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FARMAKOLOGI SUSUNAN SARAF OTONOM

PARASIMPATIS

Tri Widyawati
Kolinergik dan Antikolinergik
Syaraf pasca ganglion parasimpatik

AChE N
Acetate
+ ACh
Choline ACh ACh
M1
M2
Acetate +Choline
M3
M4
M5
Parasimpatotomimetika langsung
Cholinergic
Neurotransmission

Rate limiting step


Uptake of choline into
nerve terminal

Termination
Enzymatic by
acetylcholinesterase
(AchE)
Syaraf pasca ganglion parasimpatik

AChE N
Acetate Tidak langsung
+ ACh
Choline ACh ACh
M1
M2
Acetate +Choline
M3
M4

Langsung M5
Cholinergic Stimulants

Ach Ach Physostigmine Malathion


Pilocarpine Nicotine Neostigmine DFP
Muscarine Edrophonium Nerve gas
D
A D
Ach Parasimpatomimetik
yang bekerja langsung
Ach D reseptor
(obat kolinergik)
Ach D

Ket : D : obat parasimpatomimetik


AchE
B Ach D

Ach Ach Parasimpatomimetik yang


reseptor
/
bekerja tidak langsung
Ach Ach

D
AchE

A. Obat-obat kolinergik menyerupai asetilkolin dan bekerja langsung pada


reseptor
B. Penghambat kolinesterase menginaktivasi enzim asetilkolinesterase
(kolinesterase), sehingga memungkinkan asetilkolin bereaksi dengan reseptor
Muscarinic effects on organ systems
Heart (M2)
- HR, contractility, conduction velocity

Vasculature (not innervated)


- vasodilation: nitric oxide (NO)
Other smooth muscle
Eye: pinpoint pupil (miosis), focus for near vision

GI-tract: tone to intestine, bladder, tone to sphincters

Lung: contract bronchial SM. resistance, secretion


Exocrine glands:
sweating (cholinergic sympathetic)
salivation, gastric acid secretion (M1)
PARASIMPATOMIMETIKA TIDAK LANSUNG

MEKANISME KERJANYA: MENGHAMBAT AChE

REVERSIBLE: AChE + I AChEI


EDROFONIUM: IONIK
` NEOSTIGMINE: IONIK KOVALEN
PHYSOSTIGMINE

IRREVERSIBLE: AChE + I AChEI


SENYAWA ORGANOFOSFAT: KOVALEN
Clinical use: Acetylcholinesterase Inhibitors

Eye: miosis (sphincter contraction), accommodation block (ciliary


muscle contraction)
Use: Glaucoma (wide-angle or secondary glaucoma)
Physostigmine or echothiophate (long acting)
Efek-efek Obat Kolinergik
Jaringan tubuh Respons
Kardiovaskular* Denyut jantung , TD akibat vasodilatasi
Gastrointestinal Tonus & motilitas otot polos dari lambung dan usus
halus. peristaltik & relaksasi otot sfingter
Mata Miosis, menambah akomodasi
Kelenjar* Salivasi , berkeringat, air mata

Paru-paru (Bronki)* Kontraksi otot polos bronkial. Sekresi bronkial


Genitourinarius Kontraksi otot k. kemih, tonus ureter, relaksasi otot
sfingter k.kemih. Merangsang berkemih
Otot lurik transmisi neuromuskular dan mempertahankan
kekuatan dan tonus otot.

*Jaringan berespons terhadap dosis tinggi dari obat-obat kolinergik


Jaringan utama berespons terhadap dosis normal dari obat-obat
kolinergik
Obat-obat Kolinergik

Nama Obat Penggunaan Dosis

Bekerja langsung

Betanekol berkemih, merangsang motilitas PO : 10-50 mg, bid-qid


lambung
Karbakol Tekanan intra okuler, miosis 0,75-3%, 1 tts

Pilokarpin Tekanan intra okuler, miosis 0,5-4%, 1 tts

Bekerja Tidak
Langsung
AchE Reversibel

Fisostigmin TIO, miosis , masa kerja singkat 0,25-0,5%, 1 tts


Neostigmin Menambah kekuatan otot pada miastenia PO: mula-mula 15 mg, tid
gravis, masa kerja singkat dosis max. 50 mg, tid

AchE Irreversibel

Demekarium TIO, miotikum masa kerja panjang 0,125-0,25%, 1 tts


Ekotiofat TIO, miotikum masa kerja panjang 0,03-0,06%, 1 tts
Toxicity & Treatment of AchE Inhibitors
Adverse reactions: (SLUDE)
- Salivation (muscarinic)
- Lacrimation (muscarinic)
- Urination (muscarinic)
- Diarrhea (muscarinic)
- Emesis (vomiting) (muscarinic)
- cardiac slowing (muscarinic)
- hypertension / hypotension (nicotinic)
- NMJ paralysis (nicotinic)
- cramps (muscarinic)
- bronchoconstriction (muscarinic)
- tremor, nausea, CNS induced convulsions
Treatment: Muscarinic antagonist ie. Atropine
AchE reactivator (Pralidoxime, 2-PAM)
mechanical respiration
Toxicity of AchE Inhibitors

SLUDGE DUMBBELS
S - Salivation D - Diarrhea
L - Lacrimation U - Urination
U - Urination M - Miosis/muscle weakness
D - Diarrhea B - Bronchorrea (mucus) B - Bradycard
G - Gastric upset E - Emesis
E - Emesis L - Lacrimation
S - Salivation/sweating
Antikolinergik
parasimpatolitika

N
AChE
Acetate
+ ACh
Choline ACh ACh
M1
M2
Acetate +Choline
M3
M4

Penghambat reseptor M5
Cholinergic Inhibitors

Receptor -Antagonists

Muscarinic nicotinic

Atropine Neuromuscular

Curare, Succinylcholine
PARASIMPATOLITIKA

Antimuscarinic (parasympatholytic)
blockade is competitive and can be overcome by
increasing Ach levels
"parasympatholytic" block at the NEJ (M-3)

Antimuscarinic Drugs

block M-1 receptors in CNS and ganglia

block M-2 receptors in heart (vagus)

block M-3 receptors at the parasympathetic NEJ


Antimuscarinic Drugs

Naturally occurring Belladonna

Anticholinergics/Antispasmodics

Drugs Quaternary amine

Alkaloids Semi-syn derivatives of Belladonna Alkaloids Synthetic

cycloplegic mydriatics / Antiparkinson's


agents Ipratropium Bromide
Naturally occurring Belladonna Alakaloids
atropine

scopolamine HBr (Hyoscine HBr)

L-hyoscyamine (Anaspaz)

L-alkaloids of Belladonna (Belafoline)

tincture of belladonna alkaloids

Semi-synthetic Derivatives of Belladonna


homatropine HBr
homatropine ethylbromide
methscopolamine (Pamine)
Ipratropium Br (Atrovent) used
only treatment of asthma

Parasympathetic NEJ not all


antimuscarinic drugs :

most sensitive : salivary, sweat respiratory tract glands

next most sensitive:


pupil (mydriasis) lens (cycloplegia - loss of
accomodation - lens is thin and fixed for far (vision)
vagus nerve (tachycardia)
D
D
Ach

Ach D reseptor

Ach D

Ach

Obat-obat antikolinergik menempati tempat reseptor, sehingga menghambat asetilkolin


Obat-obat Antikolinergik

Nama Obat Penggunaan Dosis

Gastrointestinal

Atropin Prabedah untuk mengurangi salivasi dan IM:0,4 mg, IV: 0,5-2 mg
sekresi bronkial
Propantelin Antispasmodik untuk irritable bowel PO:7,7-15 mg,tid,qid
syndrome (IBS)
Skopolamin Obat praanastesi, IBS, mabuk perjalanan PO:0,5-1 mg,tid,qid. IM:0,3-0,6 mg

Mata

Homatropin Midriasis dan sikloplegia (paralisis otot siliaris sehingga


akomodasi hilang) utk pemeriksaan mata
Lar.2-5%, 1-2 tts

Neuromuskular/
antiparkisnonism
Triheksifenidil Penyakit parkinson PO: 1 mg/hr, dpt diaikkan sp. 5-
15 mg/hr, dalam dosis terbagi
Benztropin Parkinson. Mengatasi ES fenotiazin dan PO:0,5-6 mg/hr dlm dosis
agen antipsi terbagi
Clinical uses of Antimuscarinic Agents

respiratory (decrease bronchial secretion) ie. atropine


asthma ie. ipratropium
ophthalmologic (mydriasis, cycloplegia) eg. iritis (ie. atropine)
Parkinsons disease ie. benztropine
cardiovascular ie. atropine
motion sickness ie. scopolamine
GI disorders (peptic ulcers (pirenzepine), diarrhea)
pesticide poisoning (malathion) ie. atropine
mushroom poisoning (muscarine) ie. atropine
nerve gases (sarin) ie. atropine + 2-PAM
Toxicity and treatment

Toxicity:
dry mouth, mydriasis, tachycardia, hot flushed skin,
agitation and delirium.

High concentrations may cause ganglionic-blockade


leading to hypotension
Treatment:
- quaternary cholinesterase inhibitor eg. neostigmine or
physostigmine (cns action)
- for hypotension: sympathomimetics (-agonist,
eg.methoxamine)
Symptoms of Antimuscarinic Toxicity

Belladonna (beautiful lady) poisoning

mad as a hatter: CNS, delirium


red as a beet: direct vasodilation
blind as a bat: cycloplegia
hot as hell (a hare): sweat, thermoregulation
dry as a bone: decreased secretions
Mad as a
Hatter

Mercury was used to treat hats. It was applied on to the


fur to roughen the fibres and make them mat more easily
Mercury is a cumulative poison that causes kidney and
brain damage. Physical symptoms include trembling
(known at the time as hatter's shakes), loosening of
teeth, loss of co-ordination, and slurred speech; mental
ones include irritability, loss of memory, depression,
anxiety, and other personality changes. This was called
mad hatter syndrome.
Pharmacology of the Eye

The eye is a good example of an organ with multiple ANS


functions, controlled by several different autonomic
receptors. (Katzung)
Increased intraocular pressure: Untreated blindness
Glaucoma:
- Open-angle (wide, chronic) treated with beta-
blockers and other agents
- Closed-angle (narrow-angle) dilated iris can
occlude outflow. Pilocarpine or surgical removal of part of
iris (iridectomy)
Glaucoma
Increased intraocular pressure: Untreated blindness

Glaucoma:- Open angle (wide, chronic) treated with beta-blockers and other
agents
- Closed-angle (narrow-angle) dilated iris can occlude outflow
Pilocarpine or surgical removal of part of iris (iridectomy)

Glaucoma treatment
1. -Agonist: Outflow
2. M-Agonists: Outflow
3. -Blocker: Secretion
4. 2-Agonist: Secretion
5. Prostaglandins: Outflow
Ach effects on smooth muscle in the eye

Contraction of sphincter muscle miosis

Contraction of ciliary muscle for near vision


Actions on the Eye Glaucoma treatment
1. -Agonist
Outflow
2. M-Agonists
Outflow
3. -Blocker
Secretion
4. 2-Agonist
Secretion
5. Prostaglandins
Outflow
6. Carbonic acid
inhibitors
Secretion

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