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Agonis kolinergik

Herni Suprapti

agonis kolinergik
adalah obat yang menyerupai atau potensiasi efek asetilkolin

reseptor kolinergik
Muskarinik.
Namanya didapatkan dari muscarine, yaitu suatu
alkaloid yang terdapat pada jamur beracun

Nikotinik

Amanita muscaria

Nicotine from tobacco plant

jenis reseptor muskarinik


M1 M5

Lokasi Reseptor muskarinik

Ganglia
Otot polos
Miokardium
Kelenjar sekresi
SSP

2 jenis reseptor nikotinik


Neuronal nicotinic (NN), terletak di ganglia
otonomik
Muscular nicotinic (NM), terletak di
neuromuscular junction

Letak Reseptor kolinergik


Serat preganglionik pada ganglia otonomik
Serat preganglionik berakhir di medula
adrenalis
Serat postganglion sistem parasimpatis
Otot volunter sistem somatis
SSP
Kelenjar keringat diinervasi oleh post-ganglion
sistem saraf simpatis

agonis kolinergik untuk klinis


Agonis direct-acting, yang secara kimiawi terikat
dengan dan mengaktivasi reseptor muskarinik
dan nikotinik di tubuh
Agonis indirect-acting, meng-inhibisi enzim
asetilkolinesterase, sehingga meningkatkan
kadar asetilkolin di dalam sinaps.

obat yg bersifat agonis direct-acting

Acetylcholineprototype
Bethanechol
Carbachol
Pilocarpine
Methacholine
Nicotine

efek fisiologis asetilkolin


Asetilkolin mempengaruhi hampir semua
sistem dalam tubuh:
Kardiovaskuler
GIT
Paru-paru
Mata
sistem saraf perifer
sistem saraf pusat
sistem endokrin

kardiovaskuler
menurunkan denyut jantung, kontraktilitas, dan tekanan darah

GIT
meningkatkan motilitas GIT dan bladder

Paru-paru
meningkatkan sekresi bronkus

mata
kontriksi muskulus spingter pupile miosis dan akomodasi

sistem saraf perifer


kontraksi otot skeletal

sistem saraf pusat


mempengaruhi neurotransmisi

sistem endokrin
menyebabkan rilis epinefrin dari medula adrenalis (via reseptor
nikotinik) dan stimulasi sekresi kelenjar keringat.

Reseptor yg di-aktivasi o/
asetilkolin
Muskarinik dan nikotinik

Indikasi klinis penggunaan


asetilkolin
Untuk miosis saat operasi mata.
Jarang digunakan karena efeknya luas dan cepat dihidrolisa oleh
asetilkolinesterase

Efek samping
Efek samping disebabkan stimulasi kolinergik yang berlebihan.
Efek samping ini juga timbul pada semua jenis agonis kolinergik, baik direk
maupun indirek-acting, bukan hanya asetilkolin saja.

Efek samping - DUMBELS

Diare dan (decrease) penurunan tekanan darah


Urinasi (bak)
Miosis
Bronkokonstriksi
Eksitasi otot skeletal
Lakrimasi
Salivasi dan sweating (berkeringat)

BETHANECHOL (Urecholine)

What type of chemical compound is


bethanechol?
A carbamic acid ester

What receptors does it work on?


Bethanechol works primarily on muscarinic
receptors, but it also has some mild nicotinic
properties.

therapeutic uses
increases intestinal motility, especially after
surgery.
stimulates the detrusor muscle of the bladder, it
is also used to treat urinary retention.
BBBBethanechol stimulates the Bladder and
Bowel.

the adverse effects of


bethanechol
The adverse effects are those that result from generalized
cholinergic stimulation.

CARBACHOL

What type of compound is carbachol?


A carbamic acid ester similar to bethanechol

clinical use.
for glaucoma
to stimulate miosis during ophthalmic surgery.

carbachol
What receptors does carbachol work on?
Both muscarinic and nicotinic receptors

adverse effects
Those that result from excessive generalized
cholinergic stimulation

PILOCARPINE (Pilocar)
What type of compound is pilocarpine?
An alkaloid

Pilocarpines physiologic actions


Causes miosis and contraction of the ciliary
muscle
Decreases heart rate
Causes bronchial smooth muscle contraction
Increases secretions from salivary, lacrimal, and
sweat glands

Is it cleaved by acetylcholin-esterase?
No, the drug is unaffected by this enzyme.

Pilocarpine clinical use


Pilocarpine is extremely good for stimulating miosis and opening the
trabecular meshwork around the canal of Schlemm.
Therefore, pilocarpine can be used for the treatment of glaucoma.

What receptors does this drug


work on?
Primarily muscarinic receptors

adverse effects
Unlike the other direct-acting agonists previously discussed, pilocarpine is
able to enter the brain and cause CNS disturbances such as hallucinations
and convulsions, along with generalized cholinergic stimulation.

METHACHOLINE
What is methacholine used for?
Diagnosis of asthma and bronchial hyperreactivity

What receptors does it stimulate?


Muscarinic receptors

What are the adverse effects?


Generalized cholinergic stimulation

INDIRECT-ACTING AGONISTS

indirect-acting cholinergic agonists.

1. Isoflurophate
2. Echothiophate
3. Parathion
4. Edrophonium
5. Physostigmine
6. Neostigmine

How do they work?


By inhibiting the enzyme acetylcholinesterase, which is
responsible for the hydrolysis of acetylcholine. Neuronal
response to acetylcholine is therefore enhanced.

Reversible
Irreversible

irreversible
irreversibly inhibit acetylcholinesterase
the organophosphates
Isoflurophate
Echothiophate
parathion

reversible
they do not bind covalently to
acetylcholinesterase

Physostigmine
Neostigmine
Edrophonium
Pyridostigmine

ORGANOPHOSPHATES
ISOFLUROPHATE
ECHOTHIOPHATE
PARATHION

mechanism of action
Organophosphates bind covalently to
acetylcholinesterase and can permanently
inactivate the enzyme.
The effects of organophosphates can last as long
as a week, which is approximately the time
needed to synthesize a new molecule of
acetylcholinesterase.

Is it at all possible to reverse the effects of


organophosphates?
In most cases, no.
However, if pralidoxime (a cholinesterase
reactivator) is given before the organophosphate
binds to acetylcholinesterase and loses one if its
alkyl groups (a process called aging), then it may
be possible for pralidoxime to remove the
organophosphate from acetylcholinesterase.

What were these drugs used for in the past?


Organophosphates were used in wars as nerve
gases.
They produce an immense stimulation at
cholinoreceptors throughout the body, causing
respiratory muscle paralysis and convulsions.

What are these drugs used for today?


Isoflurophate and echothiophate are used
occasionally for glaucoma and accommodative
esotropia.

What drug is used to treat


organophosphate poisoning?
Atropine
gastric lavage
charcoal

What are the toxicities of the


organophosphates?
Excessive cholinergic stimulation

PHYSOSTIGMINE

When is physostigmine administered?


For glaucomasecond-choice drug after
pilocarpine
For overdoses of atropine, phenothiazines, and
tricyclic antidepressants
For intestinal and bowel atony
For accommodative esotropia (rarely)

Can physostigmine enter the


CNS?
Yes, because it is a tertiaryamine

adverse effects
Convulsions
Muscle paralysis secondary to overstimulation
Cataracts
Generalized excessive cholinergic stimulation

NEOSTIGMINE (Prostigmin)

Does this drug enter the CNS?


No, because it is a polar quaternary carbamate

Describe the therapeutic uses.


Treatment of myasthenia gravis
Treatment of urinary retention and paralytic
ileus
Antidote for nondepolarinzing neuromuscular
blockade such as with tubocurarine

What is the duration of action?


Usually 2 to 4 hours

What are the adverse effects?


Excessive cholinergic stimulation

EDROPHONIUM

clinical use
Edrophonium is similar to neostigmine except that it is
used in the diagnosis of myasthenia gravis.
It is not useful for maintenance therapy because of its short
duration of action (approximately 5 to 15 minutes).
Edrophonium is also used to differentiate myasthenia
gravis from cholinergic crisis. Both conditions can result in
muscle weakness; however, administration of edrophonium
helps myasthenia but worsens cholinergic crisis.

the adverse effects


Excessive cholinergic stimulation

PYRIDOSTIGMINE

What is pyridostigmine's duration of action?


Very longusually 3 to 6 hours

What is the clinical use?


Because of its long duration of action, pyridostigmine, like
neostigmine, can be used for long-term treatment of
myasthenia gravis.

What are the adverse effects?


Excessive cholinergic stimulation