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[MT 6314] Pharmacology & Toxicology > Introduction to CNS Drugs > Flashcards

Introduction to CNS Drugs Flashcards

1
Q

T/F: Nearly all drugs with CNS effects act on specific receptors that modulate transmission.

A

T

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2
Q

T/F: CNS drugs are among the most important tools for studying all aspects of CNS physiology.

A

T

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3
Q

T/F: Unraveling the actions of drugs with known clinical efficacy led to the hypotheses regarding the mechanism of disease.

A

T

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4
Q

Organization of the CNS

The CNS is composed of the ____ and _____ and is responsible for integrating sensory information and generating motor output and other behaviors needed to successfully interact with the environment and enhance species survival.

A

brain and spinal cord

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5
Q

Organization of the CNS

The human brain contains about 100 billion interconnected neurons surrounded by various supporting ________.

A

glial cells

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6
Q

Throughout the CNS, neurons are either clustered into groups called ______ or are present in layered structures such as the _________ or _________.

A

nuclei; cerebellum or hippocampus

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7
Q

Organization of the CNS

Electrically excitable cells that process and transmit information via an electrochemical process.

A

Neurons

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8
Q

The typical neuron, however, possesses a cell body (or soma) and specialized processes called _________ and _______

A

dendrites and axons

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9
Q

Organization of the CNS : Neurons

Form highly branched complex dendritic “trees,” receive and integrate the input from other neurons and conduct this information to the cell body.

A

Dendrites

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10
Q

Organization of the CNS : Neurons

Carries the output signal of a neuron from the cell body

A

Axon

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11
Q

T/F: Neurons have hundreds of dendrites but generally have only one axon, although axons may branch distally to contact multiple targets

A

T

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12
Q

Organization of the CNS : Neurons

Makes contact with other neurons at specialized junctions (synapses)

A

Axon Terminal

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13
Q

Organization of the CNS : Neurons

Where neurotransmitter chemicals are released that interact with receptors or other neurons

A

Synapses

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14
Q

Organization of the CNS : Neurons

Receives the synaptic responses from the dendritic tree

A

Soma

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15
Q

Organization of the CNS:

Large number of non-neuronal support cells, called glia, that perform a variety of essential functions in the CNS.

A

Neuroglia

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16
Q

T/F: These synaptic responses are integrated at the axon initial segment, which has a high concentration of voltage-gated potassium channels.

A

F; sodium channels

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17
Q

Organization of the CNS : Neuroglia

Most abundant cell in the brain and play homeostatic support roles, including providing metabolic nutrients to neurons and maintaining extracellular ion concentrations

Involved in the removal and recycling of neurotransmitters after release

A

Astrocytes

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18
Q

Organization of the CNS : Neuroglia

Cells that wrap around the axons of projection neurons in the CNS forming myelin sheath

A

Oligodendrocytes

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19
Q

Organization of the CNS : Neuroglia

Specialized macrophages derived from the bone marrow that settle in the CNS and are the major immune defense system in the brain

A

Microglia

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20
Q

Organization of the CNS

A protective functional separation of the
circulating blood from the extracellular fluid of the CNS that limits the penetration of substances, including drugs.

A

Blood-Brain Barrier

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21
Q

Ion Channels & Neurotransmitter Receptors:

Respond to changes in the membrane potential of the cell

A

Voltage-gated channels

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22
Q

Sodium Channel

Blocks channel from outside

A

Tetrodotoxin (TTX)

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23
Q

Sodium Channel

Slows inactivation, shifts activation

A

Batrachotoxoin (BTX)

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24
Q

Potassium channels

Blocks “small Ca-activated” K channel

A

Apamin

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25
Q

Potassium channels

Blocks “big Ca-activated” K channel

A

Charybdotoxin

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26
Q

Calcium channels

Blocks N-type channel

A

Omega conotoxin (ω-CTX-GVIA)

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27
Q

Calcium channels

Blocks P-type channel

A

Agatoxin (ω-AGAIVA)

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28
Q

Ligand-gated channel: Nicotinic ACh Receptor

Irreversible antagonist

A

α-Bungarotoxin

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28
Q

Ligand-gated channel: GABAA Receptor

Blocks channel

A

Picrotoxin

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29
Q

Ligand-gated channel: Glycine receptor

Competitive antagonist

A

Strychnine

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30
Q

Ligand-gated channel: AMPA receptor

Blocks channel

A

Philanthotoxin

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31
Q

Ion Channel

Apamin, Charybdotoxin

A

Voltage-gated, Potassium

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31
Q

Ion Channel

Tetrodotoxin (TTX), Batrachotoxoin (BTX)

A

Voltage-gated, Sodium

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32
Q

Ion Channel

Omega conotoxin (ω-CTX-GVIA), Agatoxin (ω-AGAIVA)

A

Voltage-gated, Calcium

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33
Q

Ion Channel

α-Bungarotoxin

A

Ligand-gated, Nicotinic Ach receptor

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34
Q

Ion Channel

Picrotoxin

A

Ligand-gated, GABAA receptor

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35
Q

Ion Channel

Strychnine

A

Ligand-gated, Glycine

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36
Q

Ion Channel

Philanthotoxin

A

Ligand-gated, AMPA

37
Q

The nerve cells contain two types of channels defined on the basis of the mechanism controlling their gating (opening and closing) :

A
  1. Voltage-gated channels
  2. Ligand-gated channels
37
Q

Ion Channels

Concentrated on the initial segment of the axons in
nerve cells.

A

Voltage-gated Ion Channels

37
Q

Ion Channels

Responsible for fast action potentials.

A

Voltage-gated Ion Channels

38
Q

Ion Channels

Responsible for action potential propagation

A

Sodium Channels

39
Q

Ion Channels

Cell bodies and dendrites also have voltage-sensitive ion channels for potassium and calcium.

A

Voltage-gated Ion Channels

40
Q

Ion Channels

Responsible for fast synaptic transmission typical of hierarchical pathways in the CNS

A

Ligand-gated channels

41
Q

Neurotransmitter Receptor:

These receptors consist of multiple subunits, and binding of the neurotransmitter ligand directly opens the channel

A

Ligand-gated Ion Channels or Ionotropic Receptors

42
Q

2 Classes of Neurotransmitter Receptor

A
  1. Ligand-gated Ion Channels or Ionotropic Receptors
  2. Metabotropic Receptors
42
Q

Neurotransmitter Receptor

Binding does not result in the direct gating of a channel

A

Metabotropic Receptors

43
Q

Neurotransmitter Receptor

Chemically-gated

A

Ligand-gated Ion Channels or Ionotropic Receptors

43
Q

Neurotransmitter Receptor

Respond to chemical neurotransmitters (NTAs) that bind to receptor subunits of the channel.

A

Ligand-gated Ion Channels or Ionotropic Receptors

44
Q

Neurotransmitter Receptor

Seven transmembrane G protein-coupled receptors (GPCRs)

A

Metabotropic Receptors

45
Q

Neurotransmitter Receptor

Binding engages the G-protein that results in the production of second messengers that modulate the voltage-gated channels.

A

Metabotropic Receptors

45
Q

In neurons, activation of metabotropic neurotransmitter receptors often leads to the modulation of voltage-gated channels. These interactions can occur entirely within the plane of the membrane are referred to as _______________ pathways

A

membrane-delimited

46
Q

Membrane-Delimited Pathways

A
  1. Potassium channels
  2. Calcium channels
47
Q

T/F: An important consequence of the involvement of G proteins in receptor signaling is that, in contrast to the brief effect of ionotropic receptors, the effects of metabotropic receptor activation can last tens of seconds to minutes.

47
Q

predominate in the diffuse neuronal systems in the CNS

A

Metabotropic receptors

48
Q

Metabotropic receptors can also modulate voltage-gated channels less directly by the generation of ______________

A

diffusible second messengers

49
Q

The Synapse and Synaptic Potentials

Types of receptor channel coupling in ligand-gated ion channels activation and inactivation

A
  1. A receptor that acts directly on the channel protein.
  2. A receptor that is coupled to the ion channel through a G protein.
  3. A receptor coupled to a G protein that modulates the formation of diffusible second messengers.
49
Q

The Synapse and Synaptic Potentials

Diffusible second messengers

A

a. Cyclic adenosine monophosphate (cAMP)
b. Inositol trisphosphate (IP3)
c. Diacylglycerol (DAG)

50
Q

Synaptic Potentials:

When an excitatory pathways is stimulated, a small depolarization or ________________________ is recorded. This potential is due to the excitatory transmitter acting on ionotropic receptor, causing an increase in cation permeability

A

Excitatory Postsynaptic Potentials (EPSPs)

50
Q

Role of the Ion current carried by the Channel

Depolarizing potential change

A

Excitatory Postsynaptic Potentials (EPSPs)

51
Q

Role of the Ion current carried by the Channel (EPSP)

Generated by

A
  1. Opening of sodium or calcium channels
  2. Closing of potassium channels in some synapses
51
Q

EPSPs

T/F: As additional excitatory synapses are activated, there is a graded summation of the EPSPs to increase the size of the depolarization.

52
Q

When an inhibitory pathway is stimulated, the postsynaptic membrane is hyperpolarized owing to the selective opening of chloride channels, producing an ___________________

A

Inhibitory Postsynaptic Potential (IPSP)

53
Q

EPSPs

__ Na+, __ K+, __ Ca2+

A

↑ Na+, ↓ K+, ↑ Ca2+

54
Q

Role of the Ion current carried by the Channel

Hyperpolarizing potential change

A

Inhibitory Postsynaptic Potentials (IPSPs)

55
Q

IPSPs

Generated by

A

Opening of potassium or chloride channels.

56
Q

IPSPs

__ K+, __ Cl- postsynaptic, __ Ca2+ presynaptic

A

↑ K+, ↑ Cl- postsynaptic, ↓ Ca2+ presynaptic

57
Q

Sites of drug action:

Steps at which drugs can alter synaptic transmission

A
  1. Action potential in presynaptic fiber
  2. Synthesis of transmitter
  3. Storage
  4. Metabolism
  5. Release
  6. Reuptake into the nerve ending or uptake into a glial cell
  7. Degradation
  8. Receptor for the transmitter
  9. Receptor-induced increase / decrease ionic conductance
  10. Retrogade signaling
57
Q

Sites and Mechanisms of Drug Action

T/F Some drugs exert their effect through indirect interactions with molecular components of ion channels on axons.

A

F; direct interactions

57
Q

Sites and Mechanisms of Drug Action

drugs exert their effect through direct interactions

A
  1. Carbamazepine
  2. Phenytoin
  3. Local anesthetics and some drugs used for
    general anesthesia
58
Q

Q
Sites and Mechanisms of Drug Action

Interfere with the action of second messengers

A

Activate or Block

58
Q

Sites of drug action:

T/F: No uptake mechanism has been found for any of the numerous CNS peptides, and it has yet to be demonstrated whether specific enzymatic degradation terminates the action of peptide transmitters

59
Q

Sites and Mechanisms of Drug Action

Most drugs exert their effect mainly at the ____.

59
Q

Sites and Mechanisms of Drug Action

T/F Drugs may act presynaptically to alter synthesis, storage, release, reuptake & metabolism of transmitter chemicals.

60
Q

Sites and Mechanisms of Drug Action

Inhibits synthesis of serotonin

A

Parachlorophenylalanine

61
Q

Sites and Mechanisms of Drug Action

Inhibits storage of catecholamines

62
Q

Sites and Mechanisms of Drug Action

Inhibits release of catecholamines

A

Amphetamine

63
Q

Sites and Mechanisms of Drug Action

Inhibits degradation of acetylcholine

A

Anticholinesterase

64
Q

Sites and Mechanisms of Drug Action

Can be depressed by blockade of transmitter synthesis or storage

A

Presynaptic Drugs

65
Q

Sites and Mechanisms of Drug Action

The transmitter receptor provides the primary site of drug action

A

Postsynaptic Region

66
Q

Cellular Organization of the Brain

Control major sensory and motor functions

A

Hierarchal System

66
Q

Cellular Organization of the Brain

Two types of neuronal system:

A
  1. Hierarchical system
  2. Diffused/Non-specific neuronal system
67
Q

Cellular Organization of the Brain

Contains large myelinated, rapidly conducting fibers; pathways are clearly delineated.

A

Hierarchal System

68
Q

Cellular Organization of the Brain

Excitability of the CNS

A

Hierarchal System

69
Q

Cellular Organization of the Brain

Small Inhibitory Interneurons (Local Circuit Neurons) Transmitters

A

Gamma amino butyric acid (GABA), Glycine

69
Q

Cellular Organization of the Brain

Major Excitatory Transmitters : Aspartate, Glutamate

A

Hierarchal System

70
Q

Cellular Organization of the Brain

Broadly distributed, with single cells frequently sending processes to many different parts of the brain-tangential

A

Diffused / Non-Specific Neuronal System

71
Q

Diffused / Non-Specific Neuronal System

Periodic enlargements that contain transmitter vesicles

A

Varicosities

71
Q

Diffused / Non-Specific Neuronal System

Located in the axons

A

Varicosities

72
Q

Diffused / Non-Specific Neuronal System (Transmitters)

NE, dopamine and serotonin

A

Noradrenergic Amines

72
Q

Diffused / Non-Specific Neuronal System (Transmitters)

Act on metabotropic receptors

73
Q

Diffused / Non-Specific Neuronal System

Noradrenergic cell bodies are found primarily in a compact cell group _________.

A

locus caeruleus

74
Q

Diffused / Non-Specific Neuronal System

found in the midline raphe nuclei in the forebrain and send extraordinarily divergent projections to nearly all regions of the CNS

A

Serotonin neurons

75
Q

Cellular Organization of the Brain

Other diffusely projecting neurotransmitter pathways include the histamine and orexin systems

A

Diffused / Non-Specific Neuronal System

[MT 6314] Pharmacology & Toxicology (20 decks)

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