03b: GABA-R

Question 1

GABA(A) Receptor is (monomer/trimer/pentamer) with which subunits?

Answer 1

Pentamer;

alpha, beta, and either gamma or delta

Question 2

(X) number of GABA bind to activate GABA(A) Receptor. (Y) number of benzos bind to modulate.

Answer 2

X = 2
Y = 1

Question 3

“Phasic” GABA(A) R location is (X) and has (gamma/delta) subunit.

Answer 3

X = at synapse

Gamma

Question 4

“Tonic” GABA(A) R location is (X) and has (gamma/delta) subunit.

Answer 4

X = extra-synaptic

Delta

Question 5

T/F: All GABA(A) receptors are responsive to benzos.

Answer 5

False - tonic GABA(A) R are not

Question 6

(Tonic/phasic) GABA(A) receptors have very fast response.

Answer 6

Phasic (at synapse)

Question 7

Most common GABA(A) receptor subtype.

Answer 7

alpha(1)beta(2)gamma(2)

Question 8

Which alpha subunit sbind benzos most efficiently?

Answer 8

Alpha(2) and Alpha(3)

Question 9

List the various effects of the Benzos.

Answer 9

1. Anxiolytic action
2. Sedation/hypnosis and muscle relaxant
3. Anticonvulsant action

Question 10

T/F: Benzo-like drugs are indicated for alcohol/cocaine withdrawal.

Answer 10

True (BUT be careful since benzos plus EtOH can be fatal!!)

Question 11

Benzos are contraindicated in patients with which diseases?

Answer 11

1. COPD
2. Alcohol abuse
3. Sleep apnea

Question 12

Benzos should be administered with caution in which patients?

Answer 12

1. Elderly (decrease clearance)
2. Suicidal (abuse potential)
3. Lung, liver, kidney disease

Question 13

T/F: Benzodiazepines have replaced barbiturates as sedative-hypnotic drugs.

Answer 13

True (safer, higher therapeutic index)

Question 14

T/F: Barbiturates have greater specificity of action in CNS than Benzos.

Answer 14

False

Question 15

Benzos are fairly (lipo/hydro)-philic, administered (IV/po) with (slow/quick) onset of CNS effect.

Answer 15

Lipophilic;
Both (high bioavailability and safety via p.o.)
Quick (immediate in case of IV)

Question 16

T/F: Benzos are primarily cleared without modification/transformation into metabolites.

Answer 16

False - biotransformation (CYP450) into active metabolites

Question 17

T/F: Duration of action of benzos is dependent strictly on the life of the parent drug.

Answer 17

False - depends also on active metabolites

Question 18

T/F: Chronic benzos use leads to psych and physical dependence.

Answer 18

True

Question 19

T/F: Signs of benzos withdrawal are typically (mild/severe) and worse with (short/long)-acting benzos.

Answer 19

Mild (anxiety, sleep issues);

Short

Question 20

T/F: Benzos efficacy is greater than barbiturates.

Answer 20

False

Question 21

List the few clinical uses of barbiturates in US.

Answer 21

IV: rapid onset/offset anesthesia (thiopental)
PO: intractable seizures in kids (phenobarbital)

Question 22

T/F: Barbiturates act as GABA(A) receptor agonists.

Answer 22

True (at high concentrations); thus can act as potentiators or agonsts

Question 23

(X) is the most commonlyused IV general anesthetic in the U.S. It acts as a(n) (Y) receptor (agonist/antagonist/modulator).

Answer 23

X = propofol
Y = GABA(A)

Positive modulator (increase affinity of receptor for GABA)

Question 24

Drugs used for simple (no loss of consciousness) seizures. Star the “drugs of choice” (as opposed to the alternatives).

Answer 24

1. Lamotrigine*
2. Carbamazepine*
3. Phenytoin

Question 25

Phenytoin mechanism of action. Which drugs work in the same way?

Answer 25

Prolongs Na channel inactivation state

Lamotrigine, carbamazepine

Question 26

Drugs used for complex (impaired consciousness) seizures. Star the “drugs of choice” (as opposed to the alternatives).

Answer 26

1. Lamotrigine*
2. Carbamazepine*
3. Phenytoin

SAME AS SIMPLE SEIZURES

Question 27

Drugs used for simple (with secondarily generalized tonic/clonic) seizures. Star the “drugs of choice” (as opposed to the alternatives).

Answer 27

1. Lamotrigine*
2. Carbamazepine*
3. Phenytoin

SAME AS COMPLEX SEIZURES

Question 28

Drug(s) of choice used for generalized tonic/clonic seizures.

Answer 28

Valproate

Question 29

Valproate MOA

Answer 29

1. Enhance GABA transmission (increase its synthesis, inhibits its degradation by GABA transaminase)
2. Reduce Ca flow through T-type Ca channels

Question 30

Drug(s) of choice used for generalized absence seizures.

Answer 30

1. Ethosuximide

2. Valproate

Question 31

T/F: Benzos are used to generalized (tonic-clonic, absence, myoclonic) seizures.

Answer 31

True - Clonazepam is used as “alternative” (not drug of choice)

Question 32

Ethosuximide

Answer 32

Reduce Ca flow through T-type Ca channels

Question 33

Drug(s) of choice used for generalized myoclonic seizures.

Answer 33

1. Valproate

2. Lamotrigine

Question 34

Drug(s) of choice for refractory seizures.

Answer 34

Benzos (diazepam, lorazepam)

Question 35

Starting epilepsy treatment is typically done after (X) number of unprovoked seizure if it occurs (Y) time after the first.

Answer 35

X = 2nd
Y = over 24h

Question 36

T/F: Monotherapy is the gold standard of treatment for epilepsy.

Answer 36

True - only a very small percentage of patients cannot be treated with a single drug.

Question 37

What are recommendations regarding switching anticonvulsant drug from brand to generic?

Answer 37

Physicians are urged to keep patients on the medication that is currently managing their disease - increased chance of breakthrough seizures if switched to generic

Question 38

List three older AEDs that are used less due to disadvantages such as CYP450 interactions.

Answer 38

1. Carbamazepine
2. Phenytoin
3. Valproate

Question 39

(X) is an old AEDs that is used less due to disadvantages such as potentially fatal hepatotoxicity.

Answer 39

X = Valproate

Question 40

(X) is an old AEDs that is used less due to disadvantages such as diplopia and ataxia.

Answer 40

Carbamazepine and Phenytoin