#10 part 1+ mind maps cholinomimetics

made by lama shatat

corrected by laith sorour

date 25/10

ANS drugs

Cholinergic agonists

Direct indirect (activates directly Cholinergic Receptor) (CE inhibitor)

reversible Natural alkaloid esters e Cholin

*resist degradation *act directly on -Neostigmine

by CE end organ like eye -Edrophonium

*have longer -Pyridostigmine

duration than Ach -Donepezil

Tacrine-

Irreversible

1-Echothionophil

2-Isoflurophate(DPF)

Choline esterase

(CE):

*protein

*Metabolize ach to

Choline & acetate

*specific for Ach in

cholinergic synapses

colethaneB

arbacolC incholethaM

e

Ipilocarpin

e

Lowers high IOP

in close angle &

open angle

chronic

glaucoma

Info:

Inhibit reversibly CE

enzyme

Accumulation of Ach

Electrostatic bonds

Stimulate nicotinic &

muscarinic receptors

Useful in myasthenia gravis

Organophosphorous compounds

irreversibly inhibit CE

Covalent bond in Enzyme-

inhibitor complex

Parathion, : insecticides Used as

Malathion

in chemical nerve gases As

warfare: Tabun, Sarin, Soman

AgonistDirectCOLBMC

Adrenergic Cholinergic

Antagonists

Psuedocholine esterase:

*found in plasma & liver

* Not specific to Ach

*Metabolizes other drugs (suxamethonium, procaine)

pilocarpine Carbacol Bethanecol

*Natural plant alkaloid *Binds to muscarinic receptor

*Resistant to CE enzyme *uncharged can enter Nervous system

and cross BBB *makes tolerance

Derivative of Ach *Has muscarinic &

nicotinic actions *Limited use:

nicotinic Because of - &ganglia on effects

edullaadrenal m

Derivative of Ach

Has:

-Little nicotinic effects effects Good muscarinic-

on bladder & GIT

it produces:: -Miosis (contraction of circular

muscle of iris) -Contraction of ciliary muscle of the eye -Reduction of IOP

-Improves outflow of aqueous humour

in glaucomaUsed topically -

-used in xerostomia(dry mouth) of

sjornes syndrome (taken orally) *because stimulates salivation

Used mainly topically as

miotic(contract pupil) to glaucomain

decrease high intraocular pressure

(IOP

Leads to easy urination & defecation

Used to treat post-operative or post-labor:

or Urinary retention-

: the paralytic ileusweakness of intestine to push its content causing constipation because of weak peristaltic activity

Side effects of Cholinomimetics:

Excessive sweating, salivation

Flushing, hypotension

Abdominal colic & diarrhea

Bronchospasm

Pilocarpine-Impaired accommodation to far vision & darkness

Contraindication of cholinomimetics:

-to whom I shouldn’t give them

Bronchial asthma

Improves outflow of aqueous

humour:

-Opens fluid pathway

-Increase aqueous flow through canal

of Schlemm

-Secondary to contraction of circular

muscle of the iris & ciliary muscle

Note:

What is glaucoma?

Disease that occur

because of increased

pressure in the eye

We use carbachol to reduce IOP in

angle glaucoma, -angle or narrow-open

became particularly in patients who

tolerant to pilocarpine

-because the cholinergic drug will increase the contraction and will worsen the asthma

Peptic ulcer

a lesion in the lining (mucosa) of the digestive tract, typically in the stomach or duodenum, caused

by the digestive action of pepsin and stomach acid

s will increase the secretion so you shouldn’t give*agonist

-------------------------------------------------------------------------------------------------------------------------------

Ach & other cholinergic agonists

Muscarinic

Nicotinic

Autonomic ganglia

-stimulation

Adrenal medulla

-increase NA & A

NMJ

-muscle

contraction

CVS:

1)negative

chronotropic intropic

effect

2)decrease stroke

volume & cardiac

output

3)decrease

ABP(arterial blood

pressure)

-stimulation of

vascular M3 receptor

-increase NO release

from endothelium

EYE:

*Miosis: contraction of

circular muscle of iris

*accomolation to near

vision

*decrease IOP

exocrine gland GI

secretion:

Increases

Bronchi

*bronchoconstriction

*increase mucosal secretion

Penile erection

increase release of

NO

Urinitation

*contraction of bladder

wall

*relaxation of sphincster

Defection

*contraction of intestinal wall

may lead to spasm and

diarrhea

*relaxation of sphinsters

What is myasenthia gravis (MG)? Is a nerve muscular disease that leads to varying degrees of muscle weakness. The myasenthia disease autoimmune disease which result from antibodies that block Ach receptor (Nm) in the junction between muscle and nerve in NMJ Which lead to reduction of receptor number. symptoms and signs : -muscle weakness *because less Ach receptors work -fatigability -difficult speaking & swallowing

*because the responsible for those

processes are muscles Treatment: 1-Thymectomy *removing of thymus gland 2-Immunosuppressant *its autoimmune diease so we lower the immunity 3-Reversible CEI *increases the number of Ach in the junction

What is cholinergic crisis? is an over stimulation at NMJ due to excess of Ach as a result of the inactivity of AchE enzyme which breaks down Ach *we see it in myasenthia gravis patients who take high dose of CEI\anticholinesterase drugs *over stimulation of nicotinic receptor(because of high concentration of Ach) will lead to blockage instead of further activation *symptoms & diagnosis: 1-muscle weakness 2-paralysis

Reversible CEI:

Inhibit reversibly CE enzyme

Accumulation of Ach

Electrostatic bonds -weak bonds so it is reversible Stimulate nicotinic & muscarinic receptors -because of the increased concentration of Ach Useful in myasthenia gravis

Neostigmine Pyridostigmine Edrophonium -Synthetic CEI

-doesn’t cross BBB

-Duration of action : 4 hours

-Mainly MG treatment

-Give orally

,SC(subcutaneous)

similar

-duration of action : 6 hours

MG treatment

given orally

similar

Duration of action: (10-20) min

-diagnose MG

-differentiate between weakness due to

myasthenic crisis or cholinergic crisis

-in treatment :

Adverse effect of CEI:

Excessive salivation

Flushing and hypotension because of

vasocontraction and decreased heart rate Abdominal colic and diarrhea

-because of increased contraction of intestine and

increased motility of GI Bronchospasm

-------------------------------------------------------------------------------------------- Alzheimer disease

Tacrine Donepezil

-Reversible CEI -Used in Alzheimer disease -Hepatotoxic

-New selective Reversible CEI -Used in Alzheimer disease -Once daily -lacks hepatotoxicity

-delay the progression of Alzheimer’s disease, none can stop its progression. -GI distress is their primary adverse effect

ImprovementMG AggravatedCholinergic crisis

1-urinary retention 2-paralytic ileus 3-antidote to competitive NM blockers tobocurine poisoning

Irreversible CEI used as organophosphorus compounds

Nerve gases (chemical weapon\warfare) insecticides

What is nerve gases? are class of phosphorous organic chemicals that disrupt the mechanism by which the nerve transfer messages to organs by Blocking CE Irreversibly by Covalent bonding in E-S complex this cause: 1-increased salivation 2-miosis of pupil 3- convulsion

4-involantary urination 5-death ex: Tabun, Sarin, Soman

Are an organophosphate

compounds.

act on the CE indirectly

ex: Tabun, Sarin, Soman

Indirect irreversible agonists

*Toxicity: excessive cholinergic stimulation

Organophosphate insectside poisoning:

Agricultural or industrial accidents

Isoflurophate (DFP) Echothiophate

*irreversible CEI *OP compound (organophosphate compound)

same -new agent

*insecticide *topically in glaucoma

*treatment of open-angle glaucoma

Duration of action about a week Long Duration of action (week)

essive cholinergic manifestations -because of CE inhibition

-because increased motility and contraction of intestine

-because of bronchial constriction

n, excessive sweating, M. paralysis -point-pupil),convulsions&death

OPI poisoning treatment

General measures IV or IM atropine

*cholinergic antagonist

for convulsionsDiazepam IM lidoximepra

difference between direct & indirect cholinomimetics : :

**Pharmacodynamics effects: -Similar

**Central effects with indirect -Cross BBB

Good Luck 0.o