Exam 4 - Yang Sleep

Question 1

Main target for drugs for sleep and anxiety disorders

Answer 1

GABA

Question 2

target for sedative hypnotics

Answer 2

GABAa receptor/chloride ion channel complex
allosteric sites: benzodiazepine site (alpha1 and gamma2)

Question 3

benzodiazepines action at their receptor site does what two things?

Answer 3

1. facilitate GABA action
2. increase frequency

Question 4

benzodiazepine antagonist and its use

Answer 4

flumazenil (Romazicon) is used for tx of BZD overdose

Question 5

Allosteric modulators MOA

Answer 5

1. activator (“superman version”)
   -high affinity/activity of enzyme
2. normal
   - normal affinity/activity of enzyme
3. inhibitor (little or no product formation)
   -low affinity/activity of enzyme

Question 6

Important modulation of GABA receptor by BZDs cause:

Answer 6

increase frequency of channel opening

Question 7

Important modulation of GABA receptor by barbiturates cause:

Answer 7

increase duration of channel opening and direct effects on GABAa with high doses (“more dangerous effects”)

Question 8

Important modulation of GABA receptor by alcohol cause:

Answer 8

enhances action of GABA at GABAa receptor

Question 9

2 important SAR of BZDs

Answer 9

1. 1 position alkylation –> source of active metabolites
2. annealating the 1-2 bond with an “electron rich” ring (triazole or imidazole) yields high affinity and decreased half-life

Question 10

does diazepam have a long, short, or moderate half-life?

Answer 10

long (therefore, it is a long acting drug)

Question 11

what drug is the active form of all other BZDs except lorazepam and flurazepam?

Answer 11

oxazepam

Question 12

SE of BZDs

Answer 12

sedation
confusion
ataxia
weakness
HA
nausea (has anticonvulsant activity though)
paradoxical effects

Question 13

BZD precautions/interactions

Answer 13

other sedatives
alcohol
pregnancy and breast feeding
dependence and abuse potential (lower than BBTs though)

Question 14

How do you use flumazenil (Romazicon) to treat a BZD OD?

Answer 14

initially: 0.2mg IV over 30 seconds
-may increase to 0.3mg IV over 30 seconds
Max cumulative dose: 3mg

Question 15

SE of flumazenil

Answer 15

induction of convulsions
panic attacks
agitation
confusion
NV
HA

Question 16

non-BZDs (Z-hypnotics) MOA

Answer 16

act at BZD binding site (BZ1 receptor)
increase FREQUENCY of channel opening
lower risk when compared to other drugs for same indication

Question 17

Of the 3 non-BZDs, which of them are for long term use , which of them are for short term use?

Answer 17

zolpidem (Ambien) and zaleplon (Sonata) are short term
eszopiclone (Lunesta) is long term

Question 18

what drug is used to tx ODs with Z-hypnotics?

Answer 18

flumazenil

Question 19

non-BZDs SE

Answer 19

drowsiness, dizziness, ataxia, NV
cause less (-) effects on sleep patterns when compared to BZDs
sleep driving, sleep cooking, etc. (FDA says you must warn pt of these if you prescribe this med)

Question 20

BBT MOA

Answer 20

bind to all GABAa (alpha1-5)
increase DURATION of channel opening
higher risk compared to other drugs for same indication

Question 21

BZD MOA

Answer 21

bind to all GABAa (alpha1-5)
increase FREQUENCY of channel opening
medium risk compared to other drugs for same indication