PHARMACOLOGICAL PROPERTIES Digoxin

Mekanisme kerja (umum) Inhibits Na/K ATPase pump

Efek terhadap atrium decreased

Efek terhadap ventrikel decreased

Efek terhadap frekuensi denyut jantung decreased

Efek terhadap kontraktilitas jantung decreased

Efek terhadap tekanan darah decreased

adult:immediete release
Waktu paruh formulation:3-6 hours, extended
release formulation 8-10 hours
PHARMACOKINETICS PROFILE
 absorsi: oral:rapid and complete,
Absorbsi dan bioaviabiliti
BA:25%

Distribusi dan ikatan protein Vd : 4L / kg in ADULTS

hepatic via CYP2D6 and

Metabolisme
CYP1A2

metabolites are excretion in urine

Ekskresi
96% -99%, 1% in unchanged drug

heart failure, angina pectoris,

phreocomochytoma, essential
Indikasi
tremor, supraventricular arhytmia,
ventricular tachycardy,

Indikasi Tambahan
 bradycardy, cardiogenic shock,
Potensi Efek Samping hypotension,raynaud's syndrome,
dizziness, death

hypersensitivity, uncompensated
congestive heart failure.
Kontra indikasi
Cardiogenic shock, bradycardy,
COPD.

Peringatan

Dosis
Frekuensi pemberian 2 - 3 / day

Rute pemberian IV, oral

Bila sediaannya oral, sebelum atau setelah makan

Bentuk sediaan dan kekuatan (contoh: tablet 25 mg)

Harga

Keamaanan Bagi wanita Hamil C

Keamanan Bagi anak-anak Enter breast milk

Arbutamine / selected
Potensi interaksi obat
antiarrhytmics (severe interaction)

worsening heart failure, adverse

Risiko bila pengentian penggunaan obat secara tiba tiba reaction

Hypertrophic obstructive
Kondisi yang berpotensi meningkatkan risiko efek samping
cardiomyopathy; dysrhytmias

TUTOR 17 / E1

1. Edwin Elian Putra

2. Khoriah Indrihutami
3. Vickya Putriani
4. Alkaustariyah Lubis
5. Yolla Sri Agustina
6. Sonia Fitriani
7. Iffa Nadifa
8. Tania
9. Ilham Nyssam Akbar
10. Muhammad Fadhil Ramadhan
11. Fariz Hadyan
12. Shifa Nadya Rahman
 TUTORIAL 17 / E1
Digitoxin g-Strophantin (Ouabain) Acetycholine

merupakan neurotransmitter yang

digunakan di neuromuscular
Na+/K+ inhibitor, menyebabkan
inhibitor of the NA(+)-K(+)- junction, bekerja di parasimpatik,
peningkatan kontraksi myokard
exchanging ATPase berikatan dengan muscarinic
(positive inotropic effect)
reseptor di jantung, akan tetapi
hanya tersedia untuk mata.

peningkatan kontraksi increased contractility menurunkan kontraksi

peningkatan kontraksi increased contractility menurunkan kontraksi

menurun decreased menurunkan

meningkat increased menurunkan

meningkat increased menurunkan

7-9 hari 21 hr
 highly lipophilic, hampir semua poorly absorbed from the GI
100%
diabsorpsi setelah administrasi oral tract and low bioavailability.

0,61 L/kg, PB >90% 60% -

disintesis dengan 2 langkah yaitu

pembentukan acetyl coenzyme A,
AcCoA, CoA S CO-CH3 dari
not bound extensively to plasma asetat dan coenzyme A,
hati, menghasilkan digoxin sebagai
albumin and is excreted largely pembentukan acetylcholine dari
metabolit aktif
unchanged. choline dan AcCoA,
didistribusikan di CNS, Vegetatife
nervous system. Presympatic
termination NMJ.

utamanya feces eliminated by renal excretion -

acute congestive heart failure,

katarak, keratoplasty, iridectomy,
arrhythmyas, CHF, nondal paroxysmal tachycardia,
ketika butuh rapid meiosis
atrial fibrillation and flutter

obesity (bahaya, dpt menyebabkan

suppressing cancer metastasis -
aritmia)
 CVS (atrial tachycardia, AV
dissociation, heart block, PR interval
prolongation, ST segment depression,
Bradycardia, flushing,
VF, VPC, VT), CNS (anxiety, apathy,
bradycardy, cardiogenic shock hypotension, headache, clouding,
blurred or yellow vision, confusion,
corneal edema, decompensation
dizziness, halusinasi, etc) GIS
(abdominal pain, anorexia, nausea
and vomitting, etc)

hipersensitivitas, ventricular
hypersensitivity, renal failure
fibrilation
hipersensitif ke acetylcholine
chloride, acute iritis, acute
inflammatory disease di anterior
chamber

gangguan keseimbangan elektrolit,

harus selalu mengunjungi dokter hanya dalam kondisi aseptik
secara reguler

rapid oral (0,6 mg kemudian 0,4 mg

4-6 jam kemudian, 0,2 mg 4-6 jam IV maintenance (Heart Failure) :
0,5-2ml
kemudian), dan slow oral (0,2 mg 2x 125-250 mcg / day
sehari selama 4 hari)
 2x sehari saat operasi katarak saja

oral IV intraocular injection

oral use is unsafe because of

sebelum atau sesudah slow and irregular absorption tidak oral
from GI tract

Ouabain (250 mg, 500mg,

tablet 0,25 mg 1000mg, 2000mg, 10mM * 1mL vial 20mg/2ml
in DMSO)

Ouabain 250 mg : $80.0, 500mg

: 4150, 1000mg : $250,
Rp. 1.598,516 (20 mg)
2000mg : $450, 10mM * 1mL in
DMSO : $61

Kategori C, tapi belum ada report

kategori C C
dipakai saat hamil
dpt menyebabkan poisoning, harus
tidak tersedia Tidak tersedia
ada penyesuaian dosis tiap individu

1. Aminoglutethimide ( Metabolism
of digitoxin accelerated (reduced
effect)) 2. Calcium (can precipitate
arrhythmias)
Frusemide or Furosemide
Acebutolol, Ambenonium, Bisoprolol, dll. (The risk or severi
(menguntungkan/merugikan)

Elicits Ca2+-Induced Delayed

worsening heart failure, adverse reaction
Afterdepolarizations

Heart block,Aortic valve

Heart block,Obstructive
disease,Acute
cardiomyopathy,Wolf-parkinson-white heart block and hypokalaemia
myocarditis,Cardiomyopathy,Cor
syndrome,Myocarditis
pulmonale,Pericarditis.
7 / E1
Atropine Adrenaline Phentolamine Propranolol

Atropine berkompetisi
dengan ACh dan
muscarinic agonist lainnya nonselective beta adrenergic
pada muscarinic receptor. blocker(class II antiarhytmic,
Saat atropine berikatan memblok reseptor alfa- competitively block response
menstimulasi alpha dan
dengan reseptor adrenergik, di samping beta 1 and beta 2 adrenergic
beta 1 adrenergic
muscarinic, atropine itu juga menstimulasi stimulation which result in
receptor
mencegah pelepasan reseptor β-adrenergic decrease heart rate,
inositol triphosphate (IP3) myocardial contractility and
dan inhibisi adenylyl myocardial oxygen demand.
cyclase yang disebabkan
oleh muscarinic agonist.

menurunkan efek vagal

menurunkan kontraksi
pada SA node

- menurunkan kontraksi

bisa meningkatkan bisa

meningkatkan heart rate menurunkan frekuensi decreased
denyut
meningkatkan
- relaksasi otot jantung decreased
kontraktilitas jantung

meningkatkan tekanan menurunkan tekanan

- decreased
darah darah adult:immediete release
formulation:3-6 hours,
4 jam 2 menit 19 menit
extended release formulation
8-10 hours
 Diabsorpsi secara baik di cepat ketika diberikan
absorsi: oral:rapid and
usus dan membran secara injeksi, 30–60 menit / 100%
complete, BA:25%
konjungtiva, BA 10-30% bioavailability 70-80%

terdistribusi ke seluruh 50% binding protein,

tubuh (melewati BBB dan melewati placenta
kurang dari 72 menit Vd : 4L / kg in ADULTS
placenta), protein binding barrier dan terekskresi
14-22% di ASI

di liver oleh hepatic via CYP2D6 and

Liver hati
monoamine oxidase CYP1A2

80% dikeluarkan bersama metabolites are excretion in

di urine dalam keadaan
Urin urin dan 20% dikeluarkan urine 96% -99%, 1% in
sudah dimetabolisme
bersama feses unchanged drug

anaphylactic shock,
sepsis,cardiac arrest,
Parkinson’s disease, motion
resistant ventricular pasien penderita hypertension, angina pectoris,
sickness, ophthalmologic
fibrillation,bronchospas hipertensi yang terjadi phreocomochytoma, essential
disorder, COPD, asthma,
m, severe asthma, dalam rangkaian tremor, supraventricular
minor inflammatory
unresponsive asystole, persitiwa yang arhytmia, ventricular
bladder disorder,
unresponsive disebabkan oleh tachycardy, prevention of MI,
cholinergic poisoning,
bradychardia, pheochromacytoma migrain.
bradycardia
laryngotracheobronchiti
s

hypertensive crisis,
pheochromocytomas,
in adjunctive therapy of necrosis caused by
Hyperhidrosis
anesthesia administration site
extravasation,
norepinephrine
 sweating, nausea,
vomit, headache,
chestpain,
hypertension,
Mydriasis, cycloplegia, dry hyperglycemia, acute and prolonged
mouth, tachycardia, hot and hypokalemia, cardiac hypotensive episodes, bradycardy, cardiogenic shock,
flushed skin, agitation, arrythmias, weakness, fast heart rate, cardiac hypotension,raynaud's
delirium, urinary retention, dizziness, anxiety, arrhythmias, weakness, syndrome, dizziness
constipation dyspnea, restlessness, dizziness
palpitation,
tachychardia,tremors,
cold extrimities, susah
buang air kecil

glaucoma, history of
prostatic hyperplasia, acid- ischemic heart disease, insufficiency, angina or
peptic disease, urinary tract
obstruction, GI obstruction
hypertension,
hyperthyroid, Myocardial infarction,
tacharrythmias, history of myocardial
ventricular fibrillation, infarction, coronary hypersensitivity,
uncompensated congestive
angle closure other evidence suggestive heart failure. Cardiogenic
galucoma, DM, of coronary artery shock, bradycardy, COPD.
idiopathic hyperthropic disease; hypersensitivity
subaortic stenosis, to Phentolamine
pheochromocytoma

Phentolamine dapat
hati hati pemberian
menyebabkan hipotensi
epinephrine pada orang
akut maupun
tua dan anak anak,
reflux esophagitis, elderly, berkepanjangan,
penyesuaian dosis pada
infants, children takikardia, aritmia,
orang orang yang
angina, infark
mempunyai penyakit
myokardium, dan spasma
ginjal dan hati
serebrovaskular

120 - 240 mg in adults twice a

500mcg (total 3mg) 5mg
day. Children: 1 mg/ kg/day
 setiap 3-5 menit tidak tersedia 2 - 3 / day

Phentolamine dapat
menyebabkan hipotensi
akut maupun
berkepanjangan,
IV/IM IV, oral
takikardia, aritmia,
angina, infark
myokardium, dan spasma
serebrovaskular

- tidak tersedia

solusi 0,1% larutan

epinefrin
Injection 5 mg/mL, capsule 60,80,120,240 mg,
Ampul 250mcg/mL x 1mL hidroklorida;solusi 0,18%
dari epinefrin hidrogen Solution 5 mg Injection 1 mg/ml
tartrat.

Phentolamine 84 USD (5
Rp41704
mg vial)

AU TGA pregnancy
category: A US FDA
pregnancy category: C
kategori C Comments: -Use with C C
caution during labor and
delivery; avoid use during
second stage of labor.
 aman dengan dosis
yang disesuaikan
tidak direkomendasikan tidak tersedia Enter breast milk
dengan umur dan juga
berat

Betaxolol (HCl) (Severe

hypertension), Cocaine
Antazoline, Azelastine (threatening cardiac Adrenaline, Clonidine
increased effet with alpha 1
(HCl) (Increased risk of arrhythmias.), Halothane (HCl), Dobutamine
blocker, alpha 2 agonist,
antimuscarinic side effects) (ventricular arrhythmias (HCl), Protirelin
and acute pulmonary
edema or death.)

vomiting, and accidental sweating, shaking, worsening

anger, mood swings,
death by aspiration can rebound effects of angina, irregular heart beat,
lethargy and depression
happen heart attack or death.

Diabetes
Glucoma,Reflux Hypotension,Obstructive Acidosis,Asthma,Heart
mellitus,Hypertension,Hy
oesophagitis,Prostatic cardiomyopathy,Cardiovascula failure,Cardiogenic
perthyroidism,Ischaemic
hypertrophy,Unstable cardiac r disease,Cerebrovascular shock,Bronchospasm,Haemorrhage,H
heart disease,Angle- disease,Aortic stenosis. eart block.
rhythm.
closure glaucoma.
 Verapamil Isosorbit dinitrate

A vasodilator used in the

treatment of angina pectoris.
inhibitor calcium channel
Effect on dilation of smooth
muscle

menurunkan kontraksi

decreased ventricular preload,

thereby reducing left ventricular
menurunkan kontraksi end- diastolic pressure and
pulmonary capillary wedge
pressure (preload).

menurunkan kontraksi decrease heart rate

Venous dilation reduces venous
pressure and decreases ventricular
preload. This reduces ventricular
menurunkan kontraksi
wall stress and oxygen demand by
the heart, thereby enhancing the
oxygen supply/demand ratio
menurunkan kontraksi decrease blood pressure

3-7 jam 1 hour

 Absorption of isosorbide dinitrate
after oral dosing is nearly
complete, but bioavailability is
highly variable (10% to 90%),
15-30%
with extensive first-pass
metabolism in the liver. The
average bioavailability of
isosorbide dinitrate is about 25%.

VOD : 2 to 4 L/kg and PB : very

70-98%
low

Norverapamil adalah
metabolit verapamil yang
masih mempunyai aktivitas hepatic
farmakodinamik yang
lemah.

Urine (70%) dan feses

(16%
partially renal

For the prevention of angina

Angina varian, angina stabil
kronik, angina tidak stabil
pectoris due to coronary artery
disease.

aritmia, hipertensi, 1. angina pectoris, 2. Hear failure

hypertrophy cardiac unspecified, 3.CAD
 Bradiaritmia, gangguan
konduksi, hipotensi,
hiperplasia gusi, konstipasi,
retensi urin, refulks
headache and lightheadedness
esophagus, efek inotropik
negatif.

Allergic to it, Obstructive

Bradikardia, AV block
derajat 2 dan 3, sick sinus
syndor
hypertrophic cardiomyopathy,
severe fluid deficiency, inferior
myocardial infarction with right
ventricular involvement, raised
intracranial pressure, cardiac
tamponade.

Complementary treatment with other

anti-anginal drugs (e.g. beta-blockers)
is often necessary during the nitrate-
free interval of angina pectoris
treatment.

for angina pectoris or HF :

20mg initial loading dose
80-320 mg
and 20-160 mg for follow
up dose. For emergency
therapy by infusion 2-
8mg/h
 2-3 times per day. should
be a nitrate-free interval of
10 hours from the very
start of the treatment; for
2x/hari (biasa), 1-2x/hari
(retard) long-term treatment the
administration of higher
doses (100-120 mg) once
daily can be taken into
consideration.

oral, intravenous sublingual

dengan makan

Tab 40, 80, 120 mg; Amp tablet. 40 mg ; 5 mg ; 2.5 mg ;

2,5 mg/mL 10 mg ; 20 mg ; 30 mg

Rp. 38.599 (80 mg) Rp 1500/1 strip of 10 tablet

kategori C FDA pregnancy category C

 Appropriate studies have not
been performed on the
Tidak tersedia relationship of age to the
effects of isosorbide dinitrate in
the pediatric population.

Amiodarone (HCl)
(enhance the bradycardic
Quinine (enhance the hypotensive
effect), Amobarbital
effect),
(reduces hypotensive
Carbamazepine, Cimetidine (HCl),
effects ), Betaxolol (HCl)
Clarithromycin (decrease the
(Severe hypotension when
metabolism of Isosorbide(Dinitrate))
and heart failure when beta
blockers)

condition may become

severe attack of angina
worse

Hypovolaemia,Myocardial
Heart infarction,Cardiac temponade,Raised
failure,Bradycardia,Platelet intracranial pressure,Low cardiac
dysfunction. output,Obstructive hypertrophic
cardiomyopathy.