1. Clinical Pharmacology of Drugs for Controlling Vascular Tone
Clinical Pharmacology of Drugs for Controlling Vascular Tone. ANTIHYPERTENSIVE DRUGS

2. ANTIHYPERTENSIVE DRUGS
I. DIURETICS Bumetanide, furosemide, hydrochlorthiazide, spironolactone, triamterene II. -BLOCKERS Atenolol, labetalol, metoprolol, propranolol, timolol III. ACE INHIBITORS Captopril, benazepril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril IV. ANGIOTENSIN II ANTAGONIST Losartan V. Ca++CHANNEL BLOCKERS Amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, verapamil VI. -BLOCKERS Doxazosin, prazosin, terazosin VII. OTHER Clonidine, diazoxide, hydralazine, -methyldopa, minoxidil, sodium nitroprusside

3. TREATMENT STRATEGIES

5. Treatment of arterial hypertension
Drugs of first row
-diuretics (furosemid, dichlothiazide, spironolacton)
-inhibitors of ACE (captopril, enalapril, ramipril)
-antagonists of angiotesine II receptors (АRА ІІ) (losartan)
-β-adrenoblockers (anaprilin, atenolol, thymolol)
-α-, β-adrenoblockers (labetolol, carvedilol)
-Ca ions antagonists (niphedipine, amlodipine, verapamil)
Drugs of second row :
-α-adrenoblockers (prasosine, terasosine)
-agonists of α2 –adrenoreceptors of central action (clopheline, methyldopa)
-sympatholytics (reserpin, octadin)
-direct vasodilators (molsidomin, hydralasin)
New drugs:
-imidasolines (moxonidine, rilmenidine)
-serotonin receptors blockers (ketanserin)
-monateril (calcium antagonist, α2 -adrenoblocker)

7. Hydrochlorothiazide+Losartan

8. Thiazide diuretics. Adverse effects:

9. Loop diuretics
The loop diuretics act promptly, even in patients who have poor renal function or who have not responded to thiazides or other diuretics.

11. -blockers. Therapeutic uses

12. β-adrenoblockers

13. ACE-INHIBITORS
The angiotensin-converting enzyme (ACE) inhibitors (captopril, enalapril, lisinopril, perindopril) are recommended when the preferred first-line agents (diuretics or -blockers) are contraindicated or ineffective.

14. MECHANISM OF ACTION OF IACE
ANGIOTENSINOGEN
sympathetic
tone
Renin (kidneys)
ANGIOTENSIN
(inactive)
peripheral
vessels tone
Decrease of
arterial
pressure
Decrease
angiotensine II
production
retention of
Na+ and H2O
ACE
Decrease
aldosterone
production -
bradicinine
IACE

16. Therapeutic uses

17. ACE inhibitors adverse effects

18. ANGIOTENSIN II ANTAGONISTS Losartan (Cozaar®), Valsartan (Diovan®), Irbesartan (Avapro®), Candesartan (Atacand®).

19. ANGIOTENSIN II ANTAGONISTS

20. CALCIUM CHANNEL BLOCKERS

22. -ADRENERGIC BLOCKING AGENTS
Prazosin, doxazosin and terazosin produce a competitive block of 1 adrenoreceptors. They decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Postural hypotension may occur in some individuals. Prazosin is used to treat mild to moderate hypertension and is prescribed in combination with propranolol or a diuretic for additive effects

24. CENTRALLY-ACTING ADRENERGIC DRUGS
Clonidine – 2-agonist – diminishes central adrenergic outflow. Clonidine does not decrease renal blood flow or glomerular filtration and therefore is useful in the treatment of hypertension complicated by renal disease. Because it causes sodium and water retention, clonidine is usually administered in combination with diuretic.

25. CENTRALLY-ACTING ADRENERGIC DRUGS

26. CENTRALLY-ACTING ADRENERGIC DRUGS
-Methyldopa. This 2-agonist is converted to methylnorepinephrine centrally to diminish the adrenergic outflow from the CNS, leading to reduced total peripheral resistance and a decreased blood pressure. Because blood flow to the kidney is not diminished by its use, -methyldopa is especially valuable in treating hypertensive patients with renal insufficiency. The most common side effects of -methyldopa are sedation and drowsiness.

27. VASODILATORS

28. VASODILATORS

29. PRINCIPLES OF THERAPY Therapeutic Regimens
Once the diagnosis of hypertension is established, a therapeutic regimen must be designed and implemented. The goal of management for most clients is to achieve and maintain normal blood pressure range (below 140/90 mm Hg). If this goal cannot be achieved, lowering blood pressure to any extent is still considered beneficial in decreasing the incidence of coronary artery disease and stroke.

31. HYPERTENSIVE EMERGENCY

32. MANAGEMENT OF HYPERTENSIVE EMERGENCY (intravenously)
Drug
Dose
Onset
Side effects
Sodium
nitroprussid
0,5-10 mcg/kg/min (dropply)
immediately
nausea, vomiting, fibrillation of muscles, sweating
Nitroglyceri-num
5-10 mcg/kg (dropply)
2-5 min
tachicardia, flushing, headache, vomiting,
Diazoxidum
mg (quickly)
300 mg (during 10 min)
2-4 min
nausea, vomiting,, hypotension, tachicardia, flushing, redness of skin, chest pain
Apressinum
10-20 mg
10 min
flushing, redness of skin, headache,
vomiting
Furosemidum
mg during sec
2-3 min
hypotension, fatigue
Clophelinum
0,5-1 ml 0,01 % solution (in ml ,9 % solution NaCI slowly)
15-20 min
somnolence
Anaprilinum
5 ml 0,1 % solution (in 20 ml 0,9 % NaCI solution slowly)
20-30 min
bradicardia
Magnesium
sulfas
ml 25 % solution (i. v. very slowly or dropply)
redness of skin
Labetololum
20-80 mg (slowly – 10 min) or 2 mg/kg (dropply); the whole dose – mg
5-10 min
nausea, vomiting,, hypotension, dizzeness