Lecture 2 Flashcards
what are the two types of cholinergic receptors
Nicotinic, Muscarinic
Most used cholinergic receptor in drug manipulation
Muscarinic
Which nicotinic and muscarinic receptors are used in therapeutic targeting
Nm, Nn & M1, M2, M3
What is a cholinergic agent
Parasympathetic mechanism involving ACh receptors
What does a direct agonist do in para sympathomimetic mechanism
activates cholinoreceptors
what does an indirect agonist do in a parasympathomimetic mechanism
Stimulate ACh release or inhibit ACHe
Many drugs exhibit ______ side effects
Anticholinergic
does acetylcholine have a higher affinity for nicotinic or muscarinic receptors`
muscarinic
What kind of tissue is M1 located in
Post ganglionic
M2 tissue location
Heart
M3 tissue location
Smooth muscle, exocrine glands, endothelium
M4 and M5 tissue location
CNS
mnemonic to remember GPCR mechanism of muscarinic receptors
QIQIQ
Mnemonic to remember GPCR mechanism of Adrenergic receptors
A1- Q
A2- I
B1,2,3- S
QISS
Gq pathway mevhanism
DAG—->IP3 and PLC and Ca2+
Gi mechanism of GPCR
Inhibition of adenylyl cyclase, K+ channel activation
WHich muscarinic receptor opposes B1 receptor in heart
M2
Most common muscarinic receptor
M3
Where is M3 found in the body
Smooth muscle, exocrine and endothelium
6 steps of ACh synthesis
1 choline transported into presynaptic nerve terminal by sodium dependent choline transporter (inhibited by Hemicholium)
2 ACh is synthesized from choline +acetyl CoA by enzyme choline acetyl transferase
3 ACh transported into storage vesicle by second carrier (VAT) (inhibited by vesamicol)
4 ACh binds to cholinoreceptors on post synaptic cell
5 Terminated by ACHe
6 Autoreceptors and receptors on pre synaptic nerve inhibit via Feedback mechanism
Acetylcholine structure
COOH-CH2-CH2-N+-(CH3)3
methacholine vs acetylcholine
CH3 added to BETA carbon in methacholine
Acetylcholine vs Carbacol
COOH replaced by COON
Bethanechol vs Acetylcholine
Beta carbon added and H2N added
Why is the methyl on B carbon in methacholine
Increases muscarinic binding and decreases nicotinic binding
PSNS symptoms of muscarinic agonist poisoning and why
Bradychardia, M2 decreases HR
Diarrhea and cramps, M3 contracts Walls
Bronchoconstriction, M2 and M3 lead to bronchoconstriction
salivation- M3 increases secretion
Visual disturbances- M3 in eye
SNS symptoms of muscarinic agonist poisoning and why
Sweating- a1 secretes sweat
Hypotension- uninnervated muscarinic receptors in blood vessel mediating vasodilation via Norepinephrine
Muscarinic agonist effect on heart
decrease in HR, conduction and force due to M2 activation
Muscarinic agonist effect on exocrine glands
Increases in secretion (Lachrymal, Tracheobronchial, salivary, digestive, sweat glands) sue to M3 activation
Muscarinic agonist effect on smooth muscle
M3 increases contraction while M2 inhibits relaxation
Muscarinic agonist effect on sphincters
M3 relaxation
stereoisomeric preference of cholinergic receptors
Only (+) sterochemistry binds well
How does pilocarpine treat glaucoma
M3 agonist leads to contraction of ciliary muscle
Why are antimuscarinic drugs contraindicated in glaucoma
M3 will be targeted by antimuscarinic drugs, we need M3 to contract ciliary muscle
When ACh is modified to carbachol what changes
ACHe sensitivity decreases, both still used for miosis in surgery and glaucoma
ACHe modified to pilocarpine ACHe sensitivity and change in use
Not sensitive, used in glaucoma