negroid race respond better to calcium channel blockers (eg, diltiazem). Thiazide diuretics have a better effect in people over 60 and African Americans.

[1], [2], [3], [4], [5]

Selecting groups of antihypertensive drugs

Medicine	Indications
Diuretics *	Elderly age. Negroid race. Heart failure. Obesity
Long-acting calcium channel blockers	Elderly age. Negroid race. Angina pectoris. Arrhythmias (eg, atrial fibrillation, paroxysmal supraventricular tachycardia). Isolated systolic hypertension in the elderly (dihydropyridines) *. High risk of PVA (not dihydropyridines) *
ACE Inhibitors	Young age. The race of Europe. Left ventricular failure due to systolic dysfunction *. Diabetes mellitus type 1 with nephropathy *. Severe proteinuria due to chronic kidney disease or diabetic glomerulosclerosis. Impotence when taking other drugs
Angiotensin II receptor blockers	Young age. The race of Europe. The states in which ACE inhibitors are indicated, but patients do not suffer from coughing. Diabetes mellitus type 2 with nephropathy
B-blockers	Young age. The race of Europe. Angina pectoris. Atrial fibrillation (to control the frequency of the ventricular rhythm). An essential tremor. Hyperkinetic type of circulation. Migraine. Paroxysmal supraventricular tachycardia. Patients after myocardial infarction (cardioprotective effect) *

¹ This view of the treatment of hypertension is at odds with modern concepts. For example, the use of thiazide diuretics increases the risk of diabetes in patients with AH.

* Reduce morbidity and mortality, according to randomized studies. Contraindicated in pregnancy. ⁺ b-Adrenoblockers without internal sympathomimetic activity.

If the initial drug is ineffective or poorly tolerated due to side effects, you can designate another. If the initial drug is partially effective and tolerated well, it is possible to increase the dose or add a second drug with a different mechanism of action.

If the initial BP> 160 mm Hg. Most often, a second drug is prescribed. The most effective combination of a diuretic with a b-adrenoblocker, an ACE inhibitor or an angiotensin II receptor blocker and a combination of a calcium channel blocker with an ACE inhibitor. The necessary combinations and doses are determined; many of them are released in one tablet, which improves pharmacodynamics. With severe refractory arterial hypertension, three or four drugs may be required.

Hypotensive drugs for high-risk patients

Concomitant disease	Class of medicinal products
Heart failure	ACE inhibitors. Blockers of angiotensin II receptors. Beta-blockers. Potassium-sparing diuretics. Other diuretics
Migrated MI	Beta-blockers. ACE inhibitors. Potassium-sparing diuretics
Risk factors for cardiovascular disease	Beta-blockers. ACE inhibitors. Calcium channel blockers
Diabetes	Beta-blockers. ACE inhibitors. Blockers of angiotensin II receptors. Calcium channel blockers
Chronic kidney disease	ACE inhibitors. Angiotensin II receptor blockers
Risk of recurrent stroke	ACE inhibitors. Diuretics

Achieving adequate control often requires an increase or a change in drug therapy. It is necessary to select or add medications until the necessary blood pressure is reached. The success of achieving adherence to patient treatment, especially given the fact that lifelong drug intake is necessary, directly affects blood pressure control. Training, empathy and support are very important in achieving success.

Combinations of medicines used to treat hypertension

Class	Medicine	Admissible doses, mg
Diuretic / diuretic	Triamterene / hydrochlorothiazide	37.5 / 25, 50/25, 75/50
	Spironolactone / hydrochlorothiazide	25/25, 50/50
	Amyloride / hydrochlorothiazide	5/50
Beta-blocker	Propranolol / hydrochlorothiazide	40/25, 80/25
	Metoprolol / hydrochlorothiazide	50 / 25,100 / 25
	Atenolol / Chlorthalidone	50 / 25,100 / 25
	Nadolol / bendroflumethiazide	40/5, 80/5
	Timolol / hydrochlorothiazide	10/25
	Prolonged propranolol / hydrochlorothiazide	80 / 50,120 / 50,160 / 50
	Bisoprolol / hydrochlorothiazide	2.5 / 6.25.5 / 6.25.10 / 6.25
Beta-blocker	Guanethidine / hydrochlorothiazide	10/25
	Methyldopa / hydrochlorothiazide	250/15, 250/25, 500/30, 500/50
	Methyldopa / chlorothiazide	250 / 150,250 / 250
	Reserpine / Chlorthiazide	0,125 / 250,0,25 / 500
	Reserpine / Chlorthalidone	0.125 / 25.0.25 / 50
	Reserpine / hydrochlorothiazide	0,125 / 25,0,125 / 50
	Clonidine / Chlorthalidone	0.1 / 15.0.2 / 15.0.3 / 15
ACE inhibitor	Captopril / hydrochlorothiazide	25 / 15.25 / 25.50 / 15.50 / 25
	Enalapril / hydrochlorothiazide	5 / 12,5,10 / 25
	Lysinopril / hydrochlorothiazide	10 / 12.5.20 / 12.5.20 / 25
	Fosinopril / hydrochlorothiazide	10 / 12.5.20 / 12.5
	Hinapril / hydrochlorothiazide	10 / 12.5.20 / 12.5.20 / 25
	Benazepril / hydrochlorothiazide	5 / 6.25.10 / 12.5.20 / 12.5.20 / 25
	Moexipril / hydrochlorothiazide	7.5 / 12.5.15 / 25
Angiotensin II receptor blocker	Losartan / hydrochlorothiazide	50 / 12,5,100 / 25
	Valsartan / hydrochlorothiazide	80 / 12.5.160 / 12.5
	And besartan / hydrochlorothiazide	75 / 12.5,150 / 12,5,300 / 12,5
	Candesartan / hydrochlorothiazide	16 / 12.5.32 / 12.5
	Telmisartan / hydrochlorothiazide	40 / 12.5.80 / 12.5
Calcium channel blocker / ACE inhibitor	Amlodipine / benazepril	2.5 / 10.5 / 10.5 / 20.10 / 20
	Verapamil (long-acting) / trandolapril	180 / 2,240 / 1,240 / 2,240 / 4
	Felodipine (long-acting) / enalapril	5/5
Vasodilator	Hydralazine / hydrochlorothiazide	25 / 25.50 / 25.100 / 25
	Prazozin / polythiazide	1 / 0.5, 2 / 0.5, 5 / 0.5
Triple Combination	Reserpine / hydralazine / hydrochlorothiazide	0.10 / 25/15

Diuretics

Oral diuretics used in the treatment of hypertension

Thiazide diuretics	Average dose *, mg	Side effects
Bendroflumethiazide	2.5-5.1 times a day (maximum 20 mg)	Hypokalemia (increasing the toxicity of cardiac glycosides), hyperuricemia, impaired glucose tolerance, hypercholesterolemia, hypertriglyceridemia, hypercalcemia, sexual disorders in men, weakness, rash; it is possible to increase the lithium content in serum
Chlorothiazide	62.5-500.2 times a day (maximum 1000)
Chlorthalidone	12,5-50,1 times a day
Hydrochlorothiazide	12,5-50,1 times a day
Hydrofluethiazide	12,5-50,1 times a day
Indapamide	1,25-5,1 times a day
Metiklothiazide	2.5-5.1 times a day
Metholazone (rapid release)	0,5-1,1 times a day
Metholazone (slow release)	2.5-5.1 times a day

Potassium-sparing diuretics

Amyloride	5-20.1 times a day	Hyperkalemia (especially in patients with renal insufficiency and treated with ACE inhibitors, angiotensin II receptor blockers or NSAIDs), nausea, gastrointestinal disorders, gynecomastia, menstrual dysfunction (spironolactone), it is possible to increase the lithium content in serum
Eplerenone **	25-100.1 times a day
Spironolactone **	25-100.1 times a day
Triamterene	25-100.1 times a day

"Higher doses may be required for patients with kidney failure." * Aldosterone receptor blockers.

Thiazides are used most often. In addition to other antihypertensive effects, they lead to vasodilation as long as the BCC is normal. In equivalent doses, all thiazide diuretics are equally effective.

All diuretics, except potassium-sparing loop diuretics, lead to a significant loss of potassium, so its content in serum should be monitored every month until stabilization. While the potassium concentration did not return to normal, the potassium channels in the arterial wall are closed; this leads to vasoconstriction, which makes it difficult to achieve the effect in the treatment of hypertension. Patients with potassium content <3.5 mmol / l require additional intake of potassium preparations. They can be prescribed for a long time in small doses, it is also possible to add potassium-sparing diuretics (for example, spironolactone in a daily dose of 25-100 mg, triamterene 50-150 mg, amiloride 5-10 mg). Additional prescription of potassium or potassium-sparing diuretics is also recommended for patients receiving cardiac glycosides with proven heart disease, changes in the electrocardiogram, rhythm disturbances, and patients who have had extrasystoles or arrhythmias after using diuretics. Despite the fact that potassium-sparing diuretics do not lead to hypokalemia, hyperuricemia or hyperglycaemia, they are less effective than thiazide in controlling hypertension and are not used for initial therapy. Potassium-sparing diuretics and additional potassium preparations are not needed for the administration of ACE inhibitors or angiotensin II receptor blockers, as these drugs increase the serum potassium content.

In most patients with diabetes mellitus, thiazide diuretics do not interfere with the control of the underlying disease. Occasionally diuretics provoke the aggravation of type 2 diabetes in patients with metabolic syndrome.

Thiazide diuretics may slightly increase serum cholesterol (predominantly low-density lipoproteins) and triglycerides, but this effect is not present for more than 1 year. In the future, figures can only be raised in some patients. An increase in these indicators appears 4 weeks after the start of treatment, it is possible to normalize them against a low-fat diet. The likelihood of a small increase in the number of lipids is not considered a contraindication to the appointment of diuretics to patients with dyslipidemia.

Hereditary predisposition probably explains some cases of gout development with diuretic-induced hyperuricemia. Hyperuricemia caused by diuretic drugs, without the development of gout, is not considered an indication for discontinuing treatment or reversing a diuretic.

[6], [7], [8], [9], [10]

Beta-blockers

These drugs slow the heart rate and reduce myocardial contractility, thus reducing blood pressure. All b-adrenoblockers are similar in antihypertensive effect. In patients with diabetes mellitus, chronic peripheral vascular disease or COPD, cardioselective b-adrenoblockers (acebutolol, atenolol, betaxolol, bisoprolol, metoprolol) can be preferred, although cardioselectivity is relative and decreases with increasing doses of drugs. Even cardioselective b-adrenoblockers are contraindicated in bronchial asthma or COPD with a pronounced bronchospastic component.

B-Adrenoblockers assigned for arterial hypertension

A drug	Daily dose, mg	Possible side effects	Comments
Acebutolol *	200-800, once a day	Bronchospasm, weakness, insomnia, sexual disorders, increased heart failure, mask manifestations of hypoglycemia, triglyceridemia, increased total cholesterol and a decrease in the number of high density lipoproteins (except for pindolol, acebutolol, penbutolol, cardiolol and labetalol)	Contraindicated in patients with bronchial asthma, atrioventricular blockade of the first degree or weakness syndrome of the sinus node. Assign with caution to a patient with heart failure or with insulin-dependent diabetes mellitus. It can not be immediately abolished in patients with coronary artery disease, carvedilol is indicated in heart failure
Atenolol *	25-100, once a day
Betaxolol *	5-20, once a day
Bisoprolol *	2,5-20, once a day
Carotenol	2,5-10, once a day
Carvedilol **	6,25-25, 2 times a day
Labetalol **	100-900, 2 times a day
Metoprolol *	25-150, 2 times a day
Metoprolol slow release	50-400, once a day
Nadolol	40-320, once a day
Penbutolol	10-20, once a day
Pindolol	5-30, 2 times a day
Propranolol	20-160, 2 times a day
Propranolol long-acting	60-320, once a day
Timolol	10-30, 2 times a day

* Cardioselective. ** alpha-beta blocker. Labetalol can be administered intravenously for hypertensive crises. Intravenous administration begins with a dose of 20 mg and, if necessary, increases to a maximum dose of 300 mg. With internal sympathomimetic activity.

B-Adrenoblockers are especially justified when prescribed to patients with concomitant angina, who underwent MI or who had HF. These drugs are now recommended to appoint and the elderly.

B-Adrenoblockers with intrinsic sympathomimetic activity (such as pindolol) have no side effect on the lipid composition of the blood, less severe development of severe bradycardia.

For b-adrenoblockers, the appearance of CNS disorders as side effects (sleep disorders, weakness, inhibition) and the development of depression are characteristic. Nadolol least affects the central nervous system and is the best drug in terms of preventing such side effects. B-Adrenoblockers are contraindicated in the II and III degrees of atrioventricular blockade, bronchial asthma and weakness syndrome of the sinus node.

[11], [12], [13], [14], [15]

Calcium channel blockers

Dihydiperidine preparations serve as potential peripheral vasodilators and reduce blood pressure due to a decrease in OPSS; sometimes they cause a reflex tachycardia. Non-dihydropyridine preparations (verapamil and diltiazem) reduce heart rate, inhibit atrioventricular conduction and reduce contractility; these drugs should not be administered to patients with grade II and III atrioventricular block or left ventricular failure.

Calcium channel blockers used to treat arterial hypertension

Benzothiazepine derivatives

Short-acting diltiazem	60-180.2 times a day	Headache, sweating, asthenia, reddening face, edema, negative inotropic effect; possible hepatic dysfunction	Contraindicated in heart failure due to systolic dysfunction, weakness syndrome sinus node, atrioventricular block 11 and more degrees
Diltiazem slow release	120-360.1 times a day

Derivatives of diphenylalkylamine

Verapamil	40-120, 3 times a day	The same as for benzothiazepine derivatives, plus constipation	The same as for benzothiazepine derivatives
Verapamil prolonged action	120-480.1 times a day

Dihydropyridines

Amlodipine	2,5-10,1 times a day	Sweating, redness of the face, headache, weakness, nausea, palpitations, edema of the feet, tachycardia	Contraindicated in heart failure, possibly with the exception of amlodipine. The use of short-acting nifedipine may be associated with a more frequent development of myocardial infarction
Felodipine	2.5-20.1 times a day
Isradipine	2,5-10,2 times a day
Nicardipine	20-40.3 times a day
Nicardipine slow release	30-60.2 times a day
Nifedipine prolonged action	30-90.1 times a day
Nisoldipin	10-60.1 times a day

Prolonged nifedipine, verapamil and diltiazem are used in the treatment of hypertension, but nifedipine and diltiazem short-acting are associated with an increased risk of myocardial infarction, therefore not recommended.

Calcium channel blockers are more preferable than b-blockers for patients with angina and bronchial obstructive syndrome, coronary spasm and Raynaud's disease.

[16], [17]

Angiotensin converting enzyme inhibitors

Drugs of this group reduce AD, affecting the conversion of angiotensin I into angiotensin II and inhibiting the release of bradykinin, thereby reducing peripheral vascular resistance without the development of reflex tachycardia. These drugs reduce blood pressure in many patients with arterial hypertension, decreasing renin plasma activity. Since these drugs have a nephroprotective effect, they become drugs of choice in diabetes mellitus and are preferred for those of the Negroid race.

The most common side effect is dry irritating cough, but the most serious is angioedema. If it develops in the oropharynx, it can be life threatening. Angioedema often develops in smokers and people of the Negroid race. ACE inhibitors can increase the concentration of serum creatinine and potassium, especially in patients with chronic renal failure and receiving potassium-sparing diuretics, potassium-containing supplements and NSAIDs. ACE inhibitors less often than all other antihypertensive drugs cause erectile dysfunction. Preparations of this group are contraindicated in pregnancy. In patients with kidney disease, monitoring the concentration of potassium and serum creatinine is performed at least once every 3 months. Patients with renal insufficiency (serum creatinine concentration> 123.6 μmol / L) receiving ACE inhibitors usually carry a 30-35% increase in serum creatinine content compared to baseline. ACE inhibitors can lead to the development of acute renal failure in patients with hypovolemia or having severe heart failure, severe bilateral renal artery stenosis, or severe stenosis of the renal artery of a single kidney.

ACE Inhibitors

Benazepril	5-40.1 times a day
Captopril	12,5-150,2 times a day
Enalapril	2.5-40.1 times a day
Fosinopril	10-80.1 times a day
Lisinopril	5-40.1 times a day
Moexipril	7,5-60,1 times a day
Hinapril	5-80.1 times a day
Ramipril	1,25-20,1 times a day
Trandolapril	1-4,1 times a day

Side Effects of ACE Inhibitors

Rash, cough, angioedema, hyperkalemia (especially in patients with renal insufficiency or taking NSAIDs, potassium-sparing diuretics or potassium preparations), perversion of taste, reversible acute renal failure in the event that one- or bilateral stenosis of the renal arteries leads to impaired renal function ; proteinuria (sometimes when prescribing drugs at recommended doses), neutropenia (rarely), arterial hypotension at the beginning of treatment (mainly in patients with high plasma renin activity or hypovolemia due to diuretics or other causes).

* All ACE inhibitors and angiotensin II receptor blockers are contraindicated in pregnancy (evidence level C in the first trimester, level of evidence D in the II and III trimesters).

Thiazide diuretics increase the hypotensive effect of ACE inhibitors more than other classes of antihypertensive drugs.

[18], [19], [20], [21], [22], [23], [24]

Blockade of angiotensin II receptors

Preparations of this group block the receptors of angiotensin II and thus interact with the renin-angiotensin system.

Angiotensin II receptor blockers

Candesartan	8-32.1 times a day
Eprosartan	400-1200.1 times a day
Ibebestan	75-300.1 times a day
Losartan	25-100.1 times a day
Olmesartan medoxomil	20-40.1 times a day
Telmisartan	20-80.1 times a day
Valsartan	80-320.1 times a day

Side effects of angiotensin II receptor blockers

Increased sweating, angioedema (very rarely), it is theoretically possible that some effect of ACE inhibitors on kidney function (except proteinuria and neutropenia), potassium content in blood serum and blood pressure

Angiotensin II receptor blockers and ACE inhibitors are equally effective antihypertensives. Blockers of angiotensin II receptors can exert additional effect due to blockade of tissue ACE. Both classes have the same positive effects on patients with left ventricular failure or nephropathy due to type 1 diabetes mellitus. Angiotensin II receptor blockers, used together with ACE inhibitors or b-blockers, reduce the number of hospitalizations in patients with heart failure. Angiotensin II receptor blockers can be safely administered to people younger than 60 years with a blood creatinine content of <264.9 μmol / L.

The risk of side effects is low; the development of angioedema may be significantly less frequent than with the use of ACE inhibitors. Precautions for the appointment of angiotensin II receptor blockers to patients with renovascular hypertension, hypovolemia and severe heart failure are the same as for ACE inhibitors. Blockers of angiotensin II receptors are contraindicated in pregnancy.

[25], [26], [27], [28], [29], [30], [31], [32],

Drugs affecting adrenergic receptors

This class of drugs includes central-action a-agonists, postsynaptic a-blockers and peripheral-action adrenergic receptor blockers.

A-Agonists (such as methyldopa, clonidine, guanabenz, guanfacine) stimulate a-adrenergic receptors in the brainstem and reduce sympathetic nervous activity by lowering blood pressure. Since they have a central effect, they are more likely than dasgs of other groups to cause drowsiness, inhibition and depression; at present they are not widely used. Clonidine can be administered in a patch (percutaneously) once a week. This can be useful for patients with whom it is difficult to reach a contact (for example, patients with dementia).

Post-synaptic a-blockers (eg, prazosin, terazosin, doxazosin) are no longer used for basic treatment of hypertension, since experience indicates that there is no positive effect on mortality. In addition, doxazosin, administered as monotherapy or with other antihypertensive drugs, other than diuretics, increases the risk of heart failure.

Blockers of adrenergic receptors of peripheral action (for example, reserpine, guanethidine, guanadrel) purify the tissue receptors of norepinephrine. Reserpine also cleanses the brain of norepinephrine and serotonin. Guanethidine and guanadrel block sympathetic transmission in the nervous synapse. In general, guanethidine is effective, but its dose is very difficult to titrate, so it is rarely used. Guanadrel is a shorter-acting drug and has some side effects. All drugs in this group are usually not recommended for initial therapy; they are used as a third or fourth drug if necessary.

A-Blockers

Doxazosin	1-16.1 times a day	Fainting of the "first dose", orthostatic hypotension, weakness, palpitation, headache	It is necessary to appoint with caution the elderly due to orthostatic hypotension. Reduce the symptoms of benign prostatic hyperplasia
Prazozin	1-10.2 times a day
Terazozin	1-20.1 times a day

Peripheral adrenoblockers

Guanadela sulfate	5-50.2 times a day	Diarrhea, sexual dysfunction, orthostatic hypotension (for guanadela sulfate and guanethidine), inhibition, nasal congestion, depression, peptic ulcer exacerbation with rauwolfia alkaloids or reserpine	Reserpine is contraindicated in patients with a history of depression. He is appointed with caution to a patient with a history of gastrointestinal ulcer. Guanadela sulfate and guanethidine are used with caution because of the risk of developing orthostatic hypotension
Guanethidine	10-50.1 times a day
Rauwolfia alkaloids	50-100.1 times a day
Reserpine	0.05-0.25 times

[33], [34], [35], [36], [37]

Direct vasodilators

These drugs (including minoxidil and hydralazine) have an effect directly on the vessels, regardless of the autonomic nervous system. Minoxidil is more effective than hydralazine, but it has more side effects, including sodium and water retention, as well as hypertrichosis, which is especially worrisome for women. Minoxidil should be a reserve agent for severe, refractory to the treatment of hypertension. Hydralazine is prescribed during pregnancy (including pre-eclampsia) and as an additional antihypertensive agent. Long-term use of high doses of hydralazine (> 300 mg / day) is associated with the development of the syndrome of drug lupus, which disappears after discontinuation of the drug.

Direct vasodilators prescribed for arterial hypertension

A drug	Dose, mg	Possible side effects	Comments
Hydralazine	10-50.4 times a day	A positive test for antinuclear antibodies, drug lupus (rarely with recommended doses) The delay of sodium and water, hypertrichosis, the appearance of new or increased exudates in the pleural cavity and pericardial cavity	Enhancement of vasodilating effects of other vasodilator drugs The drug reserve for severe refractory arterial hypertension
Minoxidil	1,25-40,2 times a day

"Both drugs can cause headache, tachycardia, fluid retention and provoke angina in patients with coronary artery disease.

[38], [39], [40], [41], [42]