Cholinergics Flashcards
Cholinoreceptors
-nicotinic (NM, NN)
-muscarinic (M1, M2, M3)
Nm receptor
-skeletal muscle
NN receptor (neural)
-postganglionic
-adrenal medulla
Nicotinic receptor responses
-depolarization
-ligand opening of Na/K
Muscarinic receptor responses
QIQ
M1 receptor
-postganglionic
-depolarization
-GQ mech
M2 receptor
-heart
-inhibition
-G1 activation
M3 receptor
-smooth muscles (contract)
-exocrine glands (secrete)
-endothelium (relax)
-Gq activation
acetylcholine has higher affinity for which receptor
muscarinic
acetylcholine biosynthesis and neurotransmission
- choline transported to presynaptic nevere terminal by CHT
- Ach synthesize from choline and acetyl-CoA by ChAT
- ACh transported to storage vesicle by VAT
- action potential opens gated channels and increases calcium, fusion of vesicles with the surface membrane results in the release of ACh
-ACh binds to cholinoreceptors on post synaptic cell - ACh action terminated by metabolism by AChE
- auto receptors and receptors on presynaptic nerve end transmitter release
sodium-dependent choline transporter (CHT)
-transport choline to presynaptic nerve terminal
-inhibited by hemicholinium
choline acetyltransferase (ChAT)
-forms ACh from choline and acetyl coA
vesicle-associated transporter (VAT)
-carries ACh to storage vesicle
-inhibited by vesamicol
botulinum toxin
-botox
-block release of ACh
acetylcholinesterase (AChE)
-metabolizes ACh
Cholinergic agents
-acetylcholine
-parasympathetic
Parasympathetic direct agonist
-activate cholinoceptors
-muscarinic receptor agonists
-choline esters and alkaloids
PSNS indirect agonist
-stimulate ACh release
-inhibit AChE
-reversible or irreversible
PSNS antagonists
-direct or indirect
-many drug side effects
Muscarinic AGONIST effect on heart
-M2
-DECREASE HR, conduction, and force
muscarinic agonist effect on exocrine glands
-M3 increase secretion
-lachrymal, tracheobronchial, salivary, digestive, sweat
muscarinic agonist effect on smooth muscles
-M3 increase contraction
-M2 inhibit relaxation
muscarinic agonist effect on sphincters
-M3
-relaxation
Muscarinic Agonist effects on CNS
-not all agonist can access CNS
-mostly M1 receptor
-tremor, hypothermia, increased locomotor activity, improved cognition
Direct acting cholinergic receptor agonists: esters
-ACh
-methacholine
-carbachol
-bethanechol
Direct acting cholinergic receptor agonists: alkaloids
-muscarine
-pilocarpine
Mushroom poisoning (muscarinic agonists)
-bradycardia
-nausea, cramps
-bronchoconstriction
-salivation
-visual disturbances
-sweating (SNS)
-hypotension (SNS)
charged muscarine
does not cross BBB well
Pilocarpine
-promote sweating, urine, salivation
-treat gluacoma (outflow aq humor = decrease pressure)
Xerostomia
-dry mouth
-treat with pilocarpine (M3)
Sjogren’s syndrome
-autoimmune disorder mostly women
-reduced salivary gland secretions
Muscarinic effect on cardiovascular
-fall in BP, HR
-M2
muscarinic agonist effect on M3
-GI (muscle contract, sphincter relax)
-bladder
-eye (miosis)
-sweating (increase)
ACh clinical use
-Muscarinic and nicotinic receptors
-cholinesterase sensitive
-use for miosis during surgery
Carbachol clinical use
-muscarinic and nicotinic receptor
-use for miosis during surgery and gluacoma
Pilocarpine clinical use
-muscarinic receptor
-glaucoma
-dry mouth
bethanechol
-muscarinic receptor
-urinary retention
-GI stimulation
Varencicline clinical use
-nicotinic receptor
-smoking cessation
Side effects of muscarinic agonists
-Diarrhea
-Urination
-Miosis
-Bradycardia
-Bronchoconstriction
-Emesis
-Lacrimation
-Salivation + Sweating (SNS effect)
Methacholine clinical use
-provacative test for hyperactive airways
