Anxiolytics Flashcards
ANXIETY
Etiology: ________________________________
Epidemiological, neurophysiological and mechanistic evidence indicates that the _____________ supports stable individual differences in ____________________ across lifespan, and contributes to ethology of anxiety disorders in adults and adolescents
Risk factor for developing anxiety disorders
Amygdala; Dispositional negativity
Anxiety’s physical symptoms in reaction to a perceived threat which is vague, internal or unknown (n=6): ___________________
Headache Sweating Palpitations Dyspepsia (indigestion) Squeezing of the chest Agitation
Activation of amygdala by environment:
- Monoamines (MA) from the locus coeruleus cause (n=7): __________________
- Benzodiazepines _____________ activation of amygdala
- Anxiety, panic attacks, tremors, sweating, tachycardia, hyperarousal, nightmares
- Inhibit
GABA
- Most abundant ___________________ in the CNS
- Synthesized from __________________ by glutamic acid decarboxylase, and is destroyed by _________________
- Benzodiazepines ________________ activation of GABA-A receptors
- Inhibitory neurotransmitter
- Glutamate; GABA transaminase
- Potentiate
Benzodiazepines are ___________________________ (PAMs) of GABA-A receptors
- Allosteric sites are all receptor sites where GABA itself ________________ bind
- Allosteric modulators can be ______________ or _________________
- Positive allosteric modulators (PAM)
- Does not
- Positive or negative
Types of anxiolytics (n=3)
- GABAergic anxiolytics
- Benzodiazepines
- Non benzodiazepines - Serotonergic anxiolytics
- Noradrenergic antagonist anxiolytics
BENZODIAZEPINES
GABAergic anxiolytics
- Drugs: (n=3)
- Increases __________ of endogenous GABA
Uses:
- Reduction of ______________ and _____________
- Sedation and induction of ________________
- Muscle ______________ (central action)
- As __________________ drugs
- Diazepam, Lorazepam, Clonazepam
- Anxiety and aggression
- Sleep
- Relaxants
- Anti-epileptic
Benzodiazepines
- Metabolite is ____________________, meaning that drugs getting metabolized through this pathway have a longer ______________
- Biologically active; half-life
Existing benzodiazepines are __________________
- Bind to GABA-A alpha subunits: (n=4) ____________
- Each s-u is associated with different ___________, so benzodiazepines don’t only cause sedation, but are also (n=3) ___________________
Non-selective
- alpha-1 (a-1), a-2, a-3, a-5
- Effects; anxiolytics, cause muscle relaxation and have alcohol potentiating actions
Benzodiazepines are anxiolytics and hypnotics:
- Anxiolytic effect: they inhibit _____________ of amygdala, by binding _______________ receptors in the amygdala
- Hypnotic effect: they promote ____________ by binding _______________ receptors in VLPO (sleep center), causing sleepiness
- Activation; GABA-A
- Sleep; GABA-A
Ventro-lateral preoptic (VLPO) nucleus of the hypothalamus: the sleep _______________
- VLPO nucleus contains __________ neurone that inhibit TMN and thus ___________ sleep
- Benzodiazepines _____________ action of __________ in VLPO nucleus
- The sleep that derives from benzodiazepines doesn’t follow normal ______________________, so it’s not a normal sleep
Promoter
- GABA; promotes
- Augment; GABA
- Sleeping patterns
Benzodiazepines side effects: (n=5) __________________
Prolonged usage can result in ____________ (i.e. n=3 _______________)
- Excessive drowsiness (danger while driving)
- Ataxia (incoordination)
- Dependence, tolerance (14 days) and abuse
- Dangerous when combined w/ alcohol
- Possible anterograde amnesia
Withdrawal; rebound insomnia, anxiety, tremors
NON BENZODIAZEPINES
- Drugs (n=2)
- Newer anxiolytics that don’t share same ___________ as benzodiazepines
- Rapidly becoming ___________________ for insomnia (they induce sleep but don’t disrupt sleep cycles like benzos)
- Demonstrate less unwanted ______________, _______________ and _________________ side effects
- Better pharmacokinetics, rapid ___________ and short _____________________
- Zolpidem and Zopiclone
- Structure
- First-line treatment
- Cognitive, memory and motor
- Onset; duration of action
Zaleplon and Zolpidem: a-1 ______________ hypnotics
- Bind selectively to _____________ receptors that contain a-1 s-u
- This s-u is important for ______________ and possibly for anticonvulsant and amnesic actions
- Induce sleep but have _______________ on sleep stages 1 to 4 or REM sleep
Selective
- GABA-A
- Sedation
- Little effect
SEROTONERGIC ANXIOLYTICS
- Hypothesis of serotonin ___________ (5HT = anxiety) led to their development and use
- ______________ (drug) is a 5HT1A partial __________ that interacts with ___________________ negative feedback receptors
- ______________ release of 5HT by _____________ negative feedback in a controlled fashion
- Dysregulation
- Buspirone; agonist; somatodendritic
- Decreases; stimulating
