cholinergic Flashcards
cholinergic
any system affected by/involving ACh
M3
secretory
any muscle contraction
circulatory muscles in eye
M2
cardiac
decrease heart rate
slows SA node and slows down AV node
M1
cholinergic pathways
affected in Alheimerz
circuits involved in memory and cognition
Muscarinic agonist
activate all
increase SLUD
decrease HR
bronchoconstriction
what would a muscarinic agonist be useful in treating
tachycardia
dry mouth
constipation
glaucoma
muscarinic antagonist
decrease SLUD
increase HR
muscarinic antagonist would be effective in treating
urinary urgency
eye surgery
IBS-D type
nicotinic receptors
Na+ gated ion channels
Nicotinic receptor types
Ng = autonomic ganglia = para or symp Nm = neuromuscular = some selective nicotinic
AChE
acetylcholinesterase
wherever ACh is released this enzyme is present
highest turnover rate of all enzymes
lack of AChE =
slower metabolism of ACh
increase SLUD
decrease HR
increase in cholinergic activity of the brain
ACh
made from ACh and choline
choline on its own would be broken down by cholinesterases => ACh is less resistant and will not be broken down as quickly
muscarinic receptors are _____ and nicotinic receptors are ____
gpcr
Na+ gated ion channels
hemicholiniums
block the transporter bring choline into the cell = result would be less formation of ACh
Vesamicol
inhibits VAT that puts ACh into the vesicle to prepare for its release
Botulinum toxin
prevents the release of the ACh vesicles
two mechanisms that block the release of ACh on the presynaptic ganglia
heteroreceptor = alpha 2
ACh autoreceptor = N2
when both are activated = decrease in ACh release
AChE is found on the post synaptic neuron awaiting binding for rapid hydrolysis, but ACh can also be broken down by
plasma esterases such as butyrylcholinesterase (BuChE)
Muscarinic receptors:
odd numbers =
even numbers =
Gq / excitatory
Gi / inhibitory
M1 function
increase cognitive function seizure activity increase secretions increase autonomic ganglia depolarization decrease DA release and locomotion
M2 function
autonomic nerve terminals / heart decrease heart rate increase smooth muscle contractions decrease ganglionic transmission neural inhibition in CNS increase tremors, hypothermia, analgesia
M3 function
CNS, smooth muscle smooth muscle contraction increase salivary glands increase food intae body fat deposits inhibition of DA release synthesis of NO
treat parkinsons using
an M1 antagonist
treat Alzheimers using
an M1 agonists
structure requirements for an muscarinic agonist
1) ammonium group - want N to be capable of bearing a positive charge
2) Ethylene bridge - 2 C atoms between N and O; Ings Rule of 5 - start at nitrogen to terminal H; no more than 5 atoms
3) acyloxy group - ester, ether, ketone; must be O atom
The B carbon works on agonist by
increasing affinity for Muscarinic over nicotinic
carbamate
slows hydrolysis by ACh
if your patient had an obstruction (bladder or GI)
do not use an agonist
functions of muscarinic agonists
non - obstructive urinary retention
disabling anticholinergic side effect from medications like tricyclic antidepressants
bronchial airway hyper-reactivity in subjects who do not have asthma
lowering of intraoccular pressure in glaucoma
miosis induction after ophthalmoscopic exmination
xerostomia caused by radiation therapy for cancer of the head and neck
when would you not give a muscarinic agonist
IBS-d
asthma - airways would close
severe bradycardia - slow down HR
SAR requirments for muscarinic antagonists
1) N is tertiary or quaternary ammonium
2) R1 and R2 are carbocyclic or heterocyclic rings
3) R3 is generally a H, OH, or part of the ring systems
4) X is usually an ester or even a C atom
5) length is usually 2 to 4 atoms
Muscarinic antagonists (antimuscarinics)
COPD Parkinsons Overactive bladder Mydriatics/Cycloplegics IBS-D
antimuscarinics ADR?
dry mouth dry eyes blurred vision dry skin increase HR hallucinations delirium limit CNS effects = if ionized
ophthalmic
used to dilate pupils
paralyze the lens for procedures
loss of accommodation
relaxation of sphincter of the iris =
midrasis = dialation
relaxation of ciliary muscle of the iris
change lens thickness
unable to accommodate
blurred vision
COPD drugs
ipratropium
umeclidium
glycopyrrolate
aclidium
parkinsons drugs
benztropine
trihexyphenydil
IBS drugs
dicyclomine
Nausea due to motion sickness drugs
scopolamine
