FA.Pharm.AutonomicDrugs Flashcards
Nicotinic ACh receptors are….
Nn are found in _____.
Nm are found in _____.
Nicotinic ACh receptors are LIGAND-GATED Na+ / K+ channels;
Nn receptors are found in AUTONOMIC GANGLIA
Nm receptors are found in NEUROMUSCULAR JUNCTIONS
What is odd about the adrenal medulla and sweat glands?
Both are part of SANS, but are innvervated by cholinergic fibers.
Botulinum toxin _____ the release of _____ at all _______ terminals.
Botulinum toxin PREVENTS the release of NEUROTRANSMITTER at all CHOLINERGIC TERMINALS.
Muscarinic ACh receptors:
General mechanism
Subtypes
Muscarinic ACh receptors are G-protein–coupled receptors that act thru 2nd MESSENGERS
Subtypes: M1-M5
However, only M1, M2, and M3 are of concern
G-protein–linked 2nd messengers
Receptor:
G-protein class:
Major functions:
¶ QISS and QIQ till you’re SIQ of SQS
{ SANS } { PANS }{ Dopa } { Hista }{ ADH }
[A1] [A2] [ß1] [ß2] [M1] [M2] [M3] [D1] [D2] [H1] [H2] [V1] [V2]
[ q ] [ i ] [ s ] [ s ] [ q ] [ i ] [ q ] [ s ] [ i ] [ q ] [ s ] [ q ] [ s ]
Receptor: A1
G-protein class:
Major functions:
Receptor: A1
G-protein class: Gq
Major functions:
/\ Vascular smooth muscle contraction,
/\ pupilary dilator muscle contraction (mydriasis),
/\ intestinal and bladder sphincter muscle contraction
Receptor: A2
G-protein class:
Major functions:
A2
Gi
\/ sympathetic outflow
\/ insulin release
Receptor: ß1
G-protein class:
Major functions:
ß1
Gs
/\ Heart Rate
/\ Contractility
/\ Renin release
/\ Lipolysis
Receptor: ß2
G-protein class:
Major functions:
ß2
Gs
Vasodilation Bronchodilation /\ Heart rate /\ Contractility /\ Lipolysis /\ INSULIN RELEASE \/ uterine tone
Receptor: M1
G-protein class:
Major functions:
M1
Gq
CNS
Enteric nervous system
Receptor: M2
G-protein class:
Major functions:
M2
Gi
\/ Heart rate
\/ contractility of atria ( ø by atropine)
Receptor: M3
G-protein class:
Major functions:
M3
Gq
/\ Exocrine gland secretions (sweat, GASTRIC ACID)
/\ Gut peristalsis
/\ Bladder contraction
BronchoCONSTRICTION
/\ Pupillary sphincter muscle contraction (miosis)
Ciliary muscle contraction (accomodation)
Receptor: D1
G-protein class:
Major functions:
D1
Gs
Relaxes renal vascular smooth muscle
Receptor: D2
G-protein class:
Major functions:
D2
Gi
Modulates transmitter release, especially in the brain
Receptor: H1
G-protein class:
Major functions:
H1
Gq
/\ Nasal and bronchial mucus production
/\ Bronchiole contraction
Pruritis (itching)
Pain
Receptor: H2
G-protein class:
Major functions:
H2
Gs
/\ Gastric acid secretion
Receptor: V1
G-protein class:
Major functions:
V1
Gq
/\ Vascular smooth muscle contraction
Receptor: V2
G-protein class:
Major functions:
V2
Gs
/\ H2O permeability and reabsorption in the COLLECTING TUBULES of the kidney
¶ V …2… is found in the …2… kidneys
Gq coupled receptors and their MOA
H1, A1, V1, M1, M3
Gq lipids Receptor—>Phospholipase C—> | DAG—> Protein Kinase C
V /
PIP2
\
IP3 —> /\ [Ca++] in cell
¶ hey cutesy! HAV 1 M&M
q C
Gs and Gi coupled receptors and their MOA
Receptor
ß1,ß2,D1 \ Gs
H2,V2 \ (+) ATP /\ [Ca++] in heart
Adenylyl Cyclase—> | /
/ (-) \/ / (+)
/ Gi cAMP—>p.k.A
Receptor \ (-)
M2,A2,D2 \
Myosin light-chain kinase
¶MAD 2’s (smooth muscle)
CHOLINERGIC Neuron
Drug that blocks reuptake of Choline
Hemicholinium
CHOLINERGIC Neuron
Drug that blocks ACh from entering vesicles
Vesamicol
CHOLINERGIC Neuron
What is needed for NT release from vesicles
Ca++
CHOLINERGIC Neuron
What blocks the release of ACh from vessicles?
Botulinum toxin
CHOLINERGIC Neuron
Postsynaptically, what breaks down ACh, and what does it break it down into?
ACh-esterase
ACh —> Acetate + Choline
NORADRENERGIC Neuron
Drug that blocks Tyrosine Hydroxylase.
This drug prevents _____ from becoming ______.
Metyrosine blocks Tyrosine hydroxylase
(-)
Metyrosine ——| Tyrosine
hydroxylase
Phenylalanine——>Tyrosine———X———> DOPA
/’ \,
THB DHB
NORADRENERGIC Neuron
Drug that blocks entry of dopamine into vessicles
Reserpine
NORADRENERGIC Neuron
Drug that blocks release of NE from vessicles
Guanethidine
NORADRENERGIC Neuron
Drug that causes NE to be released from vessicles
Amphetamine
NORADRENERGIC Neuron
3 drugs that block reuptake of NE at nerve terminal
- Cocaine
- TCAs
- Amphetamine
NORADRENERGIC Neuron
Name 3 release modifying, presynaptic receptors, and whether they inhibit or stimulate neuron.
- M2 — inhibit
- Angiotensin II — stimulate
- A2 — inhibit
All are presynaptic and found in cardiac muscle (SA node)
In general, cholinomimetic agents make you…
ooze from every orifice.
Drug: Bethanechol
Class :: Subclass
Clinical applications
Action
BethaneCHOL
Cholinomimetic, direct agonist
Postoperative and neurogenic ileus
Urinary retention
Activates Bowel and Bladder smooth muscle
Resistant to AChE
¶ BETHANY, CALL me if you want to activate your Bowels and Bladder
Drug: Carbachol
Class :: Subclass
Clinical applications
Action
CarbACHOL
Cholinomimetic, direct agonist
Glaucoma
Pupillary contraction
Relieve of intraocular pressure
¶CARBon copy of acetylcholine
