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antihypertensive

Anggelia Puspasari, MD
Pharmacology and Therapeutic Dept.
Medical Faculty University of Jambi
• Bertram G Katzung-Basic Clinical and Pharmacology;
9th Ed
• Lullman H et al, Color atlas of pharmacology, 2nd ED
• GOODMAN & GILMAN'S THE PHARMACOLOGICAL
BASIS OF THERAPEUTICS - 11th Ed
• CHEP Guideline
• NHS Guideline
• JNC VII; Complete report; 2003

Reference
Hypertensive Diagnose
(JNC VII)
JNC VII; Complete report; 2003
Regulation of Blood
Pressure
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Regulation of Blood
Pressure
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Pharmacotherapy
Antihipertensive
Preview
Lullman H et al, Color atlas of pharmacology, 2nd ED
Site of action
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
1. Angiotensin Converting Enzym Inhibitor (ACEI)
2. Angiotensin Reseptor Blocker (ARB)

Inhibitor of RAA System


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Inhibitor of RAA System (MOA)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
• Captopril
• Enalapril is an oral prodrug that is converted by
hydrolysis to a converting enzyme inhibitor, enalaprilat,
with effects similar to those of captopril
• Benazepril, fosinopril, moexipril, perindopril,
quinapril, ramipril, and trandolapril are other long-
acting members of the class. All are prodrugs, like
enalapril, and are converted to the active agents by
hydrolysis, primarily in the liver.

Inhibitor of RAA System (ACEI)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Useful role in treating patients with chronic kidney
disease because they diminish proteinuria and stabilize
renal function.
 Lower blood pressure principally by decreasing
peripheral vascular resistance. Cardiac output and heart
rate are not significantly changed.
 These agents do not result in reflex sympathetic
activation and can be used safely in persons with
ischemic heart disease.

Inhibitor of RAA System (ACEI)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Captopril
Half life : 2,2 h
Initial dosage : 50-75 mg/d
Range of dose : 75-150 mg/d

Lisinopril
Half life : 12 h
Initial dosage : 10 mg/d
Range of dosage : 10-80 mg/d

* doses of these drugs should be reduced in patients with renal


insufficiency

Inhibitor of RAA System (ACEI,


Pharmacokinetic and dosage)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Severe hypotension can occur after initial doses of any
ACE inhibitor in patients who are hypovolemic due to
diuretics, salt restriction, or gastrointestinal fluid loss.
 Hyperkalemia is more likely to occur in patients with
renal insufficiency or diabetes
 Dry cough sometimes accompanied by wheezing, and
angioedema.
 Avoid during pregnancy!!!
 Important drug interaction: K-sparing diuretic and
NSAID

Inhibitor of RAA System (ACEI,


Toxicity)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Losartan, valsartan, candesartan, eprosartan, irbesartan,
and telmisartan have been released.
 They have no effect on bradykinin metabolism and are
therefore more selective blockers of angiotensin effects than
ACEI.
 ARB provide benefits similar to those of ACEI in patients with
heart failure and chronic kidney disease
 The adverse effects are similar to those described for ACE
inhibitors, including the hazard of use during pregnancy.
Cough and angioedema can occur but are less common
than ACEI.

Inhibitor of RAA System (ARB)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Inhibitor of RAA System (Dosing)
JNC VII; Complete report; 2003
1. Dihydropyridines including amlodipine, felodipine,
isradipine, and nifedipine.
2. Diltiazem, verapamil, and non-dihydropyridine.

Calsium Chanel Blocker


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Ca2+ channel blockers lower blood pressure by relaxing
arteriolar smooth muscle and decreasing peripheral
vascular resistance (Weber, 2002).
 As a consequence of a decrease in peripheral vascular
resistance, the Ca2+ channel blockers evoke a
baroreceptor-mediated sympathetic discharge.

Calsium Chanel Blocker (MOA)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Dihydropyridine, relaxation of vascular smooth muscle in
arterial bed, no cardiac effect at therapy dose.
 Non dihydropyridine, verapamile and diltiazem,
relaxation of vascular smooth muscle in arterial bed +
heart muscle, crono_dromo_inotropic (-).
 Verapamile use in : SVT, AF. Avoid use in AV block.

Calsium Chanel Blocker (MOA)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Amlodipin
Half life : 3,5- 2,5 h
Initial dosage : 2,5 mg/d
Range of dose : 5 – 10 mg/d
 Nifedipin
Half life :2h
Initial dosage : 30 mg/d
Range of dose : 30 – 60 mg/d
 Diltiazem
Half life : 3,5 h
Initial dosage : 120-140 mg/d
Range of dose : 240-360 mg/d
 Verapamil
Half life : 4-6 h
Initial dosage : 180 mg/d
Range of dose : 240-480/d

Calsium Chanel Blocker


(Pharmacokinetic)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Headache, flushing, dizziness, and peripheral edema
 Gastroesophageal reflux
 Constipation
 Diltiazem and verapamil can lead to bradycardia and even
sinoatrial node arrest, exaggerated by concurrent use of b
adrenergic receptor antagonists.
 verapamil inhibits the elimination of digoxin
 quinidine, Ca2+ channel blockers may cause excessive
hypotension

Calsium Chanel Blocker (adverse


effect)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Diltiazem and verapamil can lead to bradycardia and even
sinoatrial node arrest, exaggerated by concurrent use of
beta adrenergic receptor antagonists.
 Verapamil inhibits the elimination of digoxin
 Quinidine, Ca2+ channel blockers may cause excessive
hypotension

Calsium Chanel Blocker (drug


interaction)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Calsium Chanel Blocker (dosing)
JNC VII; complete report; 2003
1. Thiazid Diuretic : Hidroklorotiazid, bendroflumetiazid,
indapamid.
2. Loop Diuretic : Furosemid
3. K Sparing Diuretic : Amilorid
4. Aldosteron antagonis : Spironolakton

Diuretic
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Farmacotherapy, University of Indonesia
 Several studies have shown that even modest dietary
sodium restriction lowers blood pressure
 Diuretics lower blood pressure primarily by depleting
body sodium stores. Initially decreasing CO, after 6-8
weeks declined PVR.
• Reduced Circulating Volume
• Reduced Preload
• Reduced Cardiac Output

Diuretic
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Pottasium Depletion, Increased digitalis toxicity
 HyperKalemia_K sparing diuretic using in renal
insufficiency.
 Magnesium depletion, impair glucose tolerance, and
increase serum lipid concentrations.
 Diuretics increase uric acid concentrations and may
precipitate gout.
 Loop diuretic_creatinin serum ≥ 2,5 mg/dl or heart failure

Diuretic (Toxicity)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Diuretic (Dosing)
JNC VII, complete report, 2003
1. Cardioselective (β1 antagonist) : bisoprolol, atenolol,
asebutolol, atenolol.
2. Non-cardioselective : propanolol, timolol, oksprenolol,
metoprololol.

Sympathoplegic drug (β blocker)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Sympathoplegic drug (Dosing)
JNC VII; complete report; 2003
 Reduction in myocardial contractility, HR
and CO
 Reduction renin secretion
 Alter baroreceptor reactivity and
symphatic reaction

Sympathoplegic drug (β blocker_


MOA)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Brochospasm_avoid in asthma patient giving non
selective β blocker
 Avoid used in AV or SA node disfunction
 Have to tappering off to discontinued therapy.
 Used in hypertensive with Aritmia without
conduction disfunction.
 Combined with verapamile_conduction blockade !!!!

Sympathoplegic drug (β blocker_


Adverse effect)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed

Decreased arteriole resistance, increased venous
capacity
 Positive effect in blood lipid profile and insulin
resistency.
 1st dose phenomenon_orthostatic
hypotension_less in doxazosin.

Sympathoplegic drug (α 1 blocker)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
 Metildopa, clonidine, guanabenz, guanfasin.
 Metildopa
 Decreased PVR, effect on HR and CO minimized.
 Peak plasma consentration 2-3 h
 1st line th/ hipertensi in pregnancy
 Sedation effect

Sympathoplegic drug (central


acting)
Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Vasodilator
Lullman H et al, Color atlas of pharmacology, 2nd ED
Hydralazin
 MOA unclear
 IV used for hipertensi emergency
 Fluid retention_diuretic
 Takikardi reflek_beta bloker
 Adverse effect: GIT discomfort, rash, Lupus syndrom,
neuropaty perifer.

Vasodilator (direct vasodilator)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Minoxidil
More potent and longer duration than hydralazine
Sodium Nitropruside
Dilated vein and arteriole with release of Nitroso.
Rapid onset, ultrashort duration

Vasodilator (direct vasodilator)


Bertram G Katzung-Basic Clinical and Pharmacology; 9th Ed
Condition Target
SBP and DBP mmHg
Isolated systolic hypertension <140
Age > 80 years < 150
Systolic/Diastolic Hypertension
• Systolic BP <140
• Diastolic BP <90
Diabetes
• Systolic <130
• Diastolic <80

Goal of treatment
Canadian Education Hypertension Program, Gudeline 2013
Treating hipertension
JNC VII, complete report 2003
Guideline treatment
JNC VII, complete report, 2003
Treating hypertension
JNC VII, Complete report; 2003
Guideline treatment
www.nhp.nhs.uk
• A = ACE inhibitor or low-cost A2RA. Consider a low cost A2RA, in preference
to an ACE inhibitor, incombination with a calcium channel blocker in black
people of African or Caribbean family origin at step 2
C = Calcium channel blocker (C). This is preferred but consider a thiazide-like
diuretic (D) if C is not tolerated or the person has oedema, evidence of heart
failure or a high risk of heart failure.
D = thiazide-like diuretic: Offer chlortalidone (12.5–25 mg once daily) or
indapamide (1.5 mg modified-release or 2.5 mg once daily) in preference to
bendroflumethiazide or hydrochlorothiazide if diuretic therapy is to be changed
or initiated.
Notes:
• Consider a low dose of spironolactone or higher doses of a thiazide-like diuretic.
• At the time of publication (August 2011), spironolactone did not have a UK
marketing authorisation for this indication. Informed consent should be obtained
and documented.
• Consider an alpha- or beta-blocker if further diuretic therapy is not tolerated, or is
contraindicated or ineffective.

Guideline treatment
(cont.)
www.npc.nhs.uk
Thax U

anggeliahaditirtono@gm
ail.com