Ca

Hemicholinum ---

botulinum toxin --- spider toxin++ clostiridium

Presynaptic R

Uses:

Clinically limited in use because:

- destroyed by acetylcholinesterase

- is not selective

Endogenous Ach effect???

Cholinergic receptors

-Nicotinic R( N ) : it activated by nicotine

small dose of nicotine stim ganglia release of Ach or noradrenalin

large dose inhibition to autonomic ganglia (euphoria)

Its 2 type:

*neuronal type (Nn) : in CNS, adrenal medulla & ANS ganglia

*neuromuscular type (Nm) : found in neuromuscular junction cause contraction of sk.m.

Muscarinic R : M1-M5

it activated by Muscarin poisonous mushroom used experimentally only.

M found on ganglia in PNS

M1 found in gastric parietal cell

M2 found on cardiac cell & sm

M3 on bladder, exocrine gland, sm, endothelium

M4-M5 on CNS

MOA:

nicotinic R act by ion channel linked R.

Muscarinic R act by activation G-pr but :

M 1 , 3 M2

activate phospholipase C inhibit adenylyl cyclase

IP3: i/c ca st or inh E, K conductance

heart rate & force secretion, contraction

DAG: activate pr kinase C phosphorylation pr cellular eff

NOTE: M1 agonist in Rx of Alzheimer D

M3 blocker RX COPD.

or Agonists): cholinomimeticsCholinergic drug (

1- direct acting cholinomimetic

They act where Ach is physiologically released &

amplifiers of endogenous Ach.

*** Bethanechol

- Synthetic esters of choline so not destroyed

by cholinesterase enzyme.

- Strong muscarinic activity & no nicotinic

effect

- Act on sm of bladder & git causing increase intestinal motility & stimulate detrusor muscle of bladder & relaxed the sphincter

used in:

- atonic bladder due postoperative and non obstructive urine retention

- in neurogenic atony and megacolon

SE:

All effect of cholinergic stimulation

sweating, salivation , flushing , hypotension abd pain , diarrhea & bronchospasm .

Contraindication:

-in asthmatic patients

-in bladder weakness and mechanical

obstruction ( it cause rupture of

bladder).

-in hypotension

-in peptic ulcer ( it increase git gland

secretion)

Carbachol

- Synthetic esters of choline so

-not destroyed by cholinesterase enzyme.

- have muscarinic & nicotinic effect

-has st effect on ganglia adre epinep

- mainly affect CVS & GIT

iopdecrease because glaucomaused in -and cause miosis.

***Pilocarpine

- naturally occurring alkaloid

- not destroyed by cholinesterase because

tertiary amine

-potent muscarinic agonist

-used in emergency increase in (iop)

( it opening the trabecular meshwork

around the schlemm canal .

-used as mouth spray in xerostomia due

to radiation of head & neck.(why)

SE:

-blurred vision and night blindness

-increase salivation and sweating in

toxicity with pilocarpine