TOKSIKOLOGI KLINIK

ANTIDEPRESAN TRISIKLIK
Antidepresan, ada 3 golongan :
1. Trisiklik
2. SSRI (Selective Serotonin Reuptake Inhibitor)
3. MAO Inhibitor
Antidepresan Trisiklik
Menghambat reuptake
NE & Serotonin sinaps
NE & Serotonin di sinaps
Antidepresan SSRI
Menghambat reuptake
Serotonin sinaps
Serotonin di sinaps
Antidepresan MAO Inhibitor
Menghambat penguraian
NE & Serotonin sinaps
senyawa mono amin
AsTC MAOI
ANTIDEPRESAN TRISIKLIK, Cont’d

Keracunan timbul karena :

•Absorpsi cepat
•Ikatan protein plasma dan jaringan besar
•Siklus enterohepatik berulang
•Margin terapeutik sempit

Kasus keracunan meningkat jika dibarengi dengan

penggunaan obat lain seperti antihistamin (memiliki efek
sama, antikolinergik)

…..Kilas balik Parasimpatik…..

…..Kilas balik Antikolinergik…..

…..Kilas balik Parasimpatik…..
SISTEM SARAF OTONOM
 KOLINERGIK, Parasimpatis
Action potential
1. Action potentials arriving at the
presynaptic terminal cause Ca2+
1
voltage-
Presynaptic
gated Ca2+ channels to open. Synaptic terminal
vesicle
2. Ca2+ diffuse into the cell and Voltage-gated
cause synaptic vesicles to Ca2+ channel Synaptic cleft
2
release acetylcholine, a
neurotransmitter molecule.

3. Acetylcholine diffuses from the 3

presynaptic terminal across the Acetylcholine Postsynaptic
synaptic cleft. membrane

Na+
Acetylcholine bound
to receptor site opens
4. Acetylcholine molecules combine ligand-gated Na+ 44
with their receptor sites and cause channel
ligand-gated Na+ channels to open.
Na+ diffuse into the cell and causes
depolarization. If depolarization
reaches threshold, an action
potential is produced in the
postsynaptic cell.
 1
Action potential

Ca2+
Presynaptic
terminal
Voltage-gated
Ca2+ channel

Action potentials arriving at the presynaptic terminal cause voltage-

gated Ca2+ channels to open.
2

Ca2+

Synaptic
vesicle

Acetylcholine

Ca2+ diffuse into the cell and cause synaptic vesicles to release
acetylcholine, a neurotransmitter molecule.
3

Ca2+
Presynaptic
terminal

Synaptic cleft

Acetylcholine

Acetylcholine diffuses from the presynaptic terminal across the

synaptic cleft.
4

Presynaptic
terminal
Synaptic cleft

Acetylcholine Postsynaptic
membrane
4a Na+
Acetylcholine bound
to receptor site opens
ligand-gated Na+
channel

Acetylcholine molecules combine with their receptor sites and

cause ligand-gated Na+ channels to open.
 4b Na+

Na+ diffuse into the cell and causes depolarization. If depolarization

reaches threshold, an action potential is produced in the
postsynaptic cell.
 Neurotransmitters
• Acetylcholine (ACh) binds to different
subtypes of ACh receptors. Each receptor
subtype can initiate a different response in
the target cell.
– Nicotinic – these receptors are ligand-operated
ion channels. Binding ACh opens and ion
channel. K+ and Na+ flow in and out of the cell.
Inward flow of Na+ predominated and and
EPSP is produced. If enough ACh stimulate the
neuron, an AP is produced. Found in autonomic
ganglia and skeletal muscle fibers..
Reseptor Nikotinik
– Muscarinic – when ACh binds to this receptor
another adjacent group of proteins is activated –
G proteins. A subunit of the G proteins then
moves through the membrane and binds to an
adjacent ion channel and opens the ion channel.
Found in the plasma membrane of smooth and
cardiac muscle cells, and in cells of particular
glands..
Reseptor Muskarinik
Reseptor Nikotinik & Muskarinik
• The activity of the NT is regulated by the
presence of specific enzymes, e.g.
acetylcholinesterase.
 ANTIKOLINERGIK
Na+
Action potential Cholin
Acetyl CoA
+ Na+
Cholin Presynaptic
Ca2+ Cholin
Acetyltransferace
terminal
Ach

H+
Voltage-gated O Synaptic Cholin + Acetat
Ca2+ channel vesicleSynaptic cleft

Acetylcholine Ach esterase

Postsynaptic
membrane
Kerja dominan
Antikolinergik
Manifestasi klinik
 Asetilkolin banyak di sinaps, tetapi tidak dapat berikatan
dengan reseptor

Aktivitas Asetilkolin
 Motilitas GIT menurun
 Takikardi
 Retensi urin
 Sekresi saliva menurun
 dll

Lihat tabel
Back to AsTC
ANTIDEPRESAN TRISIKLIK, Cont’d
MEKANISME TOKSISITAS
AsTC
Efek thd CNS
Menghambat reuptake
Memblok saraf vagus Pusat respirasi
NE & Serotonin
di ujung saraf Hipotalamus
Blok  adrenergik Disorientasi
perifer Agitasi
Ach + reseptor NE Delirium
Ataksia
Seizure
Aktivitas NE Loss of short term
Aktivitas Ach
memori
koma
Efek Adrenergik
Efek Antikolinergik
Reseptor  Reseptor 

Hipertensi
ANTIDEPRESAN TRISIKLIK, Cont’d

PENANGANAN KERACUNAN
1. Atasi gejala vital : Fungsi respirasi & kardiovaskular
2. .i absorpsi GIT :
• Emesis
• Lavage
• CA g i obat & metabolitnya, ex : imipramin yang mengalami siklus
enterohepatik
• Salin Katartik, castor oil peristaltik
3. Eliminasi
• Hemoperfusi
4. Antidot, fisostigmin suatu inhibitor asetilkolinesterase g hkoligernik
Macam :
• Edrophonium
• Neostigmin
Amin quartemen g / ke CNS
• Peridostigmin
• Fisostigmin g amin tersier g dapat menembus barrier otak ke CNS
– Dosis 1-2 mg (Dewasa), 0,5 mg (Anak)
– Sifat : Ikatan Reversible, cepat dimetabolisme g harus diberikan berulang
ANTIDEPRESAN TRISIKLIK, Cont’d
Tes Keracunan

Fisostigmin 1-2 mg

Respon
Tidak ada respon •Salivasi
•Berkeringat
•Motilitas usus h dll
Pemberian ke-2, stlh 20’

Pemberian Ulang
Tidak ada respon
30-90 menit g 12-24 jam

Keracunan selain
antikolinergik Jika terjadi toksisitas

Atropin Sulfat
ANTIDEPRESAN TRISIKLIK, Cont’d

Kontra Indikasi :
• Asma g kolinergik menyebabkan brontrokonstriksi
• Jantung g kolinergik menyebabkan denyut i
• Gangren g kolinergik menghambat sekresi insulin

5. Atasi gejala :
• Hipotensi dopamin/debutamin, dihidroergotamin
• KCl pencetus perpindahan K+ ke dalam otot
jantung
• Hipertermi g air dingin
• Kejang g diazepam