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Antihypertensive drugsAntihypertensive drugs
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 %
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.
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))
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
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
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)
Furosemid Furosemid ((diureticdiuretic))
Furosemid Furosemid ((diureticdiuretic))
TriampurTriampur((triamterentriamteren + + hydrochlorthiasidehydrochlorthiaside))
diureticdiuretic
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
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
Atenolol Atenolol β - β - adrenoblockeradrenoblocker
AnaprilinAnaprilin ββ11- β - β 2 2 adrenoblockeradrenoblocker
Vasocardin Vasocardin 100 100 mgmgMethoprolol tartrateMethoprolol tartrate
NadololNadolol(( ββ11, β , β 22 - - adrenoblockeradrenoblocker ) )
TenoreticTenoretic(atenolol + chlortalidon)(atenolol + chlortalidon)
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
Prasosine Prasosine (α(α11 – –adrenoblockeradrenoblocker))
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
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)
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)
Captopril Captopril ((IACEIACE))
KOZAAR KOZAAR ((LosartanLosartan)) ААRRА ІІА ІІ
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)
NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)
NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)
NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)
NIFEDIPINENIFEDIPINE(calcium channels blocker)(calcium channels blocker)
NORVASC (AMLODIPINE)NORVASC (AMLODIPINE) (calcium channels blocker)(calcium channels blocker)
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
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
CLOPHELINECLOPHELINE(decreases vasomotor centers tone)(decreases vasomotor centers tone)
SINEPRESSSINEPRESS
((dihydroergotoxine dihydroergotoxine + + reserpinereserpine ++ hydrochlorthiaside hydrochlorthiaside))
TRIRESIDETRIRESIDE((reserpine reserpine + + hydralasine hydralasine ++ hydrochlorothiaside hydrochlorothiaside))
CRISTEPINCRISTEPIN((clopamide + dihydroergocristineclopamide + dihydroergocristine + reserpine + reserpine))
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