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2nd Year 2nd Term > MT6314 INTRO TO CNS DRUGS > Flashcards

MT6314 INTRO TO CNS DRUGS Flashcards

1
Q

CNS DRUGS are among the most important tools for?

A

studying all aspects of CNS physiology.

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2
Q

Nearly ALL drugs with CNS effects act on?

A

specific receptors that modulates transmission

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3
Q

Unraveling the actions of drugs with known clinical efficacy led to what?

A

the hypotheses regarding the mechanism of disease.

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4
Q

Electrically excitable cell (via electrochemical process)

A

Neuron

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5
Q

Macrophages from bone marrow

A

Microglia

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6
Q

Limits penetration of substances

A

BBB

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7
Q

Found on the neuron for insulation

A

Myelin sheath

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8
Q

Wraps around the axons

A

Oligodendrocytes

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9
Q

Cell body is also known as?

A

Soma

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10
Q

Where the synaptic responses are integrated with high concentration of voltage gated sodium channels

A

Axon initial segment

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11
Q

Highly branched complex “trees”

A

Dendrites

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12
Q

Most drugs act on the CNS by?

A

changing ion flow through transmembrane channels of nerve cells

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13
Q

Two types of channels defined on the basis of the mechanism controlling their gating (Opening & closing)

A

Voltage Gated Channels
Ligand Gated Channels

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14
Q

VOLTAGE OR LIGAND: Respond to changes in membrane potential

A

VOLTAGE

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15
Q

VOLTAGE GATED ION CHANNELS are concentrated where?

A

INITIAL SEGMENT of the axons in nerve cells

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16
Q

VOLTAGE OR LIGAND: Responsible for fast action potentials

A

VOLTAGE

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17
Q

In voltage gated ion channels what channels are responsible for action potential propagation?

A

Sodium channels

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18
Q

What other parts of the neuron have voltage-sensitive ion channels for what specific elements?

A

Cell bodies and dendrites
potassium and calcium

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19
Q

What are the 2 CLASSES OF NEUROTRANSMITTER RECEPTORS?

A
  1. LIGAND-GATED ION CHANNELS OR IONOTROPIC RECEPTOS
  2. METABOTROPIC RECEPTORS
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20
Q

Types of Metabotropic receptors?

A

Diffusible Second Messenger Mediated Regulation
Membrane-delimited Regulation

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21
Q

METABOTROPIC OR LIGAND: Chemically-gated

A

LIGAND

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22
Q

What do ligand ion channels respond to?

A

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

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23
Q

T or F: Ligand gated ion channels are sensitive to the membrane potentials

A

F, weakly sensitive

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24
Q

How many GPCRs?

A

7

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25
Q

T or F: In Metabotropic Receptors, binding results in the direct gating of a channel

A

F, does NOT result

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26
Q

Metabotropic receptors: If there is binding, what does it result to?

A

Binding engages the G-protein that results into production of SECOND messengers that modulates the voltage gated channels

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27
Q

Membrane delimited pathways mainly target what channels?

A

Calcium and Potassium

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28
Q

METABOTROPIC (Ca or K channel): Slow inhibition in postsynaptic

A

K

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29
Q

METABOTROPIC (Ca or K channel): inhibited when metabotropic is activated in post synaptic

A

Ca

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30
Q

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 (cAMP, IP3, DAG)
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31
Q

ROLE OF THE ION CURRENT CARRIED BY
THE CHANNEL?

A

Synapse
EPSPs
IPSPs

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32
Q

EPSP or IPSP:
Generated by
* Opening of sodium or calcium channels
* Closing of potassium channels in some synapses

A

EPSP

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33
Q

EPSP or IPSP: Depolarizing

A

EPSP

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34
Q

EPSP or IPSP: high Na, low K

A

EPSP

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35
Q

EPSP or IPSP: Hyperpolarizing

A

IPSP

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36
Q

EPSP or IPSP: high Ca2+

A

EPSP

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37
Q

EPSP or IPSP: Generated by opening of potassium or chloride channels

A

IPSP

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38
Q

EPSP or IPSP: high K+ and Cl-

A

IPSP

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39
Q

EPSP or IPSP: low Ca2+ at presynaptic

A

IPSP

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40
Q

Some drugs exert their effect through?

A

direct interactions with molecular components of ion channels on axons

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41
Q

Examples of some drugs exert their effect through
direct interactions with molecular components of ion channels on axons?

A
  • Carbamazepine
  • Phenytoin
  • Local anesthetics and some drugs used for general
    anesthesia
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42
Q

Most drugs exert their effect mainly where?

A

at the synapses

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43
Q

Drugs may act presynaptically to alter?

A
  • Synthesis
  • Storage
  • Release
  • Reuptake
  • Metabolism of transmitter chemicals
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44
Q

What interferes with the action of second messengers?

A

Pre- and postsynaptic receptors for specific transmitters

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45
Q

Inhibits storage of cathecolamines

A

Reserpine

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46
Q

Inhibits synthesis of serotonin

A

Parachlorophenylalanine

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47
Q

Depletes monoamine synapses of transmitters by interfering with intracellular storage

A

Reserpine

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48
Q

Inhibits degradation of Acetylcholine

A

Anticholinesterase

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49
Q

Inhibits release of catecholamines

A

Amphetamine

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50
Q

2 TYPES OF NEURONAL SYSTEM IN CNS?

A

HIERARCHAL
NON-SPECIFIC/DIFFUSION

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51
Q

HIERARCHAL or NON-SPECIFIC: Contain large myelinated, rapidly conducting fibers

A

Hierarchal

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52
Q

HIERARCHAL or NON-SPECIFIC: Broadly distributed, with single cells frequently sending processes to many different parts of the brain

A

NON-SPECIFIC

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53
Q

HIERARCHAL or NON-SPECIFIC: Tangential organization

A

NON-SPECIFIC

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54
Q

Major excitatory transmitters of hierarchal system?

A
  • Aspartate
  • Glutamate
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55
Q

Small inhibitory interneurons transmitters in hierarchal system?

A
  • Gamma amino butyric acid (GABA)
  • Glycine
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56
Q

Periodic enlargements that contain transmitter vesicles

A

Varicosities

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57
Q

Where are varicosities located?

A

axons

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58
Q

Types of transmitters in Non-specific neuronal system?

A
  • Noradrenergic Amines (NE, dopamine and serotonin)
  • Peptides that act on metabotropic receptors
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59
Q

What part of the brain are the transmitters usually seen in a non-specific neuronal system?

A

compact cell group called locus caeruleus in the caudal pontine central gray matter

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60
Q

Marked effects on CNS functions of non-specific neuronal system?

A
  • Attention
  • Appetite
  • Emotional states
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61
Q

CRITERIA FOR TRANSMITTER STATUS?

A
  1. Present in higher concentration in the synaptic area than in other areas (localized in appropriate areas)
  2. Released by electrical or chemical stimulation via a calcium-dependent mechanism
  3. Synaptic mimicry
    * Produce the same sort of postsynaptic
    response that is seen with physiologic
    activation of the synapse
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62
Q

CHEMICALS ACCEPTED AS NTAs IN THE CNS

A

Acetylcholine
Dopamine
Norepinephrine
Opioid Peptides
GABA and Glycine
Glutamic Acid
Serotonin

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63
Q

Glycine is more numerous in the _____

A

cord

64
Q

Glycine is inhibitory or excitatory?

A

Inhibitory

65
Q

Increases Cl- conductance

A

Glycine
GABAa activation

66
Q

Excitatory for most neurons

A

Glutamic Acid

67
Q

Excitatory effects
* Activation of α1 and β1 receptors

A

Norepinephrine

68
Q

Multiple 5 hydroxytryptamine (5-HT) receptor subtypes

A

Serotonin

69
Q

G protein-coupled activation of K+ channels

A

Dopamine

70
Q

D2 receptor is the main subtype of?

A

Dopamine

71
Q

Beta-endorphins, dynorphins

A

Opioid Peptides

72
Q

Inhibitory in pre and post synaptic

A

Opioid Peptides

73
Q

Decrease Ca+2 conductance

A

Pre Opioid

74
Q

Increase K+ conductance

A

Post Opioid

75
Q

Metabotropic NTA

A

Serotonin

76
Q

Inhibitory actions at synapses in specific neuronal systems

A

Dopamine

77
Q

5% of neurons have receptors for this

A

Ach

78
Q

Slow excitation

A

Ach

79
Q

Inhibitory effects
* Activation of α2 and β2 receptors
* Increase K+ conductance

A

Norepinephrine

80
Q

Inhibition of adenyl cyclase

A

Glutamic Acid

81
Q

N-methyl-D-aspartate (NMDA) receptor for learning and memory

A

Glutamic Acid

82
Q

GABA is the primary NTA mediating?

A

IPSPs

83
Q

GABAa or GABAb: Opens Cl- conductance

A

A

84
Q

GABAa or GABAb: Opens K+ channels

A

B

85
Q

GABAa or GABAb: Closes Ca+2 channels

A

B

86
Q

GABAa or GABAb: Activated by baclofen

A

B

87
Q

GABAa or GABAb: slow component

A

B

88
Q

GABAa or GABAb: fast component

A

A

89
Q

Pre or Post of Opioid: Decrease Ca+2 conductance

A

Pre

90
Q

Pre or Post of Opioid: Increase K+ conductance

A

Post

91
Q

Increase cAMP

A

Dopamine

92
Q

Decrease permeability to potassium

A

Ach

93
Q

Types of Sodium Channels?

A

Tetrodotoxin (TTX)
Batrachotoxin (BTX)

94
Q

Types of Potassium Channels?

A

Apamin
Charybdotoxin

95
Q

Types of Calcium channels?

A

Omega-conotoxin
Agatoxin

96
Q

Types of Ligand-gated channels?

A

Nicotinic ACh receptor (a-Bungarotoxin)
AMPA receptor (Philanthotoxin)
GABAa receptor (Picrotoxin)
Glycine receptor (Strychnine)

97
Q

Blocks channel from the outside

A

TTX

98
Q

Slows inactivation or shifts activation

A

BTX

99
Q

Blocks small Calcium activated K channels

A

Apamin

100
Q

Blocks large Calcium activated K channels

A

Charybdotoxin

101
Q

Irreversible antagonist

A

Nicotine ACh receptor - a-Bungarotoxin

102
Q

Blocks the channel

A

GABAa receptor - Picrotoxin
AMPA receptor - Philanthotoxin

103
Q

Competitive antagonist

A

Glycine receptor - Strychnine

104
Q

Receptor subtypes and corresponding agonists of ACh?

A

M1 (muscarine), M2 (muscarine and bethanechol), Nicotinic (nicotine)

105
Q

Receptor subtypes and corresponding agonists of dopamine?

A

D1 (dihydrexidine) and D2 (bromocriptine)

106
Q

Receptor subtypes and corresponding agonists of GABA?

A

GABAa (muscimol) and GABAb (baclofen)

107
Q

Receptor subtypes and corresponding agonists of glutamate?

A

NMDA (NMDA), AMPA (AMPA), Kainate (kainic acid and domoic acid), metabotropic (ACPD, quisqualate)

108
Q

Receptor subtypes and corresponding agonists of glycine?

A

Taurine and b-alanine

109
Q

Receptor subtypes and corresponding agonists of serotonin?

A

5-HT1A - eptapirone
5-HT2A - LSD
5-HT3 - 2-methyl-5-HT
5-HT4 - Cisapride

110
Q

Receptor subtypes and corresponding agonists of NE?

A

a1 - phenylephrine
a2 - clonidine
b1 - isoproterenol, dobutamine
b2 - albuterol

111
Q

Receptor subtypes and corresponding agonists of histamine?

A

H1 (2-histamine), H2 (dimaprit), H3 (R-a-methyl-histamine)

112
Q

Receptor subtypes and corresponding agonists of opioid peptides?

A

Mu - bendorphin
Delta - enkephalin
Kappa - dynorphin, salvinorin A

113
Q

Receptor subtypes and corresponding agonists of orexins?

A

OX1 (orexin A), OX2 (orexin A and B)

114
Q

Receptor subtypes and corresponding agonists of tachykins?

A

NK1: substance P methyl ester
NK2: neurokinin A
NK3: neurokinin B

115
Q

Receptor subtypes and corresponding agonists of endocannabinoids?

A

CB1: anandamide, 2-arachidonyglycerol

116
Q

Receptor antagonist for opioid peptides?

A

Naltrexone

117
Q

Receptor antagonist for orexins?

A

Suvorexant

118
Q

Receptor antagonist for tachykinins?

A

NK1: aprepitant
NK2: saredutant
NK3: Osanetant

119
Q

Receptor antagonist for endocannabinoids?

A

Rimonabant

120
Q

Receptor antagonist for M1?

A

Pirenzepine and atropine

121
Q

Receptor antagonist for M2?

A

Atropine, methoctramine

122
Q

Receptor antagonist for nicotine?

A

dihydro-b-erythroidine
a-bungarotoxin

123
Q

Receptor antagonist for D1?

A

phenothiazines

124
Q

Receptor antagonist for D2?

A

Phenothiazines, butryophenones

125
Q

Receptor antagonist for GABAa?

A

bicuculline
picrotoxin

126
Q

Receptor antagonist for GABAb?

A

2-OH-saclofen

127
Q

Receptor antagonist for NMDA?

A

2-amino-5-phosphonovalerate
dizocilpine

128
Q

Receptor antagonist for AMPA?

A

NBQX

129
Q

Receptor antagonist for Kainate?

A

ACET

130
Q

Receptor antagonist for metabotropic?

A

MCPG

131
Q

Receptor antagonist for glycine?

A

Strychnine

132
Q

Receptor antagonist for 5-HT1A?

A

Metergoline, spiperone

133
Q

Receptor antagonist for 5-HT2A?

A

Ketanserin

134
Q

Receptor antagonist for 5-HT3?

A

Ondansetron

135
Q

Receptor antagonist for 5-HT4?

A

Piboserod

136
Q

Receptor antagonist for a1 NE?

A

Prazosin

137
Q

Receptor antagonist for a2 NE?

A

Yohimbine

138
Q

Receptor antagonist for b1 NE?

A

Atenolol, Practolol

139
Q

Receptor antagonist for b2 NE?

A

Butoxamine

140
Q

Receptor antagonist for H1 histamine?

A

Mepyramine

141
Q

Receptor antagonist for H2 histamine?

A

Ranitidine

142
Q

Receptor antagonist for H3 histamine?

A

Thioperamide

143
Q

Excitatory action in ACh

A

Lower K, higher IP3, DAG and cation

144
Q

Inhibitory action in ACh

A

Higher K, lower cAMP

145
Q

Inhibitory action pre and post synaptically in dopamine

A

Pre - lower Ca
Post - higher K, lower cAMP

146
Q

Inhibitory action in GABA pre and post synaptic

A

Pre - lower Ca
Post - higher K

147
Q

Excitatory action in glutamate for NMDA, AMPA, Kainate

A

Higher cation conductance

148
Q

Inhibitory action in Metabotropic receptors in glutamate

A

Lower Ca, cAMP, K
Higher IP3 and DAG

149
Q

Inhibitory action in glycine

A

Higher Cl

150
Q

Inhibitory and excitatory action in 5-HT

A

Inhibitory - higher K, lower cAMP
Excitatory - lower K, higher IP3/DAG/Cation

151
Q

Excitatory in NE

A

lower K, higher IP3/DAG/cAMP

152
Q

Inhibitory in NE

A

lower Ca/cAMP, higher K

153
Q

What NE receptors includes high cAMP for inhibition in the pre synaptic membrane?

A

B2

154
Q

Excitatory Histamine action

A

Higher IP3, DAG, cAMP

155
Q

Tachkinins excitatory

A

lower K, higher IP3 and DAG

2nd Year 2nd Term (38 decks)

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