Mekanisme Kerja Digoxin pada Miokardiak

I. Deskripsi
Digoxin adalah salah satu glikosida jantung (digitalis), yaitu suatu kelompok senyawa
yang mempunyai efek khusus pada miokardium. Digoxin diekstraksi dari daun Digitalis lanata1.
Digoxin merupakan kristal putih tidak berbau. Digoxin memiliki cincin aglycone, yang
merupakan tempat aktivitas farmakologik Senyawa ini praktis tidak larut dalam air dan dalam
eter, sedikit larut dalam alkohol dan dalam kloroform dan sangat larut dalam piridin. Digoxin
dikenal sebagai racun namun pada akhirnya dapat digunakan sebagai obat gagal jantung
kongestif khususnya pada kasus fibrikasi atrial2.

II. Farmakokinetika
Absorpsi dilakukan melalui difusi pasif pada usus halus bagian atas, makanan dapat
menyebabkan absorpsi mengalami penundaan (delay), tetapi tidak mempengaruhi jumlah yang
diabsorpsi. Distribusi: Disebar ke hampir semua jaringan, termasuk ke eritrosit, otot skelet dan
jantung. Pada keadaan seimbang, kadar dalam jaringan jantung 15-30 kali lebih tinggi daripada
kadar dalam plasma, sementara kadar dalam otot setengah kadar dalam jantung. Efek maksimal
baru timbul 1 jam atau lebih setelah kadar maksimal di jantung tercapai. Ikatan dengan protein
(protein binding) : 25%-30%. Metabolisme dilakukan melalui sequential sugar hydrolysis dalam
lambung atau melalui reduksi cincin lakton oleh bakteri di intestinal , metabolisme diturunkan
dengan adanya gagal jantung kongestif. Ekskresi dan Bioaviabilitas : dieliminasi di ginjal,
Waktu paruh eliminasi digoksin rata-rata adalah 1,6 hari8. Bioaviabilitas 60-80% dari oral. Urin
(50% hingga 70% dalam bentuk obat yang tidak berubah ). Dosis : kisaran efektif antara 1-2,5
ng/ml, Gagal jantung kongestif : 0,5 -0,8 ng/ml , aritmia : 0,8-2 ng/ml, dewasa : < 0,5 ng/ml,
toksik jika diatas 2,5 ng/ml3.

III. Mekanisme Aksi

Digoxin pada prinsipnya bekerja dengan cara menghambat pompa  Na/K ATP-ase yang
bekerja dengan meningkatkan pertukaran natrium-kalsium intraselular sehingga meningkatkan
kadar kalsium intraseluler dan meningkatkan kontraktilitas 4. Digoxin secara spesifik berikatan
dengan subunit-α dari pompa Na + / K + ATPase yang terletak di otot jantung (miokardia),
adanya ikatan ini meneyebabkan tidak berfungsinya pompa Na+/K+ ATPase3. Gambar 1.
Menujukan mekanisme kerja Na/K ATPase. Hal ini kemudian mengaktifkan Na/Ca exchanger
yang menyebabkan peningkatan konsentrasi ion natrium intraseluler, yang kemudian
menyebabkan kenaikan tingkat ion kalsium. Mekanisme inhibisi transport enzim ini juga
menghasilkan hilangnya K+ dari sel miokardium4. Gambar 2. Menunjukan mekanisme aksi dari
digoxin.
 Gambar 1. Mekanisme Kerja Na/K ATPase

Gambar 2. Mekanisme Aksi Digoxin

Kerja dari otot jantung dipengaruhi oleh beberapa ion yaitu ion Na, K dan Ca. Ion Na
terutama bertanggung jawab untuk memelihara tekanan osmosis agar tetap seimbang dalam
jaringan,yaitu menjaga kepekaan sel-sel otot jantung terhadap rangsang yang mempengaruhi
kontraktilitas dan ritmisitas. Kelebihan ion Na ekstraseluler akan menimbulkan efek keracunan
yang menyebabkan jantung berhenti berdenyut. Ion K berperan dalam iritabilitas, kelebihan ion
K ekstraseluler akan mengganggu keseimbangan potensial membrane, bila konsentrasi ion K
ekstraseluler berlebih maka akan menyebabkan berkurangnya kuat kontraksi dan jantung akan
berhenti berdenyut pada keadaan diastole. Ion Ca mempengaruhi kuat kontraksi jantung karena
ion Ca berperan dalam mekanisme sliding filament pada proses kontraksi5. Ion Ca ini akan
berikatan dengan troponin agar otot dapat berkontraksi.
Adanya kelebihan konsentrasi ion Ca akan menghasilkan potensial aksi yang mengubah
permeabilitas retikulum sarkoplasma sehingga mengekresikan ion Ca yang akan menyebabkan
meningkatnya kuat kontraksi jantung melalui mekanisme sliding filament, jika konsentrasi ion
ini terlalu banyak maka jantung akan terus berkontraksi dan tidak dapat berelaksasi sehingga
akhirnya jantung akan berhenti berdenyut pada keadaan systole yang disebut kalsium rigor5.
Kalsium mempotensiasi efek toksin digoxin karena ada Na/ Ca exchanger yang kerjanya
bergantung pada gradien natrium untuk memompa keluar kalsium, digoxin mengurangi gradien
konsentrasi natrium sehingga konsentrasi kalsium intrasel meningkat yang disebakan oleh
menurunnya efflux Ca, hal ini mengarah pada meningkatnya konsentrasi kalsium dalam sel
miokardiak dan pacemaker sehingga jantung mengalami kontraksi5. Gambar 3. Menjelaskan
hubungan ion Ca dan kontraksi miokardium.
 Gambar 3. Hubungan ion Ca dan kontraksi otot.
Mekanisme kedua dari digoxin dihubungkan dengan saraf parasimpatik, adanya
perubahan pada tekanan darah rata-rata dapat dikenali oleh baroreseptor yang akan meneruskan
informasi itu ke pusat kardiovaskuler di batang otak yang mengendalikan keluaran sistim saraf
otonom simpatik (SANS) dan parasimpatik (PANS). Suatu peningkatan pada tekanan darah rata-
rata menimbulkan perangsangan baroreseptor, menghasilkan peningkatan aktifitas PANS,
(menstimulasi vagal central ) memicu bradikardi dan mengurangi aktifitas SANS, yang pada
gilirannya menurunkan heart rate, daya kontraksi dan vasokontriksi4,6.

Gambar 4. Mekanisme kerja digoxin terhadap vagal tone

Daftar Pustaka
1. A. Hollman. 1996. Digoxin comes from Digitalis lanata. British Medical Journal 312
(7035): 912. http://www.bmj.com/cgi/content/full/312/7035/912.
2. Damian, Dodo Saputra. 2009. Farmakologi Obat Inotropik/ Vasopressor. Fakultas
Kedokteran Lambung Mangkurat : Banjarmasin.
3. AHFS Drug Information 2005
4. NN. Autonomic nervous system: physiology and pharmacology. http://www.scribd.com,
diakses 4 Februari 2010.
5. Martini. 1998. Fundamental of Anatomy and Physiology, 4th edition. Prentice Hall
International , Inc. New Jersey
6. DJ Goodman et al. 1975. Effect of digoxin on atioventricular conduction. Studies in
patients with and without cardiac autonomic innervation. Circulation 51: 251-256.
http://www.circ.ahajournals.org/cgi/reprint/51/2/251.
7. Trevor P, Nora MV, Raymon LP, Davis C. USMLE step 1 pharmacology notes. USA:
Kaplan Inc; 2002.p.109-39.
8. Muchtar,A dan Z.S.Bustami. “Obat gagal Jantung” dalam Ganiswarna ( eds.). 2002.
Farmakologi dan Terapi. Jakarta : Bagian Farmakologi Fakultas Kedokteran Universitas
Indonesia.

MEKANISME KERJA DIGOXIN PADA MIOKARDIAK

Disusun untuk memenuhi tugas mata kuliah Toksikologi Lingkungan

Oleh:

Rani 25309037

Kesehatan dan Keselamatan Lingkungan

SEKOLAH PASCASARJANA PROGRAM STUDI TEKNIK LINGKUNGAN

FAKULTAS TEKNIK SIPIL DAN LINGKUNGAN

INSTITUT TEKNOLOGI BANDUNG

2010
 bioavailability (BA) adalah persentase obat yang diresorpsi tubuh dari suatu dosis yang
diberikan dan tersedia, untuk melakukan efek terapeutisnya.BA mencakup pula
kecepatan obat muncul di sirkulasi darah.kl persentase pengikatan tergantung pada
konsentrasi obat di dalam darah.
Utk memperbaiki atrial fibrilasi à aritmia jantung dg kontraksi miokardium atrium yg
cepat dan tdk terkoordinasi
Utk memperbaiki flutter atrial à aritmia jantung dg kontraksi yg cepat 200-300
denyut/menit

Tachyarrhythmia (Fast Heart Rate)

Tachyarrhythmia (Fast Heart Rate)
View enlargement of illustration

Some fast heart rates are appropriate. For instance, if you are being chased, your body has a need
for more oxygen; therefore, it is necessary for your heart rate to rise to meet this demand. This is
called sinus tachycardia—a normal response and a normal rhythm. Other high heart rates occur
because there is a problem with the heart or its conduction system (the part of the heart that
generates electricity and allows the electricity to travel down the heart muscle, causing it to
beat).

There are two types of fast heart rates, or tachyarrhythmias:

 Tachycardia - a rate higher than 100 beats per minute

 Fibrillation - a rate higher than 350 beats per minute

Fast heart rates are also classified based on where in the heart they begin:

 The upper chambers - the atria

 The lower chambers - the ventricles

Fast heart rates that occur in the upper chambers of the heart are called supraventricular
tachycardias (SVTs) and include:

 Atrial flutter
  Atrial fibrillation (AF)
 AV nodal reentrant tachycardia (AVNRT)
 Wolf-Parkinson-White (WPW)

Those occurring in the lower chambers of the heart are:

 Ventricular tachycardia (VT)

 Ventricular fibrillation (VF)

Atrial fibrillation is the most common serious arrhythmia worldwide, with an estimated 2.5
million affected persons in North America and 4.5 million in Europe.1 Not all people with
arrythmias require treatment. Supraventricular tachycardias, such as atrial fibrillation, and
ventricular tachycardia are usually not medical emergencies, but require prompt medical
attention. Ventricular fibrillation is fatal if not treated immediately.

Normal Rhythm
Every normal heart has a normal rhythm. That rhythm varies from person to person. In most
healthy people, the heart at rest beats about 60 to 100 times per minute. A small bunch of heart
cells called the sinoatrial node keeps time.
1
Fuster V, Ruden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management
of patients with atrial fibrillation—executive summary: a report of the American College of
Cardiology/American Heart Association task force on practice guidelines and the European
Society of Cardiology Committee for practice guidelines (Writing Committee to Revise the 2001
Guidelines for the Management of Patients With Atrial Fibrillation). Circulation.
2006;114(7):700-752.

Some fast heart rates are appropriate. For instance, if you are being chased, your body has a need
for more oxygen; therefore, it is necessary for your heart rate to rise to meet this demand. This is
called sinus tachycardia—a normal response and a normal rhythm. Other high heart rates occur
because there is a problem with the heart or its conduction system (the part of the heart that
generates electricity and allows the electricity to travel down the heart muscle, causing it to
beat).

There are two types of fast heart rates, or tachyarrhythmias:

 Tachycardia - a rate higher than 100 beats per minute

 Fibrillation - a rate higher than 350 beats per minute

Fast heart rates are also classified based on where in the heart they begin:

 The upper chambers - the atria

  The lower chambers - the ventricles

Fast heart rates that occur in the upper chambers of the heart are called supraventricular
tachycardias (SVTs) and include:

 Atrial flutter
 Atrial fibrillation (AF)
 AV nodal reentrant tachycardia (AVNRT)
 Wolf-Parkinson-White (WPW)

Those occurring in the lower chambers of the heart are:

 Ventricular tachycardia (VT)

 Ventricular fibrillation (VF)

Atrial fibrillation is the most common serious arrhythmia worldwide, with an estimated 2.5
million affected persons in North America and 4.5 million in Europe.1 Not all people with
arrythmias require treatment. Supraventricular tachycardias, such as atrial fibrillation, and
ventricular tachycardia are usually not medical emergencies, but require prompt medical
attention. Ventricular fibrillation is fatal if not treated immediately.

Normal Rhythm
Every normal heart has a normal rhythm. That rhythm varies from person to person. In most
healthy people, the heart at rest beats about 60 to 100 times per minute. A small bunch of heart
cells called the sinoatrial node keeps time.
1
Fuster V, Ruden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management
of patients with atrial fibrillation—executive summary: a report of the American College of
Cardiology/American Heart Association task force on practice guidelines and the European
Society of Cardiology Committee for practice guidelines (Writing Committee to Revise the 2001
Guidelines for the Management of Patients With Atrial Fibrillation). Circulation.
2006;114(7):700-752.

Gagal jantung kongestif adalah suatu keadaan dimana jantung tidak dapat
memompa darah yang mencukupi untuk kebutuhan tubuh. Penyakit ini dapat
disebabkan oleh gangguan kemampuan otot jantung berkontraksi atau meningkatnya
beban kerja dari jantung (Mycek et al., 2001).

Digoxin Side Effects

Brand Names: Digitek, Lanoxicaps, Lanoxin
Please note - some side effects for Digoxin may not be reported. Always consult your doctor or
healthcare specialist for medical advice. You may also report side effects to the FDA at
http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

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Side Effects of Digoxin - for the Consumer

Digoxin Immune Fab

All medicines may cause side effects, but many people have no, or minor, side effects. No
COMMON side effects have been reported with Digoxin Immune Fab . Seek medical attention
right away if any of these SEVERE side effects occur when using Digoxin Immune Fab:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest;
swelling of the mouth, face, lips, or tongue); fast or irregular heartbeat; fever.

Digoxin

All medicines may cause side effects, but many people have no, or minor, side effects. Check
with your doctor if any of these most COMMON side effects persist or become bothersome
when using Digoxin:

Diarrhea; nausea.

Seek medical attention right away if any of these SEVERE side effects occur when using Digoxin:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest;
swelling of the mouth, face, lips, or tongue); blurred vision, yellow vision, or other vision
changes; confusion; fast, slow, or irregular heartbeat; hallucinations; mood or mental changes
(eg, depression); severe or persistent nausea, vomiting, or stomach pain; unusual bruising or
bleeding; unusual tiredness or weakness.
Digoxin Capsules

All medicines may cause side effects, but many people have no, or minor side effects. Check
with your doctor if any of these most COMMON side effects persist or become bothersome
when using Digoxin Capsules:

Diarrhea; nausea.

Seek medical attention right away if any of these SEVERE side effects occur when using Digoxin Capsules:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest;
swelling of the mouth, face, lips, or tongue); blurred vision, yellow vision, or other vision
changes; confusion; fast, slow, or irregular heartbeat; hallucinations; mood or mental changes
(eg, depression); severe or persistent nausea, vomiting, or stomach pain; unusual bruising or
bleeding; unusual tiredness or weakness.

Digoxin Elixir

All medicines may cause side effects, but many people have no, or minor, side effects. Check
with your doctor if any of these most COMMON side effects persist or become bothersome
when using Digoxin Elixir:

Diarrhea; nausea.

Seek medical attention right away if any of these SEVERE side effects occur when using Digoxin Elixir:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest;
swelling of the mouth, face, lips, or tongue); blurred vision, yellow vision, or other vision
changes; confusion; fast, slow, or irregular heartbeat; hallucinations; mood or mental changes
(eg, depression); severe or persistent nausea, vomiting, or stomach pain; unusual bruising or
bleeding; unusual tiredness or weakness.

Top

Side Effects by Body System

General

Side effects generally have been dose-related and occurred more frequently when serum digoxin
levels exceed 2.0 ng/mL. Cardiovascular (50%), gastrointestinal (25%), and CNS symptoms
(25%) have been reported most often.

Patients at increased risk include those with underlying renal, cardiopulmonary, or thyroid
disease, electrolyte imbalances such as hypokalemia, hypomagnesemia, or hypercalcemia, and
patients greater than 65 years of age.
Gastrointestinal

Gastrointestinal side effects reported in 25% of patients have included anorexia, nausea,
vomiting, diarrhea, and general abdominal pain. Rarely, intestinal ischemia or hemorrhagic
necrosis, dysphagia, and esophageal dystonia have been reported.

Cases of severe abdominal pain and documented intestinal ischemia have been reported in
patients after hemodialysis. Contraction of intravascular volume combined with digoxin-induced
splanchnic vasoconstriction may induce abdominal pain.

Cardiovascular

Cardiovascular side effects have been reported the most frequently. These have included
premature ventricular depolarizations (50%), AV nodal arrhythmias (50%), AV conduction
disturbances (36%), wide complex tachycardia (less than 1%), paroxysmal atrial tachycardia
with AV block, complete heart block, PR prolongation, and ST segment changes.

Ocular

Ocular side effects have included chromatopsia, snowy or blurry vision, photopsia, and
decreased visual acuity. Rarely, transient blindness has been reported. Decreased color vision has
been reported.

The development of photopsia characterized by innumerable points of light in the peripheral

visual fields or a decrease in visual acuity has been associated with therapeutic serum digitalis
concentrations in the elderly. Digitalis-induced visual disturbances other than chromatopsia or
disturbances of color vision may occur in elderly patients who have no other clinical
manifestations of digitalis intoxication.

Digoxin-mediated inhibition of sodium-potassium ATPase influences normal uptake of

extracellular potassium by Muller's cells and other retinal neurons and may result in decreased
color vision.

Nervous system

Nervous system side effects reported in 25% of patients have included headache, dizziness, and
weakness. At least one case of trigeminal neuralgia has been reported.

A 51-year-old man with ischemic cardiomyopathy complicated by congestive heart failure

developed right trigeminal neuralgia associated with hyperalgesia between attacks. The pain
resolved when digoxin was discontinued and reappeared upon rechallenge.

Psychiatric

Psychiatric side effects have included decreased cognition, memory, disorientation, emotional
lability, and depression.
A 74-year-old man with supraventricular tachycardia developed altered cognition, memory, and
depression with a serum digoxin level of 0.9 ng/mL. Symptoms resolved when digoxin levels
decreased to 0.5 ng/mL.

Endocrine

Endocrine side effects have included increased (significant) serum estrogen, decreased serum
luteinizing hormone, decreased (significant) serum testosterone, and gynecomastia.

A study of 38 patients (20 postmenopausal women) who had taken digoxin for at least two years,
revealed significantly decreased serum luteinizing hormone and testosterone levels and
significantly increased serum estrogen levels relative to a control group of men and
postmenopausal women. The study did not control for underlying disease and it is possible that
the sex hormone alterations were associated with the underlying diseases rather than use of
digoxin.

Hypersensitivity

A 77-year-old man with congestive heart failure developed a psoriasiform rash associated with a
positive macrophage inhibition factor test to digoxin. The rash resolved upon discontinuation of
the drug and reappeared on rechallenge.

Hypersensitivity reactions have been reported rarely. At least one case of psoriasiform rash has
been reported.

Hematologic

Hematologic side effects have been reported rarely. These have included thrombocytopenia.

A 60-year-old man with thyroid cancer and supraventricular tachycardia developed reversible
thrombocytopenia during digoxin and heparin therapy. The thrombocytopenia resolved when
digoxin alone was discontinued. The bone marrow examination and immunological studies were
consistent with a digoxin-induced immune thrombocytopenia due to circulating immune
complexes.

Metabolic

Three patients with Type II diabetes who experienced greater antidiabetic control and significant
reduction in requirements of hypoglycemic agents following discontinuation of digoxin has been
reported. Rechallenge in one patient resulted in increased glucose levels and subsequent dosage
increases of hypoglycemic agents.

Metabolic side effects have included hypokalemia, hypomagnesemia, and hypercalcemia.

Diabetes mellitus and glucose intolerance have been reported.
Dermatologic

Dermatologic side effects have been reported rarely. These have included maculopapular rash
and other nonspecific skin reactions.

Other

Other side effects have been reported rarely. At least one case of diaphoresis and malaise has
been reported. At least one case of digoxin cachexia, fatigue, weight loss, and decreased appetite
has been reported.

A 48-year-old man with rheumatic mitral valve disease and atrial flutter/fibrillation developed
profound diaphoresis and malaise associated with a serum digoxin level of 0.7 ng/mL. The
symptoms resolved when digoxin was discontinued, and reappeared on rechallenge.

Cachexia, fatigue, and documented weight loss have been reported in rare cases. Appetites and
weights improved after discontinuation of digoxin

Read more: http://www.drugs.com/sfx/digoxin-side-effects.html#ixzz0mP2Fqjtf