Obat Anti Hipertensi

Based on golongan :

Renin-Angiotensin-aldosteron system inhibitor (sRAA

Inhibitor)
 ACEi
Mechanism :
Inhibition of ACE → ↓ conversion of angiotensin I to angiotensin II

 ↓ Angiotensin II
o ↓ Vasoconstriction → ↓ blood pressure
o ↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure
o Dilation of efferent arteriole → ↑ renal plasma flow → ↓ filtration fraction
o ↑ Renin secretion (compensatory) → ↑ Angiotensin I

 ↓ Breakdown of bradykinin → ↑ production of arachidonic acid metabolites → ↑ vasodilation → ↓

blood pressure

Contoh Obat :
 Captopril [D] {oral}
 Adult : Initially, 12.5-25 mg daily in 2-3 divided doses. Dosage is individualised
according to clinical response and may be increased after at least 2 weeks, to 50 mg
daily in 2-3 divided doses as needed to reach target BP. Patients on diuretics or
with cardiac decompensation: Initially 12.5 mg tid.
 Child : Neonates and infants: 0.15 mg/kg. Children and adolescents: 0.3 mg/kg.
 Elderly : Initially, 6.25 mg bid.
o Sediaan obat : Tab 12.5 mg x 10 x10 | 25 mg x 10 x 10

 ARB (Angiotensin Reseptor Blocker) (sartans)

Mechanism :
 Inhibition of angiotensin II receptor type 1 (AT1 receptors) →
 ↓ Vasoconstriction → ↓ blood pressure

 ↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure

 ↑ Renin secretion (compensatory) → ↑ Angiotensin I → ↑ Angiotensin II

Contoh Obat :
 Losartan [D] {oral}
  Adult : 50 mg daily. Dosage is individualised and may be increased to 100 mg once
daily according to clinical response. Patients with intravascular volume depletion:
Initially, 25 mg daily.
 Child : 6-18 years >20-<50 kg: 0.7 mg/kg once daily (up to total of 25 mg). Max: 50
mg daily, as necessary. >50 kg: Same as adult dose. Adjust dose based on blood
pressure response.
 Elderly : >75 years 25 mg daily.
o Sediaan obat : Tab 50 mg | 100 mg

 Direct Renin Inhibitors

Mechanism :
 Direct inhibition of renin → ↓ conversion of angiotensinogen into angiotensin I → ↓ angiotensin I and angiotensin
II → vasoconstriction caused by ↓ angiotensin II

 ↓ Blood pressure

 ↓ Secretion of aldosterone → ↓ reabsorption of Na  and water → further ↓ blood pressure

+

Contoh Obat :
 Aliskiren [D] {oral}
 Adult : ≥18 yr 150 mg once daily, increased to 300 mg once daily if needed
o Sediaan obat : Tab

Diuretic
 Thiazide
Mechanism :

 Inhibition of Na+-Cl- cotransporters in the distal convoluted tubule; ↑ excretion of Na+ (saluresis)

and Cl- → ↑ excretion of potassium
 Increased reabsorption of Ca2+

Contoh Obat :
 Hydrochlorothiazide [B] {oral}
 Adult : 25-100 mg daily in 1-2 divided dose. Dose may be administered on alternate
days or on 3-5 days each week. Max: 200 mg daily.
 Child :  1-2 mg/kg daily as single or in 2 divided doses. <6 months 3 mg/kg daily in
2 divided doses. <2 years Max: 37.5 mg daily. 2-12 years Max: 100 mg daily.
 Elderly: >65 years Initially, 12.5 mg daily, titrate as necessary in increments of 12.5
mg
o Sediaan obat : Tab
 Loop Diuretic
Mechanism :
 Blockage of Na+-K+-2Cl--cotransporters in the thick ascending loop of Henle
 ↓ Reabsorption of Ca2+ and Mg2+
 ↑ PGE release

BSO : IM/IV/Parenteral/PO
Contoh Obat :
 Furosemide [C] {oral}
 Adult : 40-80 mg daily, alone or in combination w/ other antihypertensives.
o Sediaan obat : Amp 10mg/ml | Tab 40mg

 Aldosteron receptor antagonis / diuretic hemat kalsium

Mechanism :
 Competitively bind to aldosterone receptors in the late distal tubule and the collecting duct →
inhibit effects of aldosterone → decreased Na+ reabsorption and K+ excretion
 Spironolactone also acts (nonspecifically) on sex hormone receptors → endocrine side effects
BSO : IM/IV/Parenteral/PO
Contoh Obat :
 Spironolactone [C] {oral}
 Adult : As monotherapy: Initially, 50-100 mg daily in 1-2 divided doses, may
adjust dose after 2 weeks as needed based on patient response
o Sediaan obat : Tab 50 mg | 100 mg

Adrenonergik Inhibitor
 Beta adrenergic blocker
Mechanism :
 β1 : terutama pada miokard
 β2 : pada organ viseral (bronkus, genitourinaria) dan otot polos pembuluh darah
 β3 : jaringan lemak
β – blocker :
 cardioselective : Bisoprolol, atenolol, metoprolol
  non-cardioselective : Propanolol, carvedilol, timolol

Contoh Obat :
 Propanolol [C] {oral, parenteral}
 Adult : As conventional tab or oral solution: Initially, 20mg tid, may be increased to
40 mg 3 – 4 times daily.
o Sediaan obat : Tab selaput salut 10 mg

 Bisoprolol [C] {oral}

 Adult : Initially, 5 mg once daily adjusted according to response. Usual dose: 10
mg once daily. Max: 20 mg daily.
o Sediaan obat : Tab selaput salut 5 mg

 Aplha-1 blocker
Mechanism :
 Inhibit alpha-1 receptors in smooth muscle →
  ↓ Vasoconstriction → ↓ blood pressure
 Relaxation of bladder neck muscles → ↓ bladder outlet obstruction and easier micturition
 Unopposed epinephrine binding to beta-adrenergic receptors →
o ↑ Vasodilation (via beta-2 receptors) → ↓ blood pressure
o ↑ Secretion of renin (via beta-1 receptors) → ↑ water retention
 alpha blockers can reduce nightmares secondary to PTSD

Contoh Obat :
 Prazosin [C] {oral}
 Adult : Initially, 500 mcg bid or tid for 3-7 days, then increased to 1 mg bid or tid
for the next 3-7 days if tolerated, then gradually increase thereafter according to
patient's response. Max: 20 mg daily in divided doses.
o Sediaan obat : Tab

 Aplha-2 adrenergic blocker / Central Sympathollitics

Mechanism :
 Activate alpha-2 receptors in presynaptic sympathetic neurons of the central nervous system → ↑
negative feedback → ↓ catecholamine release (dopamine and norepinephrine) →
 ↓ Sympathetic tone → ↓ vasoconstriction → ↓ blood pressure
 ↑ Unopposed GABA activity → sedation
 alpha-2 adrenergic agonists improve symptoms in ADHD and Tourette syndrome

Contoh Obat :
 Clonidine [C] {Epidural/IV/Parenteral/PO/Transdermal}
 Adult : Initially, 50-100 mcg tid, increased every 2nd or 3rd day according to
response. Maintenance: 300-1,200 mcg daily, some may require ≥1,800 mcg daily.
Max: 2,400 mcg daily.
o Sediaan obat : Tab selaput salut 5 mg

Calcium Channel Blocker

 Dihiydropyridines
Mechanism :
  CCBs bind to and block L-type calcium channels → decreased frequency
of Ca2+ channel opening in response to cell membrane depolarization → decreased
transmembrane Ca2+ current
 Effects of decreased Ca2+ influx
 Vascular smooth muscle relaxation → vasodilation → decreased
peripheral vascular resistance → decreased afterload → decreased blood pressure
 Decreased cardiac
muscle contractility (negative inotropic action) → decreased cardiac output →
decreased blood pressure
 Decreased SA node discharge rate (negative chronotropic action) →
decreased heart rate (bradycardia) → decreased cardiac output → decreased blood
pressure
 Decreased AV node conduction (negative dromotropic action) → termination
of supraventricular arrhythmias

Contoh obat :
Short-acting : nifedipine, clevidipine
Medium-acting : nitrendipine, nicardipine, lercanidipine
Long-acting : amlodipine

Effects :
 Potent vasodilator
 Minimal myocardial depressant activity

 Nifedipine [C] { PO/SL}

 Adult : Immediate-release: Initially, 5 mg tid. Maintenance: 10-20 mg tid. Extended-
release: Initially, 10-40 mg bid or 20-90 mg once daily
 Elderly : Dose reduction may be necessary.
o Sediaan obat : Tab 5 mg | 10mg

 Non-Dihiydropyridines
Benzothiazepines
Mechanism :
 Moderate vasodilator
 Moderate myocardial depressant activity

Contoh Obat :
 Clonidine [C] {IV/Parenteral/PO:}
  Adult : Modified-release cap: Initially, 90-120 mg bid, may increase to 180 mg bid
if necessary. Max: 360 mg daily.
 Elderly : Modified-release cap: Initially, 60 mg bid, may increase carefully to 240
mg once daily.
o Sediaan obat : Tab

Phenylalkylamines
Mechanism :
 Less potent vasodilator than dihydropyridines
 Potent myocardial depressant

Contoh Obat :
 Hydralazine [C] { IV/Parenteral/PO}
 Adult : Initially, 240 mg daily in 2-3 divided doses. Max: 480 mg daily.
 Elderly : ≤2 yr 20 mg 2-3 times daily; >2 yr 40-120 mg 2-3 times daily, depending
on age and response.
o Sediaan obat : Tab 5 mg | 10mg

Direct Arteriolar Vasodilator

 Hydralazine is a first-line treatment in pregnancy.
 Sodium nitroprusside is used only in hypertensive emergencies.

Contoh Obat :
 Hydralazine [C] { IV/Parenteral/PO}
 Adult : In combination with ß-blockers and diuretics: Initially, 25 mg bid, increase
gradually according to response. Max: 200 mg daily.
o Sediaan obat : Tab

Treatment of hypertension in pregnancy

 First-line treatment: methyldopa; labetalol, hydralazine (vasodilator), and nifedipine (CCB)
 Second-line treatment: thiazides, clonidine (alpha-2 agonist)
 Contraindicated: furosemide, ACE-I, ARB, renin inhibitors (aliskiren)
Overview antihypertensive drugs.