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Antihypertensive drugs

Antihypertensive drugs. Lector prof. Posokhova K.A. FREQUENCY of arterial hypertension (AH) AP > 140/90 mm Hg. 20-30 % in population At elderly people - 45-50 %.

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Antihypertensive drugs

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  1. Antihypertensive drugs Lector prof. Posokhova K.A.

  2. FREQUENCY of arterial hypertension (AH)AP > 140/90 mm Hg • 20-30 % in population • At elderly people - 45-50 %

  3. Principles of treatment of arterial hypertension1.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 durationof 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. Mechanism of action of thiaside diuretics incase 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 • 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, 12-18 hours for clopamide, 48-50 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.) incase of arterial hypertension β- adrenoblockers activation of β1-adrenoreceptors of heart Cardiac output Decreasing of blood pressure Peripheral resist- ance of vessels AngiotensineΙΙ 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 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

  13. Atenolol β - adrenoblocker

  14. Anaprilinβ1- β 2 adrenoblocker

  15. Vasocardin 100 mgMethoprolol 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 recommended drug to use carefully

  32. CLOPHELINE • α2-adrenergic receptorsagonist(in brainstem stimulates α2-adrenergic receptorsandimidazoline 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)

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