- Onset of action - Maximal efficacy - Lipid solubility - Drug interactions - Duration of action - Metabolic pathways - Active Metabolites

Anxiolytic and Hypnotic Drugs Flashcards by Brent Sokola

Fluoxetine (Proxac)

MOA

SSRI

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Duloxetine (Cymbalta)

MOA

SERT & NET

Blocker

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How long does it take to see response in SSRI/SERT&NET blockers?

2-4 week delay

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Barbiturate Uses

Induction of anestesia
Epilepsy
Tension/Migraine HA

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Barbiturate synergism with which Drugs?

EtOH,
BZD’s,
Z drugs
opioids

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Barbiturates

MOA

APLs of all GABAa receptors

Increase DURATION of GABAa channel opening

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Barbiturates and tolerance

Rapid PK tolerance due to induction of CYP

Slow PD tolerance:change in receptor number and composition

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Ultrashort acting barbiturate use

Induction of anesthesia

Terminal anesthesia

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Intermediate acting barbiturate use

Single drug lethal injection

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Long acting barbiturate use

Anti-convulsant

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Long acting barbiturate example

Phenobarbital

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Phenobarbital

MOA

Barbiturate:

APL of GABAa

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ADRs for Barb»BZD»Zdrug

Sedation
Decreased cognition
Decreased REM sleep 
Hangover
-Anterograde Amnesia
-Tolerance
-Dependence
-Ataxia
-Withdrawal

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How are BZDs similar?

Therapeutic use
pharmaco action
ADRs

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How do BZDs differ?

Onset of action
Maximal efficacy
Lipid solubility
Drug interactions
Duration of action
Metabolic pathways
Active Metabolites

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BZD MOA

APL of GABAa receptor

- Binding increases affinity for endogenous GABA increasing FREQUENCY of channel opening

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Barbiturates vs BZDs which increases duration vs frequency of channel opening

Barbiturates: Duration
BZDs: Frequency

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Do BZDs directly open the chloride channel?

What is the effect of this?

No.

Difficult to produce fatal respiratory depression in normal pt

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Which GABAa subunits do BZDs interact with?

Alpha: 1,2,3, or 5

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Which GABAa alpha subunit is most widely distributed, most sedating

Alpha 1

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Where is alpha 2 subtype localized?

What is the effect?

Limbic system (Hippocampus and Striatum)
Anxiolytic

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Where are alpha 3 and 5 subtypes located?

What is the effect?

Spinal chord

Muscle relaxant

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Which subtype are Z drugs more selective for?

What is the effect?

Alpha 1
Good hypnotic
Poor muscle relaxant

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BZD metabolism

CYP3A4 and CYP2C19

-Do not induce CYP

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Do BZDs induce PK tolerance?

No. No CYP induction

BZD Withdrawal

``` Anxiety Psychosis ANS (N&V, CV, Sweating) Panic, Convulsions ```

Diazepam (Valium) | Uses

Anxiolytic, Anticonvulsant, Muscle Relaxant Preanesthetic med

What is a major source in variability for BZDs with regards to half life and potency?

Metabolites. | All have different half lives and potency

Flumazenil (Romazicon) | MOA

GABAa (BZD site) direct antagonist

Flumazenil (Romazicon) | Use and administration

IV administration for BZD overdose

Is Flumazenil Used for Barbiturate overdose?

No. It has a different binding site

What is a non-barbiturate, non-BZD drug used for anxiolytic/sedation

Buspirone (Buspar)

Buspirone (Buspar) | MOA

5-HT-1a partial agonist (Gi)

Whereis g-HT-1a highly concentrated?

amygdala and limbic regions of the cortex

Bupsirone (Buspar) primary use

GAD

Buspirone (Buspar) compared to BZDs

-Less sedation and other ADRs

Buspirone (Buspar) | Onset

-Onset delayed for 2-4 weeks

Buspirone (Buspar) ADRs

N&V, dizziness, HA

Buspirone (Buspar) | Metabolism

CYP3A4

Why is Buspirone favored over BZDs for pt with a history of drug abuse?

Non-hypnotic | Non-addictive

When to use caution with buspirone

Think Serotonin MAOIs or SSRIs -Better to use BZDs

Buspirone is used for GAD, what about acute panic attacks? Why or why not?

Nope. | Onset 2-4 weeks

Treatment of other anxiety disorders

Anti-depressant(s), buspirone, BZDs (for exacerbations) | -Or cominations

Treatment of anxiety related disorders: | Acute panic attacks

Beta-blockers

What regions regulate non-rem sleep?

The Raphe (5HT) and the nucleus of the solitary tract (NTS) [NE; autonomic control]

Which brain region thought to control REM sleep

Cholinergic regions in the forbrain and midbrain

Effect of BZDs on sleep

Decreased: latency to sleep, time until first REM cycle, number of awakenings Increased time in stage 2 non-rem sleep

BZDs and REM sleep

Decreased total REM, but increased total sleep. REM rebounds in withdrawal

BZDs and sleep ADRs

Long acting - risk for hangover | Rapid onset have increased abuse potential and rebound insomnia

Zdrug MOA

Interact selectively with Alpha 1 GABAa receptors in "sleep centers"

Zdrugs as anxiolytics, anti-convulsants, or muscle relaxants

Don't do it! | Wrong GABAa subtype

Zdrugs and abuse

Have abuse potential Tolerance an occur Not as bad as barbiturates or BZDs

Difference between Zopiclone (Imovane) and Eszopiclone (Lunesta)?

Eszopiclone (Lunesta) is chiral

Zolpidem (Ambien) | t1/2 and use

~2 h | Use only if full night of sleep is possible

Zalepon (Sonata) | t1/2 and use

~1h | Can take later at night or in the middle of the night

Z drug Use

Approved for short-term (2 weeks at a time) | Less tolerance/dependence/withdrawal, but still not perfect

Melatonin

Circadian synthesis, pineal gland Facilitates sleep induction and maintenance Ant-oxidant output decreases with age

Ramelteon (Rozerem) | MOA

MT1/MT2 receptor agonist

Ramelteon (Rozerem) | Indication

Sleep induction

Ramelteon (Rozerem) | REM

No decrease in time spent in REM

MT1/MT2 Receptor description and location

Gi coupled GPCRs. Hi concentrations in pacemaker regions of hypothalamus

Ramelteon (Rozerem) | ADRs

HA, Sedation, fategue, N/V

Ramelteon (Rozerem) | Onset and Metabolism

30 min | Metabolized by CYP1A2 (No induction)

Tasimelteon (Hetlioz) | Use

Non-24 Sleep-Wake Disorder | 70% of Blind Pt

Tasimelteon (Hetlioz) Vs Ramelteon (Rozerem)

Tasimelteon has higher affinity for M2 subtype, thought to be more important for sleep: but is 30 times more expensive

Tasimelteon (Hetlioz) | Metabolism

CYP1A2 and CYP3A4

Where are orexin synthesizing neurons located?

Lateral and posterior hypothalamus

What are orexins?

Wake promoting peptides which bind to OX1 and OX to receptors (Gs) in the CNS

Describe the awake state

Limbic/SCN/Energy balance act on orexin neurons which activate wake-active neurons which inhibit Sleep-active neurons/preoptic area (POA). POA would otherwise be inhibiting wake active and orexin neurons

Describe the sleep state

No Limbic/SCN/Energy balance to activate orexin neurons: | Pre optic area (POA) inhibits orexin neurons and wake-active neurons

Suvorexant (Belsomra) | MOA

OX1 and OX2 Receptor antagonist in hypothalamus: Sleep induction

Anxiolytic and Hypnotic Drugs Flashcards

(71 cards)