Term
|
Definition
Ach, nicotine, muscarine
Binding Affinity:
Nicotinic - nico > Ach > musc
Muscarinic - musc > Ach > nico
*nicotinic/muscarinic drugs will only bind their opposite receptor if their serum concentration is very high (much greater then its Kd value) |
|
|
Term
| Where are nicotinic receptors? |
|
Definition
On all post ganglionic cell bodies (which are inside the ganglia)
Adrenal Medulla
Neuromuscular Junction (somatic) |
|
|
Term
|
Definition
5 subunits (each with 4 transmembrane domains)
Functions as a ligand-gated ion channel
Ach binding -> conformational change -> Na+ entry -> depolarization |
|
|
Term
| Where are muscarinic receptors? |
|
Definition
On effector organs:
M2 - cardiac muscle
M3 - bladder/GI muscle and secretory organs |
|
|
Term
|
Definition
GPCR with 7 transmembrane domains
M2 receptors -> Gi -> inhibit AC pathway -> decrease cAMP -> decrease PKA -> decrease Ca++ -> decrease contraction (BP)
M3 receptors -> Gq -> PLC pathway -> increase DAG/IP3 -> increase PKC -> increase Ca++ -> increase contraction (motility) |
|
|
Term
| parasympathomimetics/parasympatholytics |
|
Definition
parasympathomimetics- muscarinic agonists
parasympatholytics- muscarinic antagonists |
|
|
Term
|
Definition
|
Drug: Ach
Therapeutic class: n/a
Pharmacological class: choline ester
Med Chem: quaternary amine, charged
ADME:
Distribution = synthesized and restricted to cytoplasm, vesicles, synaptic cleft
Metabolism = degraded rapidly in synapse (short duration of action)
Target MOA: nicotinic receptors (ion channels) and muscarinic receptors (GPCR)
Tissue MOA: CNS, Autonomic (Parasymp and Symp), Somatic |
|
|
Term
| Direct Muscarinic Agonist (proto) |
|
Definition
Drug: bethanechol
Therapeutic class: treat urinary retention
Pharmacological class: direct muscarinic agonist, parasympathomimetic, negative chronotrope
Med Chem: Ach derivative, differences in its molecular structure protect it from Ach-esterase and make it selective to muscarinic over nicotinic
Target MOA: selective for muscarinic receptors
Tissue MOA:
Therapeutic = increase urination and GI motility
Side effects = nausea, diarrhea, low BP, low HR, miosis (pupils), diaphoresis (saliva, sweat, tears)
Interactions = reduce absorption of other drugs due to increase GI motility |
|
|
Term
| Direct Muscarinic Antagonist (proto) |
|
Definition
|
Drug: atropine
Therapeutic class: pupil dilation, antispasmotic for GI, antisecretory for bronchi
Pharmacological class: direct muscarinic antagonist (competitive with Ach), parasympatholytic, positive chronotrope
Med Chem: tertiary amine, NOT charged
Target MOA: selective for muscarinic receptors (not nicotinic therefore no action at ganglia or NMJ)
Tissue MOA:
Therapeutic = inhibits optical, GI, and bronchial smooth muscle
Side effects = (anticholinergic effects) dry mouth, constipation, blurred vision |
|
|
Term
| Other muscarinic antagonists (3) |
|
Definition
scopolamine – motion sickness
ipatropium – bronchodilation
tiotropium – bronchodilation |
|
|
Term
|
Definition
choline & Na+ co-transported into cell
energy dependent bc they're charged
rate limiting step bc its energy dependent |
|
|
Term
|
Definition
Ach active transport into vesicles
strict amount in each vesicle
ATP & sugars also present |
|
|
Term
|
Definition
| action potential -> increased Ca++ -> exocytic release |
|
|
Term
|
Definition
post-synaptic: sends nerve impulse
pre-synaptic: negative feedback |
|
|
Term
|
Definition
| rapid (millisecond) degradation by Ach-esterase |
|
|
Term
|
Definition
keep Ach in synapse
short term = prolonged signaling
long term = desensitization/down regulation |
|
|
Term
| Indirect cholinergic agonists/antagonists |
|
Definition
| work by modulating the Ach pathway |
|
|
Term
| Indirect Cholinergic Agonist (proto) |
|
Definition
Drug: physostigmine
Therapeutic class: enhance GI/bladder motility, induce miosis (pupil constricting) to reduce pressure from glaucoma
Pharmacological class: indirect cholinergic agonist (competitive with Ach), parasympathomimetic
Target MOA: Ach-esterase inhibitor
Tissue MOA:
Therapeutic = contracts pupil (miosis) to reduce pressure, enhance GI/bladder motility
Side effects = nausea, diarrhea, low BP, low HR, diaphoresis
|
|
|
Term
| Indirect Cholinergic Antagonists [3] (proto) |
|
Definition
Drug: hemicholinium
Target MOA: inhibit Ach reuptake into neurons
Drug: vesamicol
Target MOA: inhibit Ach transport into vesicles
Drug: botulinum toxin
Target MOA: inhibit Ach release
|
|
|
