Introduction to CNS Drugs

Question 1

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

Answer 1

T

Question 2

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

Answer 2

T

Question 3

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

Answer 3

T

Question 4

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.

Answer 4

brain and spinal cord

Question 5

Organization of the CNS

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

Answer 5

glial cells

Question 6

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

Answer 6

nuclei; cerebellum or hippocampus

Question 7

Organization of the CNS

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

Answer 7

Neurons

Question 8

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

Answer 8

dendrites and axons

Question 9

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.

Answer 9

Dendrites

Question 10

Organization of the CNS : Neurons

Carries the output signal of a neuron from the cell body

Answer 10

Axon

Question 11

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

Answer 11

T

Question 12

Organization of the CNS : Neurons

Makes contact with other neurons at specialized junctions (synapses)

Answer 12

Axon Terminal

Question 13

Organization of the CNS : Neurons

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

Answer 13

Synapses

Question 14

Organization of the CNS : Neurons

Receives the synaptic responses from the dendritic tree

Answer 14

Soma

Question 15

Organization of the CNS:

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

Answer 15

Neuroglia

Question 16

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

Answer 16

F; sodium channels

Question 17

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

Answer 17

Astrocytes

Question 18

Organization of the CNS : Neuroglia

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

Answer 18

Oligodendrocytes

Question 19

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

Answer 19

Microglia

Question 20

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.

Answer 20

Blood-Brain Barrier

Question 21

Ion Channels & Neurotransmitter Receptors:

Respond to changes in the membrane potential of the cell

Answer 21

Voltage-gated channels

Question 22

Sodium Channel

Blocks channel from outside

Answer 22

Tetrodotoxin (TTX)

Question 23

Sodium Channel

Slows inactivation, shifts activation

Answer 23

Batrachotoxoin (BTX)

Question 24

Potassium channels

Blocks “small Ca-activated” K channel

Answer 24

Apamin

Question 25

Potassium channels Blocks “big Ca-activated” K channel

Answer 25

Charybdotoxin

Question 26

Calcium channels Blocks N-type channel

Answer 26

Omega conotoxin (ω-CTX-GVIA)

Question 27

Calcium channels Blocks P-type channel

Answer 27

Agatoxin (ω-AGAIVA)

Question 28

Ligand-gated channel: Nicotinic ACh Receptor Irreversible antagonist

Answer 28

α-Bungarotoxin

Question 28

Ligand-gated channel: GABAA Receptor Blocks channel

Answer 28

Picrotoxin

Question 29

Ligand-gated channel: Glycine receptor Competitive antagonist

Answer 29

Strychnine

Question 30

Ligand-gated channel: AMPA receptor Blocks channel

Answer 30

Philanthotoxin

Question 31

Ion Channel Apamin, Charybdotoxin

Answer 31

Voltage-gated, Potassium

Question 31

Ion Channel Tetrodotoxin (TTX), Batrachotoxoin (BTX)

Answer 31

Voltage-gated, Sodium

Question 32

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

Answer 32

Voltage-gated, Calcium

Question 33

Ion Channel α-Bungarotoxin

Answer 33

Ligand-gated, Nicotinic Ach receptor

Question 34

Ion Channel Picrotoxin

Answer 34

Ligand-gated, GABAA receptor

Question 35

Ion Channel Strychnine

Answer 35

Ligand-gated, Glycine

Question 36

Ion Channel Philanthotoxin

Answer 36

Ligand-gated, AMPA

Question 37

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

Answer 37

1. Voltage-gated channels 2. Ligand-gated channels

Question 37

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

Answer 37

Voltage-gated Ion Channels

Question 37

Ion Channels Responsible for fast action potentials.

Answer 37

Voltage-gated Ion Channels

Question 38

Ion Channels Responsible for action potential propagation

Answer 38

Sodium Channels

Question 39

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

Answer 39

Voltage-gated Ion Channels

Question 40

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

Answer 40

Ligand-gated channels

Question 41

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

Answer 41

Ligand-gated Ion Channels or Ionotropic Receptors

Question 42

2 Classes of Neurotransmitter Receptor

Answer 42

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

Question 42

Neurotransmitter Receptor Binding does not result in the direct gating of a channel

Answer 42

Metabotropic Receptors

Question 43

Neurotransmitter Receptor Chemically-gated

Answer 43

Ligand-gated Ion Channels or Ionotropic Receptors

Question 43

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

Answer 43

Ligand-gated Ion Channels or Ionotropic Receptors

Question 44

Neurotransmitter Receptor Seven transmembrane G protein-coupled receptors (GPCRs)

Answer 44

Metabotropic Receptors

Question 45

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

Answer 45

Metabotropic Receptors

Question 45

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

Answer 45

membrane-delimited

Question 46

Membrane-Delimited Pathways

Answer 46

1. Potassium channels 2. Calcium channels

Question 47

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.

Answer 47

T

Question 47

predominate in the diffuse neuronal systems in the CNS

Answer 47

Metabotropic receptors

Question 48

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

Answer 48

diffusible second messengers

Question 49

The Synapse and Synaptic Potentials Types of receptor channel coupling in ligand-gated ion channels activation and inactivation

Answer 49

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.

Question 49

The Synapse and Synaptic Potentials Diffusible second messengers

Answer 49

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

Question 50

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

Answer 50

Excitatory Postsynaptic Potentials (EPSPs)

Question 50

Role of the Ion current carried by the Channel Depolarizing potential change

Answer 50

Excitatory Postsynaptic Potentials (EPSPs)

Question 51

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

Answer 51

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

Question 51

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

Answer 51

T

Question 52

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

Answer 52

Inhibitory Postsynaptic Potential (IPSP)

Question 53

EPSPs __ Na+, __ K+, __ Ca2+

Answer 53

↑ Na+, ↓ K+, ↑ Ca2+

Question 54

Role of the Ion current carried by the Channel Hyperpolarizing potential change

Answer 54

Inhibitory Postsynaptic Potentials (IPSPs)

Question 55

IPSPs Generated by

Answer 55

Opening of potassium or chloride channels.

Question 56

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

Answer 56

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

Question 57

Sites of drug action: Steps at which drugs can alter synaptic transmission

Answer 57

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

Question 57

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

Answer 57

F; direct interactions

Question 57

Sites and Mechanisms of Drug Action drugs exert their effect through direct interactions

Answer 57

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

Question 58

Q Sites and Mechanisms of Drug Action Interfere with the action of second messengers

Answer 58

Activate or Block

Question 58

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

Answer 58

T

Question 59

Sites and Mechanisms of Drug Action Most drugs exert their effect mainly at the ____.

Answer 59

synapses

Question 59

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

Answer 59

T

Question 60

Sites and Mechanisms of Drug Action Inhibits synthesis of serotonin

Answer 60

Parachlorophenylalanine

Question 61

Sites and Mechanisms of Drug Action Inhibits storage of catecholamines

Answer 61

Reserpine

Question 62

Sites and Mechanisms of Drug Action Inhibits release of catecholamines

Answer 62

Amphetamine

Question 63

Sites and Mechanisms of Drug Action Inhibits degradation of acetylcholine

Answer 63

Anticholinesterase

Question 64

Sites and Mechanisms of Drug Action Can be depressed by blockade of transmitter synthesis or storage

Answer 64

Presynaptic Drugs

Question 65

Sites and Mechanisms of Drug Action The transmitter receptor provides the primary site of drug action

Answer 65

Postsynaptic Region

Question 66

Cellular Organization of the Brain Control major sensory and motor functions

Answer 66

Hierarchal System

Question 66

Cellular Organization of the Brain Two types of neuronal system:

Answer 66

1. Hierarchical system 2. Diffused/Non-specific neuronal system

Question 67

Cellular Organization of the Brain Contains large myelinated, rapidly conducting fibers; pathways are clearly delineated.

Answer 67

Hierarchal System

Question 68

Cellular Organization of the Brain Excitability of the CNS

Answer 68

Hierarchal System

Question 69

Cellular Organization of the Brain Small Inhibitory Interneurons (Local Circuit Neurons) Transmitters

Answer 69

Gamma amino butyric acid (GABA), Glycine

Question 69

Cellular Organization of the Brain Major Excitatory Transmitters : Aspartate, Glutamate

Answer 69

Hierarchal System

Question 70

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

Answer 70

Diffused / Non-Specific Neuronal System

Question 71

Diffused / Non-Specific Neuronal System Periodic enlargements that contain transmitter vesicles

Answer 71

Varicosities

Question 71

Diffused / Non-Specific Neuronal System Located in the axons

Answer 71

Varicosities

Question 72

Diffused / Non-Specific Neuronal System (Transmitters) NE, dopamine and serotonin

Answer 72

Noradrenergic Amines

Question 72

Diffused / Non-Specific Neuronal System (Transmitters) Act on metabotropic receptors

Answer 72

Peptides

Question 73

Diffused / Non-Specific Neuronal System Noradrenergic cell bodies are found primarily in a compact cell group _________.

Answer 73

locus caeruleus

Question 74

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

Answer 74

Serotonin neurons

Question 75

Cellular Organization of the Brain Other diffusely projecting neurotransmitter pathways include the histamine and orexin systems

Answer 75

Diffused / Non-Specific Neuronal System