RATIONAL THERAPI

obat-obat dalam sistem ginjal, sal. kemih dan kardiovaskuler

obat-obat dalam sistem hematoimunologi

Nafi’uddin Mahfudz, dr. SpPD., MKes.

• Learning objective dari materi persistem :
• Membantu mahasiswa membedah formularium nasional
• Membantu mahasiswa lebih memahami dalam pemilihan obat untuk
penulisan resep.
•
• Dari sekian banyak nama obat dan keterbatasan waktu penyampaian,
mohon bisa dipilih obat-obat yang sering dipakai dilapangan.
•
• Kisi-kisi materi kuliah dari obat-obat dalam sistem, penyampaiannya
ditekankan pada :
• Nama obat, sediaan, dosis, lama pemberian
• Mekanisme kerja, indikasi dan kontraindikasi
• Interaksi obat (untuk obat-obat tertentu)
•
• Pustaka :
• DOEN
• Formularium Nasional
• Buku-buku farmakologi (FK UI, katzung, godman-gilman, dll)
• Buku-buku pegangan masing-masing bagian/sistem
 obat-obat dalam sistem ginjal, sal. kemih
dan kardiovaskuler
• Diuretik : amilorid, furosemid, hidroklorotiazid, manitol,
spironolakton,
• Antidiuretik : desmopresin, vasopresin
• Obat hipertrofi prostat : doksazosin, dutasterid, finasterid,
tamsulosin, terazosin
• Antihipertensi : amlodipin, atenolol, bisoprolol, diltiazem,
doksazosin, hidroklorotiazid, imidapril, irbesartan,
kandesartan, kaptopril, klonidin, klortalidon, lisinopril,
metildopa, metoprolol tartat, nefedipin, nikardipin, nimodipin,
perindorpil arginin, proataglandin, ramipril, telmisartan,
valsartan, verapamil, beraprost sodium,
• Antiangina : amlodipin, atenolol, diltiazem, gliseril
trinitart, isosorbid dinitrat
• Antiaritmia : amiodaron, digoksin, diltiazem, lidokain,
propranolol, verapamil,
• Antiagregasi platelet : asetosal, klopidogrel,
silostazol, alteplase, streptokinase,
• Obat gagal jantung : bisoprolol, digoksin, furosemid,
isosorbid dinitrat, kaptopril, karvedilol, ramipril,
spironolakton, dobutamin, dopamin, epinefrin,
norepinefrin
• Antihiperlipidemia : atorvastatin, fenofibrat,
gemfibrozil, kolestiramin, pravastatin, simvastatin,
- Obat hipertrofi prostat : doksazosin, dutasterid, finasterid, tamsulosin,
terazosin
• Vasopressin is a neurotransmitter; among its actions
in the CNS are apparent roles in the secretion of
ACTH and in the regulation of the cardiovascular
system, temperature, and other visceral functions.
• REGULATION OF VASOPRESSIN SECRETION
• An increase in plasma osmolality is the physiological
stimulus for vasopressin secretion Severe
hypovolemia/hypotension also is a powerful stimulus
for vasopressin release.
• In addition, pain, nausea, and hypoxia can stimulate
vasopressin secretion.
• CLINICAL USE OF VASOPRESSIN PEPTIDES
• THERAPEUTIC USES
• Only two antidiuretic peptides are available for clinical use in
the U.S.
• Vasopressin (synthetic 8-L-arginine vasopressin;
PITRESSIN) is available as a sterile aqueous solution; it may
be administered subcutaneously, intramuscularly, or
intranasally.

• Desmopressin acetate (synthetic 1-deamino-8-D-arginine

vasopressin; DDAVP, others) is available as a sterile aque-
ous solution packaged for intravenous or subcutaneous
injection, in a nasal solution for intranasal administration with
either a nasal spray pump or rhinal tube delivery system, and
in tablets for oral administration.
• Oral administration of desmopressin in doses 10–
20 times the intranasal dose provides adequate
blood levels of desmopressin to control polyuria.

• Daily subcutaneous administration of 1–2 mg of

desmopressin also is effective.
HYPERTENSION
• Screen Shot 2017-10-26 at 1.01.46 PM
Pilihan terapi
 Diuretics
• Mekanisme Kerja
– Ekskresi sodium, klorida dan air  volume
plasma & cairan ekstrasel (-)  curah
jantung  & Tahanan perifer tetap
– Pemberian kronis  volume plasma ~
normal, tahanan perifer 
– Badan lemah
– Effective <<  renal dysfunction
 Thiazide
 Hidroklortiazid
 Indapamid
 Efek antihipertensi  dosis <<  lama 2-3 hari
 Drug of choice pd ginjal normal
 Hipertensi ringan – sedang
 Pemberian 1x / hr
 Kombinasi  << dosis AH
 ES  hypokalemia, hyperuricemia, glucose
intolerance
 Interaksi dng NSAID  indometasin  retensi na &
air  efek AH 
 Furosemide
 Diuretik kuat : HT disertai gagal jantung / gangg fgs
ginjal  kreatinin ≥ 2,5 mg/dl
 OA cepat, efek > tiazid
 DOA cepat  pemberian 2x
 ES = Tiazid  tdk hiperkalsemia

 Diuretik Hemat Kalium (spironolakton)

 Diuretik lemah
 Kombinasi dgn diuretik lain  m’cegah hipokalemia
 Efek hipotensi ~ hidroklortiazid
 Antagonis aldosteron
 ACE Inhibitors
 Mekanisme Kerja
 Block the enzyme that converts angiotensin I to angiotensin II ( a
vasoconstrictor)
 Promote vasodilatation
 Lowers aldosterone secretion
 ES :
 Cough
 Rash
 Angioneurotic edema
 Ganggunan Taste
 Hyperkalemia especially with renal impairment
 Especially useful
 HTN with CHF or DM
 KI :
 Pregnancy
 Bilateral renal artery stenosis
 ACEIs
Captopril (Capoten®)
*Enalapril (Vasotec®)
Lisinopril (Prinivil®; Zestril®)
*Benazepril (Lotensin®)
*Fosinopril (Monopril®)
*Trandolapril (Marik®)
*Quinopril (Accupril®)
*Ramipril (Altace®)
*Moexipril (Univasc®)
*Perindopril (Aceon®)

*Ester prodrugs activated by liver esterases

 RAS ↓NaCl Delivery
Sympathoadrenal to TAL ↓Pressure in Afferent
Activation Arteriole

Macula Densa
B1-Adrenoreceptor Activation Intrarenal Baroreceptor
Activation Activation

JUXTAGLOMERULAR CELLS
Liver
(340AA glycoprotein cleaves
RENIN substrate on amino terminus between
residues 10 and 11)
Angiotensinogen (452AA
Angiotensin I Angiotensin Converting Enzyme
glycoprotein in circulation)
(decapeptide) (ACE; 1277AA glycoprotein in
vascular endothelium)
Other Peptides: Angiotensin II
• Ang (2-8) (octapeptide)
• Ang ( 1-7) AT1 Receptor AT2 Receptor
• Ang (2-10) + -
• Ang (3-8) Blood Pressure
Cell Growth
Apoptosis
 Angiotensin II receptor
blockers
• Mekanisme Kerja

• Block the AT1 receptor  peripheral

resistance <<

• Efek = ACE inhibitors  cough (-)

• ARBs are eliminated  liver.
• ES = ACEIs except  cough (-)
 ARBs
®
Losartan (Cozaar )
®
Candesartan (Atacand )*
®
Irbesartan (Avapro )
®
Telmisartan (Micardis )
®
Valsartan (Diovan )
®
Olmesartan (Benicar )*
®
Eprosartan (Teveten )
*Ester prodrugs activated by liver esterases
 RAS Inhibitor

ACEIs → Block ACE

ARBs → Block AT1 Receptor
Renin Inhibitors* → Block Renin

(*In late clinical development)

 Beta Blockers
 Mekanisme kerja : me  cardiac output and menghambat
sympathetically mediated renin release di ginjal
 KI :
 Asthma/COPD
 Decompensated CHF
 Raynaud’s phenomenon
 Peripheral vascular disease
 Depression
 ES :
 Tiredness
 Cold hands and feet
 Impotence and sexual dysfunction
 May mask the effect of hypoglycemia in DM
 Beta blockers

• Propanolol  non selektif

• Atenolol
Calcium Channel Antagonists
• Mekanisme Kerja  Direct vasodilators
• KI : hati-hati CHF
• ES :
Constipation
Peripheral edema
Headache
• Nifedipine
• Amlodipine
 Alfa-1 blocker

• Prazosin, doxazosin
• Vasodilator
• Selektif alfa-1 reseptor
• Takhikardi (-)
• Postural hipotensi
• Indikasi  HT dgn BPH
 Evaluasi HT sekunder
• < 5%  penderita HT
• Recent or sudden onset
• Dewasa muda  family history (-)
• Patients resistant to treatment
• Penderita :
• Physical findings (abdominal bruits)
• Biochemical abnormalities (unprovoked
hypokalemia)
- Obat hipertrofi prostat : doksazosin, dutasterid, finasterid, tamsulosin,
terazosin
2009 Focused Update: ACCF/AHA Practice Guidelines for the Diagnosis and
Management of Heart Failure
Dosis obat yang umumnya dipakai pada gagal jantung
 Pharmacological therapy of heart failure
due to left Ventricular Systolic Dysfunction

For survival / morbidity

For symptom
Mandatory therapy

NYHA I Cont ACE-inhibition/ARB if ACE-inhibition Reduce / stop

intolerant, continue Aldosterone Antagonist if diuretic
post-MI, add Beta-blockers if post-MI
NYHA II ACE-inhibitors as first-line treatment ARB if + / - diuretic
ACE-inhibitors intolerant, Add Beta-blockers depending on
and Aldosterone Antagonist if post MI fluid refention
NYHA III ACe-inhibitors plus ARB or ARB alone if ACE- + diuretic
intolerant, add Beta blockers add Aldosterone + digitalis if still
Antagonist symptomatic
NYHA IV Continue ACE-inhibitors / ARB + diuretic
Beta blockers + digitalis
Aldosterone antagonist + consider
temporary
inotropic support
ESC Guidlines for the Diagnosis and Treatment of CHP – 2005
 Recommended Drugs
Condition
Diuretik BB ACE-I ARB CCB ALD-antag
Subclinical organ damaged
LVH
Atherosclerosis
Renal Dysfunction
Clinical event
Previous stroke
Previous MI
Angina pectoris
Heart Failure
Atrial fibrillation
Recurrent
Permanent
ESRD/proteinuria
PAD.
Condition
ISH (elderly)
Metabolic Syndrome
Diabetes Melitus
Pregnancy
Blacks

ESC-ESH. 2007 Guidelines for the management of hypertension

INDICATIONS FOR INDIVIDUAL DRUG CLASSES - JNC7

Diuretic -blocker ACE ARB CCB

inhibitor

Heart failure • • • •
Post-MI • •
High coronary
disease risk • • • •
Diabetes • • • • •
Chronic
kidney disease • •
Stroke
prevention • •
The JNC VII Report. JAMA 2003;289:2560-2572
 Clinical Trial and Guideline Basis for Compelling Indications for
Individual Drug Classes
BP
Classification D BB ACEI ACB CCB Ald Ant Clinical Trial Basis

Heart failure ACC/AHA Heart failure Guideline,

MERIT-HF, COPERNICUS, CIBIS,
SOLVD, AIRE,TRACE, ValHEFT,
RALES

Post-MI ACC/AHA Post-Mi Guideline,

BHAT, SAVE, Capricorn,
EPHESUS

High coronary ALLHAT, HOPE, ANBP2, LIFE,

CONVINCE
disease risk
Diabetes NKF-ADA Guideline, UKPDS,
ALLHAT

Chronic kidney NKF Guideline, Captopril Trial,

RENAAL, idnt, REIN, AASK
disease
Recurrent stroke PROGRESS
prevention

JNC VII 2003

47
 Re-appraisal of ESH/ESC Guidelines suggests
4 Preferred
2007 Antihypertensive Drug Classes
2009

Diuretics Diuretics

β-blockers
ARB ONTARGET® ARB
ACCOMPLISH
HYVET

CCB CCB
α-blockers

ACE-I ACE-I

Most rational combinations

Combinations used as necessary

Mancia et al. Eur Heart J. 2007;28:1462–1536; 48

Mancia et al. J Hypertens. 2009;27:2121–2158.
Antiaritmia :
amiodaron, digoksin, diltiazem, lidokain, propranolol,
verapamil,
MECHANISMS OF CARDIAC ARRHYTHMIAS
When the normal sequence of impulse initiation and propagation
is perturbed, an arrhythmia occurs. Failure of impulse initiation
may result in slow heart rates (bradyarrhythmias), whereas
failure of impulses to propagate normally from atrium to ventricle
results in dropped beats (heart block) that usually reflect an
abnormality in either the AV node or the His–Purkinje system.

These abnormalities may be caused by drugs or by structural

heart disease.
Abnormally rapid heart rhythms (tachyarrhythmias) are common
clinical problems that may be treated with antiarrhythmic drugs.

Three major underlying mechanisms have been identified:

enhanced automaticity, triggered automaticity, and reentry.
CHOOSING AMONGST THERAPEUTIC APPROACHES

In choosing among therapeutic options, it is important to establish

clear goals.
For example, three options are available in patients with atrial
fibrillation:
(1) Reduce the ventricular response using AV nodal blocking agents
such as digitalis, verapamil, diltiazem, or b adrenergic antagonists
(Table 34–2);
(2) restore and maintain normal rhythm using drugs such as
quinidine, flecainide, or amiodarone; or
(3) decide not to implement antiarrhythmic therapy, especially if the
patient truly is asymptomatic. Most patients with atrial fibrillation
also benefit from anticoagulation to reduce stroke incidence
regardless of symptoms.
Factors contributing to choice of therapy include not only symptoms
but also the type and extent of structural heart disease
ANTIARRHYTHMIC DRUGS CAN CAUSE ARRHYTHMIAS

One well-recognized risk of antiarrhythmic therapy is the

possibility of provoking new arrhythmias, with potentially life-
threatening consequences. Antiarrhythmic drugs can provoke
arrhythmias by different mechanisms (Table 34–1).

These drug-provoked arrhythmias must be recognized

because further treatment with antiarrhythmic drugs often
exacerbates the problem.

Targeting therapies at underlying mechanisms of the

arrhythmias may be required.
• Antiagregasi platelet :

• asetosal, klopidogrel, silostazol,

alteplase, streptokinase,
• Antihiperlipidemia :
• atorvastatin, fenofibrat, gemfibrozil, kolestiramin,
pravastatin, simvastatin
Thank you for your attention!