Anxiolytics Flashcards
what’s the difference between anxiety and fear
anxiety = anticipated threat, vague fear = present danger
similarities between fear and anxiety
the threat may be real or perceived
both responses: defensive behaviours, autonomic reflexes, arousal, corticosteroid production, negative emotions
Psychological manifestations of anxiety states
- negative emotions: worry, nervousness, unease
- arousal
- lack of concentration
- insomnia
Physical manifestation of anxiety states
- tachycardia
- SOB
- nausea
- gastric acid hypersecretion
- trembling (skeletal muscles activated)
what is the biochemical basis that cause psychological and physical manifestation of anxiety states
- central and peripheral noradrenergic/adrenergic activation –> flight or fight response
- stress response –> HPA axis –> secretion of stress hormones (cortisol)
main anxiety disorder that is discussed in lecture
generalised anxiety disorder (GAD)
what is GAD?
- excessive worrying over everyday matters
- interferes w daily functioning
- both psychological and physical manifestation
- diagnosed when present for at least 6 months
- most common cause of disability in the workplace
what are the 3 different therapeutic effects that can be seen in anxiolytic drug?
CNS depressant:
- sedative = cause sedation/relaxation but still aware
- hypnotic = induce drowsiness and sleep,may have amnestic effects
- anxiolytic = reduced anxiety
at what doses can i see the different types of therapeutic effect?
- low dose: anxiolytic, sedative effects
- higher dose: hypnotic
- even higher dose –> cause anaesthesia, used for surgery
which BZDs is used as anxiolytics /sedatives?
diazepam, lorazepam
which BZDs is used as hypnotics?
diazepam, triazolam, temazepam
which BZDs is used as pre-anaesthetics?
diazepam, midazolam
which BZDs used for anti-convulsant effect?
diazepam
MOA of BZDs
binds to the BZD site (allosteric site) away from the GABA site
potentiate GABA actions by increasing the frequency of GABA-induced channel opening
potentiates influx of CL- ions leading to greater hyperpolarization –> neurons not firing
what happens when the GABA is activated or potentiated in this case with BZDs?
- alters mood via the limbic system
- cause drowsiness via reticular activating system
- relax muscles vis motor cortex
what are the short acting BZDs and their uses?
midazolam (anaesthetic), triazolam (hypnotic)
what are the intermediate BZDs and their uses?
Temazepam (hypnotic), Lorazepam (anxiolytic/sedative)
what are the long acting BZDs and their uses
diazepam
(anxiolytic/sedative, hypnotic, anaesthetic, status epilepticus (anti-convulsant)
- longer acting for chronic conditions
Adverse effects of BZDs
- acute toxicity/ overdose –> severe respiratory depression, esp w concurrent use of alcohol
–> treated w flumazenil, a benzodiazepine antagonist
- SE: drowsiness, confusion, amnesia
- impaired muscle co-ordination (impair manual skills - cannot use machinery) - tolerance: depends on freq of use
- develops faster for epilepsy than for use to induce sleep - dependence: withdrawal effect = disturbed sleep, rebound anxiety, tremor, convulsion
- to withdraw GRADUALLY
- has abuse potential
What are the names of the non-BZDs
- zolpidem
- buspirone
- barbiturates
- pregabalin
- hydroxyzine
- propanolol
MOA of Zolpidem
- potentiates GABAa mediated CL- currents at the same site as BZD
Therapeutic effects of zolpidem
- good hypnotic effect: PRIMARILY used to treat insomnia
- NOT effective as an anxiolytic
MOA of buspirone
- serotonin 5-HT1A receptor partial agonist
- bind to dopamine receptors
Therapeutic effects of buspirone
- GAD, but anxiolytic effect takes 1-2 weeks
- lacks anti-convulsant and muscle relaxant properties
MOA of barbiturates
potentiates the GABAa mediated CL- current, at barbiturate site (not at BZD site)
Therapeutic effect of barbiturates
- sedative-hypnotic BUT
- NOT used freq due to higher tolerance and dependence compared to BZDs (barbiturates: directly proportional vs BZDs: increases and plateaus)
- severe withdrawal symptoms
- flumazenil not effective in treating barbiturate overdose
- at anaesthetic doses (higher doses) –> e.g. phenobarbital can DIRECTLY open CL- channels and block Na+ channels
3 different types of barbiturates
- long-acting (1-2 days)
- short (3-8hrs)
- ultra-short (20min)
therapeutic effect of long acting barbiturates?
- anticonvulsant –> phenobarbital
therapeutic effect of short acting barbiturates?
sedative & hypnotic –> pentobarbital, amobarbital
therapeutic effect of ULTRA short acting barbiturates?
IV induction of anesthesia –> thiopental
MOA of pregabalin
- GABA analogue increases synaptic GABA –> GABA receptor mediated CL- current –> hyperpolarization
- acts on voltage-gated Ca2+ channels
SE of pregabalin
- assoc w worsening of suicidal thoughts
Therapeutic effect of pregabalin
- treat GAD, also has anticonvulsant effect
MOA of hydroxyzine
- first gen antihistamine;
- anxiolytic effect: antagonism of serotonin 5-HT2 receptors
- activity on a-adrenergic receptors as well
Use of hydroxyzine
- low addictive potential (compared to BZD/barb)
- helps w itching and nausea manifestation of anxiety
MOA of propanolol
BB: b-adrenergic receptor antagonist
Use of propanolol
- treat performance anxiety and social phobias
- reduce PHYSICAL symptoms assoc w adrenergic activation
CI of propanolol
asthma and heart conditions
Other anxiolytics names:
NaSSA: Mirtazapine
TCA: Clomipramine
SSRI: fluoxetine, citalopram, sertraline, paroxetine
SNRI: venlafaxine, duloxetine
