Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PT 1 > L12 Synaptic Transmission: Targets of Drug Action > Flashcards

L12 Synaptic Transmission: Targets of Drug Action Flashcards

1
Q

What are the 5 major steps in neurotransmission?

A
  1. NT synthesis
  2. Vesicular storage
  3. Synaptic release
  4. Binding to receptor
  5. Termination of transmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the process of neurotransmitter synthesis.

A

A precursor is transported into the cell; this is acted on by various enzymes, including the rate-limiting enzyme.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the process of vesicular storage.

A

Synthesized NT (or a precursor) is transported into various vesicles, which protects the NT from degradative enzymes and allows for transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

True or false - typically, a pre-synaptic cell has low free NT in the cytosol.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the process of synaptic release.

A

An action potential is propagated to the nerve terminal. Voltage-gated calcium channels open. This serves as a signal for proteins (SNARES) on the vesicles to fuse with proteins (SNAREs) on the pre-synaptic membrane. The NT is then exocytosed after being docked.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the process of NT binding to its receptor.

A

Released NT can bind to both pre- and post-synaptic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the process of termination of transmission.

A
  1. Re-uptake of the NT out of the cleft
  2. Diffusion out of the synaptic cleft
  3. Metabolic transformation and degradation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why do we avoid targeting transport of NT precursors into the cell with drugs?

A

This can cause a lot of widespread damage/side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which NTs are not stored in vesicles?

A

Gases and some nucleoside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can drugs act on the second step of neurotransmission, vesicular storage?

A

Vesicular transport can be inhibited; this leads to NT degradation in the cytoplasm via degradative enzymes; NT are ultimately depleted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How can drugs act on the third step of neurotransmission, synaptic release?

A
  1. Drugs can interfere with the propagation of the AP at the nerve terminal
  2. Drugs can inhibit fusion of the vesicle with the membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the effect of botulinum toxin on the third step of neurotransmission (synaptic release).

A

Botulinum toxin binds to and cleaves sequences on both SNAREs; the proteins are no longer able to interact. The NT cannot be released.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where does botulinum toxin exert its effects?

A

Cholinergic neuromuscular junctions (leads to skeletal muscle paralysis from loss of ACh release)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Where does tetanus toxin exert its effects?

A

Targets neurons that inhibit motor neurons, resulting in excessive muscle tone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do indirect acting drug work?

A

These drugs facilitate the increase of NT in the synapse indirectly; they do not act on the receptor themselves. Instead, they act on the neuron to stimulate release of the endogenous NT, which then bind to receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the mechanism of action of amphetamine.

A

Amphetamine has an affinity for monoamine reuptake transporters. It is transported through these. The transporter is phosphorylated; vesicular uptake proteins are also inhibited. The transporter is reversed, leading to calcium-independent release of NT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What provides the most selective manipulation of synaptic transmission?

A

Drugs that bind directly to receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Various NT transporters have different ___ and ___, and can transport the same NT.

A

Affinities; location

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Glutamate, an excitatory NT, can be terminated in which ways?

A
  1. Reuptake proteins on the post-synaptic neuron

2. Surrounding glial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Monoamines (5-HT, NE, E) can be terminated in which ways?

A

Transporters on the pre-synaptic neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Choline, a metabolite of ACh, can be terminated in which ways?

A

Transporters on the pre-synaptic neurons after ACh is metabolized by acetylcholinesterase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

GABA, an inhibitory NT, can be terminated in which ways?

A

Pre-synaptic, post-synaptic, and glial cell transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the manipulation of neurotransmitter synthesis by metyrosine.

A

Normally, tyrosine is taken up via an amino acid transporter (co-transported with Na+). It is then converted to DOPA (via tyrosine hydroxylase) and then to dopamine (via DOPA decarboxylase). Metyrosine uses the same transporter as tyrosine; it binds to tyrosine hydroxylase and prevents tyrosine from binding to the enzyme. This depletes dopamine (and also NE production).

24
Q

Describe the manipulation of neurotransmitter synthesis by L-DOPA.

A

L-DOPA is a precursor of dopamine. It can be loaded to increase dopamine in Parkinson’s disease,

25
Q

Why is L-DOPA problematic and how can this be addressed?

A

It can enhance NE neurotransmission in the peripheral ANS and cause adverse effects.; administering carbadopa with L-DOPA allows for L-DOPA in the systemic circulation to be broken down; it will not affect the brain, as it cannot cross the BBB.

26
Q

Describe the manipulation of NT vesicular storage with reserpine.

A

Normally, dopamine is transported into vesicles via VMAT and then transformed to NE by dopamine beta-hydroxylase. Reserpine blocks VMAT, leading to depletion of dopamine by degradative enzymes.

27
Q

Why is use of reserpine problematic?

A

It was used for high blood pressure (depletion of NE) but at high doses, patients would die by suicide (depletion of dopamine).

28
Q

Describe the manipulation of NT release by bretylium.

A

Bretylium inhibits the excitability of the nerve terminal membrane (by activating potassium channels that hyperpolarize the nerve) and the calcium dependent fusion of the synaptic vesicle with the plasma membrane; this reduces NE release.

29
Q

Activation of pre-synaptic adrenergic receptors on nerve terminals influences NT release. Pre-synaptic ___ receptors can inhibit, while pre-synaptic ___ receptors can facilitate NT release.

A

Alpha-adrenergic; beta-adrenergic

30
Q

What is the primary mode of terminating monomaine actions?

31
Q

What does COMT do?

A

Degrades NE and E in the plasma (outside the nerve)

32
Q

What does MAO do?

A

Degrades dopamine and NE in the cell

33
Q

Describe the manipulation of enzyme-mediated degradation in the cytoplasm by monoamine oxidase inhibitors.

A

MAO inhibitors lead to increased catecholamines in the cytoplasm. As NE accumulates, the concentration gradient can reverse and the transporter can also reverse, leading to expulsion of NE into the synapse.

34
Q

What can be problematic when using MAO inhibitors?

A

Tyramine, an amino acid, is metabolized by MAO. Using inhibitors can lead to dangerous levels, which can then enter adrenergic cells and compete with NE for transport into vesicles. This results in even higher cytoplasmic levels and increased release.

35
Q

What does cocaine do to the re-uptake process?

A

It inhibits re-uptake of NE, DA, and 5-HT.

36
Q

What do tri-cyclic antidepressants do to the re-uptake process?

A

Block re-uptake of several monoamines

37
Q

Describe the process of neuropeptide transmission.

A
  1. Synthesis of a pre-pro-peptide
  2. Cleavage via peptidases to produce an active neuropeptide
  3. Storage in a large dense core vesicle and transport to the nerve terminal
  4. Release
  5. Binding of neurotransmitter
  6. Termination of action via cleavage by peptidases
38
Q

What does neuropeptide synthesis require?

A

mRNA within the nucleus

39
Q

Because core vesicles reside farther away from the pre-synaptic membrane than do small synaptic vesicles, what must be done to stimulate peptide release?

A

Increases in intracellular calcium concentration of longer duration

40
Q

What is the major mechanism of drugs targeting peptidergic neurotransmission?

A

Inhibition of peptide receptors

41
Q

Describe the mechanism of action of naloxone.

A

Naloxone is a non-peptide opioid receptor antagonist used to reverse opioid overdose.

42
Q

True or false - neuropeptides are not taken up into the nerve terminal.

43
Q

What is the indication and mechanism of action of metyrosine?

A

I: Hypertension
M: competitive inhibition of tyrosine hydroxylase

44
Q

What is the indication and mechanism of action of reserpine?

A

I: Hypertension
M: inhibition of VMAT uptake of monoamines

45
Q

What is the indication and mechanism of action of bretylium?

A

I: Ventricular arrhythmia
M: Inhibition of action potential generation and calcium dependent synaptic vesicle fusion

46
Q

What is the indication and mechanism of action of cocaine?

A

I: analgesia in surgery
M: blocks monoamine reuptake

47
Q

What is the indication and mechanism of action of amphetamine or ephedrine?

A

I: narcolepsy, ADHD
M: reverse monoamine reuptake transporters

48
Q

What is the indication and mechanism of action of naloxone/naltrexone?

A

I: opioid overdose/depenence
M: non-peptide blockers of opioid receptors in CNS

49
Q

What is the indication and mechanism of action of SSRIs?

A

I: depression/anxiety
M: selective inhibition of serotonin reuptake transporter

50
Q

What is the indication and mechanism of action of ACE inhibitors (eg, lisinopril)?

A

I: hypertension
M: inhibits peptide cleavage of angiotensin I to II

51
Q

What is the indication and mechanism of action of phenylephrine?

A

I: hypotension during surgery
M: direct agonist of adrenergic receptor

52
Q

What is the indication and mechanism of action of MAO inhibitors?

A

I: depression
M: blockade of cytoplasmic metabolism of monoamines

53
Q

What is the indication and mechanism of action of L-DOPA?

A

I: Parkinson’s disease
M: precursor of dopamine, stimulates dopamine production

54
Q

What is the indication and mechanism of action of carbidopa?

A

I: Parkinson’s disease
M: Blocks L-DOPA conversion to dopamine, prevents peripheral adrenergic neurons from producing too much dopamine and NE

55
Q

What is the indication and mechanism of action of tyramine?

A

I: ingested in diet, not therapeutic
M: competes with ME for transport into synaptic vesicle

PT 1 (34 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions