Lecture 8

Question 1

What is the inhibitory neurotransmitter?

Answer 1

GABA

Question 2

What is the excitatory neurotransmitter?

Answer 2

Glutamate

Question 3

What mediates the decarboxylation of glutamate to GABA?

Answer 3

Glutamic acid decaroxylase (GAD)

Question 4

What inhibits the decarboxylation of glutamate to GABA?

Answer 4

Allylglycine (convulsant)

Question 5

What vitamine is required by GAD as a cofactor?

Answer 5

Pyridoxine (vitamin B6)

Question 6

What packages GABA into storage vesicles?

Answer 6

VGAT

Question 7

What inhibits GABA release into synaptic cleft?

Answer 7

Tetanus toxin

Question 8

The neurons and glia take up GABA via _________________.

Answer 8

GABA transporters (GATs)

Question 9

What is a competitive inhibitor of GAT-1 and is used for epilepsy?

Answer 9

Tiagabine

Question 10

What inhibits GABA-T? used as an antivonvulsant.

Answer 10

Vigabatrin

Question 11

What are the 2 types of GABA receptors?

Answer 11

Iontropic (GABA A and GABA C)

Metabatropic (GABA B)

Question 12

What type GABA receptor binds GABA and opens an intrinsic chloride ion channel?

Answer 12

Inotropic GABA receptors (GABA A and C)

Question 13

What type GABA receptor is G-protein couples and affects neuronal ion currents via second messenger?

Answer 13

Metabatropic GABA receptors (GABA b)

Question 14

The activation of GABAa requires the binding of how many molecules of GABA?

Answer 14

2, one to each agonist site

Question 15

All of these (Pregnenolone, DHEA, DHDOC, THDOC, oleamide) are neurosteroids that modulate GABAa by binding to _____ sites on the receptor and cause increased reception activation.

Answer 15

Allosteric

Question 16

What are 2 drugs that bind directly to GABAa receptors?

Answer 16

Muscimol and gaboxadol

Question 17

What are 2 drug classes that are modulators of GABA a receptors and bind to allosteric sites to enhance GABAergic neurotransmission.

Answer 17

Benzodiazepines

Barbiturates

Question 18

What suffix do benzodiazepines typically end in?

Answer 18

Pam

exception- triazolam, zolpidem

Question 19

Do benzodiazpeines activate a receptor in the absence of GABA?

Answer 19

nope

Question 20

Are benzodiazepines bound to protein usually?

Answer 20

Yes- highly protein bound

Question 21

What is the potency of benzodiazepines correlated to?

Answer 21

Hydrophobicity

Question 22

What metablizes benzodiazepines?

Answer 22

CYP3A4

Question 23

What is an ADR of benzos?

Answer 23

amnesia

Question 24

When can benzos cause death?

Answer 24

When combined with alcohol (CYP3A4 inhibitor and CNS depressant)

Question 25

What is an antagonist of benzos?

Answer 25

Flumazenil

Question 26

What are some uses of benzos?

Answer 26

``` sleep enhances anxiolytics sedatives antiepileptics muscle relaxers treatment for alcohol withdrawal ```

Question 27

What suffix do barbiturates usually end with?

Answer 27

"tal"

Question 28

What CNS sites do barbiturates affect?

Answer 28

spinal cord brain stem brain

Question 29

What do barbiturates do?

Answer 29

Sedation Amnesia Loss of consciousness by affecting GABA receptors in the brain

Question 30

What are these barbiturates used for? | Thiopental, pentobarbital, methohexital

Answer 30

Anesthetic barbiturates | Act as agonists at GABA a

Question 31

What are is a barbiturates used as anticonvulsants?

Answer 31

Phenobarbital | less direct agonism

Question 32

What does the termination of barbiturates effects depend primarily on?

Answer 32

Redistribution from CNS to highly perfused areas

Question 33

What happens with chronic use of barbiurates?

Answer 33

High uptake into adipose tissue and there is a longer elimination 1/2 life

Question 34

What metabolizes barbiturates?

Answer 34

Hepatic metabolism, P450

Question 35

What 2 drugs enhance the activaiton of GABA a by GABA and at high doses act as agonists? They also help induce anesthesia.

Answer 35

Etomidate | propofol

Question 36

Where are most GABA B receptors found?

Answer 36

Spinal cord

Question 37

What is a GABA B agonist that is used primarily for treatment of spasticity associated with motor neuron diseases. Can be administered orally in mild cases and intrathecal in severe cases.

Answer 37

Baclofen

Question 38

Can withdrawl occur with baclofen?

Answer 38

yes, can result in acute hypersensitivty, rhabdomyolysis, pruritis, delerium and fever. Especially found with intrathecal route

Question 39

What targets does Ethanol have?

Answer 39

GABA A and glutamate receptors as well as others

Question 40

What is a GABA isomer clinically used for narcolepsy?

Answer 40

Gamma hydroxybutyric acid (GHB)

Question 41

What are the 2 pathways for glutamate synthesis?

Answer 41

1. Product formed in Kerbs cycle is transaminated to glutamate 2. Glutamien produced in glial clles can enter Krebs cycle and converted to glutamate in nerve terminal

Question 42

How is glutamate terminated?

Answer 42

REuptake transporters take glutamate up and plutamine synthetase converts glutamate into glutamine

Question 43

What are the 3 inotropic glutamate receptors?

Answer 43

AMPA Kainate NMDA

Question 44

What 2 glutamate receptors are foudn throughout the CNS and activation results in NA influx and K efflux (possible Ca permeability)

Answer 44

AMPA and Kainate

Question 45

What inotropic glutamate receptor is foudn primarily in hippocampus, cerebral cortex and spinal cord. Requires binding of glutamate and glycine for activation and then allows for K efflux, Na and CA influx. Requires a depolorization to remove Mg block

Answer 45

NMDA

Question 46

What type of metabotropic glutamate receptor causes neuronal excitation through phospholipase C activation?

Answer 46

Group I

Question 47

What 2 types of metabotropic glutamate receptors work by inhibiting adenyl cyclase and decrease cAMP production?

Answer 47

Group II and Group III

Question 48

What can happen with too much glutamate release or decreased reuptake?

Answer 48

Increased intracellular Ca resulting in cellular damage and further glutamate release

Question 49

What are some conditions where you see excitotxicity?

Answer 49

Stroke Trauma Hyperalgesia Epilepsy

Question 50

What are 3 NMDA agntagonists?

Answer 50

Riluzole Memantine Amatadine

Question 51

What NMDA antagonist works by blocking Na channels and decreasing glutamate

Answer 51

Riluzole

Question 52

What 2 NMDA antagonists are non-competitive blockers of NMDA?

Answer 52

Memantine and Amatadine

Question 53

What NMDA antagonist is used in Alzheimers?

Answer 53

Memantine

Question 54

What NMDA antagonist is used in Parkinson's to decrease dyskinesia?

Answer 54

Amatadine

Question 55

What is an drug that stabilizes inactivate state of Na channel reducing excitability and glutamate release-seizures?

Answer 55

Lamotrigine

Question 56

What is a drug that inhibits NMDAs and is used in seizures?

Answer 56

Felbamate