cholinergic drugs

muscarinic

nerve
heart/smooth m
glands/endotheilum

nicotinic

Neuromusc end plate
skeletale m
autonomic ggl cells

musc agonists
cholinesters

ACh
carbachol
bethanechol

musc agnoists
alkaloids

pilocarpine
muscaine

cholinesterASE inhibitors
reversible

edrophonium
physiotigmine
neostigmine
donepezil

cholinesterASE inhibitors
IRRVS

organophosphates
parathion

cholinesterASE Reactivators

pralidoxime

choline esters/alkaloids
mechanisms

act of PREsynapic receptors inhibts release of various NT

some activate NICOTINIC receptors...(POSTGGLinc) prolonged act = ....no change in resting potential therefore no respones by organ (depolization blockade)

M, 1,3,5

IP3 formation DAG cascade
ca+2 increase
cell excite

M 2,4

inhibit cAMP
open K+ channels
cell INHIBITion

Heart

M2

SMooth muscle

M3

brain

all 5

endothelium

M3

exocrine gland

m3

carbachol-sensitity

M3 and Nm

bethancehol - sensitivity

M3 and no Nm

ACh- sensitiivy

all three and Nm....VERY sensitve to cholinesterase

Cholinesters - dynamics

Heart SA node (m2) decrease hr
atira - refractiveness decreased
av - decrease in conduction
venticles - minimal change

cholinesters - dynamics 2

vessles vasodilation (m3, w/ NO)
GI - increased tone/contractions/peristalsis

rlx of spincters
- contact LES

mild stimulation of INSULIN

Genitouninary - contract detrussor m, errection

Resp - bronch muscle contraction
increased secretions

eye - miosis (spintcer contractions)

cyclospam - leans curvature increase for near vision (ciliary m contracts)
aq humor outflow/lacrimal glands increase

skin - sweat glands

pharmokinetics

oral - low
distripution - periph tissues only, No CNS

biotrans - achASE & butASE (breaksdown)....Carbachhol and bethanechol resistance

AcH & carbachol - topical on conjuctivia
Bethanechol - (AVOID IV or IM)

adverse affects (on conjuctiva))
(carbacol/acH)

CATARACTS!!
difficult seeing far

advrese affects bethaechol

nausea/vomit/hypotension

contraindications

asthma, COPD, hyperthyoridsm, arrhymithas, Pep ucler disease

Alkaloids

pilocarine tertiary
muscarine quaternary

only M1,2,3 ( no Nm)

stimulates sweating/salivation
arousal/excite/headache/tremors

alkaloids - adverse

similar to choiline esterrs...nausea sweating with posiion mushrooms....no muscle tone affected

alkaloids USES

open angle glaucoma - pilocarpine
xerostomia (in sjorgnes syndrome)

muscarine (no use)

cholinestASE INHIBITORS

reversible - carbamates (physotigmene & neostigmeans....alcohols...donepezil (good for CNS)
irrves - organophosphates

cASE inhib cont

edrophonium - short lived
carbates - 1-6 hour 1/2 life

organophosphates - esteratic site (w/ AGING) then it becomes irrvs

pharmokinetics

CNS - MD - alterness/
HD - confusion, ataxia, loss of reflex

eye,resp, GI, urinary = same as choloniestere

CVS - symp ggl/psns ggl
- M3 receptors
m2 on heart
relase of epi from adrenal medulla
-MD = bracycardia
HD- markked bradycardia

NMJ - MD (contractions)
HD - fasculations, NM blockage...small muscles first paralyzed diaphram last to go

pharmokineites of cASE inhib

oral - ok for teritary
low for quant
very good for ORGANOPHOSPHATES

Distribution
teritary CNS
quat - perio
organo - all tissue

Biotrans -carbamates plasma esterase
organophosphates - paraoxases

physotigmene 1-2 t1/2

adverese affects of cASE inhib

fatigue,muscle cramps, fasiculations
CATARACTS

death - resp failure
diagnosis - check enz activity of cholinestease act

treatment - with Diazpam, atropine

posining of cASE inhib

eye - miosis, lacrimation
resp - rhinorreaha, salivary & bronch sections
skin - sweating/flush
skeletal - weakness/paralysis
GI - invol urination/penil erection
cvs - bradicardia, hypotension
CNS - ataxias, slurred speech. coma convulsions

cholinesterase reactivators

oximes...PRALIDOOXIME

works as long as AGING did not happen to the complex

oral bio - <1%
no brain
t1/2 - 1.-1.5 hours

use with organophosphate posining

use of chol drugs

open angle glaucoma
MG (use edrophonium IV) for diagnosis

Neostigmine for MG (TREATMENT PO)

GI - exosteoma, post op

CNS - AD ...donepezil inhib achASE of brain)