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Pharmacodynamics > Speth Exam 2 > Flashcards

Speth Exam 2 Flashcards

1
Q

Which receptor can modulate monoamine neurotransmission and, in particular, the dopamine system?

A

TAAR1

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2
Q

What must be considered an essential element of any comprehensive model of psychostimulant action?

A

TAAR1

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3
Q

What place do B1 adrenergic receptors favorite?

A

the heart

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4
Q

When heart rate is increased, what neurotransmitters is the heart responding to?

A

norepinephrine or epinephrine (increases HR)

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5
Q

What neurotransmitter decreases heart rate?

A

acetylcholine

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6
Q

What nervous system is the fundamental of pharmacology?

A

the autonomic nervous system

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7
Q

What neurotransmitter controls the sympathetic nervous system?

A

norepinephrine

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8
Q

What neurotransmitter controls the parasympathetic nervous system?

A

acetylcholine

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9
Q

Epinephrine is a hormone that is released from where?

A

the adrenal gland

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10
Q

Gαi (an inhibitory G protein) inhibits ____, which decreases _____.

A

adenylyl cyclase; cAMP

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11
Q

Gαi (an inhibitory G protein) acts on what channel?

A

GIRK (G protein inward rectifying potassium channel)

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12
Q

What neurotransmitter has a tendency to open calcium channels?

A

norepinephrine

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13
Q

What mineral is important for fractal events?

A

calcium

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14
Q

Too much calcium inside a cell can eventually lead to cell death. What is this called? (hint: this is NOT apoptosis)

A

excitotoxicity

(toxic actions of excitatory neurotransmitters that ultimately leads to the loss of neuronal function and cell death)

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15
Q

Digitalis (a medicine used to treat certain heart conditions) increases _____ in the heart.

A

calcium

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16
Q

An excessive amount of digitalis can cause too much calcium in _____, which can lead to cell death.

A

myocytes

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17
Q

An M2 receptor coupled with a Gi (inhibitory G protein) does what to a cell?

A

hyperpolarizes it

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18
Q

Phospholipase generates IP3 which opens up the smooth endoplasmic reticulum to release calcium into cells. This increases what type of force?

A

contractile force

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19
Q

The a1 (alpha adrenergic) receptor will _____ contractile force because it couples with ___

A

increase; Gq (excitatory)

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20
Q

In the sympathetic nervous system, what is the post ganglionic neurotransmitter?

A

norepinephrine

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21
Q

What are the major players in the sympathetic nervous system? What aren’t major players?

A

major players = a1, B1, B2
not major players = a2 & B3

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22
Q

Two muscarinic receptors do most of the heavy lifting in the parasympathetic nervous system, what are they?

A

M2 & M3

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23
Q

What muscarinic receptor subtype is predominately on the heart?

A

M2

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24
Q

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?

A

M2 muscarinic receptors

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25
Q

______ is the natural agonist of muscarinic and nicotinic receptors.

A

acetylcholine

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26
Q

What muscarinic subtype is on the heart?

A

Gi (inhibitory)

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27
Q

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?

A

M3 receptor (Gq = excitatory)

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28
Q

What receptor is also known as the cholinergic/acetylcholine receptor?

A

M3 (muscarinic 3 receptor)

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29
Q

What muscles in the iris cause constriction of the pupil known as myosis?

A

circular muscle of iris (aka iris sphincter muscle)

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30
Q

Stimulation of lacrimal glands that lubricate the eye’s surface causes what 4 things to increase?

A
  • increased salivary glands
  • increased bronchoconstriction
  • increased stimulation of intestinal track
  • increased stimulation on bladder/bowels
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31
Q

B2 adrenergic stimulation increases several things, what are they?

A
  • inc. air in lungs
  • inc. blood (to run faster)
  • inc. energy (from release of glucose)
  • inc. adrenal gland stimulation
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32
Q

Activation of the parasympathetic nervous system increases what? (Hint: 5 things)

A
  • salivary glands
  • bronchoconstriction
  • stimulation of intestinal track
  • stimulation of bladder/bowels
  • iris muscle contraction
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33
Q

What cranial nerves are considered “parasympathetic”?

A

CN III (oculomotor)
CN VII (facial)
CN IX (glossopharyngeal)
CN X (vagus)

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34
Q

The sympathetic division of the autonomic nervous system can also be called what?

A

thoracolumbar

(thoracic + lumbar intermediate lateral column)

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35
Q

The parasympathetic division of the autonomic nervous system can also be called what?

A

craniosacral

(brain/sacral part of spinal cord)

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36
Q

What nervous system is considered voluntary?

A

somatic nervous system

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37
Q

Motor neurons release what neurotransmitter in the neuromuscular junction?

A

acetylcholine

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38
Q

What type of receptor for acetylcholine is on skeletal muscles?

A

nicotinic

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39
Q

What nervous system(s) uses acetylcholine as a preganglionic neurotransmitter?

A

sympathetic + parasympathetic (PREganglionic)

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40
Q

What receptor increases antibodies that develop against receptors in myasthenia gravis?

A

acetylcholine

(in myasthenia gravis, the immune system blocks receptors for acetylcholine = fewer nerve signals)

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41
Q

Acetylcholine pairs to what effector organ via motor neurons?

A

skeletal muscle

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42
Q

Acetylcholine and norepinephrine pairs to what effector organ via preganglion (short)?

A

smooth muscle (e.g. in a blood vessel)

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43
Q

Acetylcholine, epinephrine (80%), and norepinephrine (20%) pairs to what effector organ via the adrenal medulla?

A

glands

44
Q

Acetylcholine pairs to what effector organ via postganglion (long)?

A

cardiac muscle

45
Q

Sympathetic nerves go a short distance to the paravertebral ganglion, what is this synapse called?

A

nicotinic cholinergic synapse

46
Q

What two things is acetylcholine made out of?

A

choline + acetate

47
Q

The half life of AChE is measured in ______.

A

milliseconds (short lived)

48
Q

Which neuron has a recycling stage?

A

adrenergic neuron

49
Q

What type of cation is calcium?

A

divalent cation

50
Q

ACh release is triggered by _____ influx through specific presynaptic ____ channels.

A

calcium; Ca2+

51
Q

What depolarizes an action potential?

A

large influx of sodium ions

52
Q

Where does ‘action’ occur in the lifecycle of catecholamines?

A

in the nerve terminal

53
Q

Cholinergic parasympathetic innervation of glands act on M3 receptors and couples with _____ to release calcium.

A

phospholipase c

54
Q

If norepinephrine had been discovered first it would have been epinephrine, and epinephrine would have been ______.

A

methyl epinephrine

55
Q

A catechol is made up of an aromatic ring with 2 _____.

A

hydroxyls

56
Q

What are two catecholamines and what is also a catecholamine but doesn’t have a beta hydroxyl group?

A

norepinephrine + epinephrine
no beta hydroxyl group = dopamine

57
Q

3, 4-dihydroxyphenylalanine is called also what?

A

L-DOPA

58
Q

Catecholamine synthesis starts with ______.

A

tyrosine

59
Q

What is the rate limiting step in catecholamine synthesis?

A

tyrosine hydroxylase

60
Q

What receptor is considered the “traitor” of the sympathetic nervous system according to Dr. Speth?

A

a2 receptor (alpha 2 adrenergic)

61
Q

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.

A

dopamine carboxylase

62
Q

What is the precursor for epinephrine and norepinephrine?

A

dopamine

63
Q

How does dopamine get taken up into a vessel?

A

via vascular monoamine transporter (VMAT)

64
Q

What lives inside the noradrenergic vesicle?

A

dopamine beta hydroxylase

65
Q

How is norepinephrine formed?

A

from dopamine inside the neurotransmitter vesicle

66
Q

Phenylethanolamine-N-methyltransferase is found where?

A

outside the cytoplasm

67
Q

How is epinephrine made?

A
  • 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
68
Q

How do you preserve dopamine in Parkinson’s disease?

A

use an MOA inhibitor
(keeps dopamine on receptor for longer)

69
Q

How can norepinephrine come back and stimulate the presynaptic a2 receptor and postsynaptic receptors resulting in a negative feedback loop?

A

by having the inhibitory as (alpha 2 adrenergic) receptor on the presynaptic nerve terminal

70
Q

COMT (catechol-o-methyltransferase) is involved in the inactivation of the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. What causes the inactivation?

A

COMT puts methyl group on catechol ring

71
Q

What do adrenergic receptors do?

A

mediate the effects of norepinephrine and epinephrine

72
Q

Name 3 adrenergic receptors:

A

a1, a2, B

73
Q

Name 2 cholinergic receptors:

A

nicotinic and muscarinic

74
Q

What receptor stimulates sympathetic (adrenergic) response and increases the rate of contraction of the heart?

A

B1 receptor

75
Q

What receptor stimulates sympathetic (adrenergic) response and increases the force of contraction of the heart?

A

B1 receptor

76
Q

What receptor stimulates sympathetic (adrenergic) response and vasoconstrics most arteries?

A

a1 (a2) receptor

77
Q

What receptor stimulates sympathetic (adrenergic) response and vasodilates skeletal muscles?

A

B2 receptor

78
Q

What receptor stimulates sympathetic (adrenergic) response and vasoconstrics veins?

A

a2 (a1) receptor

79
Q

What receptor stimulates parasympathetic (cholinergic) response and decreases the rate of contraction of the heart?

A

M2 receptor

80
Q

What receptor stimulates parasympathetic (cholinergic) response and decreases the force of contraction of the heart?

A

M2 receptor

81
Q

T/F there is very little innervation of blood vessels by the parasympathetic nervous system:

A

TRUE

82
Q

What agent enhances cholinergic neurotransmission by releasing ACh from vesicles?

A

black widow spider venom (latrotoxins)

83
Q

What agent(s) enhances cholinergic neurotransmission by inhibiting ACh hydrolysis (AChE inhibitors)?

A
  • physostigmine (crosses BBB)
  • neostigmine (doesn’t cross BBB)
84
Q

What agent(s) enhances cholinergic neurotransmission via a nicotinic receptor agonist?

A
  • nicotine
  • varenicline (selective nicotinic agonist to help people stop smoking)
85
Q

What agent(s) enhances cholinergic neurotransmission via a muscarinic receptor agonist?

A
  • methacholine
  • bethanechol (used for urinary problems)
86
Q

What agent inhibits cholinergic neurotransmission by inhibition of high-affinity choline uptake?

A

hemicholinium-3
(a pharmacologic tool that decreases ACh)

87
Q

What agent inhibits cholinergic neurotransmission by inhibition of exocytosis?

A

botulinum toxin = botox
(“worst poison ever” -Dr. Speth)

88
Q

What agent inhibits cholinergic neurotransmission by inhibition of vesicular ACh transport (VAChT)?

A

vesamicol

89
Q

What agent(s) inhibits cholinergic neurotransmission via ganglionic blockers?

A
  • hexamethonium
  • mecamylamine (used as antihypertensive med, affects sympathetic and parasympathetic ns)
90
Q

What agent inhibits cholinergic neurotransmission via nicotinic receptor blockers?

A

D-Tubocurarine
(South American Indian poison derived from a plant used on tip of arrow to kill animals)

91
Q

What agent inhibits cholinergic neurotransmission via muscarinic receptor blockers?

A

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”

92
Q

Atropine is derived from what plant?

A

atropa belladonna
(= beautiful woman in Italian)

used in renaissance to give women big beautiful eyes to attract rich men

93
Q

“Mad as a hatter” refers to an excess dosage of which drug?

A

atropine

94
Q

“Blind as a bat” refers to which condition?

A

cycloplegia
(paralysis of ciliary muscle, dilation of pupils, accommodation paralysis)

95
Q

The antimuscarinic affects you get from atropine are attributed to what?

A

l-isomer

96
Q

What agent(s) enhances adrenergic neurotransmission by releasing NE from cytoplasmic stores?

A
  • tyramine (stimulates adrenergic receptors)
  • amphetamine (psychostimulant)
97
Q

What agent(s) enhances adrenergic neurotransmission by a-Adrenergic receptor agonists?

A
  • phenylephrine (a1, selective)
  • clonidine (a2)
  • zylizine (sedative properties, decreases BP by inhibiting NE release)
98
Q

What agent(s) enhances adrenergic neurotransmission by a-Adrenergic receptor agonists?

A
  • isoproterenol (B, nonselective)
  • dobutamine (B1)
  • terbutaline (B2) (albuterol = B2 agonist)
99
Q

What agent(s) enhances adrenergic neurotransmission by inhibiting NE catabolism?

A
  • pargyline (inhibits MOA)
  • tolcapone (inhibits COMT)
100
Q

What agent inhibits adrenergic neurotransmission by inhibiting NE biosynthesis?

A

a-Methyltyrosine (inhibits tyrosine hydroxylase)
(not used very much anymore, was used for BP)

101
Q

What agent inhibits adrenergic neurotransmission by inhibiting NE release?

A

guanethidine (inhibits release of NE from neurons)

102
Q

What agent inhibits adrenergic neurotransmission by inhibiting vesicular NE transport?

A

reserpine (natural product from browalia plant)
(inhibits NE uptake in vesicles)

103
Q

What agent inhibits adrenergic neurotransmission by inhibiting uptake1?

A

cocaine
(inhibits reuptake of catecholamine neurotransmitters, especially dopamine)

104
Q

What agent(s) inhibits adrenergic neurotransmission via a-Adrenergic receptor antagonists?

A
  • 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)
105
Q

What agent inhibits adrenergic neurotransmission via B-Adrenergic receptor antagonists?

A

propranolol (nonselective)
(classic beta adrenergic blocker, B1 + B2)

(metoprolol acts on B1 and is a better B1 antagonist)

106
Q

Name 2 medications that are selective for muscarinic ACh receptors:

A
  • pilocarpine (glaucoma medication)
  • cevimeline (saliva production stimulator)

Pharmacodynamics (4 decks)

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