Presynaptic Drugs Flashcards
Rate limiting step of ACh synthesis
Transport of choline into pre-synaptic nerve endings by a Na+ choline co-transporter
ACh is stored in ____.
Nerve terminal vesicles
ACh is released when ____
Stimulated by an action potential/Ca2+ influx; causes exocytosis of ACh vesicle
OnabotulinumtoxinA (Botox) function
Inhibit ACh release
OnabotulinumtoxinA MOA
Neurotoxic proteases endocytosed into cholinergic nerve terminals and inactive SNAP-25 needed to dock vesicle membrane
OnabotulinumtoxinA causes _____ paralysis and inactivates _____ glands
Flaccid; sweat
OnabotulinumtoxinA duration of action
3-4 months
Clinical uses of OnabotulinumtoxinA
Muscle spasms
Cosmetic
Hyperhidrosis
Migraines
Overactive bladder
Sides effect of OnabotulinumtoxinA
Dysphasia
Difficulty breathing
Muscle weakness
Urinary retention
OnabotulinumtoxinA black box warning
Distant spread beyond injection site
What tissues are M3 receptors found in?
Smooth muscle, glands, endothelium
M3 receptors are a ____ G-protein coupled receptor
Gq (activate PLC to initiate cascade to increase Ca2+)
M2 receptors are found in the _____
Heart
M2 receptors are ___ G-protein coupled receptors
Gi ( decrease cAMP, increase K+ efflux to cause hyperpolarization)
Prototype muscarinic ACh agonist
Muscarine
Muscarine activates ____
All muscarinic receptor types
Prototype muscarinic ACh antagonist
Atropine
Atropine blocks ____
All muscarinic receptor subtypes
Nicotinic receptors are ____ ion channels
Ligand-gated
When stimulated nicotinic receptors increase ___ permeability, causing ______
Na+; depolarization
Nn receptors are located in _____
Ganglia and adrenal medulla
Nn receptor high affinity agonist
Nicotine
Nn receptor prototype antagonist
Mecamylamine
Nm receptors are located in the ______ junction
Neuromuscular
Nm receptor low affinity agonist
Nicotine
Nm receptor prototype antagonist
D-tubocurarine
After stimulating N receptors, nicotine ____ the receptor
Desensitizes (acts like an antagonist)
What enzyme rapidly hydrolyzes ACh to terminate cholinergic neurotransmission?
Acetylcholinesterase (AchE)
Inhibition of AChE causes ACh to ____
Accumulate in the synapse, resulting in increased stimulation and then desensitization
Butyrylcholinesterase function
Drug metabolizing enzyme that controls plasma levels of choline ester drugs
Synthesis of Catecholamine Pathway
Tyrosine —> dopa —> dopamine —> norepinephrine—> epinephrine
Tyrosine is converted to dopa in the ____
Cytosol
Dopamine is converted to norepinephrine in ____
Vesicles
Norepinephrine is converted to epinephrine in the ___ of the ____.
Cytosol; adrenal medulla
Catecholamines are degraded by ____ if they are not stored
Mitochondrial monoamine oxidase
Catecholamines are actively transported into vesicles by ___
Vesicular monoamine transporter-2 (VMAT-2)
Tyramine can cause a ___ crisis
Hypertensive
Tyramine mechanism
Displaces NE from storage vesicles; increased cytosolic NE triggers it’s release by reverse transport through NET
Patients on MAOIs need to have ____ restrictions to reduce intake of ____
Dietary; tyramine (wine and cheese effect)
Methyldopa is a prodrug that is converted to ____
Methyl-NE
Methyldopa MOA
Lowers BP by decreasing sympathetic outflow from the CNS to the heart, vasculature, and kidneys
Methyldopa clinical use
Gestational hypertension
Methyldopa side effects
Sedation
Dry mouth
Edema
Autoimmune hemolytic anemia (long term use)
Pre-synaptic adrenergic receptor subtype
Alpha 2
Post synaptic adrenergic receptor subtypes
Alpha 1, Beta 1,2, and 3
All adrenergic receptors are coupled to ____
G Proteins
Alpha 1 receptors are G_
Gq
Alpha 2 receptors are G_
Gi
All Beta receptors are G_
Gs
Beta 1 receptors cause ___
Beta 2 receptors cause ___
Contraction
Relaxation
Monoamine oxidase inhibitors (MAOIs) are used for:
Depression
Parkinson’s
Cocaine blocks ____ from being reabsorbed
Norepinephrine
____ clears circulating Catecholamines
Catecholo-methyltransferase (COMT)
Major Catecholamine metabolite excreted in urine
VMA
