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Obat-obat anti

kolinergik, penyelamat
hidup, dan anti aritmia
Gama Natakusumawati
I1111017

OBAT ANTI ARITMIA

Causes of arrhythmias
Abnormal

Schematic representation of reentry

Penggolongan obat anti


aritmia

Antiaritmia

Actions of antiarrhythmic drugs

Schematic diagram of the effects of Class


IA agents

Class IB drug
Lidocaine
Actions: Lidocaine, a local anesthetic,
shortens Phase 3 repolarization and
decreases the duration of the action
potential.
Therapeutic uses: Lidocaine is useful in
treating ventricular arrhythmias arising
during myocardial ischemia, such as
during a myocardial infarction

Pharmacokinetics: given intravenously because of


extensive first-pass transformation by the liver,
which precludes oral administration dealkylated
and eliminated almost entirely by the liver;
consequently, dosage adjustment in patients
with liver dysfunction or those taking drugs that
lower hepatic blood flow, such as propranolol.
Adverse effects: It shows little impairment of left
ventricular function and has no negative inotropic
effect. CNS effects drowsiness, slurred speech,
paresthesia, agitation, confusion, and convulsions.
Cardiac arrhythmias may also occur.

Mexiletine
These Class IB drugs have actions similar to those
of lidocaine, and they can be administered orally.
used for chronic treatment of ventricular
arrhythmias associated with previous myocardial
infarction.
Tocainide
Used for treatment of ventricular
tachyarrhythmias.
Pulmonary toxicity, which may lead to pulmonary
fibrosis.

Schematic diagram of the effects of Class


IB agents

Schematic diagram of the effects of


Class IC agents

Class II Antiarrhythmic
Drugs
Class II agents are -adrenergic
antagonists. These drugs diminish Phase 4
depolarization, thus depressing
automaticity, prolonging AV conduction,
and heart rate and contractility.
Class II agents are useful in treating
tachyarrhythmias caused bysympathetic
activity. Also used for atrial flutter and
fibrillation and for AV-nodal reentrant
tachycardia.

Propranolol
Reduces the incidence of sudden
arrhythmic death after myocardial
infarction (the most common cause of
death in this group of patients).
The mortality rate in the first year
after a heart attack is significantly
reduced by propranolol, partly
because of its ability to prevent
ventricular arrhythmias.

Class III Antiarrhythmic


Drugs

Amiodarone
Actions:
contains iodine and is related structurally to thyroxine.
It has complex effects, showing Class I, II, III, and IV
actions. Its dominant effect is prolongation of the action
potential duration and the refractory period.
Amiodarone has antianginal as well as antiarrhythmic
activity.
Therapeutic uses:
Amiodarone is effective in the treatment of severe
refractory supraventricular and ventricular
tachyarrhythmias.
Despite its side-effect profile, amiodarone is the most
commonly employed antiarrhythmic

Adverse effects:
Some of the more common effects include
interstitial pulmonary fibrosis, gastrointestinal
tract intolerance, tremor, ataxia, dizziness,
hyper- or hypothyroidism, liver toxicity,
photosensitivity, neuropathy, muscle weakness,
and blue skin discoloration caused by iodine
accumulation in the skin.
recent clinical trials have shown that
amiodarone does not reduce the incidence of
sudden death or prolong survival in patients
with congestive heart failure

Sotalol
A class III antiarrhythmic agent, also has
potent nonselective Beta-blocker activity. It
is well established that beta blockers reduce
mortality associated with acute myocardial
infarction.
Actions: blocks a rapid outward potassium
current, known as the delayed rectifier. This
blockade prolongs both repolarization and
duration of the action potential, thus
lengthening the effective refractory period.

Therapeutic uses:
used for long-term therapy to decrease the rate of
sudden death following an acute myocardial infarction.
have a modest ability to suppress ectopic beats and to
reduce myocardial oxygen demand.
strong antifibrillatory effects, particularly in the
ischemic myocardium.
Sotalol was more effective in preventing recurrence of
arrhythmia and in decreasing mortality than imipramine,
mexiletine, procainamide, propafenone, and quinidine in
patients with sustained ventricular tachycardia

Adverse effects:
This drug also has the lowest rate of
acute or long-term adverse effects
prolong the QT interval
the syndrome of torsade de pointes
is a serious potential adverse effect,
typically seen in three to four percent
of patients

Schematic diagram of the effects of Class


III agents

Class IV Antiarrhythmic
Drugs
Class IV drugs are calcium-channel blockers .
They decrease the inward current carried by
calcium, resulting in a decreased rate of Phase 4
spontaneous depolarization.
They also slow conduction in tissues that are
dependent on calcium currents, such as the AV
node.
Although voltage-sensitive calcium channels
occur in many different tissues, the major effect
of calcium-channel blockers is on vascular
smooth muscle and the heart.

Verapamil and diltiazem


Actions:
Calcium enters cells by voltage-sensitive
channels and by receptor-operated channels that
are controlled by the binding of agonists, such as
catecholamines, to membrane receptors.
Calcium-channel blockers, such as verapamil
and diltiazem, are more effective against the
voltage-sensitive channels, causing a decrease
in the slow inward current that triggers cardiac
contraction

Schematic diagram of the effects of


Class IV agents

Therapeutic uses:
Verapamil and diltiazem are more effective against
atrial than against ventricular arrhythmias. They are
useful in treating reentrant supraventricular
tachycardia and in reducing the ventricular rate in
atrial flutter and fibrillation. In addition, these drugs
are used to treat hypertension and angina.
Pharmacokinetics:
Verapamil and diltiazem are absorbed after oral
administration.
Verapamil is extensively metabolized by the liver;
thus, care should be taken when administering this
drug to patients with hepatic dysfunction.

Adverse effects:
Verapamil and diltiazem have
negative inotropic properties and,
therefore, may be contraindicated in
patients with preexisting depressed
cardiac function.
Both drugs can also produce a
decrease in blood pressure because of
peripheral vasodilation an effect that
is actually beneficial in treating

Other Antiarrhythmic Drugs


Digoxin
Shortens the refractory period in atrial and
ventricular myocardial cells while prolonging the
effective refractory period and diminishing
conduction velocity in the AV node.
Used to control the ventricular response rate in
atrial fibrillation and flutter.
At toxic concentrations, digoxin causes ectopic
ventricular beats that may result in ventricular
tachycardia and fibrillation. [Note: This
arrhythmia is usually treated with lidocaine or
phenytoin.]

Adenosine
Adenosine is a naturally occurring nucleoside,
but at high doses, the drug decreases
conduction velocity, prolongs the refractory
period, and decreases automaticity in the AV
node.
Intravenous adenosine is the drug of choice for
abolishing acute supraventricular tachycardia.
It has low toxicity but causes flushing, chest
pain, and hypotension. Adenosine has an
extremely short duration of action
(approximately 15 seconds).

Cardiac impulse generation and


conduction

OBAT ANTIKOLINERGIK

Gambar daerah kerja agonis kolinergik


pada sistem saraf somatik dan
atonomik

Gambar sintesis dan pelepasan


asetilkolin dari neuron kolinergik

Reseptor kolinergik
(kolinoseptor)
Berdasarkan
perbedaan
afinitas
terhadap zat
yang mampu
meniru
asetilkolin
(ACh)

R.
Muskarinik

R. Nikotinik

Reseptor Muskarinik
Afinitas kuat terhadap muskarin
Afinitas lemah terhadap nikotin
Terdiri dari subkelas : M1, M2, M3, M4, M5
Terdapat dlm ganglia SS perifer dan organ

efektor otonom (jantung, otot polos, kel


eksokrin)
Lebih dominan dalam kerja kolinergik

Reseptor Nikotinik
Afinitas kuat terhadap nikotin
Afinitas lemah terhadap muskarin
Terdpt di SSP, medula adrenalis, ganglia

otonom, dan persambungan


neuromuskular
Nikotin mula-2 memicu reseptor, tapi

akhirnya justru menghambat

Subtipe dan karakteristik


kolinoseptor
Subtipe

Nama lain

Lokasi

Mekanisme

M1

M1a

Saraf

IP3; aliran DAG

M2

M2a; M2 jantung

Jantung, saraf,
otot polos

Penghambatan prod. cAMP;


aktivasi kanal K+

M2b; m2 kelenjar

Kelenjar, otot
polos, endotel

IP3; aliran DAG

SSP ??

Penghambatan prod. cAMP

SSP ??

IP3; aliran DAG

NM

Tipe otot, endplate


receptor

Sambungan
neuromuskular
otot skelet

Depolarisasi kanal Na+ dan K+

NN

Tipe neuronal,
reseptor ganglion

Badan sel
pascaganglion

Depolarisasi kanal Na+ dan K+

M3
M4
M5

a. Obat antimuskarinik
Obat golongan ini seperti atropin dan

skopolamin bekerja menyekat reseptor


muskarinik yang menyebabkan hambatan
semua fungsi muskarinik
Bertentangan dengan obat agonis

kolinergik yang kegunaan terapeutiknya


terbatas, maka obat penyekat kolinergik ini
sangat menguntungkan dalam sejumlah
besar situasi klinis
Obat-obat antimuskarinik : atropin,

ipratropium, skopolamin

Kompetisi atropin dan skopolamin


dengan asetilkolin untuk reseptor
muskarinik

ATROPIN
Golongan antikolinergik
INDIKASI:
Asystole/PEA (2nd line setelah adrenalin)
Unstable bradikardia
Keracunan kolinergik (organofosfat)
SEDIAAN:
Ampul 0,25 mg/ 1 mL
DOSIS:
Asistol/PEA : 1 mg IV flush, diulang 3 5 menit (maks 3 mg)
2 3 mg dilarutkan dalam 10 ml NS
Bradikardia : 0,5 mg IV flush, diulang tiap 3 5 menit (maks
3 mg)
Keracunan organofosfat: 1-2 mg, diulang tiap 2-5 menit
sampai terdapat tanda atropinisasi

EFEK:
Meningkatkan konduksi HR naik
Menurunkan sekresi klj antikolinergik
PERHATIAN:
Dapat memperburuk iskemia miokard
(takikardi, palpitasi)
Menyebabkan bradikardia paradoksal (< 0,5
mg)
Hipertensi, kejang
Tidak berguna untuk blok AV node derajat 2
tipe II dan derajat 3

b. Obat penyekat
neuromuskular
Obat ini menyekat transmisi kolinergik antara

ujung saraf motor dengan reseptor nikotinik


pada cekungan neuromuskular otot rangka
Penyekat neuromuskular bermanfaat secara

klinik selama operasi guna melemaskan otot


secara sempurna tanpa memperbanyak obat
anastesi yang sebanding dalam melemaskan
otot.
Obat-obat penyekat neuromskular : atrakurium,

doksakurium, metokurin, mivakurium,


pankuronium, piperkuronium, rokuronium,
suksinilkolin, tubokurarin, vekuronium

Daerah kerja antagonis


kolinergik

OBAT PENYELAMAT HIDUP

ADRENALIN (EPINEPHRIN).
INDIKASI:
VF, Pulseless VT, PEA, Asystole
Mengatasi gangguan sirkulasi (Syok distributif)
menghilangkan bronchospasme
SEDIAAN:
ampul 1:1000 (1 mg/1 ml)/ ampul 1:10000 (0,1 mg / 1 ml)
Rute: IV flush, ET (2-3 x dosis IV), Infusion 1 mg/500 ml
D5%/NS (2 ug/mL)
DOSIS:
CPR: 1 mg IV flush (diikuti 10 ml NS), diulang 3-5 menit
2- 2,5 mg ET (dilarutkan dlm 10 ml NS)
Anafilaktik : 0,5 mg SC/IM
Shock : infusion 1 ug/menit, titrasi sampai max 10 ug/mnt
Bronkodilator : 0,3 mg SC (syarat kondisi jantung bagus)

Meningkatkan kekuatan kontraksi jantung


Meningkatkan konduksi HR meningkat
Meningkatkan resistensi vaskuler BP naik
mengubah Fine Ventricular Fibrillation menjadi
Coarse Ventricular Fibrillation lebih mudah di
DC
Dosis besar dapat menyebabkan iskemia miokard,
angina, dan peningkatan kebutuhan oksigen
miokard

DOPAMINE
INDIKASI:
Shock (refrakter terhadap pemberian cairan)
obat pilihan kedua untuk bradikardia simtomatis
(setelah atropin)
Hipotensi (TDS < 70 mmHg)
SEDIAAN: Ampul 200 mg/ 5 mL
DOSIS:
2 5 ug/kg/menit meningkatkan renal blood
flow
5 10 ug/kg/mnt meningkatkan kontraksi
jantung
> 10 ug/kg/ mnt konstriksi sistemik

PERHATIAN:
Setelah target tercapai, turunkan
bertahap (tapering)
Jangan mencampur/melarutkan
dengan natrium bikarbonat, lakukan
pengenceran dengan D5%, D5 1/2
NS, D10 0,18 NS; RL
Diberikan dengan syringe pump atau
infusion pump, harus selalu drip,
bukan IV bolus
Bisa menyebabkan takiaritmia,

DOBUTAMIN
INDIKASI:
Dipertimbangkan untuk kasus pump
problems (gagal jantung kongestif,
sembab paru/congestive pulmonum)
dengan TDS 70 100 mmHg dan
tidak ada tanda-tanda syok
SEDIAAN: Ampul 250 mg/ 10 mL
DOSIS:
2 20 g/kg per menit, titrasi
sehingga HR tidak sampai meningkat

PERHATIAN:
Cegah pemberian pada TDS < 100
mmHg dan ada tanda-tanda syok
Menyebabkan takiaritmia
Tidak boleh mencampur dengan
natrium bikarbonat

MORFIN
INDIKASI:
Chest pain dengan Acute Coronary Syndrome (ACS)
yang tak respon dengan nitrat
Edema paru akut kardiogenik (bila TD adekuat)
SEDIAAN: Ampul 10 mg/ 1 mL
DOSIS:
Dosis inisial : 2 4 mg IV dalam 1 5 menit, setiap 5
sampai 30 menit
Dosis ulangan : 2 8 mg pada interval 5 sampai 15
menit
Masukkan pelan-pelan dan titrasi sampai tercapai efek

PERHATIAN
Tidak untuk infark inferior
Bisa menyebabkan depresi napas
Menyebabkan hipotensi (pada pasien
dengan deplesi volume cairan)
Gunakan dengan hati-hati/perhatian
penuh pada kasus infark ventrikel kanan
Antidotum : nalokson (0,4 2 mg IV)

ALHAMDULILLAH.