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AntiHypertensive

Drugs
dr. Ave Olivia Rahman, MSc.
Bagian farmakologi FKIK UNJA
Tujuan Pembelajaran : Kompetensi 4A
• Memahami penggolongan obat antihipertensi
• Memahami mekanisme kerja obat antihipertensi
• Memahami efek samping obat antihipertensi
• Memahami pemilihan obat antihipertensi dengan
co morbid tertentu
• Memahami algoritma terapi hipertensi JNC 7
• Memahami terapi hipertensi emergensi
• Menulis resep obat antihipertensi
Hypertension

High Blood Pressure, Persistently

What is
Normal
Blood
Pressure?
Classfication of Blood Pressure
• SBP < 120 mmHg
Normal
• DBP < 80 mmHg
• SBP 120 -139 mmHg
Prehypertension
• DBP 80-89 mmHg
Hypertension • SDP 140-159 mmHg
stage 1 • DBP 90-99 mmHg
Hypertension • SDP ≥ 160 mmHg
stage 2 • DBP ≥ 100 mmHg
Hypertensive • SDP > 180 mmHg
Crisis • DBP > 120 mmHg
Blood Pressure
Arterial
 Cardiac X Peripheral
Blood Output Resistance
Pressure

Heart Filling Arteriolar


Contractility Volume
Rate Pressure

Blood Venous
Volume Tone
Groups of Antihypertensive Drugs

Ca Channnel ACE
Diuretics
Blockers Inhibitors

Angiotensin II
Receptor β Blockers α1 Blockers
Blockers

Centrally α2 Direct
others
agonist Vasodilator
Diuretics
Trigger the excretion of water and
electrolytes from the kidneys

 Sodium water retention

 Blood Volume

 Peripheral Retention  Cardiac Output

Decrease Blood Pressure


Diuretics
I. Thiazide& Thiazide-like diuretics :
– Thiazide diuretics include: bendroflumethiazide,
chlorothiazide, hydrochlorothiazide (HCT),
hydroflumethiazide, methyclothiazide,
polythiazide.
– Thiazide-like diuretics include: chlorthalidone,
indapamide, metolazon
II. Loop diuretics : bumetanide, ethacrynic acid,
and furosemide
Continue...
III. Potassium Sparing Diuretic
• Diuretics that do not promote secretion of
potassium in the urine.
• As adjunctive drugs, combination with other
drugs
• Actions :
– Aldosterone antagonis : spironolactone,
eplerenone
– Block sodium channel : amiloride, triamteren
Thiazide Diuretics
• Diuretic that most widespread use. Derived from
sulfonamides.
• Thiazide diuretics are absorbed rapidly but
incompletely from the GI tract. Cross the
placenta and are secreted in breast milk.
• Therapeutic Uses : long-term treatment of
hypertension. Particularly useful in the treatment
of black or elderly. Also used to treat edema.
• Not effective in patient with inadequate kidney
function (Cr Cl < 50 mL/min).
• Decrease the level of calcium in urine  prevent
the development and recurrence of renal calculi.
Continue...

• Side effects : hyperurecemia (70%),


hyperglycemia (10%), hypomagnesemia.
Increase the excretion of chloride, potassium,
and bicarbonate  electrolyte imbalance
• Potassium levels should be monitored closely
in patient who are predisposed to arrhythmias
or using digitalis glycosides.
Loop Diuretics
• Highly potent diuretics. Loop diuretics, with the
exception of ethacrynic acid, contain sulfa.
• Act on proximal tubule the thick, ascending loop
of Henle.
• Cause decreased renal vascular resistance,
increase renal blood flow, increase Ca2+ content
of urine.
• Used to treat edema, hypertension (usually with
a potassium-sparing diuretic or potassium
supplement to prevent hypokalemia)
CALCIUM CHANNEL BLOCKERS

Blocking the slow calcium channel in


myocardial and vascular smooth
muscle cell membranes

Inhibits the influx of


extracellular calcium ions

Have intrinsic No Contraction =


natriuretic effect Dilatation

Decrease Blood Pressure


Pharmacokinetics
• When administered orally, calcium channel
blockers are absorbed quickly and almost
completely.
• Because of the first -pass effect, however, the
bioavailability of these drugs is much lower.
• The calcium channel blockers are highly bound
to plasma proteins.
3 classes of CCB
• Diphenylalkylamine : verapamil.
• Benzothaizepines : diltiazem.
• Dihydropyridines :
• 1 st generation : nifedipine
• 2nd generation : amlodipine, felodipine,
isradipine, nicardipine, nisoldipine.
Differences
Classes /Drugs Properties
Verapamil Has significant effect on both
cardiac and vascular smooth
muscle
Diltiazem Affect both cardiac and vascular
smooth muscle, but less
pronounced negative inotropic
effect compare to verapamil
Nifedipine etc Much greater affinity for
vascular smooth muscle
Continue...CCB
• Useful in the treatment of hypertensive (mild-
moderate) who also have asthma, diabetes,
angina, peripheral vascular disease.
• Side effects: constipation (10%), dizzines,
headache, feeling fatique. Verapamil
contraindication for congestive heart failure
due to its negative inotropic effects.
ACE INHIBITORS
• Benazepril
• Captopril
• Enalapril
• Enalaprilat (the only ACE inhibitor that’s administered
I.V.)
• Fosinopril
• Lisinopril
• Moexipril
• Quinapril
• Ramipril
• Trandolapril
Actions

• ACE inhibitors prevent the conversion of


angiotensin I to angiotensin II.
Continue...

• ACEI slow progression of diabetic nephropathy


and decrease albuminuria.
• Side effect : dry cough (10%) , rash, fever,
altered taste, hypotension, hyperkalemia
(must be monitored). Angioedema (rarely)
• Combination with potassium supplement,
spironolactone is contraindicated
• Fetotoxic
ANGIOTENSIN II RECERPTOR BLOCKERS
• Candesartan cilexetil
• Eprosartan
• Irbesartan
• Losartan
• Olmesartan
• Telmisartan
• Valsartan
Actions
• Block the binding of angiotensin II to the AT1
receptor  This prevents angiotensin II from
exerting its vasoconstricting properties and
from promoting the excretion of aldosterone -
 lowered blood pressure.
Continue...
• Valsartan may also be used for the
management of heart failure.
• Decrease nephrotoxicity of diabetes 
therapy in hypertensive diabetics (Irbesartan
and losartan).
• Losartan is also used to reduce the risk of
stroke in high-risk patients with hypertension
and left ventricular hypertrophy.
• Side effect similar with ACEI, but risk of cough
and angiodema sigificantly decrease
β Blockers
Continue...

• Selective β1 Blockers : metoprolol, atenolol


• Non selective β Blockers (block β1 & β2) :
Propanolol
• May take several (1-2) weeks to develop full
effects
Continue...

• Side effect : bradycardia, fatique, insomnia,


hallucination, hypotension, decrease libido, cause
impotence, disturb lipid metabolism, decreasing
HDL, increasing Trigliseride, drug withdrawl
(rebound hypertension  should be tapering off)
• Caution in obstructive lung disease, chronic
congestive heart failure, severe symptomatic
occlusive peripheral vascular disease, acute heart
failure, diabetes.
α1 Blocker
• Actions : competitive block α1 adrenoceptor  relaxation
arterial and venous smooth muscle  decrease peripheral
vascular resistance and lower arterial blood pressure.
• Have minimal change in cardiac output, renal blood flow,
glomerular filtration rate.
• Cause short term effect of reflex tachycardia  to blunt this
effect concomitant use of β blocker may be needed.
• Prazosin, doxazosin, terazosin.
• Side effect : postural hypotention, reflex tachycardia, first
dose syncope.
α-1 and β Blockers

• Actions : blocking both α-1 and β receptors in


the body  lowers blood pressure.
• Carvedilol, labetalol
• Contraindication : heart block, heart failure,
asthma, obstructive airway disease, severe
slow heartbeat, severe low blood pressure
Clonidine
• It is α2 presinaptic agonist, work centrally
• Action: inhibit the released of noradrenaline
from symphatetics nerves.
• Does not decrease renal blood flow & GFR 
Useful in the treatment of hypertention
complicated by renal disease.
• Causes sodium and water retention  usually
used in combination with diuretic.
• Side effect : sedation, drying nasal mucosa,
rebound hypertention in abrupt withdrawal
(should be withdrawn slowly)
α methyldopa
• It Inhibits dopa decorboxylase and deplete
norepinephrine
• Also valuable in treating hypertensive patient
with renal insufficiency.
• Reduce total peripheral resistance and
decreased blood pressure.
• Cardiac output not decreased  Does not
decrease renal blood flow & GFR
• Side effect : sedation, drowsiness.
Direct Vasodilators
• Actions : act on arteries, veins, or both.
• Include :
– Diazoxide
– Hydralazine
– Minoxidil
– Nitroprusside
Continue...Indications
• They’re usually combined with other drugs to
treat the patient with moderate to severe
hypertension (hypertensive crisis).
• Hydralazine and minoxidil are usually used to
treat resistant or refractory hypertension.
• Diazoxide and nitroprusside are reserved for use
in hypertensive crisis.
• Hydralazine monotherapy accepted method for
controlling blood pressure in pregnancy-induced
hypertension.
Continue... Side effect
• Produce reflex stimulation of heart 
increased myocardial contractility, heart rate,
oxygen consumption  may prompt angina
pectoris, MI, cardiac failure in predisposed
individuals.
• Increase plasma renin concentration 
sodium and water retention
• Those undesirable side effects can be blocked
by concomitant use of diuretic and β blocker.
Others : Reserpin
• Actions : Norephinefrine depletors.
Sediaan dan Dosis
Nama Obat Sediaan Dosis Awal
Hydrochlorthiazide tablet 12.5; 25; 50 mg 1 x 12,5 mg
(HCT)
Furosemide Tablet 40 mg, 2 x 20 mg
Ampul 2 ml, 10mg/ml,
Spironolakton Tablet 25 mg, 100 mg 1-2 x 25 mg
Clonidin Tab 0,075; 0,15; 0,25 mg 2 x 0,075 mg
Injeksi 0,15 mg/ml
Metildopa Tab 125; 250 mg 2 x 125 mg
Bisoprolol Tab 5 mg 1 x 5 mg
propanolol Tab 10,40 mg 2 x 20 mg
Asebutolol Tab 200; 400 mg 2 x 100 mg
Atenolol Tab 50, 100 mg 1 x 25 mg
Metoprolol Tab 50; 100 mg 1-2 x 50 mg
Nama Obat Sediaan Dosis Awal
Captopril Tablet 12,5; 25; 50 mg 2 x 12,5 mg
Ramipril tab 1,25 ; 2,5; 5 mg 1x 1,25 mg
Lisinopril Tab 5, 10 mg 1x 5 mg
Amlodipin Tab 5, 10 mg 1x 2,5 mg
Felodipin Tab 5 ; 10 mg 1 x 5 mg
Nikardipin Tab 20 mg 3 x 20 mg
Ampul 2; 10 mg
Nifedipin Tab 5;10 mg 3 x 5 mg
Losartan Tab 50 mg 1 x 50 mg
Irbesartan Tab 75;150;300 mg 1 x 150 mg
Kandesartan Tab 8;16 mg 1 x 4 mg
Telmisartan Tab 40;80 mg 1 x 40 mg
Olmesartan Tab 20;40 mg 1x 20 mg
Valsartan Tab 80 ; 160 mg 1 x 80 mg
Causes of Resistant Hypertension
• Improper BP measurement
• Excess sodium intake
• Inadequate diuretic therapy
• Medication:
– Inadequate doses
– Drug actions and interactions (e.g., nonsteroidal anti-
inflammatory drugs (NSAIDs), illicit drugs,
sympathomimetics, oral contraceptives)
– Over-the-counter (OTC) drugs and herbal supplements
• Excess alcohol intake
• Identifiable causes of hypertension
Recommendations for initiating and modifying
pharmacotherapy for patients with elevated
blood pressure (BP) : "2014 Evidence-Based
Guideline for the Management of High Blood
Pressure in Adults: Report From the Panel
Members Appointed to the Eighth Joint National
Committee (JNC 8), published online Dec. 18 by
JAMA: The Journal of the American Medical
Association
Initiation pharmacologic treatment (1)
Population Blood Pressure
In the general population SBP ≥150 mm Hg or DBP
aged ≥60 years ≥90 mm Hg
In the general population SBP ≥140 mmHg or at DBP
<60 years ≥90 mmHg
In the population aged SBP ≥140 mmHg or DBP
≥18 years with chronic ≥90 mmHg
kidney disease (CKD)
Initiation pharmacologic treatment (2)
Population Drugs
In the general nonblack a thiazide-type diuretic,
population, including those calcium channel blocker
with diabetes (CCB), angiotensin-
converting enzyme inhibitor
(ACEI), or angiotensin
receptor blocker (ARB).
In the general black a thiazide-type diuretic or
population CCB.
In the population aged ≥18 ACEI or ARB
years with CKD
Evaluation
If goal BP cannot be reached ,
Initiate with 1 drugs for 1 increase the dose of the
month initial drug or add a second
drug .

Do not
combine
together ACEI
and an ARB
Referral to a hypertension
specialist may be indicated
for patients in whom goal BP If goal BP cannot be reached
cannot be attained using the with 2 drugs, add and titrate
above strategy or for the a third drug .
management of complicated
patients
CRISIS HYPERTENSIVE
• Rarely but life threatening situation
(emergency)
• DBP > 150 mmHg in healthy person; DBP >130
mmHg in individual with preexixting
complication (encelopathy, cerebral
hemorrhage, left ventricular failure, aortic
stenosis)
• Therapeutic goal : Rapidly reduce blood
pressure  choose drugs with rapid onset
Sodium Nitroprusside.
• Administered IV
• Cause reflex tachycardia
• Acting equally in arterial and veous smooth
muscle  can reduce cardiac preload.
• Metabolized rapidly  require continuous
infusion to maintain hypotensive action.
• Metabolit : cyanide ion
• Labetalol
– α and βblocker
– Administered by IV bolus or infusion.
– Does not cause reflex tachycardia

• Fenoldopam
– Peripheral dopamine- 1 receptor agonist.
– Administerd by IV infusion
– Lower blood pressure and also increase renal
perfusion
– Contraindicated in patient with glucoma.
• Nicardipne
– Can be given as intravenous infusion.

• Minoxidil
– Dilatation of arteriole but not venules.
– For severe to malignant hypertention that is
refractory to other drugs.
– Concomitant with other drug to diminish side
effect.
– Side effect : hypertrichosis, water nad sodium
retention.
Post Test
1. Candesartan adalah obat antihipertensi golongan ....
2. Lisnopril adalah obat antihipertensi golongan ....
3. Furosemid adalah obat antihipertensi golongan ....
4. Amlodipine adalah obat antihipertensi golongan ....
5. Penderita hipertensi denngan penyakit ginjal kronis, maka pilihan obat
antihipertensinya adalah ....
6. Untuk hipertensi emergensi dipilih obat antihipertensi yang ........,
contoh : .....
7. Efek samping kaptopril antara lain ...
8. Seorang pasien hipertensi derajat 1 dengan riwayat asma bronkiale,
golongan obat antihipertensi yang harus dihindari adalah ...
9. Seorang pasien terdiagnosis hipertensi dan edema pretibial. Obat
antihipertensi yang juga dapat menurunkan edemanya adalah ....
10. Seorang pasien 50 tahun dengan riwayat hipertensi, pada
pemeriksaan tekanan darah didapatkan 200/150 mmHg. Obat
antihipertensi pilihan untuk pasien tersebut adalah ....
Tuliskan Resep
• Ny. T, 50 tahun. Hasil pemeriksaan tekanan
darah masih tinggi setelah dilakukan
modifikasi gaya hidup. Tekanan darah terakhir
: 150/90 mmHg. Tidak ada penyakit komorbid
lainnya. Berikan resep obat antihipertensi
untuk Ny. T.
Tugas : Buat Artikel
Rumusan Masalah :
1. Bagaimana pedoman pemilihan obat
antihipertensi yang akan diberikan kepada
pasien yang terdiagnosis hipertensi ?
2. Apakah ada golongan obat antihipertensi yang
lebih superior dibandingkan golongan
antihipertensi lainnya?