Download MINISTRY OF HEALTH OF UZBEKISTAN

MINISTRY OF HEALTH OF UZBEKISTAN
CENTRE FOR MEDICAL EDUCATION
Tashkent Medical Academy
Department of Clinical Pharmacology
Subject CLINICAL PHARMACOLOGY
Topic: "Pharmacological Approaches to rational prescribing of drugs for treatment of the
syndrome
ARTERIAL HYPERTENSION "
Educational-methodical development
(For teachers, students)
6. The content of lessons
6.1. Theoretical part
- Classification of antihypertensive drugs
- Select the most effective and safe drug or combination of drugs depending on the
severity of hypertension, patient age and comorbidity
- Select the most effective and safe drug, depending on the goals of treatment (mild
hypertensive crisis, long-term therapy)
- Side effects of antihypertensive drugs and measures to help
Arterial hypertension (AH) - a syndrome that is the increase in blood pressure (BP)
(systolic blood pressure above 140 mm Hg or diastolic blood pressure above 90 mm
Hg).
Current treatment is aimed at hypertension syndrome restoration of blood pressure at
normal or optimal levels of binding effect on all risk factors are modified.
Treatment should be early in the GB, differentiated, aimed at preventing the progression
of the disease and prevent complications, and active longer. In essence, it continues
throughout life. Intermittent, exchange treatment is permissible only if I st. GB.
Indications for drug therapy:
• family history for hypertension, heart attacks, strokes, their relatives;
• increased blood pressure during the night and morning, and pronounced variability in
blood pressure;
• presence of target organ damage (heart, blood vessels, brain, kidneys);
• identification of other major cardiovascular risk factors: hyperlipidemia, impaired
carbohydrate tolerance, hyperuricemia.
Currently, several classes of antihypertensive drugs recommended for long-term
treatment of hypertension. Antihypertensive drugs, suitable for both monotherapy and
combination therapy are: 1) angiotensin-converting enzyme (ACE), 2) AT1-blockers,
angiotensin receptors, and 3) thiazide (and tiazidopodobnye) diuretics, 4) calcium
channel blockers, 5) β -blockers, and 6) selective adrenoceptor blockers, α1-7) agonist
of central α2-adrenergic receptors, and 8) I1-imidazoline agonist receptors.
When choosing antihypertensive medication for long-term therapy should consider not
only the pathogenic mechanisms of GB, and comorbidities in this patient. Are also
important mechanisms of antihypertensive action of vasoactive drugs, particularly its
pharmacodynamics and pharmacokinetics, side effects and contraindications to.
Angiotensin-converting enzyme
Under the influence of long-term therapy of ACE inhibitors is reversed left ventricular
hypertrophy and arterial wall in patients with GB. ACE inhibitors have a number of
pharmacological properties that may be useful in patients with GB, in particular,
renoprotektivnym, anti-ischemic, anti-atherogenic, etc.
Doses of ACE inhibitors are selected empirically, from the smallest of the
recommended. Under the control of blood pressure medication dose is increased to a
selected sredneterapevticheskoy.
All ACE inhibitors are characteristic side effects such as hypotension, renal failure,
hyperkalemia, dry cough and angioedema, change in taste.
It is not recommended to use ACE inhibitors as antihypertensives in bilateral renal
artery stenosis, stenosis of the artery the only functioning kidney, severe renal failure,
severe hyperkalemia during pregnancy and childhood, as well as individual
hypersensitivity to this group of medications (or dry cough angioedema in history).
With great care, ACE inhibitors should be used in patients with obliterative
atherosclerosis of arteries of lower limbs (because of the frequent combination of
atherosclerotic lesions of the peripheral and renal arteries), atherosclerosis common in
coronary and carotid arteries, moderate renal insufficiency, mild hyperkalemia (5 to 5 5
mEq / L), chronic active hepatitis or cirrhosis, as well as in women of childbearing age
not using adequate contraceptive methods (including the adverse effects of drugs on
fetal development).
AT1-blockers, angiotensin receptor
The most important differences between pharmacodynamic effects of AT II receptor
antagonists of ACE inhibitors:
1) absence of adverse effects associated with activation of the bradykinin system;
2) a more complete blocking of the effects of AT II;
3) a milder effect on renal hemodynamics (changes in activity due to the absence of
intrarenal kinin system);
4) the growing influence of AT II on AT2 receptors, which complements the vasodilator
and antiproliferative effects.
Blockers in hypertension, angiotensin receptor AT1 to use for the same indications as
the ACE inhibitors: 1) GB (particularly in patients with left ventricular systolic dysfunction
or diabetes), 2) diabetic nephropathy (especially in diabetes mellitus type I), as well as
when the patient has a history of an indication of the cough caused by ACE inhibitors.
AT1-blockers, angiotensin receptors are distinguished from modern antihypertensive
excellent tolerability. Headache, dizziness and weakness - the most frequent adverse
events in patients receiving angiotensin AT1-blockers (frequency 1%).
Contraindications to blockers of AT1-angiotensin receptor only three - individual
hypersensitivity to the drug, II and III trimester of pregnancy and breastfeeding. Caution
should be exercised in the appointment of AT1-blockers, angiotensin receptor women of
childbearing age not using effective contraception, in connection with a possible
adverse effect of drugs on fetal development in the event of an unplanned pregnancy.
Diuretics
Currently, thiazide (and tiazidopodobnye) Diuretics are effective, safe and the cheapest
antihypertensive drugs, which can be used both as monotherapy and in combination
with other drugs, in addition, these drugs, as well as other antihypertensive drugs, can
cause the opposite development of left ventricular hypertrophy in patients with GB.
The most common side effects of thiazide diuretics metabolic (biochemical):
hypokalemia, hypomagnesemia, and hyperuricemia (Table 2). Excessive loss of
potassium and magnesium in the treatment of high doses of thiazide diuretics due to
their other well-known side effects - occurrence of ventricular arrhythmias and
disturbance of carbohydrate metabolism in susceptible individuals long-term therapy
with thiazide diuretics may contribute to the development of diabetes. Indapamide, in
contrast to other thiazide diuretics and tiazidopodobnyh quite safe for prolonged use in
diabetic patients. Thiazide diuretics can cause impotence in men.
Indapamide, in contrast to other thiazide diuretics and tiazidopodobnyh certainly has a
direct vasodilating action. When a drug in doses subdiureticheskih PR is reduced by 1018%. Suggest the following mechanisms vasodilating action of indapamide: 1) blockade
of calcium channels, 2) stimulation of prostaglandin I2 (prostacyclin), prostaglandin E2,
with vasodilating properties, and 3) agonism with respect to potassium channels.
Contraindications for long-term use of thiazide diuretics and in patients tiazidopodobnyh
GB are hypokalemia, gout, asymptomatic hyperuricemia, decompensated cirrhosis,
intolerance to sulfa derivatives (diuretics, antidiabetic and antibacterial drugs). In high
doses, thiazide diuretics are contraindicated in patients with diabetes, especially type I.
With great care should be given diuretics to patients with ventricular arrhythmias or
cardiac glycosides or receiving lithium.
β-blockers
Most patients with GB, as you know, PR is raised, therefore, other things being equal,
for its long-term therapy is clearly preferable to the use of β-blocker with vasodilating
properties.
For long-term therapy GB recommended average doses of β-blockers without BCA,
giving preference to drugs effective in taking one or two times a day. With a choice is
obviously better to use a β1-selective drugs with lipophilic properties, ie betaxolol,
bisoprolol, carvedilol, metoprolol or nebivolol.
If, within 2-4 weeks of blood pressure can not be reduced to the desired level using
medium-dose β-blocker, should not increase the dose of the drug, but to add a thiazide
diuretic (hydrochlorothiazide, indapamide, chlorthalidone), dihydropyridine calcium
channel blocker (amlodipine, nifedipine, felodipine) or α1-blocker (doxazosin, prazosin).
Calcium channel blockers
Calcium antagonists, long-acting especially shown in the following situations:
1. With isolated systolic hypertension in elderly patients - in those cases when thiazide
diuretics are contraindicated and tiazidopodobnye are ineffective or cause serious side
effects, is recommended to first use a dihydropyridine calcium antagonists, long-lasting.
2. After myocardial infarction - in cases where β-blockers are contraindicated,
ineffective (as antihypertensive drugs) or cause side effects, recommended to use
verapamil or diltiazem.
3. In patients with concomitant angina - in cases where counter-β-blockers or
ineffective, you can use any calcium channel blockers.
4. In patients with diabetic nephropathy - in cases where ACE inhibitors are
contraindicated or ineffective (as antihypertensive medications), use verapamil or
diltiazem.
As for short-and calcium channel blockers dihydropyridine derivatives in particular (eg,
nifedipine), they are not recommended for long-term therapy GB. It is particularly
important to avoid the use of short-range calcium antagonists for the treatment of
hypertension in patients with coronary artery disease, acute myocardial infarction.
Α1-blockers, adrenergic
Selective α1-blocker doxazosin in particular, are effective antihypertensive drugs, which
have a number of useful additional properties (beneficial effect on the metabolism of
lipids and carbohydrates, platelet aggregation, urination and sexual function in men).
Because of its additional properties doxazosin α1-blocker (especially his retardnaya
form) and to a lesser extent, other α1-blockers in some situations are preferable to longterm therapy GB than thiazide diuretics, β-blockers, calcium antagonists and ACE
inhibitors, namely: the patients with concomitant benign prostatic hyperplasia, erectile
dysfunction, diabetes, atherogenic dyslipidemia, chronic obstructive pulmonary disease
and obliterating atherosclerosis of lower extremities.
Α2-agonists of adrenergic receptors
Hyperactivity of sympathetic nervous system (SNS) is one of the main mechanisms to
increase blood pressure and unfavorable prognostic sign in patients with GB. SNS
hyperactivity is manifested not only elevated blood pressure, and tachycardia, increased
cardiac output, renal vasoconstriction, fluid retention, as well as insulin resistance.
At the heart of antihypertensive action of a-methyldopa, clonidine, guanfacine and
guanabenz are guided by their agonism on α2-adrenergic receptors located on neurons
of the nucleus solitary tract of the medulla oblongata.
At present, α-methyldopa is the drug of first line treatment of hypertension in pregnant
women because its safety for the embryo and fetus proved long-term supervision for
children whose mothers received the drug during pregnancy. Clonidine is also safe
during pregnancy, but it is worse tolerated than α-methyldopa.
Agonists of I1-imidazoline receptor
Currently in clinical practice, used only two selective agonist I1-imidazoline receptors moxonidine and rilmenidine.
Clinical importance is the fact that agonists of I1-imidazoline receptors have a favorable
effect on the metabolism of carbohydrates and lipids, in particular, moxonidine reduces
insulin resistance and improves glucose tolerance and lowers plasma levels of
triglycerides and cholesterol.
Given the high antihypertensive efficacy of moxonidine and rilmenidine, and their good
tolerability and a favorable effect on glucose metabolism, agonists I1-imidazoline
receptors may be considered first-line drugs for long-term treatment of patients with GB
obesity, diabetes type II, as well as in women during menopause.
DIFFERENTIAL TREATMENT OF ARTERIAL HYPERTENSION IN VIEW OF
RELATED DISEASES AND OTHER RISK FACTORS
criteria
Coronary heart disease
Congestive failure
circulation:
- Systolic dysfunction
Recommended group
Beta-blockers
Calcium channel blockers
(ACE inhibitors)
Diuretics
ACE inhibitors
(Alpha-blockers)
- Diastolic dysfunction
Beta blockers
Calcium channel blockers
ACE inhibitors
(Alpha-blockers, diuretics)
Cerebrovascular disease
Peripheral circulatory disorders
Diabetes mellitus
Calcium channel blockers
(Beta-blockers, diuretics, ACE inhibitors)
calcium antagonists (diuretics, ACE
inhibitors, alpha-blockers)
ACE inhibitors
Alpha-blockers
(Calcium antagonists)
Renal failure
Loop diuretics
Thiazides only when creatinine clearance
30 ml / min
Calcium channel blockers
ACE inhibitors
(Alpha-blockers)
Dyslipidemia
Alpha-blockers
(Calcium antagonists, ACE inhibitors)
Bronchial asthma
Obstructive bronchitis
ACE inhibitors
Calcium channel blockers
Diuretics
Alpha-blockers
Diuretics
Calcium channel blockers
ACE inhibitors
Alpha-blockers
Methyldopa
Advanced age
ARTERIAL HYPERTENSION IN PREGNANCY
Treatment with antihypertensive drugs is carried out if the level of diastolic blood
pressure above 90 mmHg in the sitting position (supine blood pressure in pregnant
women may decrease by 10-15 mm Hg). The goal of treatment is not only the
prevention of complications of hypertension, but also prevention of late toxemia of
pregnancy. When selecting antihypertensive drugs and their dosage should be aware
that a sharp decrease in blood pressure affects utero-placental circulation and that
some drugs are not indifferent to the fetus.
AH 1-2 degrees First-line agents:
Methyldopa 500 mg (2-4 times)
Second-line drugs:
Pindolol 5-15 mg (2 times)
Nifedipine SR 20-40 mg (2 times)
Third-line drugs:
Methyldopa + second-line drugs or
Hydralazine 10-50 mg 2-4 times
Clonidine 0.05-0.2 mg (2-4)
In the presence of renal disease:
Diuretics
hypertension grade 3
First-line agents:
Hydralazine 5-10 mg bolus of a / c, if
necessary again after 20 minutes up to 30
mg / introduction of 3-10 mg / h
Nifedipine 10 mg every 1-3 hours
When refractory to first-line drugs:
Diazoxide
Sodium nitroprusside
Hypertensive STATE EMERGENCY
Urgent hypertensive state found in 1% of cases, one of the criteria of these states is to
increase the diastolic blood pressure over 120-130 mm Hg It was under this pressure,
there is a danger of eye, brain, heart and kidneys.
By pressing hypertensive states include:
- Hypertensive encephalopathy
- Malignant gipertneziya
- Hemorrhagic stroke
- Unstable angina!
- Acute myocardial infarction! against high
- Pulmonary edema! Blood Pressure
- Dissecting aortic aneurysm!
- Eclampsia
- Withdrawal of antihypertensive drugs
- Acute intoxication antihypertensives
The main goal is to reduce blood pressure in a relatively short period of time. Blood
pressure was lowered to 100-110 mm Hg or diastolic blood pressure by 25-40% of the
mean arterial pressure (MAP). This should be done in 30 minutes. Further therapy is
strictly individual.
INDIVIDUAL THERAPY WITH ALGORITHM IMMEDIATE GIPERTEZIVNYH STATES
Neurological symptoms
Angina and acute
myocardial infarction is
recommended nitroglycerin,
, the alternative is
nitroprusside. Avoid use of
Heart
Symptoms
In the presence of
encephalopathy, malignant
hypertension or
haemorrhage
recommended
Spetseficheskie etiological
factors
. When pregnancy begins
with the introduction of
magnesium sulfate. Next,
go to hydralazine, betablockers and sedatives
hydralazine, nifedipine and
diazoxide. If you have back
pain should think about
having dissecting aortic
aneurysm before
prescribing.
Lung edema nitroglycerin
or nitroprusside, should be
combined with loop
diuretics.
nitroprusside or trimetafan.
The dose of drugs carefully
titrated to avoid the
appearance of ischemic
disorders
In case of overdose or
severe intoxications with
benzodiazepines start, then
switch to a combination of
beta-blockers with
nitroprusside or
phentolamine.
When dissecting aortic
aneurysm recommend
nitroprusside + short-range
beta-blockers or trimetafan.
Hypertensive crisis
If the patient suffers from hypertension and has noted the rise in diastolic blood
pressure equal or above 120 mmHg, it is called hypertensive crisis. The main goal of
therapy to lower blood pressure to target levels within 24 hours of therapy. In most
cases, satisfactory effect is obtained in the first 60 minutes of treatment. Reduce
pressure so that in 30 minutes diastolic blood pressure decreased by 10-15 mmHg
Stroke Therapy should be individual, depending on the preceding state, the type of
hypertension. Most often, when crises are using oral or sublingual appointment of
clonidine, nifedipine or captopril.
Nifedipine is not recommended for patients with discomfort or chest pain, signs of
ischemia or the presence of CHD, as a reflex tachycardia may increase symptoms of
ischemia.
Clonidine is not recommended for patients with neurological symptoms (drowsiness).
Usually drug given sublingually, the effect comes quickly: within 30 minutes of DBP
decreased by 10 mmHg To enhance the effect of drugs in 60 minutes of sublingual
administration, the same drug administered by mouth.
Treatment algorithm Hypertensive crisis
Medical history should include data on physical examination the patient, as the nervous,
cardiovascular and urinary systems, description of drug therapy
Required laboratory data: ECG, chest x-ray, hematocrit, electrolytes, creatinine, urea.
DRUGS USED IN THE INSIDE sublingual hypertensive crisis and Hypertensive
IMMEDIATE STATES
The initial dose of drug (mg) Onset of action, min. The length sequence of q-I, h
Repeated doses every hour side effects
Nifedipine 10 5-15 3-6 10 mg to 30 mg tachycardia, flushing, rarely, shock and heart
attack due to the rapid decline in blood pressure.
Clonidine 0.2 5-15 6.12 to 0.1 mg to 0.5 mg drowsiness, dry mouth, bradyarrhythmias
Captopril 25 5-15 4-6 25 mg to 50 mg of flavor violation
Labetalol 200 4.6 15-30 100-200 mg to 1200 mg. Hypotension
RATIONAL TREATMENT OF ARTERIAL HYPERTENSION SYNDROME IN
PEDIATRICS
For a number of serious diseases of renal parenchyma in children is peculiar syndrome
of hypertension. That's why antihypertensive therapy is one of the most common types
of treatment in pediatric syndromological in children with kidney disease. When
expressed mild hypertension preferably start with the central action of sedatives such as
valerian, Motherwort, bromine. These drugs belong to a group of antihypertensive
drugs, are often used by a small increase in pressure transient nature.
In pediatric nephrology practice widely used beta-blockers, which in renal hypertension
to some extent weaken the activation of the renin-angiotensin system. In recent years in
pediatrics for the treatment of hypertension are widely used drugs from two groups of
substances:
1. Drugs affecting the renin-angiotensin system - angiotensin-converting enzyme (ACE);
2. Medicines that block calcium channels.
Preference will be given captopril and its analogs, which are synthetic analogs of an
ACE inhibitor. It is increasingly used in pediatric practice enalapril - angiotensinconverting enzyme inhibitor, which is taken one time a day. It is important to only pick
up a dose of Nephrology monitoriruya blood pressure patient. There is information
about the possibility of eliminating proteinuria in long-term use of captopril and its
analogues.
Drugs that block calcium channels, in particular, began to be used in the nifedipine
nephrology clinic recently. That captopril and nifedipine can be attributed to the group of
antihypertensive drugs, which are now increasingly being assigned to children with
renal pathology in cases of persistent high blood pressure.