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

Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

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

Antihypertensive drugsAntihypertensive drugs

Lector prof. Posokhova K.A.Lector prof. Posokhova K.A.

Page 2: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

FREQUENCY FREQUENCY of arterial hypertension (AH)of arterial hypertension (AH)

AP > 140/90 mm Hg

20-30 % in population20-30 % in population At elderly people - 45-50 %At elderly people - 45-50 %

Page 3: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

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.

Page 4: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Treatment of arterial hypertensionTreatment of arterial hypertension

Drugs of first rowDrugs of first row--diureticsdiuretics ( (furosemid, dichlothiazide, spironolactonfurosemid, dichlothiazide, spironolacton) ) --inhibitors of ACEinhibitors of ACE ( (captopril, enalapril, ramiprilcaptopril, enalapril, ramipril))--antagonists of angiotesine II receptorsantagonists of angiotesine II receptors (А (АRRА ІІ) А ІІ) (losartan)(losartan)-β--β-adrenoblockersadrenoblockers ( (anaprilinanaprilin, , atenololatenolol, , thymololthymolol) ) -α--α-adrenoblockersadrenoblockers ( (prasosine, terasosineprasosine, terasosine))-α-, β--α-, β-adrenoblockersadrenoblockers ( (labetolol, carvedilollabetolol, carvedilol))--Ca ions antagonistsCa ions antagonists ( (niphedipine, amlodipine, verapamilniphedipine, amlodipine, verapamil))Drugs of second rowDrugs of second row : :--agonists of agonists of αα22 – –adrenoreceptors of central actionadrenoreceptors of central action ( (clophelineclopheline, , methyldopamethyldopa))

--sympatholytics sympatholytics ((reserpin, octadinreserpin, octadin))--direct vasodilatorsdirect vasodilators ( (molsidominmolsidomin, , hydralasinhydralasin))New drugsNew drugs::--imidasolinesimidasolines ( (moxonidine, rilmenidinemoxonidine, rilmenidine))--serotonin receptors blockersserotonin receptors blockers ( (ketanserinketanserin) ) --monaterilmonateril ( (calcium antagonistcalcium antagonist, α, α22 - -adrenoblockeradrenoblocker))

Treatment of arterial hypertensionTreatment of arterial hypertension

Drugs of first rowDrugs of first row--diureticsdiuretics ( (furosemid, dichlothiazide, spironolactonfurosemid, dichlothiazide, spironolacton) ) --inhibitors of ACEinhibitors of ACE ( (captopril, enalapril, ramiprilcaptopril, enalapril, ramipril))--antagonists of angiotesine II receptorsantagonists of angiotesine II receptors (А (АRRА ІІ) А ІІ) (losartan)(losartan)-β--β-adrenoblockersadrenoblockers ( (anaprilinanaprilin, , atenololatenolol, , thymololthymolol) ) -α--α-adrenoblockersadrenoblockers ( (prasosine, terasosineprasosine, terasosine))-α-, β--α-, β-adrenoblockersadrenoblockers ( (labetolol, carvedilollabetolol, carvedilol))--Ca ions antagonistsCa ions antagonists ( (niphedipine, amlodipine, verapamilniphedipine, amlodipine, verapamil))Drugs of second rowDrugs of second row : :--agonists of agonists of αα22 – –adrenoreceptors of central actionadrenoreceptors of central action ( (clophelineclopheline, , methyldopamethyldopa))

--sympatholytics sympatholytics ((reserpin, octadinreserpin, octadin))--direct vasodilatorsdirect vasodilators ( (molsidominmolsidomin, , hydralasinhydralasin))New drugsNew drugs::--imidasolinesimidasolines ( (moxonidine, rilmenidinemoxonidine, rilmenidine))--serotonin receptors blockersserotonin receptors blockers ( (ketanserinketanserin) ) --monaterilmonateril ( (calcium antagonistcalcium antagonist, α, α22 - -adrenoblockeradrenoblocker))

Page 5: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Mechanism of action of thiaside diureticsin case of arterial hypertension

Dychlothiaside(hypothiaside)

Oxodolin (chlortalidon, hygroton)

Thiaside diuretics

Holding sodium and water

Volume of circulating blood

Cardiac output

Peripheral vascular resistance

Decreasing of arterial pressure

Page 6: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

FUROSEMIDEFUROSEMIDE

High ceiling (loop) diureticHigh ceiling (loop) diuretic Properties :Properties :

1. diuretic action1. diuretic action

2. dilation of peripheral venous2. dilation of peripheral venous

3. decrease left ventricular filling pressure3. decrease left ventricular filling pressure

4. potent anti-inflammatory effect (similar to 4. potent anti-inflammatory effect (similar to indometacine and other NSAID)indometacine and other NSAID) Administration:Administration: hypertensive emergencies, long- hypertensive emergencies, long-term treatment of arterial hypertension term treatment of arterial hypertension Adverse reactions: Adverse reactions: dehydration, hypokalemia, dehydration, hypokalemia, hearing loss - deafness, hypocalcaemia hearing loss - deafness, hypocalcaemia

Page 7: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

THIAZIDES and RELATED DIURETICSTHIAZIDES and RELATED DIURETICS

Medium efficacy diureticsMedium efficacy diuretics Benzothiadiazines (chlorothiazide, hydrochlorothiazide, Benzothiadiazines (chlorothiazide, hydrochlorothiazide,

clopamide), related thiazide like (chlorthalidone, clopamide), related thiazide like (chlorthalidone, indapamide)indapamide)

for long-term treatment of arterial hypertesion (oral for long-term treatment of arterial hypertesion (oral administration)administration)

Duration of action (6-12 hours for hydrochlorothiazide, Duration of action (6-12 hours for hydrochlorothiazide, 12-18 hours for clopamide, 48-50 hours for 12-18 hours for clopamide, 48-50 hours for chlorthalidone)chlorthalidone)

Adverse reactions: dehydration,Adverse reactions: dehydration, hypokalemia, hypokalemia, hyperuricaemia (rise of blood urate level)hyperuricaemia (rise of blood urate level)

Page 8: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Furosemid Furosemid ((diureticdiuretic))

Page 9: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Furosemid Furosemid ((diureticdiuretic))

Page 10: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

TriampurTriampur((triamterentriamteren + + hydrochlorthiasidehydrochlorthiaside))

diureticdiuretic

Page 11: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

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

Angiotensine ΙΙ Renin

Aldosterone

Holding sodium and water

Peripheral resist- ance of vessels

Volume of blood circulation

Decreasing of blood pressure

Page 12: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

ββ-adrenoblockers-adrenoblockers

Used for mostly mild to moderate cases of AH Used for mostly mild to moderate cases of AH (frequently in combinations with other drugs)(frequently in combinations with other drugs)

Stable hypotensive response develops over Stable hypotensive response develops over 1-3 weeks1-3 weeks

Titration the effective doseTitration the effective dose Antihypertensive action is maintained over Antihypertensive action is maintained over

24 hr after single daily dose24 hr after single daily dose Withdrawal syndrome if discontinue quickly Withdrawal syndrome if discontinue quickly Contraindications: bronchial asthma, Contraindications: bronchial asthma,

peripheral vascular disease, diabetesperipheral vascular disease, diabetes

Page 13: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Atenolol Atenolol β - β - adrenoblockeradrenoblocker

Page 14: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

AnaprilinAnaprilin ββ11- β - β 2 2 adrenoblockeradrenoblocker

Page 15: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Vasocardin Vasocardin 100 100 mgmgMethoprolol tartrateMethoprolol tartrate

Page 16: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

NadololNadolol(( ββ11, β , β 22 - - adrenoblockeradrenoblocker ) )

Page 17: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

TenoreticTenoretic(atenolol + chlortalidon)(atenolol + chlortalidon)

Page 18: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

αα11-adrenergic blockers-adrenergic blockers

(prazosin, terazosin, doxazosin)(prazosin, terazosin, doxazosin)

Do not block presynaptic Do not block presynaptic αα22-adreno-receptors, -adreno-receptors,

so do not cause reflex cardiac stimulation (as so do not cause reflex cardiac stimulation (as compared to nonselective compared to nonselective αα-adrenoblockers)-adrenoblockers)

Dilate resistance and capacitance vesselsDilate resistance and capacitance vessels

Adverse effects: postural hypotension (“effect Adverse effects: postural hypotension (“effect of first dose”), tolerance gradually develops of first dose”), tolerance gradually develops with monotherapy with monotherapy

Page 19: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Prasosine Prasosine (α(α11 – –adrenoblockeradrenoblocker))

Page 20: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

αα, , ββ – adrenoreceptors blockers – adrenoreceptors blockers(labetalol, carvedilol)(labetalol, carvedilol)

Labetalol is used for long-term treatment of AH Labetalol is used for long-term treatment of AH and for emergencies (i. v. - hypertensive crisis, and for emergencies (i. v. - hypertensive crisis, clonidine withdrawal, cheese reaction)clonidine withdrawal, cheese reaction)

Carvedilol – produces vasodilatation, Carvedilol – produces vasodilatation, antioxidant/free radical scavenging properties, it antioxidant/free radical scavenging properties, it is used for HD and for CHFis used for HD and for CHF

Page 21: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

MECHANISM OF ACTION OF IACE

Decrease of arterial pressure

sympathetic tone

peripheral vessels tone

retention of Na+ and H2O

bradicinine

ANGIOTENSINOGEN

ANGIOTENSIN

(inactive)

IACE

Decrease angiotensine II

production

Decrease aldosteroneproduction

-

ACE

Renin (kidneys)

Page 22: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

IACE (ANGIOTENSIN CONVERTING IACE (ANGIOTENSIN CONVERTING ENZYME INHIBITORS)ENZYME INHIBITORS)

Captopril, enalapril, ramipril, perindopril etc.Captopril, enalapril, ramipril, perindopril etc. Decrease the levels of mortality and morbidityDecrease the levels of mortality and morbidity When used for monotherapy control AP in 50% of patientsWhen used for monotherapy control AP in 50% of patients Frequently combined with diuretics (not with potassium-Frequently combined with diuretics (not with potassium-

sparing diuretics !) and sparing diuretics !) and ββ-adrenoblockers-adrenoblockers - the - the effectiveness of therapy grows to 90%effectiveness of therapy grows to 90%

Adverse effects: cause the retention of potassium ions, dry Adverse effects: cause the retention of potassium ions, dry persistent cough (requires discontinuation of IACE or persistent cough (requires discontinuation of IACE or treatment with NSAID)treatment with NSAID)

Contraindicated for the patients with bilateral renal artery Contraindicated for the patients with bilateral renal artery stenosis)stenosis)

Page 23: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Captopril Captopril ((IACEIACE))

Page 24: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

KOZAAR KOZAAR ((LosartanLosartan)) ААRRА ІІА ІІ

Page 25: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

CALCIUM CHANNEL BLOCKERS CALCIUM CHANNEL BLOCKERS (dihydropyridines – DHPs)(dihydropyridines – DHPs)

Short acting DHPs (nifedipine) can increase mortality Short acting DHPs (nifedipine) can increase mortality as a result of reinfarction (long term controlled trials)as a result of reinfarction (long term controlled trials)

Retard forms of DHPs (Retard forms of DHPs (AmlodipineAmlodipine) are used widely for ) are used widely for AHAH

Do not contraindicated in asthma, do not impair renal Do not contraindicated in asthma, do not impair renal perfusion, do not affect male sexual functionperfusion, do not affect male sexual function

Can be used during pregnancy Can be used during pregnancy Can be given to diabeticsCan be given to diabetics Adverse reactions: Adverse reactions: ankle edema, slight negative ankle edema, slight negative

inotropic / dromotropic action, nifedipine decreases inotropic / dromotropic action, nifedipine decreases insulin release (diabetes accentuating) insulin release (diabetes accentuating)

Page 26: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)

Page 27: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)

Page 28: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)

Page 29: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)

Page 30: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

NORVASC (AMLODIPINE)NORVASC (AMLODIPINE) (calcium channels blocker)(calcium channels blocker)

Page 31: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

Arterial Arterial hypertensionhypertension

VerapamilVerapamil DilthiasemDilthiasem NiphedipinNiphedipin FelodipinFelodipin AmlodipinAmlodipin

Ischemic Ischemic heart diseaseheart disease

DilthiasemDilthiasem NiphedipinNiphedipin AmlodipinAmlodipinVerapamilVerapamil

SupraventriculeSupraventricule

tachicardia tachicardia

VerapamilVerapamil DilthiasemDilthiasem

Possibility to Possibility to combine with combine with beta-blockersbeta-blockers

DilthiasemDilthiasem

ДилтіаземДилтіазем

NiphedipinNiphedipin AmlodipinAmlodipin

recommended drug to use carefully

diseases DRUGS

FelodipinFelodipin

Calcium channels blockers administrationCalcium channels blockers administration

Page 32: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

CLOPHELINECLOPHELINE αα22 -- adrenergic receptorsadrenergic receptors agonistagonist (in brainstem (in brainstem

stimulates stimulates αα22 -- adrenergic receptorsadrenergic receptors andand imidazoline imidazoline

receptors)receptors) decreases vasomotor centers tone - reduces decreases vasomotor centers tone - reduces

sympathetic tone - fall in APsympathetic tone - fall in AP Increases vagal tone - bradycardiaIncreases vagal tone - bradycardia Has analgesic activityHas analgesic activity For hypertensive emergencies (i. v. dropply or very For hypertensive emergencies (i. v. dropply or very

slowly)slowly) Side effects and complications: Side effects and complications: postural hypotension, postural hypotension,

sedation, mental depression, sleep disturbance, dry sedation, mental depression, sleep disturbance, dry mouth, constipation, withdrawal syndromemouth, constipation, withdrawal syndrome

Page 33: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

CLOPHELINECLOPHELINE(decreases vasomotor centers tone)(decreases vasomotor centers tone)

Page 34: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

SINEPRESSSINEPRESS

((dihydroergotoxine dihydroergotoxine + + reserpinereserpine ++ hydrochlorthiaside hydrochlorthiaside))

Page 35: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

TRIRESIDETRIRESIDE((reserpine reserpine + + hydralasine hydralasine ++ hydrochlorothiaside hydrochlorothiaside))

Page 36: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

CRISTEPINCRISTEPIN((clopamide + dihydroergocristineclopamide + dihydroergocristine + reserpine + reserpine))

Page 37: Antihypertensive drugs Antihypertensive drugs Lector prof. Posokhova K.A

MANAGEMENT OF HYPERTENSIVE EMERGENCY (intravenously)MANAGEMENT OF HYPERTENSIVE EMERGENCY (intravenously)

Drug Dose Onset Side effects

Sodiumnitroprussid

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 50-100 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 20-60-100 mg during 10-15 sec 2-3 min hypotension, fatigue

Clophelinum 0,5-1 ml 0,01 % solution (in 15-20 ml 0,9 % 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

Magnesiumsulfas

5-10-20 ml 25 % solution (i. v. very slowly or dropply)

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, vomiting,, hypotension, dizzeness