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SIROSISdan KOMPLIKASINYA

Nama
NIM

Etiologi

Etiology Examples
Biliary obstruction Biliary atresia/neonatal hepatitis, congenital biliary cysts, cystic
fibrosis
Infection Brucellosis, congenital or tertiary syphilis, echinococcosis,
schistosomiasis
Drugs and toxins Alcohol, methotrexate, isoniazid, methldopa, organic hydrocarbons
Immune-mediated Primary biliary cirrhosis, porphyria, α1-antitrypsin deficiency,
Wilson’s disease
Cardiovascular Chronic right heart failure, Budd-Chiari syndrome, veno-occlusive
disease
Cryptogenic Unknown
Other Nonalcoholic steatohepatitis, sarcoidosis, gastric bypass

Patofisiologisirosis(deskriptifatau diagram)

SelStelatateraktivasi retinoid menghilang selberpoliferasi produksimatriksekstraseluler, sertamenjadisel myofibril yang


mampuberkontraksi deposisisel-selfibrosadalam sinusoid mengganggualirandarahpadalobushatijaringanfibrosayang
terakumulasidanalirandarah yang meningkathipertensi portal adaperubahanjumlah mediator
vasodilatasidanvasokonstriksimeningkatkanalirandarahkevaskulatursplanknik

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Tandadangejalasirosis (termasukhasillaboratorium)

Tanda dan Gejala Hasil Laboratorium


Asimptomatik Hipoalbuminemia
Hepatomegali, splenomegali Elevated propthrombin time
Pruritis, jaundice, palmar erythema, spider angiomata, Thromocytopenia
hyperpigmentation
Gynecomastia, reduced libido Elevated alkaline phosphatase
Ascites, edema, pleural effusion, dan respiratory difficulties Elevated aspartate transaminase (AST), alanin transaminase (ALT),
dan γ-glutamyl transpeptidase (GGT)
Malaise, anorexia, dan berat badan turun
encephalopathy

Child-Pugh Classification

Parameter 1 2 3
Ascites Tidakada Sedikit Sedang-besar
Encephalopathy Tidakada Derajat 1-2 Derajat 3-4
Albumin >3,5 2,8-3,5 <2,8
Bilirubin <2 2-3 >3
Prothrombin time <4 detik 4-6 detik >6 detik
INR <1,7 1,7-2,3 2,3

Child-Pugh Score

Grade Score Condition


A 5-6 One year survival = 100%, two year survival = 85%

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B 7-9 One year survival = 81%, two year survival = 57%
C 10-15 One year survival = 45%, two year survival = 35%

Komplikasisirosis

Komplikasi Tandadangejala
Ascites Penumpukancairanlimfapadarongga peritoneal
Encephalopathy Gagalginjal fulminant akutdankelainan mental
Variceal bleeding Muntah darah, tinja berdarah, tekanan darah rendah, denyut jantung cepat, lightheadedness,
syok
Portal hypertension Tinja berdarah, ascites, encephalopathy, berkurangnya kadar platelet

Patofisiologi (deskriptifataupun diagram)

a. Ascites

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA

b. Encephalopathy

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
c. Variceal bleeding dan portal hipertensi

Tujuanterapi

Kondisi Tujuanterapi

Sirosis Memperlambat atau membalikkan penyebab penyakit; menghambat, mengidentifikasi, dan

menangani komplikasi; melindungi liver dari kerusakan lain; meringankan gejala dan

memperbaiki abnormalitas darah; menentukan apakah transplantasi hati diperlukan atau tidak

Ascites Untuk mengontrol ascites; untuk mencegah atau mengurangi gejala ascites seperti dispnea,

abdominal pain, dan abdominal distention; serta untuk mencegah komplikasi seperti SBP dan

hepatorenal sindrom

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Encephalopathy Mempertahankan kapasitas fungsional, menurunkan kadar amonia

Variceal bleeding Menurunkan denyut jantung dan tekanan portal

Portal hypertension Mencegah atau menghambat pendarahan

Terapi non farmakologi

Terapi non farmakologi Alasan


Variceal bleeding  Pemasangangelangkaret di sepanjangtitikvarises
 Sclerotherapy, penginjeksianblood-clotting solution
 Transjugular Intrahepatic Portosystemic Shunt (TIPS), pemasangan stent yang
menghubungkanantara vena hepatic dengan vena porta
 Tranplantasihati
Ascites  Diet garam
 Tidak mengkonsumsi alkohal

Encephalopathy  Lactosa
 Mengatur pola makan
 Menghindari alkohol

Portal hypertension  Pemasangangelangkaret di sepanjangtitikvarises


 Sclerotherapy, penginjeksianblood-clotting solution

Sirosis  Menghindari alkohol


 Diet
 Mengatur pola makan
 Olah raga

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Terapifarmakologi

Golongan Nama obat Mekanismekerja Parameter Kontraindikasi Efeksampingobat


Farmakokinetik (3 tertinggi)
Ascites Spironolakton Aldosterone antagonist with diuretic and Increased with food Hypersensitivity Ginekomasia
antihypertensive effects in distal tubules
results in increased excretion of Na+, Cl-, Bioavailability: 73% Anuria
and H2O and retention of K+ and H+
Sakit kepala
Onset: 2-4 hr Severe renal
impairment, acute mengantuk
Duration: 2-3 days renal insufficiency
Metabolisme di hati
dan ginjal

Half-life: Parent drug


(1.3-1.4 hr);
metabolite
[canrenone] (9-23 hr)

Excretion: Urine (47-


57%); feces (35-41%)

Furosemid inhibits reabsorption of sodium and Bioavailability: 47- hypersensitivity to Hyperuricemia


chloride ions at proximal and distal renal 64% (PO) furosemide or (40%)
tubules and loop of Henle; by interfering sulfonamides
with chloride-binding cotransport system, Onset: 30-60 min Hypokalemia (14-
causes increases in water, calcium, (PO/SL); 30 min (IM); Anuria 60%)
magnesium, sodium, and chloride 5 min (IV)

Peak effect: <15 min


(IV); 1-2 hr (PO/SL)

Duration: 2 hr (IV); 6-
8 hr (PO)

Metabolisme di hati

Half-life: 30-120 min


(normal renal
function); 9 hr (end-
stage renal disease)

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Excretion: Urine (PO,
50%; IV, 80%)

Amilorid Direct effect on renal distal convoluted Half-Life: 6-9 hr Hypersensitivity Hyperkalemia
tubule to inhibit Na+ reabsorption from (10%)
the lumen Duration: 24 hr to amiloride
Anorexia (3-8%)
Onset: initial effect: 2- Hyperkalemia
3 hr, max effect: 6-10 (K+ >5.5 mEq/L Diarrhea (3-8%)
hr
[5.5 mmol/L])
Peak Plasma Time:
3-4 hr

Bioavailability: 30-
90%

Protein Bound: 23%

Vd: 350-380 L

Metabolism: NOT
metabolized in the
liver; no active
metabolites

Metolazon Inhibits reabsorption of sodium in distal Bioavailability: 40- hypersensitivity to Chest pain
tubules, causing increased excretion of 65% metolazone or
water and of sodium, potassium, and sulfonamides Depression
hydrogen ions Onset: Diuresis, 1 hr
Anuria Dizziness
Duration: 24 hr

Peak plasma time:


Zaroxolyn, 8 hr

Half-life: 20 hr

Excretion: Urine
(80%), bile (10%)

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Ensefalopati Laktulosa inhibiting diffusion of ammonia back to Bioavailability: <3% Galactosemia Dehydration
blood; agent also enhances diffusion of absorbed (patients require
NH3 from blood into gut, where it is low-galactose diet) Diarrhea
converted to NH4+ Onset: 24-48 hr
Excessive bowel
Excretion: Urine activity

Metronidazol Inhibits nucleic acid synthesis by Bioavailability: 80% Hypersensitivity Candidiasis


disrupting DNA and causing strand absorption from GI
breakage; amebicidal, bactericidal, tract (PO) Pregnancy, 1st Diarrhea
trichomonacidal trimester
Protein binding Dizziness
(<20%)

Peak serum time: 1-2


hr

Half-life: 25-75 hr
(neonates); 8 hr
(others); prolonged in
patients with hepatic
impairment

Excretion: Urine
(77%); feces (14%)

Neomisin Interferes with bacterial protein synthesis Half Life: 3 hr Hypersensitivity Diarrhea
by binding to 30S ribosomal subunits,
thus reducing the number of ammonia- Peak Plasma Time: Ulcerative bowel Nausea/vomiting
producing bacteria in the intestine oral: 1-4 hr; IM ~2 hr disease
Irritation or
Absorption: oral, Intestinal soreness of mouth
percutaneous: poor obstruction or rectal area
(3%)

Vd: 0.36 L/kg

Metabolism: slightly
hepatic

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Pendarahan Oktreotid Somatostatin analog; decreases GH Absorption rapid and Hypersensitivity Gallbladder
varises secretion, secretion of gastrin, VIP, complete (SC) problems (>60%):
glucagon, secretin, serotonin release and Decreased
pancreatic polypeptide Bioavailability: SC, gallbladder
100%; IM, 60% contractility,
gallstones,
Peak plasma time: IV, cholecystitis,
immediately after cholestatic hepatitis
injection; SC, 15-30
min; PO, 90-120 min; Dysglycemia (25%)
IM, 60 min
Hypothyroidism
Half-life: 1.7 hr (25%)
Total body clearance:
10 L/hr

Excretion: Urine
(32%)

Terlipressin Terlipressin, an analogue of blood pressure Abdominal cramps


dengan atau tanpa vasopressin, acts on three different
gliseril trinitrat receptors, vasopressin receptor V1a asthma chest pain
( vasoconstriction, liver
gluconeogenesis, platelet hardening of the abnormal heart
aggregation and release of factor arteries rhythm
VIII), vasopressin receptor V1b (
mediates corticotrophin secretion
from the pituitary) and vasopressin
receptor V2 which controls free water
reabsorption in the renal medullar.

Portal Octreoide Somatostatin analog; decreases GH Absorption rapid and Hypersensitivity Gallbladder
Hipertension secretion, secretion of gastrin, VIP, complete (SC) problems (>60%):
glucagon, secretin, serotonin release and Decreased
pancreatic polypeptide Bioavailability: SC, gallbladder
100%; IM, 60% contractility,
gallstones,
Peak plasma time: IV, cholecystitis,
immediately after cholestatic hepatitis
injection; SC, 15-30

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
min; PO, 90-120 min; Dysglycemia (25%)
IM, 60 min
Hypothyroidism
Half-life: 1.7 hr (25%)

Total body clearance:


10 L/hr

Excretion: Urine
(32%)

Propanolol Nonselective beta adrenergic receptor Bioavailability: 30- Asthma Bradycardia


blocker; competitive beta1 and beta2 70% (food increases
receptor inhibition results in decreases in bioavailability) Cardiogenic shock Hypotension
heart rate, myocardial contractility,
myocardial oxygen demand, and blood Onset: Hypertension, Hypersensitivity Arthropathy
pressure 2-3 wk; beta
blockade, 2-10 min
(IV) or 1-2 hr (PO)

Duration: 6-12 hr
(immediate release);
24-27 hr (extended
release)

Peak plasma time: 1-


4 hr (immediate
release); 6-14 hr
(extended release)

Half-life: Children,
3.9-6.4 hr; adults,
3.9-6.4 hr (immediate
release) or 8-10 hr
(extended release)

Excretion: Urine (96-


99%)

Vasopresin Vasoconstrictor without inotropic or Bioavailability: Hypersensitivity Abdominal cramps


chronotopic effects; stimulates smooth Destroyed by trypsin
muscle in GI tract to cause peristalsis in GI tract; must be Allergic reaction
administered
parenterally or

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
intranasally Angina

Onset (antidiuretic
activity): IM/SC, 2-8
hr

Onset (pressor
activity) IV, 30-60 min

Half-life: 10-20 min


(parenteral)

Excretion: Urine (5-


10%)

Nitroglycerin PO Organic nitrate which causes systemic onset: within 1- hr4 Hypersensitivity Headache
venodilation, decreasing preload
Duration antianginal glaucoma Hypotension
effects: Up to 12 hr
Tachycardia
Bioavailability: 38.5%

Protein Bound: 11-


60%

Vd: 3 L/kg

Metabolism: Liver,
extrahepatic sites:
vascular wall, RBC

Metabolites: 1,3-
glyceryl dinitrate, 1,2-
glyceryl dinitrate, &
glyceryl mononitrate
(inactive)

Clearance: 5.5-11
L/min

Excretion: urine

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Golongan Namaobat Mekanismekerja Parameter Kontraindikasi Efeksampingobat
Farmakokinetik (3 tertinggi)

Worksheet Farmakoterapi 1 - DMV


SIROSISdan KOMPLIKASINYA
Algoritmaterapiuntuksirosisdankomplikasinya

Worksheet Farmakoterapi 1 - DMV

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