OBAT-OBAT

KARDIOVASKULER
ARIFAH SRI WAHYUNI
081329008616
 Hypertension: A Significant CV and
Renal Disease Risk Factor

CAD
CHF
Stroke LVH

Blood
Pressure 
Renal disease  Morbidity
 Disability
Peripheral vascular
disease

National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.
Regulation of Blood Pressure

• Main coordinating
center is in the
medulla oblongata
of the brain;
medullary
cardiovascular
control center
• Reflex control of
blood pressure
• Baroreceptor reflex
 Factors determining ABP :

Blood Pressure = Cardiac Output X Peripheral Resistance

(BP) (CO) (PR)

Flow Diameter of
arterioles
■ BP depends on:
1. Cardiac output  CO = SV X HR.
2. Peripheral resistance.
3. Blood volume.
 Heart rate, stroke volume and cardiac output

The pulse rate is not the only way of measuring the heart.
Stroke volume is the amount of blood pumped
out of the left ventricle per beat.

Cardiac output is the amount of blood pumped

out of the left ventricle of the heart per minute.

Cardiac output can be calculated by multiplying the

stroke volume by the heart rate:
cardiac output = stroke volume × heart rate

What is the cardiac output of someone with a heart

rate of 60 bpm and stroke volume of 90 ml?

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Normal Blood Pressure Regulation

Blood Pressure = Cardiac output (CO) X

Resistance to passage of blood through
precapillary arterioles (PVR)
• Physiologically CO and PVR is maintained
minute to minute by – arterioles (1)
postcapillary venules (2) and Heart (3)
Kidney is the fourth site – volume of
intravascular fluid
• Baroreflex, humoral mechanism and renin-
angiotensin- aldosterone system regulates
the above 4 sites
• Local agents like Nitric oxide
• In hypertensives – Baroreflex and renal
blood-volume control system – set at
higher level

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 Mechanisms Controlling CO and TPR

Diuretics Vasodilators

• Sympatholytic drugs

RAAS

9
 DIURETIC
• Adalah obat-obat yang bekerja pada ginjal
untuk meningkatkan ekskresi air dan Na.

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 Tubular reabsorption
Nephron


 Small molecules
 Water

 Glucose, amino acids,

sodium, chloride, calcium,
bicarbonate
 Tubular secretion
 Larger molecules
 Potassium,phosphate,
Hydrogen, Ammonium
DIURETIC

•Bagaimana meningkatkan ekskresi urine?

↑ Filtrasi Glomerular atau ↓ reabsorbsi Tubular

•Tujuan penggunaan diuretic

1. Menjaga jumlah volume urine yang dikeluarkan ( e.g.: renal
failure)
2. Untuk mengurangi edema (e.g.: heart failure, liver failure;
nephrotic syndrome)
3. Untuk mengontrol tekanan Darah .

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Klasifikasi Diuretics

• Diuretik penghambat transport

dalam Tubulus proksimal 
Diuretic Osmotic,
penghambat karbonat
anhydrase
• Diuretics Thiazides
• Loop diuretics
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A. Diuretics Osmosis

Osmotic Diuretics (e.g.: Mannitol)

• Mekanisme aksi : merupakan senyawa hidrofilik yang mudah
disaring melalui glomerulus dengan sedikit penyerapan kembali,
dengan demikian meningkatkan keluaran urin melalui osmosis ..
• Pemberian: Diberikan secara i.v
• Adverse Reactions:
– dehidrasi
– Hypernatremia karena yang diekskresikan lebih banyak air daripada garam
elektrolit.

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Carbonic anhydrase inhibitors

Acetazolamide inhibits carbonic

anhydrase (CA) manly in proximal tubules.

CA
H 2O + CO 2 H 2CO 3 H 2CO 3– + H +
B. Penghambat karbonik anhidrase
• Carbonic Anhydrase Inhibitors
(Acetazolamide (Oral) ; Dorsolamide
(Ocular) ; Brinzolamide (Ocular)
• Mekanisme aksi : Menurunkan
reabsorbsi bikarbonat pada tubulus
proksimal melalui inhibisi katalis
hidrasi CO2 dan reaksi dehidrasi. Na +
yang meningkat akan dialirkan nefron
distal, meningkatkan sekresi K
• ESO Acetazolamide: Sedasi,
Acidosis; Renal stone (Phosphate and
Calsium stone) ; Hyperchloremia,
hyponatremia dan hypokalemia
Thiazide Diuretic
• (e.g.: Thiazides and Thiazide-like
(Indapamide; Metolazone)
• Mekanisme aksi : Menghambat Na
+ melalui penghambatan Na + / Cl-
cotransporter. Terjadi peningkatan
ekskresi Na+ / Cl- yang disertai
H2O, beban Na+ yang meningkat
dalam tubulus distal menstimulasi
pertukaran cotransporter
• ESO : hiponatremia, hiperglikemia
Bagaimana? hypelipidemia dan
hyperurecemia
Mechanisms of Action: Loop diuretics
 Obat ini bekerja dengan
menghambat reabsorpsi NaCl
dalam ansa Henle ascending.
Karena kapasitas absorpsinya yang
besar, maka menyebabkan diuresis
yang lebih besar.
 Mekanisme Menghambat
kotransport Na+/K+/2Cl-
 3. Therapeutic Uses
2. Side effects:.
a) Edema
Ototoxicity; Hypokalemic
metabolic alkalalosis; b) Acute renal failure
hypocalcemia (hypercalceuria) c) Hyperkalemia
and hypomagnesemia;
hypochloremia; Hypovolemia; d) Hypercalcemia
hyperuricemia (How?);
hypersensitivity reactions.
Potassium-Sparing Diuretics
e.g : amiloride, triamterene, and spironolactone.
Termasuk diureik lemah, aksinya pada saluran
pengumpulcollecting ducts.

Amiloride dan triamterene  mengeblok Channel Na +

sehingga mengurangi Na + yang masuk melalui membran
luminal dan mengurangi reabsorpsi NaCl.
Aldosterone antagonist (Spironolactone, eplerenone)
– Aldosterone induces the expression of Na/K- ATPase and
Na+ channel
– Spironolactone and eplerenone blocks aldoserone
receptor  reduces Na+ reabsorption and K+ secretion 21
Mechanisms of Action: Collecting tubule
and potassium-sparing diuretics
 Two cell types in collecting tubule
1. Principal cells – transport Na, K, water
2. Intercalated cells – secretion of H+ and
HCO3
3. Blocking Na+ movement in also prevents
K+ movement out
 Peripheral a-1 Adrenergic Antagonists
Drugs: prazosin (Minipres); terazosin (Hytrin), doxazosin (Cardura ®)
1. Site of Action- peripheral arterioles, smooth muscle
2. Mechanism of Action
α1 stimulation cause VC : Vasoconstriction in the skin & viscera cause
increase TVR causing increase BP So, hypertension may be treated by
blocking α1 . Competitive antagonist at a-1 receptors on vascular, smooth
muscle.
3. Effects on Cardiovascular System
Vasodilation, reduces peripheral resistance

Stimulate alpha1 receptors -> hypertension

Block alpha1 receptors -> hypotension

 only class of antihypertensive agents

that may have the combined effect of 
LDL-cholesterol,  (HDL)-cholesterol,
and improving insulin sensitivity
 Peripheral a-1 Adrenergic Antagonists, cont.
4. Adverse effects
nausea; drowsiness; postural hypotenstion;

5. Contraindications : Hypersensitivity

6. Therapeutic Considerations
• no reflex tachycardia; small 1st dose;
• tidak mengganggu toleransi latihan
• dapat untuk pasien : diabetes, asthma, and/or
hypercholesterolemia
• mild to moderate hypertension
• Sering dikombinasi dengan diuretic,  antagonist

Doses: Available as 0.5 mg, 1 mg, 2.5 mg, 5 mg etc. dose:1-4

mg thrice daily (Minipress/Prazopress)
 Central Sympatholytics (a-2 Agonists)
Drugs: clonidine (Catapres), methyldopa (Aldomet)
1. Site of Action
• CNS medullary
• cardiovascular centers
clonidine; direct a-2 agonist
methyldopa: “false neurotrans.”
2. Mechanism of Action
CNS a-2 adrenergic stimulation
Peripheral sympathoinhibition
Decreased norepinephrine release
3. Effects on Cardiovascular System
Decreased NE-->vasodilation--> Decreased TPR
CRITICAL POINT!
Stimulation of a-2 receptors in the medulla decreases peripheral
sympathetic activity, reduces tone, vasodilation and decreases TPR.
 Clonidine
• Stimulate central α2 –adrenoceptors
• Decreasing PVR
• Useful in hypertension complicated by
renal disease
• Sedation & drying of the nasal mucosa
• Rebound hypertension
 α-METHYL DOPA
• α2-agonist
• Valuable in treating hypertensive
patients with renal insufficiency
• In pregnant women
  Adrenergic Antagonists
Drugs: propranolol (Inderal); metoprolol (Lopressor)
atenolol (Tenormin); nadolol (Corgard);
pindolol (Visken)
1. Sites of Action
1 : eye, kidney, heart
2 : lung, vascular system,
metabolic system
  Adrenergic Antagonists, cont.
2. Mechanism of Action
competitive antagonist at - adrenergic receptors

β1 Reduce heart rate, blood pressure, myocardial

contractility, myocardial oxygen consumption

selective  blocker : atenolol, metoprolol

2 Menghambat relaksasi otot di sirkulasi

sistemik, paru dan GI system
Non selective  blocker : propranolol, carvidelol,
sotalol, Timolol
  Adrenergic Antagonists, cont.

3. Effects on Cardiovascular System

a. Cardiac--  HR,  SV  CO

b. Renal--  Renin   Angiotensin II   TPR

4. Adverse Effects
impotence; bradycardia;
fatigue; exercise intolerance;

5. Contraindications
asthma; diabetes; bradycardia;
hypersensitivity
VASODILATOR
 Vasodilators
Drugs: hydralazine (Apresoline); minoxidil (Loniten); 
nitroprusside (Nipride); diazoxide (Hyperstat I.V.);
fenoldopam (Corlopam) 
1. Site of Action­ vascular smooth muscle
2. Mechanism of action nitroprusside

NO
fenoldopam
DA


Na+ Ca++ K+ minoxidil
diazoxide
Ca++
hydralazine
 Vasodilators, Cont
3. Effect on cardiovascular system vasodilation, decrease TPR
4. Adverse Effects
          reflex tachycardia
          Increase SymNS activity (hydralazine, minoxidil,diazoxide)
lupus (hydralazine) hypertrichosis (minoxidil)
cyanide toxicity (nitroprusside)
5. Therapeutic Considerations
nitroprusside­ iv only
hydralazine­ safe for pregnancy
diazoxide­ emergency use for severe hypertension

Uses: 1) Moderate hypertension when 1 st line fails – with beta­blockers and 
diuretics  2) Hypertension in Pregnancy, Dose 25­50 mg OD
 Minoxidil :
0 Orally not used any more
0 Topically as 2-5% lotion/gel and takes months to get effects
0 Mechanism in hair growth:
0 Enhanced microcirculation around hair follicles and also by direct
stimulation of follicles
0 Alteration of androgen effect of hair follicles
0 More often in alopecia to promote hair growth
 Vasodilators
Na Diazoxide Minoxidil Hdralazine
nitropruside
Arterio &  Arteriodilator Arteriodilator Arteriodilator Site of 
venodilator action
Release of nitric  Opening of  Opening  of   Direct Mechanism 
oxide (NO)  potassium  potassium channels  of action
NO→activation of  channels in smooth muscle 
guanylyl cyclase  membranes by 
→↑intracellular  minoxidil sulfate 
cGMP ( active metabolite )

Intravenous  Rapid  Oral Oral Route of 

infusion intravenous admin.
 Na  Diazoxide Minoxidil Hdralazine Continue
nitropruside Vasodilators

1.Hpertensive  1.Hypertensive  1.Moderate – 1.Moderate 

emergency emergency severe  ­severe 
hypertension hypertension.

In combination with diuretic & β­blockers
Therapeutic 
uses
2.Severe heart  2.Treatment of  2.correction of  2.Hypertensive 
failure hypoglycemia due to  baldness pregnant 
insulinoma woman
Na nitropruside Diazoxide Minoxidil Hdralazine Continue
Vasodilators

Severe  Hypotension, reflex tachycardia, 
hypotension palpitation, angina, salt and water 
retention  ( edema) Adverse effects

1.Methemoglobin Inhibit insulin  Hypertrichosis.  lupus  Specific 

during infusion release from β  erythematosus  adverse effects
2. Cyanide  cells of the  like syndrome
toxicity pancreas  
3. Thiocyanate  causing 
toxicity  hyperglycemia

Contraindicated  Contraindicated 
in diabetic in females
The Renin-Angiotensin-Aldosterone (RAA) System

Kidneys Adrenal cortex

Liver secretes secrete secretes
angiotensinogen renin aldosterone

Β-BLOCKER
Angiotensin
converting
Blood Renin enzyme SPIRONOLACTON

(ACE)
ACE I

Angiotensinogen Angiotensin I Angiotensin II Aldosterone

ARB

NA+ retention
Growth Vascular H2O retention
factor Sympathetic
smooth muscle K+ excretion
stimulation activation
constriction Mg+ excretion
 ANTIHYPERTENSIVE DRUGS

DRUGS AFFECTING RAAS [renin angiotensin aldosterone system]-

 RENIN INHIBITOR: Beta blockers [Propranolol, Atenolol, etc]

 ACE INHIBITORS: Enalapril, Ramipril

 ANGIOTENSIN II RECEPTOR [AT1-receptor] BLOCKERS: Eprosartan, Losartan

 ALDOSTERONE ANTAGONIST [ potassium sparing diuretic ]: Spironolactone

Sites of action of ACE inhibitors & Receptor blockers
 Nama Obat Dosis
ACE I
Captopril 12,5-25 mg 2-3
times/daily
enalapril, 5-20 mg OD
Ramipril Start with low
dose; 2.5 to 10
mg daily
Lisinopril available as 1.25,
2.5, 5, 10 1nd 20
mg tab – start
with low dose
2-ANGIOTENSIN RECEPTOR –BLOCKING AGENTS

Mechanism of action :
 Block AT 1 receptors.
Advantages over ACEI :
They have no effect on bradykinin system: No cough,wheezing
or angioedema.
Complete inhibition of angiotensin action compared with ACEI
Losartan is the specific AT1 blocker
CALCIUM CHANNEL BLOCKERS
Calcium Channel Blockers - Classification
Inhibit calcium influx into arterial smooth muscles & cardiac muscles.
Dihydropyridine group (amlodipine, nifedipine) are more selective as
arteriodilators ( decreasing afterload)
Verapamil &Diltiazem are more selective as cardiac depressant
( decreasing C.O) .
CCB Site of Action

diltiazem & verapamil

nifedipine
(and other
dihydropyridines)
 CCB Action

diltiazem & verapamil

 decrease automaticity & conduction in SA & AV nodes
 decrease myocardial contractility
 decreased smooth muscle tone
 decreased PVR
nifedipine
 decreased smooth muscle tone
 decreased PVR
 Side Effects of CCBs

Cardiovascular
 hypotension, palpitations & tachycardia
Gastrointestinal
 constipation & nausea
Other
 rash, flushing & peripheral edema