Transcript Antihypertensive agents

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 %
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 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)
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
Decreasing of arterial
pressure
Cardiac output
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, longterm treatment of arterial hypertension
 Adverse reactions: dehydration, hypokalemia,
hearing loss - deafness, hypocalcaemia
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)
Furosemid
(diuretic)
Furosemid (diuretic)
Triampur
(triamteren + hydrochlorthiaside)
diuretic
Mechanism of action of beta-adrenoblockers
(anaprilin, atenolol, methoprolol etc.)
in case of arterial hypertension
activation of
β1-adrenoreceptors
of heart
βadrenoblockers
Cardiac
output
Peripheral resistance of vessels
Angiotensine
Renin
Decreasing of
blood pressure
ΙΙ
Aldosterone
Holding sodium
and water
Volume of
blood circulation
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
Atenolol
β - adrenoblocker
Anaprilin
β1- β 2 adrenoblocker
Vasocardin 100 mg
Methoprolol tartrate
Nadolol
( β1, β 2 - adrenoblocker )
Tenoretic
(atenolol + chlortalidon)
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
Prasosine
(α1 –adrenoblocker)
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
MECHANISM OF ACTION OF
IACE
ANGIOTENSINOGEN
sympathetic
tone
Renin (kidneys)
ANGIOTENSIN
(inactive)
Decrease
angiotensine II
production
ACE
IACE
Decrease
aldosterone
production
peripheral
vessels tone
retention of
Na+ and H2O
bradicinine
Decrease of
arterial
pressure
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 potassiumsparing 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)
Captopril (IACE)
KOZAAR (Losartan)
АRА ІІ
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)
NIFEDIPINE
(calcium channels blocker)
NIFEDIPINE
(calcium channels blocker)
NIFEDIPINE
(calcium channels blocker)
NIFEDIPINE
(calcium channels blocker)
NORVASC (AMLODIPINE)
(calcium channels blocker)
Calcium channels blockers administration
DRUGS
diseases
Arterial
hypertension
Verapamil
Dilthiasem
Niphedipin
Ischemic
heart disease
Verapamil
Dilthiasem
Niphedipin
Supraventricule
tachicardia
Verapamil
Dilthiasem
Possibility to
combine with
beta-blockers
recommended drug
Dilthiasem
Дилтіазем
Niphedipin
to use carefully
Felodipin
Amlodipin
Amlodipin
Felodipin
Amlodipin
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
CLOPHELINE
(decreases vasomotor centers tone)
SINEPRESS
(dihydroergotoxine + reserpine + hydrochlorthiaside)
TRIRESIDE
(reserpine + hydralasine + hydrochlorothiaside)
CRISTEPIN
(clopamide + dihydroergocristine + reserpine)
MANAGEMENT OF HYPERTENSIVE EMERGENCY (intravenously)
Drug
Sodium
nitroprussid
Dose
0,5-10 mcg/kg/min (dropply)
Nitroglycerinum
5-10 mcg/kg (dropply)
Onset
immediately
Side effects
nausea, vomiting,
muscles, sweating
2-5 min
tachicardia,
vomiting,
fibrillation of
flushing,
headache,
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
Magnesium
sulfas
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,
dizzeness
vomiting,,
hypotension,