Anxiolytics Flashcards
Manifestation of anxiety states?
- psychological components e.g. negative emotions
- phsyical symptoms like tachycardia, shortness of breath, nausea, gastric acid hypersecretion and trembling
Biochemical basis of anxiety?
- central and peripheral noradrenergic or adrenergic activation-> fight or flight response
- stress response -> HPA axis -> secretion of stress hormones (cortisol)
Therapeutic rationale for anxiety?
Since the CNS is too aroused/overactivated, you want to use a CNS depressant:
Anxiolytic -> reduces anxiety
Sedative -> causes sedation, relaxation
Hypnotic -> induces drowsiness and sleep, may have amnestic effects
Same drug can have more than one action depending on the dose.
What are the drugs used in treating anxiety?
Benzodiazepine:
- used as anxiolytic/sedative: diazepam, lorazepam
- uses as hyponotic: diazepam, triazolam, temazepam
- used as pre- anesthetic: diazepam, midazolam
- anti convulsant effect: diazepam
Non benzodiazepine:
- barbiturates: phenobarbital
- buspirone
- zolpidem
- propranolol
MOA of benzodiazepine?
Benzodiazepines potentiate GABA actions by increasing the frequency of GABA-induced channel opening.
Benzodiazepines bind to benzodiazepine site on GABA receptor -> potentiates binding of GABA to GABA site.
What are the different durations of actions of benzodiazepines?
Short acting - a few hours ; can be used to induce general anaesthesia (fast onset and short acting so patient becomes conscious quickly)
Intermediate acting - several hours
Long acting - days ; not used for induction for surgery bc you want pt to wake up quickly. Useful for chronic conditions like alcohol withdrawal syndrome.
Short acting:
Midazolam - used as anaesthetic adjuvant
Triazolam - Used for insomnia
Intermediate acting:
Temazepam: Used for insomnia
Long acting:
Diazepam: Used as anxiolytic/sedative, hypnotic, anti convulsant and anaesthetic adjuvant
Unwanted effects of benzodiazepines?
- acute toxicity/overdose: can cause respiratory depression especially when used concurrently with alcohol -> treat using flumazenil, a benzodiazepine antagonist.
side effects (bc of depression of CNS):
- drowsiness, confusion, amnesia.
- impaired muscle coordination (impairs manual skills)
Tolerance and dependence:
- depends on frequency of use. Tolerance develops faster for epilepsy than for use to induce sleep
- dependence can develop, withdrawal effects include disturbed sleep, rebound anxiety, tremor and convulsions -> impt to withdraw gradually
- has ABUSE POTENTIAL!!!
Non benzodiazepine: Zolpidem
What is the MOA of zolpidem?
What is zolpidem useful for?
- potentiates GABAA mediated chloride currents at the same site as benzodiazepines
- has good hypnotic effect -> primarily used to treat insomnia
- not effective as anxiolytics
Non-benzodiazepine: Buspirone
MOA of buspirone?
What is buspirone useful for?
- serotonin partial agonist + bind dopamine receptor
- indicated for GAD but anxiolytic effects takes 1-2 weeks
- lacks anticonvulsant and muscle relaxant properties
Non-benzodiazepine: Barbiturates
MOA of barbiturates?
Overdose from barbiturates?
- potentiates GABAA mediated chloride currents, but at a site distinct from benzodiazepines
- tendency to develop tolerance and dependence -> use as sedative-hypnotic replaced by benzodiazepine
- severe withdrawal symptoms
- flumazenil not effective for treating barbiturate overdose (bc barbiturate doesnt bind to benzo site)
- at anesthetic doses, barbiturates such as phenobarbital can directly open chloride channels as well as block sodium channels
What are the durations of action for barbiturates?
Long acting - a few days - useful for chronic conditions e.g. as anticonvulsant
Short acting - 3-8 hours
Ultrashort acting: 20min - IV induction of anaesthesia
Is the depression of CNS dose dependent?
For baribiturates, it is a straight line (doesnt taper off, hence more dangerous).
For benzodiazepines, it tapers off so less dangerous
Non-benzodiazepine: Pregabalin
MOA of pregabalin?
What is pregabalin used for?
Side effect of pregabalin?
- GABA analogue, increases synaptic GABA -> GABA receptor mediated chloride currents resulting in hyperpolarisation.
- also acts on voltage gated calcium channels
- used to treat GAD, also has anti convulsant effects
- may be associated with emergence of worsening of suicidal thoughts
Non-benzodiazepine: hydroxyzine
What is hydroxyzine used for?
- first gen antihistamine
- anxiolytic effect due to antagonism of serotonin 5HT2 receptors
- low addictive potential compared to BZD and barbiturates
- bc of antihistamine activity, also helps with itching
Non-benzodiazepine: Propanolol
MOA of propranolol?
What is propranolol used for?
Contraindica for propranolol?
- beta adrenergic receptor antagonist
- used for performance anxiety and social phobias
- reduces physical symptoms associated with adrenergic activation
- CI in asthma and heart conditions
