Obat Antihypertensi: DR Med DR - Widharto PH, SPFK Farmakologi Dan Terapi Fak - Kedokteran Ugm
Obat Antihypertensi: DR Med DR - Widharto PH, SPFK Farmakologi Dan Terapi Fak - Kedokteran Ugm
Obat Antihypertensi: DR Med DR - Widharto PH, SPFK Farmakologi Dan Terapi Fak - Kedokteran Ugm
Drug Halflife(h) Bioavailability(%) Suggested Initial Dose Usual Maintenance Dose Range
Atenolol 6 60 50 mg/d 50–100 mg/d
Captopril 2.2 65 50–75 mg/d 75–150 mg/d
Clonidine 8–12 95 0.2 mg/d 0.2–1.2 mg/d
Guanethidine 5 50 10 mg/d 25–50 mg/d
Hydralazine 1 25 100 mg/d 40–200 mg/d
Hydrochlorothiazide 12 70 25 mg/d 25–50 mg/d
Lisinopril 12 25 10 mg/d 10–80 mg/d
Losartan 1–22 36 50 mg/d 2.5–100 mg/d
Methyldopa 2 25 1 g/d 1–2 g/d No
Minoxidil 4 90 5–10 mg/d 40 mg/d No
Nifedipine 2 50 30 mg/d 30–90 mg/d
Prazosin 3–4 70 3 mg/d 10–30 mg/d
Propranolol 3–6 25 80 mg/d 80–480 mg/d
Reserpine 24–48 NA 0.25 mg/d 0.25 mg/d
Verapamil 4–6 22 180 mg/d 240–480 mg/d
Centrally Acting Sympathoplegic Drugs
Mechanisms & Sites of Action
• These agents reduce sympathetic outflow from
vasopressor centers in the brainstem but allow
these centers to retain or even increase their
sensitivity to baroreceptor control. Accordingly,
the antihypertensive and toxic actions of these
drugs are generally less dependent on posture
than are the effects of drugs that act directly on
peripheral sympathetic neurons
Methyldopa (L- -methyl-3,4-dihydroxyphenylalanine)
• is an analog of L-dopa and is converted to –
methyl-dopamine and -methylnorepinephrine;
• this pathway directly parallels the synthesis of
norepinephrine from dopa illustrated in Figure
6–5. Alpha-methylnorepinephrine is stored
inadrenergic nerve vesicles, where it
stoichiometrically replaces norepinephrine,
and is released by nerve stimulation to
interact with postsynaptic adrenoceptors
clonidine, a 2-imidazoline derivative
• The antihypertensive action of, was discovered in the course of testing the drug
for use as a topically applied nasal decongestant.
• After intravenous injection, clonidine produces a brief rise in blood pressure
followed by more prolonged hypotension.
• The pressor response is due to direct stimulation of -adrenoceptors in arterioles.
• The drug is classified as a partial agonist at -receptors because it also inhibits
pressor effects of other -agonists.
• Considerable evidence indicates that the hypotensive effect of clonidine is
exerted at -adrenoceptors in the medulla of the brain. In animals, the
hypotensive effect of clonidine is prevented by central administration of
-antagonists. Clonidine reduces sympathetic and increases para-sympathetic
tone, resulting in blood pressure lowering and bradycardia.
• The reduction in pressure is accompanied by a decrease in circulating
catecholamine levels.
Guanabenz and guanfacine
• are centrally active antihypertensive drugs
that share the central - adrenoceptor-
stimulating effects of clonidine. They do not
appear to offer any advantages over clonidine.
Pharmacokinetics & Dosage
Toxicity
Dry mouth and sedation are frequent and may be severe. Both effects are centrally mediated
and dose-dependent and coincide temporally with the drug's antihypertensive effect.
The drug should not be given to patients who are at risk for mental depression and should be
withdrawn if depression occurs during therapy
Reserpine
Adrenoceptor Antagonists
Enalapril:
• By mouth, inital dose 2.5 mg
• Should be given twice daily for 24-hour cover.
• May be increased to 5 mg, 10 mg, 20 mg, and a maximum of 40 mg
daily, in divided doses.
Lisinopril:
• By mouth, initially 2.5 mg daily.
• May be increased to 10 mg, 20 mg, and a maximum of 40 mg daily(in
hypertension).
• Usual maintenance dose 10–20 mg daily.
Ramipril:
• By mouth, initially 2.5 mg daily.
• May be increased to 5 mg, then to a maximum of 10 mg daily .
Angiotensin receptor antagonists/blockers (ARBs)
Losartan:
• By mouth, 50 mg daily.
• May be increased in increments of 25 mg daily to a maximum of 100 mg daily.
• Reduce the initial dose to 25 mg daily in renal or hepatic insufficiency .
Irbesartan
• By mouth, 150 mg daily.
• May be increased to a maximum of 300 mg daily.
• Reduce the initial dose to 75 mg daily in renal insufficiency.
Candesartan
• By mouth, initially 4 mg daily; increase to 8 mg daily if tolerated.
• May be increased to a maximum of 16 mg daily.
• Reduce the initial dose to 2 mg daily in renal or hepatic insufficiency.
Valsartan
• By mouth, initially 80 mg daily.
• May be increased to a maximum of 160 mg daily.
• Reduce the initial dose to 40 mg daily in renal or hepatic insufficiency.
Calcium channel blockers
The contraction of vascular smooth muscle cells
depends on influx of calcium into the cell in
response to depolarization. Inhibition of this
influx of calcium causes vasodilatation.
These drugs have differential effects on the
heart and peripheral vasculature, depending
on their chemical structures
Groups of calcium channel blockers
Dihydropyridines
• Typified by nifedipine
• Principally affect the peripheral vasculature
Phenyalkylamines
• Typified by verapamil
• Principally affect the heart
Benzthiazepines
• Typified by diltiazem
• Affect the heart and peripheral vasculature
Dihydropyridines (nifedipine-like)