7.1: Introduction to Pharmacology of CNS Drugs Flashcards
1
Q
True or False
Nearly ALL drugs with CNS effects act on a specific receptors that modulates transmission.
A
True
2
Q
True or False
CNS DRUGS are among the most important tools for studying all aspects of CNS physiology.
A
True
3
Q
True or False
Unraveling the actions of drugs with known clinical efficacy led to the hypotheses regarding the mechanism of disease.
A
True
4
Q
True or False
In ion channels & neurotransmitter receptors, most drugs that act on the CNS do so by changing ion flow through transmembrane channels of nerve cells.
A
True
5
Q
What are the two channel types defined on the basis of the mechanism controlling their gating?
A
- Voltage-gated channels
- Ligand-gated channels
6
Q
What are the channel types found in Voltage-Gated Channels?
A
- Sodium channels
- Potassium channels
- Calcium channels
7
Q
This blocks channel from outside
A
Tetradotoxin (TTX)
8
Q
Slows inactivation, shifts activation
A
Batrachotoxin (BTX)
9
Q
Blocks “small Ca-activated” K channel
A
Apamin
10
Q
Blocks “big Ca-activated” K small
A
Charybdotoxin
11
Q
Blocks N-type channel
A
Omega conotoxin (ω-CTX-GVIA)
12
Q
Blocks P-type channel
A
Agatoxin (ω-AGAIVA)
13
Q
Nicotinic ACh receptor:
Irreversible antagonist
A
α-Bungarotoxin
14
Q
Blocks GABA-A receptor
A
Picrotoxin
15
Q
Glycine receptor:
Competitive antagonist
A
Strychnine
16
Q
Blocks AMPA receptor channel
A
Philanthotoxin
17
Q
What are the channel types found in Ligand-Gated Channels?
A
- Nicotonic ACh receptor
- GABA-A receptor
- Glycine receptor
- AMPA receptor
18
Q
Identify if Voltage or Ligand:
- Respond to changes in membrane potential
- Concentrated on the INITIAL SEGMENT of the axons in nerve cells
- Responsible for FAST action potentials
A
Voltage-gated ion channels
19
Q
The voltage-gated ion channels includes the sodium channels responsible for?
A
Action potential propagation
20
Q
True or False:
The voltage-gated ion channels have cell bodies and dendrites also have voltage-sensitive ion channels for potassium and calcium.
A
True
21
Q
What are the two classes of neurotransmitter receptor?
A
- Ligand-gated ion channels or Ionotropic receptors
- Metabotropic receptors
22
Q
Identify if Ionotropic or Metabotropic:
- Chemically-gated
- Respond to chemical neurotransmitters (NTAs) that bind to receptor subunits of the channel
A
Ionotropic Receptors
23
Q
Identify if Ionotropic or Metabotropic:
- SEVEN transmembrane G protein coupled
- Binding does not result in the direct gating of a channel
- Binding engages the G-protein that results into production of SECOND messengers that modulates the voltage gated channels
A
Metabotropic Receptor
24
Q
What are the two channels in metabotropic receptors that delimited the pathways of the membrane?
A
- Potassium channels
- Calcium channels
25
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
26
Three receptors that are coupled to a G protein that modulates the formation of diffusible second messengers:
A. cyclic adenosine monophosphate (cAMP)
B. inositol trisphosphate (IP3)
C. diacylglycerol (DAG)
27
What are the two types of synapse?
1. Excitatory Postsynaptic Potentials (EPSPs)
2. Inhibitory Postsynaptic Potentials (IPSPs)
28
Identify if EPSPs or IPSPs:
- Depolarizing potential change
- Opening of sodium or calcium channels
- Closing of potassium channels in some synapses
Excitatory Postsynaptic Potentials (EPSPs)
29
Identify if EPSPs or IPSPs:
↑ Na+, ↓K+, ↑ Ca+2
Excitatory Postsynaptic Potentials (EPSPs)
30
Identify if EPSPs or IPSPs:
- Hyperpolarizing potential change
- Opening of potassium or chloride channels
Inhibitory Postsynaptic Potentials (IPSPs)
31
Identify if EPSPs or IPSPs:
↑ K+, ↑ Cl- at the postsynaptic, ↓Ca+2 at the presynaptic
Inhibitory Postsynaptic Potentials (IPSPs)
32
What are the drugs that 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
33
True or False:
In sites and mechanisms of drug action, most drugs exert their effect mainly at the synapses.
True
34
Inhibits synthesis of serotonin
Parachlorophenylalanine
35
Inhibits storage of cathecolamines
Reserpine
36
Inhibits release of catecholamines
Amphetamine
37
Inhibits degradation of Acetylcholine
Anticholinesterase
38
What are the two types of neuronal system?
1. Hierarchical system
2. Diffused/Non-specific Neuronal System
39
Identify if Hierarchical or Diffused Non-Specific:
- Contain large myelinated, rapidly conducting fibers
- Control major sensory and motor functions
- Excitability of the CNS
Hierarchical system
40
What are the two major excitatory transmitters in hierarchical system?
- Aspartate
- Glutamate
41
What are the small inhibitory interneurons transmitter in the hierarchical system?
- Gamma amino butyric acid (GABA)
- Glycine
42
Identify if Hierarchical or Diffused Non-Specific:
Broadly distributed, with single cells frequently sending processes to many different parts of the brain-tangential
Diffused Non-Specific
43
Periodic enlargements that contain transmitter vesicles and is located in the axons.
Varicosities
44
Peptides that act on metabotropic receptors and is found primarily in a compact cell group called locus caeruleus in the caudal pontine central gray matter.
Transmitters
45
Varicosities is located in the:
Axons
46
Transmitters are located in the:
Locus caeruleus in the caudal pontine central gray matter
47
What are the marked effect on CNS functions in the diffused/non-specific neuronal system?
- Attention
- Appetite
- Emotional states
48
What are the 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
49
Identify this neurotransmitter in the CNS:
- 5% of neurons have receptors for Ach
- G protein-coupled muscarinic M1 receptors
- Slow excitation
- Decrease permeability to potassium
Acetylcholine (Ach)
50
Identify this neurotransmitter in the CNS:
- Inhibitory actions at synapses in specific neuronal systems
- G protein-coupled activation of K+ channels
- D2 receptor is the main dopamine subtype
- Increase cAMP
Dopamine
51
What are the excitatory effects of norepinephrine?
- Activation of α1 and β1 receptors
- Decrease K+ conductance
52
What are the inhibitory effects of norepinephrine?
- Activation of α2 and β2 receptors
- Increase K+ conductance
53
Identify this neurotransmitter in the CNS:
- Multiple 5 hydroxytryptamine (5-HT) receptor subtypes
- Metabotropic
- Inhibitory at many CNS sites
- Excitatory depending on the receptor subtype activated
Serotonin
54
Identify this neurotransmitter in the CNS:
- Excitatory for most neurons
- N-methyl-D-aspartate (NMDA) receptor
- Learning and memory
- Inhibition of adenyl cyclase
Glutamic acid
55
Identify this neurotransmitter in the CNS:
- Primary NTA mediating IPSPs
- GABA-A & GABA-B receptor activation
- Glycine is more numerous in the cord
- Glycine is inhibitory
GABA and Glycine
56
Function of GABA-A receptor activation in GABA and Glycine:
Opens Cl- conductance
57
Function of GABA-B receptor activation in GABA and Glycine:
- Opens K+ channels
- Closes Ca+2 channels
58
# Identify this neurotransmitter in the CNS:
- **Beta-endorphins, dynorphins**
- Inhibitory (presynaptic)
- Decrease Ca+2 conductance
- Inhibitory (postsynaptic)
- Increase K+ conductance
Opioid peptides
59
Identify the specific receptor antagonist/s of Acetylcholine
(Mechanisms)
Excitatory:
⬇ in K+ conductance;
⬆ IP3, DAG
Pirenzepine, atropine
60
Identify the specific receptor antagonist/s of Acetylcholine:
(Mechanisms)
Inhibitory:
⬆in K+ conductance; ⬇ cAMP
Atropine, methoctramine
61
Identify the specific receptor antagonist/s of Acetylcholine:
(Mechanisms)
Excitatory: ⬆ cation conductance
Dihydro-B-erythroidine, a-bungarotoxin
62
Identify the specific receptor antagonist/s of Dopamine:
(Mechanisms)
Inhibitory (?): ⬆cAMP
Phenothiazines
63
Identify the specific receptor antagonist/s of Dopamine (D2):
(Mechanisms)
Inhibitory (presynaptic) ⬇Ca2+;
Inhibitory (postsynaptic): ⬆in K+ conductance, ⬇ cAMP
Phenothiazines, butyrophenones
64
Identify the specific receptor antagonist/s of GABA-A muscimol:
(Mechanisms)
Inhibitory: ⬆︎Cl- conductance
Bicuculline, picrotoxin
65
Identify the specific receptor antagonist/s of GABA-B baclofen:
(Mechanisms)
Inhibitory (presynaptic): ⬇︎Ca2+ conductance; Inhibitory (postsynaptic): ⬆︎K+ conductance
2-OH saclofen
66
Identify the specific receptor antagonist/s of Glutamate:
(Mechanisms)
Excitatory: ⬆︎ cation conductance, particularly Ca2+
2-Amino-5-phosphonovalerate, dizocilpine
67
Identify the specific receptor antagonist/s of Glutamate:
(Mechanisms)
Excitatory: ⬆︎cation conductance
NBQX, ACET
68
Identify the specific receptor antagonist/s of Glutamate:
(Mechanisms)
Inhibitory (presynaptic): ⬇︎Ca2+ conductance, ⬇︎cAMP; Excitatory: ⬇︎K+ conductance, ⬆︎IP3, DAG
MCPG
69
Identify the specific receptor antagonist/s of Glycine:
(Mechanisms)
Inhibitory: ⬆︎Cl- conductance
Strychnine
70
Identify the specific receptor antagonist/s of Serotonin (5-Hydroxytryptamine):
(Mechanisms)
Inhibitory: ⬆︎K+ conductance, ⬇︎cAMP
Metergoline, spiperone
71
Identify the specific receptor antagonist/s of Serotonin (5-Hydroxytryptamine):
(Mechanisms)
Excitatory: ⬇︎ K+ conductance, ⬆︎ IP3, DAG
Ketanserin
72
Identify the specific receptor antagonist/s of Serotonin (5-Hydroxytryptamine):
(Mechanisms)
Excitatory: ⬆︎cation conductance
Ondansetron
73
Identify the specific receptor antagonist/s of Serotonin (5-Hydroxytryptamine):
(Mechanisms)
Excitatory: ⬇︎ K+ conductance
Piboserod
74
Identify the specific receptor antagonist/s of Norepinephrine:
(Mechanisms)
Excitatory: ⬇︎K+conductance, ⬆︎IP3, DAG
Prazosin
75
Identify the specific receptor antagonist/s of Norepinephrine:
(Mechanisms)
Inhibitory (presynaptic): ⬇︎Ca2+ conductance; Inhibitory: ⬆︎K+ conductance, ⬇︎cAMP
Yohimbine
76
Identify the specific receptor antagonist/s of Norepinephrine:
(Mechanisms)
Excitatory: ⬇︎K+conductance, ⬆︎ cAMP
Atenolol, practolol
77
Identify the specific receptor antagonist/s of Norepinephrine:
(Mechanisms)
Inhibitory: may involve ⬆︎ in electrogenic sodium pump; ⬆︎cAMP
Butoxamine
78
Identify the specific receptor antagonist/s of Histamine:
(Mechanisms)
Excitatory: ⬇︎K+ conductance, ⬆︎IP3, DAG
Mepyramine
79
Identify the specific receptor antagonist/s of Histamine:
(Mechanisms)
Excitatory: ⬇︎K+ conductance, ⬆︎cAMP
Ranitidine
80
Identify the specific receptor antagonist/s of Histamine:
(Mechanisms)
Inhibitory autoreceptors
Thioperamide
81
Identify this neurotransmitter in the CNS:
Receptor Antagonist - Naloxone
Mechanism- Inhibitory (presynaptic): ⬇︎Ca2+ conductance, ⬇︎ cAMP
Inhibitory (postsynaptic): ⬆︎K+ conductance, ⬇︎ cAMP
Opioid peptides
82
Identify this neurotransmitter in the CNS:
Receptor Antagonist - Suvorexant
Mechanism - Excitatory, glutamate co-release
Suvorexant
83
Identify the specific receptor antagonist/s of Tachykinins:
(Mechanisms)
Excitatory: ⬇︎K+ conductance, ⬆︎IP3, DAG
Aprepitant, Sardutant, Osanetant
84
Identify the specific receptor antagonist/s of Endocannabinoids:
(Mechanisms)
Inhibitory (presynaptic): ⬇︎Ca+ conductance, ⬇︎ cAMP
Rimonabant
