Glutamate and GABA Amino Acid Neurotransmitters, Receptors, and Drugs PT 2

Question 1

Benzodiazepine drugs types

Answer 1

• allosteric agonists

- allosteric antagonists

Question 2

allosteric agonists used clinically names and fxs

Answer 2

they are minor tranquilizers or anxiolytics

• chlordiazepoxide (Librium)
• Diazepam (Valium)
• flurazepam (Dalmane)
• Oxazepam
• Lorazepam
• Prazepam

Question 3

Competitive antagonists at benzodiazepine allosteric site drug class and name

Answer 3

• competitive antagonists

- flumazenil

Question 4

Mechanism of action benzodiazepine

Answer 4

• enhance inhibitory actions GABA
• Interact with specific site on GABAa receptor-chloride channel complex associated with receptor containing gama2 subunit

Question 5

Benzodiazepines are both

Answer 5

• anxiolytic

- sedating

Question 6

allosteric agonists benzodiazepines require

Answer 6

the presence of gama2 subunit

Question 7

Benzodiazepine agonists prefer what subunits be present or not present

Answer 7

• alpha 1,2,3,5 present

- alpha 4,6

Question 8

Benzodiazepine antagonists prefer

Answer 8

• alpha 1 subunits to alpha 2 and alpha 3 and they do not interact with alpha 5
• this means they are not complete reversal agents

Question 9

GABA bound with vs without diazepam effect

Answer 9

GABA bound opens channels, GABA and Diazepam bound -> channels open longer

Question 10

Benzodiazepine drugs toxicity

Answer 10

• fairly safe no remarkable acute toxicity
• withdraw following chronic uses can -> seizures
• use benzodiazepines with barbiturates or alcohol can -> death

Question 11

clinical uses benzodiazepine drugs

Answer 11

• anxiolytic (anti-anxiety) (used in combo with other CNS deprassants in pre-anesthetic protocols)
• anti-convulsant at v high doses give IV can control status epileptics
• muscle relaxant- increases inhibition in spinal cord

Question 12

Excitatory animo acid neurotransmitters

Answer 12

-mainly L-glutamate
May also include
- L-asparate
- L-homocystetic acid

Question 13

Receptor class for excititaroy amino acid neurotransmitters name

Answer 13

glutamate receptors or excitatory amino acid receptors

Question 14

glutamate receptors and CNS

Answer 14

• nearly all CNS neurons have excitatory glutamate receptors

- nearly 1/3 CNS neurons= glutamatergic

Question 15

Glutamate receptors and excitatory amino acid receptors subclasses

Answer 15

• provide some specificity and different patterns of regional distribution of different glutamate receptor subtypes occur in brain and spinal cord

Question 16

NMDA-type glutamate receptors

Answer 16

• pain pathways

- hippocampus (role in learning and memory)

Question 17

synthesis of L-glutamate

Answer 17

can be:

• by deamination L-glutamine
• from a-ketoglutarate

Question 18

synthesis L-aspartate

Answer 18

can be:

• by transmission oxalacetate
• by deacetylation of N-acetylaspartate

Question 19

degradation L-glutamate

Answer 19

pathway unknown

Question 20

synaptic action L-glutamte stopped how?

Answer 20

• mainly by high affinity uptake mechanisms
• diffusion also plays a role
• non-specific processes

Question 21

what cells have glutamate uptake systems

Answer 21

neuronal and glial cells

Question 22

Glutaminergic synapses compartments

Answer 22

• tripartite, have 3 components
• presynaptic terminal
• postsynaptic button
• enveloping astrocyte

Question 23

Astrocytes fx

Answer 23

• pt of glutaminergic synapse

- respond to glutamate and transmit info throughout network of neurons that contact astrocyte

Question 24

Inotropic Glutamate receptors (excitatory amino acid receptors) receptor subtypes

Answer 24

• named for agonists
• N-methyl-D-aspartate (NMDA)
• AMPA
• kainate

Question 25

Ionotropic glumate receptors permeable to

Answer 25

Na+ and K+ ions, NMDA to Ca2+

Question 26

AMPA receptors important for

Answer 26

generating fast excitatory postsynaptic potentials (EPSPs) in CNS

Question 27

important binding sites on NMDA receptors

Answer 27

1. glutamate receptor site where neurotransmitter binds 2. Mg2+ site inside pore 3. PCP site

Question 28

Mg2+ site at normal resting potentials

Answer 28

Mg2+ ions block flow other ions through pore

Question 29

PCP site

Answer 29

binds dissociative anesthetic drugs (ketamine and tiletamine)

Question 30

Uncompetitive antagonists

Answer 30

- dissociate anesthetic drugs | - use-dependent antagonists of NMDA receptor-channels (aka NMDA channel blockers)

Question 31

How do uncompetitive antagonists work

Answer 31

- they're use depdnet so active glutamate synapses more likely to be inhibited by dissociated anesthetics than less active ones details: - drug enters binding site inside channel, channel closes drug trapped, drug can't leave channel until its re-opened by release neurotransmitter again

Question 32

Dissociate anesthetics characterized by

Answer 32

loss of awareness accompanied by body surface analgesia

Question 33

examples drugs used in dissociative anesthesia

Answer 33

- ketamine - tiletamine - phencyclidine (PCP)

Question 34

Ketamine

Answer 34

- dissociative anesthetic | - preanesthetic drug

Question 35

ketamine as a preanesthetic drug

Answer 35

- b/c it causes dysphoria use with nonadrenergic alpha-2 agonist or benzodiazepines which provide sedation or tranquilization

Question 36

noradrenergic alpha2 agonist examples

Answer 36

detomidine, medetomidine

Question 37

benzodiazepine example

Answer 37

diazepam

Question 38

Tiletamine

Answer 38

- dissociate anesthetic drug | - can use in combo with benzodiazepine or noradrenergic alpha 2 agonist

Question 39

Phencyclidine

Answer 39

- dissociate anesthetic drug - PCP - UK primary anesthetic US illegal street drug

Question 40

disadvantages of dissociative anesthetics

Answer 40

- strong dysphoric rxns as drug wears off - uncompetitive agonist so no possibility of reversal agent (bc any drug competing for same sit will have same effect) - do not give as sole agent for anesthesia recovery difficult if not given with sedative or anxiolytic drug

Question 41

advantages of dissociative anesthetics

Answer 41

- analgesia - cause amnesia - may protect brain from exotic cell death during hypoxic episodes - maintain or increase cardiac output

Question 42

why analgesia with dissociative anesthetics

Answer 42

- blockade of NMDA channels (which are pt pain pathway at glutamatergic synapses)

Question 43

excitotoxic cell death with excitatory amino acid neurotransmitter

Answer 43

continuous glutamate exposure depolarizes neurons for prolonged periods b/c NMDA channels highly permeable to Ca2+; overly active NMDA channels cause sustained increase in intracellular Ca2+ concentration activating Ca2+ dependent proteases (caspases) -> mitochondrial damage and subsequently to neuronal death

Question 44

excitatory amino acid receptors aka

Answer 44

glutamate receptors

Question 45

Examples excitotoxicity

Answer 45

1. Hypoxic/ Ischemic reprofusion damage | 2. In untreated seizure disorders

Question 46

excitotoxicity hypoxic/ischemic reperfusion damage

Answer 46

1. cerebral ischemia | 2. glutamate released from injured and dying neurons goes into extracellular space and bathes nearby neurons

Question 47

excitotoxicity in untreated seizure disorder

Answer 47

excessive glutametergic stimulation kills neurons