SEDATIVES, HYPNOTICS, ANXIOLYTICS

Question 1

anxiety

Answer 1

• irrational fears or worry of disabling intensity
• GAD, social, PTSD, OCD

Question 2

phobias

Answer 2

• persistent, disproportionate fear of specific object or situation
• object/situation poses little actual danger

Question 3

insomnia

Answer 3

• habitual sleeplessness, inability to sleep
• somewhat strong association with anxiety
• direct cause unknown → associated with psychiatric disorders
• depression, stress, personality, bipolar, psychosis

Question 4

combined anxiety & insomnia treatment

Answer 4

• self-medicate with alcohol
• barbiturates
• miltown
• benzodiazepines

Question 5

barbiturates

Answer 5

• sedatives & hypnotics
• varied medical use
• meds differ from another in PK (intensity & duration)
• use has declined
• small therapeutic window → small dose difference between anti-anxiety and sedative
• high misuse potential

Question 6

benzodiazepines (BZs)

Answer 6

• sedative/hypnotic effects
• effective anticonvulsants
• muscle relaxants
• reduce aggressive tendencies
• less likely to work for individuals with chronic dissatisfaction, insecurity, and/or character disorders

Question 7

why are BZs better than barbiturates?

Answer 7

• longer effects
• pharmacologically better (bigger dose dif. between sedation, hypnosis, coma)
• wider therapeutic window
• doesn’t knock out completely
• more specific and similar compounds
• works on limbic system (helps mood disorders)
• not effective as anethstetic

Question 8

GABAa receptors

Answer 8

• major inhibitory receptors in brain
• heteromeric ligand-gated channels
• 2 alphas, 2 betas, 1 accessory (accessory distinguishes between receptors)
• similar structure to nicotinic ACh
• permeable to chloride ions (- charge) to hyperpolarize neuron

Question 9

anxiolytics mechanism of action

both benzos & barbiturates

Answer 9

• increase GABA system (inhibitory)
• acts as positive allosteric modulator (PAM) of GABAa
• increase chloride currents by binding to allosteric sites
• enhances actions of main ligand → acting as agonist of GABA
• more chloride = more negative → harder to generate action potentials

Question 10

barbiturates binding

Answer 10

• bind between alpha and beta subunits
• all GABAa receptors have alpha & beta
• can bind anywhere

Question 11

benzos binding

Answer 11

• bind between alpha and gamma subunits
• only some GABA receptors have gamma subunits
• high levels of receptors in limbic system → why they can help with mood disorders

Question 12

BZs nondependent (not anxious)

Answer 12

• suppresses stress network with more dopamine release
• increased activity in NAC → the positive reinforcing effects
• positive reinforcing effects = calm, not stressesd

Question 13

BZs dependent (anxious)

Answer 13

• negative reinforcing system more active (similar to withdrawal with chronic drug use)
• targets negative reinforcement to silence/inhibit it
• GABAergic system inhibited, shutting down neg. reinforcement
• drug itself is ACTIVATING POSITIVE REINFORCEMENT STRUCTURES

Question 14

neuroactive steroid site

Answer 14

• functions as allosteric modulator of GABAa
• agonists = progesterone, pregnanolone, allopregnanolone

Question 15

body anxiety baseline

Answer 15

• body naturally produces more GABA to counteract anxiety BUT
• this production alone not enough for anxiety disorders
• need to add BZs to enhance naturally existing GABA

Question 16

PK clinical uses

Answer 16

• peak plasma levels after several hours (exception of diazepam ~1hr)
• dependent on route of administration
• converted to active metabolites, contributing to long duration

Question 17

dependence liability

Answer 17

• issue with PK properties of BZs
• quick rewarding feelings = favored
• quick good also creates high misuse

Question 18

ultra short acting BZ

Answer 18

• pre anesthesia
• intra operatively
• status epilepticus (helps with seizures)

Question 18

ultra short acting BZ

Answer 18

• pre anesthesia
• intra operatively
• status epilepticus (helps with seizures)

Question 19

short acting BZ

Answer 19

• treats insomnia, status epilepticus
• high misuse liability

Question 20

intermediate acting BZ

Answer 20

• alleviate anxiety symptoms
• alcohol detoxification

Question 21

long acting BZ

Answer 21

treatment of seizure disorders

Question 22

tolerance

Answer 22

• slow development for anxiolytic effects
• fast development for sedative anticonvulsant effects
• not associated with metabolism or conditioning
• related to neuroadaptations
• cross-tolerance to other sedative drugs (like alcohol)

Question 23

misuse

Answer 23

• higher risk in individuals with pattern of multiple drug misuse
• BZs used to enhance effects or reduce effects, already vulnerable population
• taken for other reasons
• misuse → dependence, withdrawal from neuroadaptations
• withdrawal may not appear for a week or so (low: anxiety, agitation, sleep disturbances; high: panic, seizures, delirium)

Question 24

therapeutic uses BZ

Answer 24

• reports of amnesia
• now can be used to treat pre-anxiety of procedures or traumatic experiences

Question 25

atypical anxiolytics

Answer 25

• don’t act as GABA allosteric modulators
• not acting on GABAa receptors
• can act on serotonin system (Buspirone used for people needing daytime alertness)
• MAOIs and SSRIs

Question 26

BZs and insomnia

Answer 26

• can be used to treat insomnia
• can restore normal sleep patterns
• some raise arousal threshold