FARMAKOLOGI SUSUNAN SARAF OTONOM PARASIMPATIS

Kolinergik dan Antikolinergik

Acetate +CholineACh AChAChNM1M2M3M4M5AChEAcetate +CholineSyaraf pasca ganglion parasimpatikParasimpatotomimetika langsung

Cholinergic NeurotransmissionRate limiting step Uptake of choline into nerve terminal Termination Enzymatic by acetylcholinesterase (AchE)Cholinergic NeurotransmissionRate limiting step Uptake of choline into nerve terminal Termination Enzymatic by acetylcholinesterase (AchE)Cholinergic NeurotransmissionRate limiting step Uptake of choline into nerve terminal Termination Enzymatic by acetylcholinesterase (AchE)

Acetate +CholineACh AChAChNM1M2M3M4M5AChEAcetate +CholineSyaraf pasca ganglion parasimpatikTidak langsungLangsung

Cholinergic StimulantsAch Pilocarpine MuscarineAch NicotinePhysostigmine Neostigmine EdrophoniumMalathion DFP Nerve gas

AchAchAchDDDDDreseptorParasimpatomimetik yang bekerja langsung(obat kolinergik)/AchAchAchAchAchDDreseptorABParasimpatomimetik yang bekerja tidak langsungKet : D : obat parasimpatomimetikAchEAchEObat-obat kolinergik menyerupai asetilkolin dan bekerja langsung pada reseptorPenghambat kolinesterase menginaktivasi enzim asetilkolinesterase (kolinesterase), sehingga memungkinkan asetilkolin bereaksi dengan reseptor

Muscarinic effects on organ systemsOther smooth muscle Eye: pinpoint pupil (miosis), focus for near vision GI-tract: tone to intestine, bladder, tone to sphincters Lung: contract bronchial SM. resistance, secretionExocrine glands: sweating (cholinergic sympathetic) salivation, gastric acid secretion (M1)Heart (M2) - HR, contractility, conduction velocityVasculature (not innervated) - vasodilation: nitric oxide (NO)

PARASIMPATOMIMETIKA TIDAK LANSUNGMEKANISME KERJANYA: MENGHAMBAT AChEREVERSIBLE: AChE + I AChEI EDROFONIUM: IONIK`NEOSTIGMINE: IONIK KOVALENPHYSOSTIGMINEIRREVERSIBLE: AChE + I AChEI SENYAWA ORGANOFOSFAT: KOVALEN

Clinical use: Acetylcholinesterase InhibitorsEye: 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 berespons terhadap dosis tinggi dari obat-obat kolinergik Jaringan utama berespons terhadap dosis normal dari obat-obat kolinergik

Jaringan tubuhResponsKardiovaskular*Denyut jantung , TD akibat vasodilatasiGastrointestinal Tonus & motilitas otot polos dari lambung dan usus halus. peristaltik & relaksasi otot sfingterMataMiosis, menambah akomodasiKelenjar*Salivasi , berkeringat, air mataParu-paru (Bronki)*Kontraksi otot polos bronkial. Sekresi bronkial

GenitourinariusKontraksi otot k. kemih, tonus ureter, relaksasi otot sfingter k.kemih. Merangsang berkemihOtot lurik transmisi neuromuskular dan mempertahankan kekuatan dan tonus otot.

Obat-obat Kolinergik

Nama ObatPenggunaanBekerja langsungBetanekol berkemih, merangsang motilitas lambungKarbakol Tekanan intra okuler, miosisPilokarpin Tekanan intra okuler, miosisBekerja Tidak LangsungAchE ReversibelFisostigmin TIO, miosis , masa kerja singkatNeostigminMenambah kekuatan otot pada miastenia gravis, masa kerja singkatAchE IrreversibelDemekarium TIO, miotikum masa kerja panjangEkotiofat TIO, miotikum masa kerja panjang

Dosis

PO : 10-50 mg, bid-qid0,75-3%, 1 tts0,5-4%, 1 tts

0,25-0,5%, 1 ttsPO: mula-mula 15 mg, tid dosis max. 50 mg, tid

0,125-0,25%, 1 tts0,03-0,06%, 1 tts

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 convulsionsToxicity & Treatment of AchE Inhibitors Treatment:Muscarinic antagonist ie. Atropine AchE reactivator (Pralidoxime, 2-PAM) mechanical respiration

SLUDGE S - Salivation L - Lacrimation U - Urination D - Diarrhea G - Gastric upset E - Emesis DUMBBELS D - Diarrhea U - Urination M - Miosis/muscle weakness B - Bronchorrea (mucus) B - Bradycardia E - Emesis L - Lacrimation S - Salivation/sweating Toxicity of AchE Inhibitors

Antikolinergik

Acetate +CholineACh AChAChNM1M2M3M4M5AChEAcetate +Cholineparasimpatolitika Penghambat reseptor

Cholinergic InhibitorsReceptor -AntagonistsIndirect -AntagonistsMuscarinic NicotinicBlock Synthcsis Ganglionic Neuromuscularhemicholinium Botox Block Rcleasc Hexamcthonium trimethaphanCurare,SuccinylcholineAtropine

Cholinergic InhibitorsReceptor -AntagonistsMuscarinic nicotinicAtropine NeuromuscularCurare, Succinylcholine

PARASIMPATOLITIKAAntimuscarinic (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 gangliablock M-2 receptors in heart (vagus)block M-3 receptors at the parasympathetic NEJ

Antimuscarinic DrugsNaturally occurring Belladonnacycloplegic mydriatics / Antiparkinson's agents Ipratropium Bromide Alkaloids Semi-syn derivatives of Belladonna Alkaloids SyntheticDrugs Quaternary amineAnticholinergics/Antispasmodics

atropine scopolamine HBr (Hyoscine HBr) L-hyoscyamine (Anaspaz) L-alkaloids of Belladonna (Belafoline) tincture of belladonna alkaloids Semi-synthetic Derivatives of Belladonnahomatropine HBr homatropine ethylbromide methscopolamine (Pamine)Naturally occurring Belladonna Alakaloids

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)

AchAchAchDDDDAchreseptorObat-obat antikolinergik menempati tempat reseptor, sehingga menghambat asetilkolin

Obat-obat Antikolinergik

Nama ObatPenggunaanGastrointestinalAtropinPrabedah untuk mengurangi salivasi dan sekresi bronkialPropantelinAntispasmodik untuk irritable bowel syndrome (IBS)SkopolaminObat praanastesi, IBS, mabuk perjalananMataHomatropinMidriasis dan sikloplegia (paralisis otot siliaris sehingga akomodasi hilang) utk pemeriksaan mataNeuromuskular/antiparkisnonismTriheksifenidilPenyakit parkinsonBenztropinParkinson. Mengatasi ES fenotiazin dan agen antipsi

Dosis

IM:0,4 mg, IV: 0,5-2 mgPO:7,7-15 mg,tid,qidPO:0,5-1 mg,tid,qid. IM:0,3-0,6 mg

Lar.2-5%, 1-2 tts

PO: 1 mg/hr, dpt diaikkan sp. 5-15 mg/hr, dalam dosis terbagiPO:0,5-6 mg/hr dlm dosis terbagi

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-PAMClinical uses of Antimuscarinic Agents

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)Toxicity and treatment

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 secretionsSymptoms of Antimuscarinic ToxicityBelladonna (beautiful lady) poisoning

Mad as a HatterMercury 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 EyeThe 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)

GlaucomaIncreased 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 6. Carbonic acid inhibitors: Secretion

Ach effects on smooth muscle in the eye Contraction of sphincter muscle miosis Contraction of ciliary muscle for near vision

Actions on the EyeGlaucoma 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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