MT6314 INTRO TO CNS DRUGS Flashcards
(155 cards)
1
Q
CNS DRUGS are among the most important tools for?
A
studying all aspects of CNS physiology.
2
Q
Nearly ALL drugs with CNS effects act on?
A
specific receptors that modulates transmission
3
Q
Unraveling the actions of drugs with known clinical efficacy led to what?
A
the hypotheses regarding the mechanism of disease.
4
Q
Electrically excitable cell (via electrochemical process)
A
Neuron
5
Q
Macrophages from bone marrow
A
Microglia
6
Q
Limits penetration of substances
A
BBB
7
Q
Found on the neuron for insulation
A
Myelin sheath
8
Q
Wraps around the axons
A
Oligodendrocytes
9
Q
Cell body is also known as?
A
Soma
10
Q
Where the synaptic responses are integrated with high concentration of voltage gated sodium channels
A
Axon initial segment
11
Q
Highly branched complex “trees”
A
Dendrites
12
Q
Most drugs act on the CNS by?
A
changing ion flow through transmembrane channels of nerve cells
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
14
Q
VOLTAGE OR LIGAND: Respond to changes in membrane potential
A
VOLTAGE
15
Q
VOLTAGE GATED ION CHANNELS are concentrated where?
A
INITIAL SEGMENT of the axons in nerve cells
16
Q
VOLTAGE OR LIGAND: Responsible for fast action potentials
A
VOLTAGE
17
Q
In voltage gated ion channels what channels are responsible for action potential propagation?
A
Sodium channels
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
19
Q
What are the 2 CLASSES OF NEUROTRANSMITTER RECEPTORS?
A
- LIGAND-GATED ION CHANNELS OR IONOTROPIC RECEPTOS
- METABOTROPIC RECEPTORS
20
Q
Types of Metabotropic receptors?
A
Diffusible Second Messenger Mediated Regulation
Membrane-delimited Regulation
21
Q
METABOTROPIC OR LIGAND: Chemically-gated
A
LIGAND
22
Q
What do ligand ion channels respond to?
A
Respond to chemical neurotransmitters (NTAs) that bind to receptor subunits of the channel
23
Q
T or F: Ligand gated ion channels are sensitive to the membrane potentials
A
F, weakly sensitive
24
Q
How many GPCRs?
A
7
25
T or F: In Metabotropic Receptors, binding results in the direct gating of a channel
F, does NOT result
26
Metabotropic receptors: If there is binding, what does it result to?
Binding engages the G-protein that results into production of SECOND messengers that modulates the voltage gated channels
27
Membrane delimited pathways mainly target what channels?
Calcium and Potassium
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METABOTROPIC (Ca or K channel): Slow inhibition in postsynaptic
K
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METABOTROPIC (Ca or K channel): inhibited when metabotropic is activated in post synaptic
Ca
30
Types of receptor channel coupling in LIGAND
GATED ion channels activation and inactivation?
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)
31
ROLE OF THE ION CURRENT CARRIED BY
THE CHANNEL?
Synapse
EPSPs
IPSPs
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EPSP or IPSP:
Generated by
* Opening of sodium or calcium channels
* Closing of potassium channels in some synapses
EPSP
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EPSP or IPSP: Depolarizing
EPSP
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EPSP or IPSP: high Na, low K
EPSP
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EPSP or IPSP: Hyperpolarizing
IPSP
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EPSP or IPSP: high Ca2+
EPSP
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EPSP or IPSP: Generated by opening of potassium or chloride channels
IPSP
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EPSP or IPSP: high K+ and Cl-
IPSP
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EPSP or IPSP: low Ca2+ at presynaptic
IPSP
40
Some drugs exert their effect through?
direct interactions with molecular components of ion channels on axons
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Examples of some drugs exert their effect through
direct interactions with molecular components of ion channels on axons?
* Carbamazepine
* Phenytoin
* Local anesthetics and some drugs used for general
anesthesia
42
Most drugs exert their effect mainly where?
at the synapses
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Drugs may act presynaptically to alter?
* Synthesis
* Storage
* Release
* Reuptake
* Metabolism of transmitter chemicals
44
What interferes with the action of second messengers?
Pre- and postsynaptic receptors for specific transmitters
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Inhibits storage of cathecolamines
Reserpine
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Inhibits synthesis of serotonin
Parachlorophenylalanine
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Depletes monoamine synapses of transmitters by interfering with intracellular storage
Reserpine
48
Inhibits degradation of Acetylcholine
Anticholinesterase
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Inhibits release of catecholamines
Amphetamine
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2 TYPES OF NEURONAL SYSTEM IN CNS?
HIERARCHAL
NON-SPECIFIC/DIFFUSION
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HIERARCHAL or NON-SPECIFIC: Contain large myelinated, rapidly conducting fibers
Hierarchal
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HIERARCHAL or NON-SPECIFIC: Broadly distributed, with single cells frequently sending processes to many different parts of the brain
NON-SPECIFIC
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HIERARCHAL or NON-SPECIFIC: Tangential organization
NON-SPECIFIC
54
Major excitatory transmitters of hierarchal system?
* Aspartate
* Glutamate
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Small inhibitory interneurons transmitters in hierarchal system?
* Gamma amino butyric acid (GABA)
* Glycine
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Periodic enlargements that contain transmitter vesicles
Varicosities
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Where are varicosities located?
axons
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Types of transmitters in Non-specific neuronal system?
* Noradrenergic Amines (NE, dopamine and serotonin)
* Peptides that act on metabotropic receptors
59
What part of the brain are the transmitters usually seen in a non-specific neuronal system?
compact cell group called locus caeruleus in the caudal pontine central gray matter
60
Marked effects on CNS functions of non-specific neuronal system?
* Attention
* Appetite
* Emotional states
61
CRITERIA FOR TRANSMITTER STATUS?
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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CHEMICALS ACCEPTED AS NTAs IN THE CNS
Acetylcholine
Dopamine
Norepinephrine
Opioid Peptides
GABA and Glycine
Glutamic Acid
Serotonin
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Glycine is more numerous in the _____
cord
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Glycine is inhibitory or excitatory?
Inhibitory
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Increases Cl- conductance
Glycine
GABAa activation
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Excitatory for most neurons
Glutamic Acid
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Excitatory effects
* Activation of α1 and β1 receptors
Norepinephrine
68
Multiple 5 hydroxytryptamine (5-HT) receptor subtypes
Serotonin
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G protein-coupled activation of K+ channels
Dopamine
70
D2 receptor is the main subtype of?
Dopamine
71
Beta-endorphins, dynorphins
Opioid Peptides
72
Inhibitory in pre and post synaptic
Opioid Peptides
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Decrease Ca+2 conductance
Pre Opioid
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Increase K+ conductance
Post Opioid
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Metabotropic NTA
Serotonin
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Inhibitory actions at synapses in specific neuronal systems
Dopamine
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5% of neurons have receptors for this
Ach
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Slow excitation
Ach
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Inhibitory effects
* Activation of α2 and β2 receptors
* Increase K+ conductance
Norepinephrine
80
Inhibition of adenyl cyclase
Glutamic Acid
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N-methyl-D-aspartate (NMDA) receptor for learning and memory
Glutamic Acid
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GABA is the primary NTA mediating?
IPSPs
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GABAa or GABAb: Opens Cl- conductance
A
84
GABAa or GABAb: Opens K+ channels
B
85
GABAa or GABAb: Closes Ca+2 channels
B
86
GABAa or GABAb: Activated by baclofen
B
87
GABAa or GABAb: slow component
B
88
GABAa or GABAb: fast component
A
89
Pre or Post of Opioid: Decrease Ca+2 conductance
Pre
90
Pre or Post of Opioid: Increase K+ conductance
Post
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Increase cAMP
Dopamine
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Decrease permeability to potassium
Ach
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Types of Sodium Channels?
Tetrodotoxin (TTX)
Batrachotoxin (BTX)
94
Types of Potassium Channels?
Apamin
Charybdotoxin
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Types of Calcium channels?
Omega-conotoxin
Agatoxin
96
Types of Ligand-gated channels?
Nicotinic ACh receptor (a-Bungarotoxin)
AMPA receptor (Philanthotoxin)
GABAa receptor (Picrotoxin)
Glycine receptor (Strychnine)
97
Blocks channel from the outside
TTX
98
Slows inactivation or shifts activation
BTX
99
Blocks small Calcium activated K channels
Apamin
100
Blocks large Calcium activated K channels
Charybdotoxin
101
Irreversible antagonist
Nicotine ACh receptor - a-Bungarotoxin
102
Blocks the channel
GABAa receptor - Picrotoxin
AMPA receptor - Philanthotoxin
103
Competitive antagonist
Glycine receptor - Strychnine
104
Receptor subtypes and corresponding agonists of ACh?
M1 (muscarine), M2 (muscarine and bethanechol), Nicotinic (nicotine)
105
Receptor subtypes and corresponding agonists of dopamine?
D1 (dihydrexidine) and D2 (bromocriptine)
106
Receptor subtypes and corresponding agonists of GABA?
GABAa (muscimol) and GABAb (baclofen)
107
Receptor subtypes and corresponding agonists of glutamate?
NMDA (NMDA), AMPA (AMPA), Kainate (kainic acid and domoic acid), metabotropic (ACPD, quisqualate)
108
Receptor subtypes and corresponding agonists of glycine?
Taurine and b-alanine
109
Receptor subtypes and corresponding agonists of serotonin?
5-HT1A - eptapirone
5-HT2A - LSD
5-HT3 - 2-methyl-5-HT
5-HT4 - Cisapride
110
Receptor subtypes and corresponding agonists of NE?
a1 - phenylephrine
a2 - clonidine
b1 - isoproterenol, dobutamine
b2 - albuterol
111
Receptor subtypes and corresponding agonists of histamine?
H1 (2-histamine), H2 (dimaprit), H3 (R-a-methyl-histamine)
112
Receptor subtypes and corresponding agonists of opioid peptides?
Mu - bendorphin
Delta - enkephalin
Kappa - dynorphin, salvinorin A
113
Receptor subtypes and corresponding agonists of orexins?
OX1 (orexin A), OX2 (orexin A and B)
114
Receptor subtypes and corresponding agonists of tachykins?
NK1: substance P methyl ester
NK2: neurokinin A
NK3: neurokinin B
115
Receptor subtypes and corresponding agonists of endocannabinoids?
CB1: anandamide, 2-arachidonyglycerol
116
Receptor antagonist for opioid peptides?
Naltrexone
117
Receptor antagonist for orexins?
Suvorexant
118
Receptor antagonist for tachykinins?
NK1: aprepitant
NK2: saredutant
NK3: Osanetant
119
Receptor antagonist for endocannabinoids?
Rimonabant
120
Receptor antagonist for M1?
Pirenzepine and atropine
121
Receptor antagonist for M2?
Atropine, methoctramine
122
Receptor antagonist for nicotine?
dihydro-b-erythroidine
a-bungarotoxin
123
Receptor antagonist for D1?
phenothiazines
124
Receptor antagonist for D2?
Phenothiazines, butryophenones
125
Receptor antagonist for GABAa?
bicuculline
picrotoxin
126
Receptor antagonist for GABAb?
2-OH-saclofen
127
Receptor antagonist for NMDA?
2-amino-5-phosphonovalerate
dizocilpine
128
Receptor antagonist for AMPA?
NBQX
129
Receptor antagonist for Kainate?
ACET
130
Receptor antagonist for metabotropic?
MCPG
131
Receptor antagonist for glycine?
Strychnine
132
Receptor antagonist for 5-HT1A?
Metergoline, spiperone
133
Receptor antagonist for 5-HT2A?
Ketanserin
134
Receptor antagonist for 5-HT3?
Ondansetron
135
Receptor antagonist for 5-HT4?
Piboserod
136
Receptor antagonist for a1 NE?
Prazosin
137
Receptor antagonist for a2 NE?
Yohimbine
138
Receptor antagonist for b1 NE?
Atenolol, Practolol
139
Receptor antagonist for b2 NE?
Butoxamine
140
Receptor antagonist for H1 histamine?
Mepyramine
141
Receptor antagonist for H2 histamine?
Ranitidine
142
Receptor antagonist for H3 histamine?
Thioperamide
143
Excitatory action in ACh
Lower K, higher IP3, DAG and cation
144
Inhibitory action in ACh
Higher K, lower cAMP
145
Inhibitory action pre and post synaptically in dopamine
Pre - lower Ca
Post - higher K, lower cAMP
146
Inhibitory action in GABA pre and post synaptic
Pre - lower Ca
Post - higher K
147
Excitatory action in glutamate for NMDA, AMPA, Kainate
Higher cation conductance
148
Inhibitory action in Metabotropic receptors in glutamate
Lower Ca, cAMP, K
Higher IP3 and DAG
149
Inhibitory action in glycine
Higher Cl
150
Inhibitory and excitatory action in 5-HT
Inhibitory - higher K, lower cAMP
Excitatory - lower K, higher IP3/DAG/Cation
151
Excitatory in NE
lower K, higher IP3/DAG/cAMP
152
Inhibitory in NE
lower Ca/cAMP, higher K
153
What NE receptors includes high cAMP for inhibition in the pre synaptic membrane?
B2
154
Excitatory Histamine action
Higher IP3, DAG, cAMP
155
Tachkinins excitatory
lower K, higher IP3 and DAG
