2. Parasimpatomimetika kuliah

7/26/2019 2. Parasimpatomimetika kuliah

http://slidepdf.com/reader/full/2-parasimpatomimetika-kuliah 1/22

PARASIMPATOMOMETIKA

Prof.Dr.dr.Jazanul Anwar SpFK

Departemen Farmakologi dan Terapetik

Universitas Sumatera Utara

Prof.Dr.dr.Jazanul Anwar SpFK

Departemen Farmakologi dan Terapetik

Universitas Sumatera Utara



ANS Diagram

Key Points

Division – Anatomical

Usually dual innervation

Usually antagonistic

Usually one dominates

Usually some ANS tone!

ANS Diagram

Key Points

Division – Anatomical

Usually dual innervation

Usually antagonistic

Usually one dominates

Usually some ANS tone!



Key PointsPreganglionic "i#ers

– mylinated

Postganglionic "i#ers

– non mylinated

SNS $re % $ost &%'(PNS $re % $ost &%&

)e*ce$tion &%&(+(((

Auer#ac,s $le*us-

Key role o" Ac,

Motor "i#er not $art o" ANS



.,olinergic Rece$tors

• Muscarinic (7 transmembrane)

- M1 -autonomic ganglia, CNS- M2 -heart

- M3 -smooth muscle, glands

- M4, M

- M13 ↑ !"C, M24 ↓ #C

- $-%rotein cou%led

• Nicotinic (ion channel)

- %entamer, subunits- NN or N1 -ganglia, adrenal

medulla (α2β3, α3β2)

- NM or N2 -s&eletal muscle

(in'ant α2βδε, adult α2βδγ )

- α subunit, #ch binding (2)

Na - in

- out



Acetate

+

Choline

ACh

ACh ACh

N

M1

M2

M3

M4

M5

AChE

Acetate +Choline

Syara" $asca ganglion $arasim$ati/

Tidak langsung

Langsung



Muscarinic e""ects on organ systems

•Ot,er smoot, muscle

• 0 Eye% %in%oint %u%il (miosis), 'ocus 'or near *ision

• 0 1I0tract% ↑tone to intestine, bladder, ↓ tone to s%hincters

• 0 2ung% contract bronchial SM+ → ↑resistance, ↑ secretions

• 0 E*ocrine glands%↑ seating (cholinergic sm%athetic)↑ sali*ation, ↑ gastric acid secretion (M1)

•3eart )M'-

- ↓ ./, ↓ contractilit, ↓conduction *elocit

0asculature (not inner*ated)

- *asodilation nitric oide (N)



.,olinergic Stimulants

#ch

!ilocar%ine

Muscarine

#ch

Nicotine

!hsostigmine

Neostigmine

dro%honium

Malathion

56!

Ner*e gas



Muscarinic rece$tor agonistsMuscarinic rece$tor agonists

•.,oline esters- #C. (muscarinic nicotinic action)- bethanechol (oral or sc, ne*er i* or im → cardiac arrest)- methacholine (not common)- carbachol (direct8indirect9 muscarinic nicotinic)

• Al/aloids%- muscarine (mushrooms)- %ilocar%ine (5C, used in glaucoma emergence)- ootremorine (snthetic) CNS action (basal ganglia)

• Uses%- o%hthalmic (#ch, brie' miosis)- diagnostic 'or belladonna %oisoning (methacholine)- urinar retention (bethanechol)- re*erse $:; de%ression (bethanechol)



• Adverse reactions% (S"<5)

- Sali*ation

- 2acrimation- Urination- Diarrhea- Emesis (*omiting)

- cardiac sloing (arrest, es%+ bethanechol)

- nausea, cram%s- bronchoconstriction, can %reci%itate asthma- in*oluntar de'ecation, urination- tremor, CNS induced con*ulsions

Adverse Reactions 0 .,olinergics



1anglionic stimulants

• Clinicall not im%ortant

•

• #cetlcholine (natural transmitter)

• 5M!! (e%erimental)• Nicotine (al&aloid, tobacco)

• "obeline (tobacco)

Nicotinic rece$tor agonists



Acetylc,olinesterase 4 Irreversi#le In,i#ition

D5P+ Iso"luro$,ate

P

OR1

R2 X

2-!#M

!ralidoime

No cns action

56! #ging3=-4= min

Ner*e gas

secs 8 min

Malathion

4 > ? hr

Acetylc,olinesterase 4 Irreversi#le In,i#ition

D5P+ Iso"luro$,ate

P

OR1

R2 X

2-!#M

!ralidoime

No cns action

56! #ging3=-4= min

Ner*e gas

secs 8 min

Malathion

4 > ? hr



Indirectly0Acting Parasym$at,omimeticsIndirectly0Acting Parasym$at,omimetics

• Interact 6it, acetylc,olinesterase

;rue and8or %seudocholinesterase (serum)• T6o sites%

- anionic site that binds the @uaternar amine and

%ositions the #ch molecule

- esteratic site hich attac&s the acl carbon

In,i#itors o" c,olinesterase%

- /e*ersible inhibitors (eg+ %hsostigmine)- :rre*ersible inhibitors (eg+ organo%hos%hates)



Reversi#le in,i#itors

• 7uarternary ammonium com$ounds

- dro%honium (snthetic, ater stable, -1= min)

;ensilon test > Masthenia gra*is

- #mbenonium (snthetic, 4-A hr)

.ar#amates

- !hsostigmine (=+-2 hr)

(tertiar amine, ell absorbed, cns acti*it,

can gi*e to%icall)

- Neostigmine (=+-2 hr)

(@uaternar amine, no cns acti*it, snthetic,

some direct action)



US Military '0PAM 8 Atro$ine In9ector

':; mg Atro$ine+ <((mg '0PAM

US Military '0PAM 8 Atro$ine In9ector

':; mg Atro$ine+ <((mg '0PAM



.linical use% Acetylc,olinesterase In,i#itors

• Eye% miosis (s%hincter contraction), accommodation bloc& (ciliar

muscle contraction)<se $laucoma (ide-angle or secondar glaucoma)

!hsostigmine or echothio%hate (long acting)



Actions on t,e Eye$laucoma treatment

1+ α-#gonist↑ut'lo

2+ M-#gonists↑ut'lo

3+ β-Bloc&er

↓Secretion4+ α2-#gonist

↓Secretion

+ !$s ↑ut'lo

?+ Carbonic acid

inhibitors ↓Secretion



•1I tract% ↑motilit in %araltic ileus (%ost-o%) or aton o' urinar bladder+Neostigmine (bethanechol better)

Neuromuscular 9unction%

- Neostigmine in Masthenia gra*is

- dro%honium as diagnostic Masthenia gra*is

- /e*erse NM bloc& a'ter surger, Neostigmine

Reverse to*icity #y antic,olinergic agents%- ie+ atro%ine, tricclic antide%ressants (high doses)

- !hsostigmine is %re'erred (CNS action)



Acetylc,olinesterase In,i#itors



• Adverse reactions% (S"<5)

- Sali*ation (muscarinic)

- 2acrimation (muscarinic)

- Urination (muscarinic)

- Diarrhea (muscarinic)

- Emesis (*omiting) (muscarinic)

- cardiac sloing (muscarinic)- h%ertension 8 h%otension (nicotinic)

- NM %aralsis (nicotinic)

- cram%s (muscarinic)

- bronchoconstriction (muscarinic)- tremor, nausea, CNS induced con*ulsions

To*icity 4 Treatment o" Ac,E In,i#itors

• Treatment% Muscarinic antagonist ie+ #tro%ine

#ch reacti*ator (!ralidoime, 2-!#M)

mechanical res%iration



S2UD1E

S - Sali*ation" - "acrimation

< - <rination

5 - 5iarrhea

$ - $astric u%set - mesis

DUM==E2S

5 - 5iarrhea< - <rination

M - Miosis8muscle ea&ness

B - Bronchorrea (Dmucus) B - Bradcar

- mesis

" - "acrimationS - Sali*ation8seating

To*icity o" Ac,E In,i#itors

2. Parasimpatomimetika kuliah

Documents

Transcript of 2. Parasimpatomimetika kuliah