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#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
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