Download diuretics

Clinical Pharmacology of
Drugs for Controlling
Vascular Tone.
ANTIHYPERTENSIVE
DRUGS
ANTIHYPERTENSIVE DRUGS
I. DIURETICS
Bumetanide, furosemide, hydrochlorthiazide, spironolactone,
triamterene
II. -BLOCKERS
Atenolol, labetalol, metoprolol, propranolol, timolol
III. ACE INHIBITORS
Captopril, benazepril, enalapril, fosinopril, lisinopril, moexipril,
quinapril, ramipril
IV. ANGIOTENSIN II ANTAGONIST
Losartan
V. Ca++CHANNEL BLOCKERS
Amlodipine, diltiazem, felodipine, isradipine, nicardipine,
nifedipine, nisoldipine, verapamil
VI. -BLOCKERS
Doxazosin, prazosin, terazosin
VII. OTHER
Clonidine, diazoxide, hydralazine, -methyldopa, minoxidil,
sodium nitroprusside
TREATMENT STRATEGIES
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-, β-adrenoblockers (labetolol, carvedilol)
-Ca ions antagonists (niphedipine, amlodipine, verapamil)
Drugs of second row :
-α-adrenoblockers (prasosine, terasosine)
-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
Hydrochlorothiazide+Losartan
Thiazide diuretics. Adverse effects:
Loop diuretics
The loop diuretics act promptly, even in
patients who have poor renal function or
who have not responded to thiazides or
other diuretics.
-blockers. Therapeutic uses
β-adrenoblockers
ACE-INHIBITORS
The angiotensin-converting enzyme (ACE)
inhibitors (captopril, enalapril, lisinopril,
perindopril) are recommended when the
preferred first-line agents (diuretics or blockers) are contraindicated or
ineffective.
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
Therapeutic uses
ACE inhibitors adverse effects
ANGIOTENSIN II ANTAGONISTS
Losartan (Cozaar®), Valsartan (Diovan®),
Irbesartan (Avapro®), Candesartan
(Atacand®).
ANGIOTENSIN II ANTAGONISTS
CALCIUM CHANNEL BLOCKERS
-ADRENERGIC BLOCKING AGENTS
Prazosin, doxazosin and terazosin produce a
competitive block of 1 adrenoreceptors. They decrease
peripheral vascular resistance and lower arterial blood
pressure by causing the relaxation of both arterial and
venous smooth muscle. These drugs cause only minimal
changes in cardiac output, renal blood flow, and
glomerular filtration rate. Postural hypotension may
occur in some individuals. Prazosin is used to treat
mild to moderate hypertension and is prescribed in
combination with propranolol or a diuretic for additive
effects
Prasosine
(α 1 –
–adrenoblocker
adrenoblocker))
CENTRALLY-ACTING
ADRENERGIC DRUGS
Clonidine – 2-agonist – diminishes central adrenergic
outflow. Clonidine does not decrease renal blood flow or
glomerular filtration and therefore is useful in the
treatment of hypertension complicated by renal disease.
Because it causes sodium and water retention, clonidine
is usually administered in combination with diuretic.
CENTRALLY-ACTING
ADRENERGIC DRUGS
CENTRALLY-ACTING
ADRENERGIC DRUGS
-Methyldopa. This 2-agonist is converted to
methylnorepinephrine centrally to diminish the
adrenergic outflow from the CNS, leading to
reduced total peripheral resistance and a
decreased blood pressure. Because blood flow
to the kidney is not diminished by its use, methyldopa is especially valuable in treating
hypertensive patients with renal insufficiency.
The most common side effects of -methyldopa
are sedation and drowsiness.
VASODILATORS
VASODILATORS
Mechanisms of Action of Vasodilators.
Mechanism
Examples
Release of nitric oxide from drug or endothelium
Nitroprusside, hydralazine, nitrates,
histamine, acetylcholine
Reduction of calcium influx
Verapamil, diltiazem, nifedipine
Hyperpolarization of smooth muscle membrane
through opening of potassium channels
Minoxidil, diazoxide
Activation of dopamine receptors
Fenoldopam
PRINCIPLES OF THERAPY
Therapeutic Regimens
Once the diagnosis of hypertension is established, a
therapeutic regimen must be designed and
implemented. The goal of management for most
clients is to achieve and maintain normal blood
pressure range (below 140/90 mm Hg). If this goal
cannot be achieved, lowering blood pressure to any
extent is still considered beneficial in decreasing the
incidence of coronary artery disease and stroke.
HYPERTENSIVE EMERGENCY
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,