1. Antihypertensive drugs

2. FREQUENCY of arterial hypertension (AH) AP > 140/90 mm Hg
20-30 % in population
At elderly people %

3. Principles of treatment of arterial hypertension 1
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 don’t treat the patient at all.

4. 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-adrenoblockers (prasosine, terasosine)
-α-, β-adrenoblockers (labetolol, carvedilol)
-Ca ions antagonists (niphedipine, amlodipine, verapamil)
Drugs of second row :
-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)

5. (chlortalidon, hygroton) Decreasing of arterial
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

6. FUROSEMIDE Properties : 1. diuretic action
High 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 indometacine and other NSAID)
Administration: hypertensive emergencies, long-term treatment of arterial hypertension
Adverse reactions: dehydration, hypokalemia, hearing loss - deafness, hypocalcaemia

7. THIAZIDES and RELATED DIURETICS
Medium efficacy diuretics
Benzothiadiazines (chlorothiazide, hydrochlorothiazide, clopamide), related thiazide like (chlorthalidone, indapamide)
for long-term treatment of arterial hypertesion (oral administration)
Duration of action (6-12 hours for hydrochlorothiazide, hours for clopamide, hours for chlorthalidone)
Adverse reactions: dehydration, hypokalemia, hyperuricaemia (rise of blood urate level)

8. Furosemid (diuretic)

9. Furosemid (diuretic)

10. Triampur (triamteren + hydrochlorthiaside) diuretic

11. Mechanism of action of beta-adrenoblockers
(anaprilin, atenolol, methoprolol etc.)
in case of arterial hypertension β-
adrenoblockers
activation of
β1-adrenoreceptors
of heart
Cardiac
output
Decreasing of
blood pressure
Peripheral resist-
ance of vessels
Angiotensine ΙΙ
Renin
Aldosterone
Holding sodium
and water
Volume of blood circulation

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

13. Atenolol β - adrenoblocker

14. Anaprilin β1- β 2 adrenoblocker

15. Vasocardin 100 mg Methoprolol tartrate

16. Nadolol ( β1, β 2 - adrenoblocker )

17. Tenoretic (atenolol + chlortalidon)

18. α1-adrenergic blockers (prazosin, terazosin, doxazosin)
Do not block presynaptic α2-adreno-receptors, so do not cause reflex cardiac stimulation (as compared to nonselective α-adrenoblockers)
Dilate resistance and capacitance vessels
Adverse effects: postural hypotension (“effect of first dose”), tolerance gradually develops with monotherapy

19. Prasosine (α1 –adrenoblocker)

20. α, β – adrenoreceptors blockers (labetalol, carvedilol)
Labetalol is used for long-term treatment of AH and 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

21. 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

22. 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 potassium-sparing diuretics !) and β-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)

23. Captopril (IACE)

24. KOZAAR (Losartan) АRА ІІ

25. 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 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)

26. NIFEDIPINE (calcium channels blocker)

27. NIFEDIPINE (calcium channels blocker)

28. NIFEDIPINE (calcium channels blocker)

29. NIFEDIPINE (calcium channels blocker)

30. NORVASC (AMLODIPINE) (calcium channels blocker)

31. Calcium channels blockers administration
diseases
DRUGS
Arterial hypertension
Verapamil
Dilthiasem
Niphedipin
Felodipin
Amlodipin
Ischemic heart disease
Verapamil
Dilthiasem
Niphedipin
Amlodipin
Supraventricule
tachicardia
Verapamil
Dilthiasem
Possibility to
combine with beta-blockers
Dilthiasem
Дилтіазем
Niphedipin
Felodipin
Amlodipin
recommended drug
to use carefully

32. CLOPHELINE
α2 - adrenergic receptors agonist (in brainstem stimulates α2 - 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

33. CLOPHELINE (decreases vasomotor centers tone)

34. SINEPRESS (dihydroergotoxine + reserpine + hydrochlorthiaside)

35. TRIRESIDE (reserpine + hydralasine + hydrochlorothiaside)

36. CRISTEPIN (clopamide + dihydroergocristine + reserpine)

37. 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