Speth Exam 2 Flashcards
Which receptor can modulate monoamine neurotransmission and, in particular, the dopamine system?
TAAR1
What must be considered an essential element of any comprehensive model of psychostimulant action?
TAAR1
What place do B1 adrenergic receptors favorite?
the heart
When heart rate is increased, what neurotransmitters is the heart responding to?
norepinephrine or epinephrine (increases HR)
What neurotransmitter decreases heart rate?
acetylcholine
What nervous system is the fundamental of pharmacology?
the autonomic nervous system
What neurotransmitter controls the sympathetic nervous system?
norepinephrine
What neurotransmitter controls the parasympathetic nervous system?
acetylcholine
Epinephrine is a hormone that is released from where?
the adrenal gland
Gαi (an inhibitory G protein) inhibits ____, which decreases _____.
adenylyl cyclase; cAMP
Gαi (an inhibitory G protein) acts on what channel?
GIRK (G protein inward rectifying potassium channel)
What neurotransmitter has a tendency to open calcium channels?
norepinephrine
What mineral is important for fractal events?
calcium
Too much calcium inside a cell can eventually lead to cell death. What is this called? (hint: this is NOT apoptosis)
excitotoxicity
(toxic actions of excitatory neurotransmitters that ultimately leads to the loss of neuronal function and cell death)
Digitalis (a medicine used to treat certain heart conditions) increases _____ in the heart.
calcium
An excessive amount of digitalis can cause too much calcium in _____, which can lead to cell death.
myocytes
An M2 receptor coupled with a Gi (inhibitory G protein) does what to a cell?
hyperpolarizes it
Phospholipase generates IP3 which opens up the smooth endoplasmic reticulum to release calcium into cells. This increases what type of force?
contractile force
The a1 (alpha adrenergic) receptor will _____ contractile force because it couples with ___
increase; Gq (excitatory)
In the sympathetic nervous system, what is the post ganglionic neurotransmitter?
norepinephrine
What are the major players in the sympathetic nervous system? What aren’t major players?
major players = a1, B1, B2
not major players = a2 & B3
Two muscarinic receptors do most of the heavy lifting in the parasympathetic nervous system, what are they?
M2 & M3
What muscarinic receptor subtype is predominately on the heart?
M2
Which receptors act via a Gi type receptor, which causes a decrease in cAMP in the cell, inhibition of voltage-gated Ca2+ channels, and increasing efflux of K+, in general, leading to inhibitory-type effects?
M2 muscarinic receptors
______ is the natural agonist of muscarinic and nicotinic receptors.
acetylcholine
What muscarinic subtype is on the heart?
Gi (inhibitory)
What receptor is Gq-coupled and mediates an increase in intracellular calcium, which typically causes constriction of smooth muscle, such as that observed during bronchoconstriction?
M3 receptor (Gq = excitatory)
What receptor is also known as the cholinergic/acetylcholine receptor?
M3 (muscarinic 3 receptor)
What muscles in the iris cause constriction of the pupil known as myosis?
circular muscle of iris (aka iris sphincter muscle)
Stimulation of lacrimal glands that lubricate the eye’s surface causes what 4 things to increase?
- increased salivary glands
- increased bronchoconstriction
- increased stimulation of intestinal track
- increased stimulation on bladder/bowels
B2 adrenergic stimulation increases several things, what are they?
- inc. air in lungs
- inc. blood (to run faster)
- inc. energy (from release of glucose)
- inc. adrenal gland stimulation
Activation of the parasympathetic nervous system increases what? (Hint: 5 things)
- salivary glands
- bronchoconstriction
- stimulation of intestinal track
- stimulation of bladder/bowels
- iris muscle contraction
What cranial nerves are considered “parasympathetic”?
CN III (oculomotor)
CN VII (facial)
CN IX (glossopharyngeal)
CN X (vagus)
The sympathetic division of the autonomic nervous system can also be called what?
thoracolumbar
(thoracic + lumbar intermediate lateral column)
The parasympathetic division of the autonomic nervous system can also be called what?
craniosacral
(brain/sacral part of spinal cord)
What nervous system is considered voluntary?
somatic nervous system
Motor neurons release what neurotransmitter in the neuromuscular junction?
acetylcholine
What type of receptor for acetylcholine is on skeletal muscles?
nicotinic
What nervous system(s) uses acetylcholine as a preganglionic neurotransmitter?
sympathetic + parasympathetic (PREganglionic)
What receptor increases antibodies that develop against receptors in myasthenia gravis?
acetylcholine
(in myasthenia gravis, the immune system blocks receptors for acetylcholine = fewer nerve signals)
Acetylcholine pairs to what effector organ via motor neurons?
skeletal muscle
Acetylcholine and norepinephrine pairs to what effector organ via preganglion (short)?
smooth muscle (e.g. in a blood vessel)
Acetylcholine, epinephrine (80%), and norepinephrine (20%) pairs to what effector organ via the adrenal medulla?
glands
Acetylcholine pairs to what effector organ via postganglion (long)?
cardiac muscle
Sympathetic nerves go a short distance to the paravertebral ganglion, what is this synapse called?
nicotinic cholinergic synapse
What two things is acetylcholine made out of?
choline + acetate
The half life of AChE is measured in ______.
milliseconds (short lived)
Which neuron has a recycling stage?
adrenergic neuron
What type of cation is calcium?
divalent cation
ACh release is triggered by _____ influx through specific presynaptic ____ channels.
calcium; Ca2+
What depolarizes an action potential?
large influx of sodium ions
Where does ‘action’ occur in the lifecycle of catecholamines?
in the nerve terminal
Cholinergic parasympathetic innervation of glands act on M3 receptors and couples with _____ to release calcium.
phospholipase c
If norepinephrine had been discovered first it would have been epinephrine, and epinephrine would have been ______.
methyl epinephrine
A catechol is made up of an aromatic ring with 2 _____.
hydroxyls
What are two catecholamines and what is also a catecholamine but doesn’t have a beta hydroxyl group?
norepinephrine + epinephrine
no beta hydroxyl group = dopamine
3, 4-dihydroxyphenylalanine is called also what?
L-DOPA
Catecholamine synthesis starts with ______.
tyrosine
What is the rate limiting step in catecholamine synthesis?
tyrosine hydroxylase
What receptor is considered the “traitor” of the sympathetic nervous system according to Dr. Speth?
a2 receptor (alpha 2 adrenergic)
To prevent the body from being flooded with dopamine (and epinephrine/norepinephrine) you want to inhibit ______ _______ peripherally so the only place you’re getting an increase of dopamine is the brain.
dopamine carboxylase
What is the precursor for epinephrine and norepinephrine?
dopamine
How does dopamine get taken up into a vessel?
via vascular monoamine transporter (VMAT)
What lives inside the noradrenergic vesicle?
dopamine beta hydroxylase
How is norepinephrine formed?
from dopamine inside the neurotransmitter vesicle
Phenylethanolamine-N-methyltransferase is found where?
outside the cytoplasm
How is epinephrine made?
- norepinephrine has to go outside of vesicle (but stays in cytoplasm)
- gets converted to epinephrine by phenylethanolamine-N-methyltransferase
- epinephrine then goes back into synaptic vesicle
How do you preserve dopamine in Parkinson’s disease?
use an MOA inhibitor
(keeps dopamine on receptor for longer)
How can norepinephrine come back and stimulate the presynaptic a2 receptor and postsynaptic receptors resulting in a negative feedback loop?
by having the inhibitory as (alpha 2 adrenergic) receptor on the presynaptic nerve terminal
COMT (catechol-o-methyltransferase) is involved in the inactivation of the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. What causes the inactivation?
COMT puts methyl group on catechol ring
What do adrenergic receptors do?
mediate the effects of norepinephrine and epinephrine
Name 3 adrenergic receptors:
a1, a2, B
Name 2 cholinergic receptors:
nicotinic and muscarinic
What receptor stimulates sympathetic (adrenergic) response and increases the rate of contraction of the heart?
B1 receptor
What receptor stimulates sympathetic (adrenergic) response and increases the force of contraction of the heart?
B1 receptor
What receptor stimulates sympathetic (adrenergic) response and vasoconstrics most arteries?
a1 (a2) receptor
What receptor stimulates sympathetic (adrenergic) response and vasodilates skeletal muscles?
B2 receptor
What receptor stimulates sympathetic (adrenergic) response and vasoconstrics veins?
a2 (a1) receptor
What receptor stimulates parasympathetic (cholinergic) response and decreases the rate of contraction of the heart?
M2 receptor
What receptor stimulates parasympathetic (cholinergic) response and decreases the force of contraction of the heart?
M2 receptor
T/F there is very little innervation of blood vessels by the parasympathetic nervous system:
TRUE
What agent enhances cholinergic neurotransmission by releasing ACh from vesicles?
black widow spider venom (latrotoxins)
What agent(s) enhances cholinergic neurotransmission by inhibiting ACh hydrolysis (AChE inhibitors)?
- physostigmine (crosses BBB)
- neostigmine (doesn’t cross BBB)
What agent(s) enhances cholinergic neurotransmission via a nicotinic receptor agonist?
- nicotine
- varenicline (selective nicotinic agonist to help people stop smoking)
What agent(s) enhances cholinergic neurotransmission via a muscarinic receptor agonist?
- methacholine
- bethanechol (used for urinary problems)
What agent inhibits cholinergic neurotransmission by inhibition of high-affinity choline uptake?
hemicholinium-3
(a pharmacologic tool that decreases ACh)
What agent inhibits cholinergic neurotransmission by inhibition of exocytosis?
botulinum toxin = botox
(“worst poison ever” -Dr. Speth)
What agent inhibits cholinergic neurotransmission by inhibition of vesicular ACh transport (VAChT)?
vesamicol
What agent(s) inhibits cholinergic neurotransmission via ganglionic blockers?
- hexamethonium
- mecamylamine (used as antihypertensive med, affects sympathetic and parasympathetic ns)
What agent inhibits cholinergic neurotransmission via nicotinic receptor blockers?
D-Tubocurarine
(South American Indian poison derived from a plant used on tip of arrow to kill animals)
What agent inhibits cholinergic neurotransmission via muscarinic receptor blockers?
atropine
(soldiers would keep atropine on them incase they got exposed to organic phosphate cholinesterase inhibitors)
atropine in greek mythology was to “cut the stream of life”
Atropine is derived from what plant?
atropa belladonna
(= beautiful woman in Italian)
used in renaissance to give women big beautiful eyes to attract rich men
“Mad as a hatter” refers to an excess dosage of which drug?
atropine
“Blind as a bat” refers to which condition?
cycloplegia
(paralysis of ciliary muscle, dilation of pupils, accommodation paralysis)
The antimuscarinic affects you get from atropine are attributed to what?
l-isomer
What agent(s) enhances adrenergic neurotransmission by releasing NE from cytoplasmic stores?
- tyramine (stimulates adrenergic receptors)
- amphetamine (psychostimulant)
What agent(s) enhances adrenergic neurotransmission by a-Adrenergic receptor agonists?
- phenylephrine (a1, selective)
- clonidine (a2)
- zylizine (sedative properties, decreases BP by inhibiting NE release)
What agent(s) enhances adrenergic neurotransmission by a-Adrenergic receptor agonists?
- isoproterenol (B, nonselective)
- dobutamine (B1)
- terbutaline (B2) (albuterol = B2 agonist)
What agent(s) enhances adrenergic neurotransmission by inhibiting NE catabolism?
- pargyline (inhibits MOA)
- tolcapone (inhibits COMT)
What agent inhibits adrenergic neurotransmission by inhibiting NE biosynthesis?
a-Methyltyrosine (inhibits tyrosine hydroxylase)
(not used very much anymore, was used for BP)
What agent inhibits adrenergic neurotransmission by inhibiting NE release?
guanethidine (inhibits release of NE from neurons)
What agent inhibits adrenergic neurotransmission by inhibiting vesicular NE transport?
reserpine (natural product from browalia plant)
(inhibits NE uptake in vesicles)
What agent inhibits adrenergic neurotransmission by inhibiting uptake1?
cocaine
(inhibits reuptake of catecholamine neurotransmitters, especially dopamine)
What agent(s) inhibits adrenergic neurotransmission via a-Adrenergic receptor antagonists?
- phentolamine (a1 and a2)
- prazosin (a1) (don’t want to inhibit a2 if you’re trying to block NE transmission)
- yohimbine (a2) (enhances sexual arousal)
What agent inhibits adrenergic neurotransmission via B-Adrenergic receptor antagonists?
propranolol (nonselective)
(classic beta adrenergic blocker, B1 + B2)
(metoprolol acts on B1 and is a better B1 antagonist)
Name 2 medications that are selective for muscarinic ACh receptors:
- pilocarpine (glaucoma medication)
- cevimeline (saliva production stimulator)
