hypnotics & anxiolytics 1

What are the stimulating neurotransmitters for sleep and wakefulness

SE

DA

NE

ACh

Histamine

What inhibitory neurotransmitters are for sleep and wakefulness

GABA

Anxiety has the overactivity of which system

Adrenergic

Anxiety has the dysregulation of which system

Serotonergic

Persistent and excessive worry about various aspects of life

Generalized Anxiety Disorder (GAD)

Recurrent, unexpected panic attacks involving intense fear and physical Sx like chest pain, tachycardia, dizziness, SOB

Panic Disorder

Intense fear of being judged or embarrassed in social situations

Social Anxiety Disorder (SAD)

Irrational and intense fear of a specific object or situation

Specific Phobias

T/F: Anxiolytics can also be sleep inducing (hypnotic)

False

Sedative hypnotics are general depressants of which system

CNS

Reduces daytime anxiety, decrease excitement and promote calm state

Sedatives

Produce drowsiness, helps sleep onset and maintenance of sleep

Hypnotics

What receptors affect arousal and attention, memory formation, anxiety, sleep, and muscle tone

GABA

Modulating GABA signals is important to treat focal/widespread neuronal hyperactivity in ____

Epilepsy

MOA of Ionotropic GABA-A receptors

Opens intrinsic chloride ion channel

MOA of Metabotropic GABA-B receptors

Activate neuronal K+ channels Heterodimer G protein-coupled receptors

What happens during Hyperpolarization from GABA

Direct effect: Increased intracellular Cl-

Indirect effect: Intracellular K+ leaves; Ca++ channel closed

What happens during Repolarization from Glutamate

Direct effect: Increased intracellular Na+ & Ca++

Indirect effect: Increased intracellular Ca++; closed K+ channel

GABA-B produces what cascade of events

Decreased Adenylyl cyclase & cAMP

Minor effects on cellular excitability

List of course-relevant anxiolytic Benzodiazepines

Diazepam

Alprazolam

Midazolam

Flurazepam

Triazolam

Clonazepam

Benzodiazepines highly selectively bind to what receptors as an agonist for channel opening

GABA-A

What requirement is needed for Benzos to bind to GABA-A receptors

GABA molecule has to bind between Alfa and Beta subunits → hyperpolarization → open Cl- channels

T/F: Benzos are positive allosteric modular to enhance GABA → increased Cl- entry

True

Indications for Benzos

Reduce anxiety

Sedative/hypnotic/Epilepsy (alpha-1-GABA-A receptors)

Muscle relaxant (alpha-2-GABA-A receptors)

Ethanol withdrawal syndromes

Long acting Benzo

Diazepam (Valium)

Anxiolytic for chronic/severe anxiety

Anti-epileptic

Muscle relaxant

Diazepam (Valium)

Intermediate acting Benzo

Alprazolam (Xanax)

Mitigates chronic/severe anxiety

Anxiety associated depression/schizophrenia

Alprazolam (Xanax)

Rapid/Short acting Benzo

Midazolam

Anxiolytic

Sedative

Amnestic (memory loss)

Midazolam

Benzo combo’d with ___ causes a synergistic effect that can cause sedation and respiratory depression

Opioids

T/F: Benzos increases REM and decreases Non-REM sleep

False

Long acting Benzo with a 74hr half-life

Flurazepam

Benzo with fast onset and short duration of action

Triazolam

Benzo used for panic disorder and has anticonvulsant effect

Clonazepam (Klonopin)

which Benzo is not an anxiolytic

Clonazepam

Benzos are what CYP substrate

CYP3A4

What drugs are CYP3A4 inhibitors that enhance benzo effects

Ketoconazole

Macrolides

What drugs are CYP3A4 enhancers that decrease benzo effects

Rifampicin

Omeprazole

Nifedipine

High dose benzos can cause death when administered with what drugs

Ethanol

CNS depressants

Opioid analgesics

Tricyclic antidepressants

Why are benzos relatively safe

Lethal dose is > 1000-fold greater than typical dosing

How to prevent Benzo dependence (typically after long Tx periods)

Taper

Which short-acting benzo has severe withdrawal problems due to rapid elimination / tolerance development, early morning insomnia, and daytime anxiety

Triazolam

What benzo antagonist has a rapid onset, short duration, and 1hr half-life

Flumazenil

What medication can reverse benzo overdose (antagonist)

Flumazenil

Flumazenil MOA

Competitive enzyme for GABA-A receptors

list of meds that are hypnotics

Triazolam

Estazolam

Temazepam

Flurazepam

Quazepam

Benzos that are anxiolytics

Clorazepate

Alprazolam

Lorazepam

Chlordiazepoxide

Diaxepam

Midazolam