Antihypertensive drugs

Lector prof. Posokhova K.A.

FREQUENCY of arterial hypertension (AH)

AP > 140/90 mm Hg
 20-30 % in population 20 At elderly people - 45-50 % 45-

Principles of treatment of arterial hypertension 1.

Treatment should be started as soon as possible and should be hold till the end of life. Canceling antihypertensive drugs administration causes relapse of AH. 2. All the individuals with increased arterial pressure should obtain drugless treatment (modifying lifestyle): -rejection from smoking and alcohol; -increasing of physical activity; -restriction of salt consumption (less than 6 g per day); -decreasing of body weight in a case of obesity. 3. Scheme of drug treatment should be the most availably simple 1 tablet per day if possible; it is better to use drugs with long duration of action (prophylaxis of considerable fluctuation of blood pressure during the day). 4. Rapid decreasing of blood pressure to low figures is dangerous, especially for elderly patients. 5. Main aim of the treatment is to decrease blood pressure to 140/90 mm Hg. To improve life prognosis is the aim that has a more significant meaning than character of drugs used to reach this aim. It is better to prescribe cheap and non modern drugs than dont treat the patient at all.

Treatment of arterial hypertension

Drugs of first row -diuretics (furosemid, dichlothiazide, spironolacton) spironolacton) -inhibitors of ACE (captopril, enalapril, ramipril) ramipril) -antagonists of angiotesine II receptors ( R ) (losartan) - -adrenoblockers (anaprilin, atenolol, thymolol) anaprilin, atenolol, thymolol) - -adrenoblockers (prasosine, terasosine) terasosine) - -, -adrenoblockers (labetolol, carvedilol) carvedilol) -Ca ions antagonists (niphedipine, amlodipine, verapamil) verapamil) Drugs of second row : -agonists of 2 adrenoreceptors of central action (clopheline, methyldopa) clopheline, methyldopa) -sympatholytics (reserpin, octadin) octadin) -direct vasodilators (molsidomin, hydralasin) molsidomin, hydralasin) New drugs: drugs: -imidasolines (moxonidine, rilmenidine) rilmenidine) -serotonin receptors blockers (ketanserin) ketanserin) -monateril (calcium antagonist, 2 -adrenoblocker) antagonist, adrenoblocker)

Mechanism of action of thiaside diuretics in case of arterial hypertension

Dychlothiaside (hypothiaside)

Oxodolin (chlortalidon, hygroton)

Thiaside diuretics

Holding sodium and water

Volume of circulating blood Peripheral vascular resistance

Cardiac output

Decreasing of arterial pressure

FUROSEMIDE
ceiling (loop) diuretic  Properties : 1. diuretic action 2. dilation of peripheral venous 3. decrease left ventricular filling pressure 4. potent anti-inflammatory effect (similar to antiindometacine and other NSAID)  Administration: hypertensive emergencies, longlongterm treatment of arterial hypertension  Adverse reactions: dehydration, hypokalemia, hearing loss - deafness, hypocalcaemia
 High

THIAZIDES and RELATED DIURETICS

 Medium efficacy diuretics  Benzothiadiazines (chlorothiazide, hydrochlorothiazide, clopamide), related thiazide like (chlorthalidone, indapamide)  for long-term treatment of arterial hypertesion (oral longadministration)  Duration of action (6-12 hours for hydrochlorothiazide, (61212-18 hours for clopamide, 48-50 hours for 48chlorthalidone)  Adverse reactions: dehydration, hypokalemia, hyperuricaemia (rise of blood urate level)

Furosemid
(diuretic) diuretic)

Furosemid (diuretic) diuretic)

Triampur
(triamteren + hydrochlorthiaside) hydrochlorthiaside) diuretic

Mechanism of action of beta-adrenoblockers (anaprilin, atenolol, methoprolol etc.) in case of arterial hypertension

adrenoblockers

activation of 1-adrenoreceptors of heart

Cardiac output

Peripheral resistance of vessels

Decreasing of blood pressure

Renin

Angiotensine

Aldosterone Holding sodium and water Volume of blood circulation

-adrenoblockers
 Used for mostly mild to moderate cases of AH (frequently in combinations with other drugs)  Stable hypotensive response develops over 1-3 weeks  Titration the effective dose  Antihypertensive action is maintained over 24 hr after single daily dose  Withdrawal syndrome if discontinue quickly  Contraindications: bronchial asthma, peripheral vascular disease, diabetes

Atenolol
- adrenoblocker

Anaprilin
12 adrenoblocker

VASOCARDIN 100 MG
METHOPROLOL TARTRATE

Nadolol (
1, 2-

adrenoblocker )

Tenoretic
(atenolol + chlortalidon)

blockers (prazosin, terazosin, doxazosin)

 Do not block presynaptic 2-adreno-receptors, adrenoso do not cause reflex cardiac stimulation (as compared to nonselective -adrenoblockers)  Dilate resistance and capacitance vessels  Adverse effects: postural hypotension (effect of first dose), tolerance gradually develops with monotherapy

1-adrenergic

Prasosine
(
1

adrenoblocker) adrenoblocker)

adrenoreceptors blockers (labetalol, carvedilol)

 Labetalol is used for long-term treatment of AH longand for emergencies (i. v. - hypertensive crisis, clonidine withdrawal, cheese reaction)  Carvedilol produces vasodilatation, antioxidant/free radical scavenging properties, it is used for HD and for CHF

MECHANISM OF ACTION OF IACE

ANGIOTENSINOGEN

Renin (kidneys)
ANGIOTENSIN

sympathetic tone

(inactive)

Decrease angiotensine II production

peripheral vessels tone

Decrease of arterial pressure

ACE

IACE

Decrease aldosterone production

retention of Na+ and H2O

bradicinine

IACE (ANGIOTENSIN CONVERTING ENZYME INHIBITORS)

Captopril, enalapril, ramipril, perindopril etc. Decrease the levels of mortality and morbidity When used for monotherapy control AP in 50% of patients Frequently combined with diuretics (not with potassiumpotassiumsparing diuretics !) and -adrenoblockers - the effectiveness of therapy grows to 90%  Adverse effects: cause the retention of potassium ions, dry persistent cough (requires discontinuation of IACE or treatment with NSAID)  Contraindicated for the patients with bilateral renal artery stenosis)    

Captopril (IACE) IACE)

KOZAAR (Losartan) Losartan)

R

CALCIUM CHANNEL BLOCKERS (dihydropyridines DHPs)

 Short acting DHPs (nifedipine) can increase mortality as a result of reinfarction (long term controlled trials)  Retard forms of DHPs (Amlodipine) are used widely for (Amlodipine) AH  Do not contraindicated in asthma, do not impair renal perfusion, do not affect male sexual function  Can be used during pregnancy  Can be given to diabetics  Adverse reactions: ankle edema, slight negative inotropic / dromotropic action, nifedipine decreases insulin release (diabetes accentuating)

NIFEDIPINE (calcium channels blocker)

NIFEDIPINE (calcium channels blocker)

NIFEDIPINE (calcium channels blocker)

NIFEDIPINE (calcium channels blocker)

NORVASC (AMLODIPINE)

(calcium channels blocker)

Calcium channels blockers administration

diseases
Arterial hypertension Ischemic heart disease Supraventricule tachicardia Possibility to combine with betabeta-blockers
Verapamil Dilthiasem

DRUGS
Niphedipin Felodipin Amlodipin

Verapamil

Dilthiasem

Niphedipin

Amlodipin

Verapamil

Dilthiasem

Dilthiasem

Niphedipin

Felodipin

Amlodipin

recommended drug

to use carefully

CLOPHELINE
 receptors agonist (in brainstem stimulates 2 - adrenergic receptors and imidazoline receptors) decreases vasomotor centers tone - reduces sympathetic tone - fall in AP Increases vagal tone - bradycardia Has analgesic activity For hypertensive emergencies (i. v. dropply or very slowly) Side effects and complications: postural hypotension, sedation, mental depression, sleep disturbance, dry mouth, constipation, withdrawal syndrome
2 - adrenergic

    

CLOPHELINE (decreases vasomotor centers tone)

SINEPRESS
(dihydroergotoxine + reserpine + hydrochlorthiaside) hydrochlorthiaside)

TRIRESIDE
(reserpine + hydralasine + hydrochlorothiaside) hydrochlorothiaside)

CRISTEPIN
(clopamide + dihydroergocristine + reserpine) reserpine)

MANAGEMENT OF HYPERTENSIVE EMERGENCY (intravenously)

Drug Sodium nitroprussid Nitroglycerinum Diazoxidum Dose 0,5-10 mcg/kg/min (dropply) 5-10 mcg/kg (dropply) 50-100 mg (quickly) 300 mg (during 10 min) 10-20 mg 20-60-100 mg during 10-15 sec 0,5-1 ml 0,01 % solution (in 15-20 ml 0,9 % solution NaCI slowly) 5 ml 0,1 % solution (in 20 ml 0,9 % NaCI solution slowly) 5-10-20 ml 25 % solution (i. v. very slowly or dropply) Onset
immediately

Side effects

nausea, vomiting, muscles, sweating

tachicardia, vomiting,

fibrillation of
headache,

2-5 min 2-4 min

flushing,

nausea, vomiting,, hypotension, tachicardia, flushing, redness of skin, chest pain flushing, redness of skin, headache, vomiting hypotension, fatigue
somnolence

Apressinum Furosemidum Clophelinum

10 min 2-3 min 15-20 min 20-30 min

Anaprilinum Magnesium sulfas

bradicardia

15-20 min

redness of skin

Labetololum

20-80 mg (slowly 10 min) or 2 mg/kg (dropply); the whole dose 50-300 mg

5-10 min

nausea, dizzeness

vomiting,,

hypotension,