Sedatives. Anxiolytics Flashcards
Classes of Anxiolytics
- Barbituates (dependence; still in use as 3rd/4th line of AED)
- Benzodiazepines (dependence)
- Z-drugs
- Beta blockers (to reduce sympathetic somatic symptoms such as tchycardia, sweating etc)
- Antidepressants(SSRI)
- Melatonin
Benzodiazepines
MOA
Librium
Lorazepam - short duration 8-12hrs
Diazepam - long duration 1-3days
MOA:
- Allosterically (not the same site as endogenous agent) binding to GABAa receptors alpha 2,3 subunits
- ligand-gated Cl- channels open - influx of Cl- - hyperpolarisation - potentiate inhibitory effect of GABA
Clinical uses:
- Sedative/hypnotic (alpha1)
- Anxiolytics (alpha2,3)
- Reduce muscle tone (used to treat anxiety induced backpain)
- AED (Lorazepam 4mg IV)
- cause Anterograde Amnesia (not remembering after administration)
Benzodiazepines
Pharmacodynamics and pharmacokinetics
Highly lipophilic - transport across lipid membrane
Well absorbed orally, but can be given IV, intranasal and via rectal route
Highly protein bound,
Hepatic metabolism but active metabolites remain in the body, excreted as glucoronide conjugate
FLUMAZENIL
FLUMAZENIL
Inverse agonist (binds to the same receptor but induce opposite effect) of benzodiazepine.
Rarely used to reverse benzodiazepine overdose as may cause withdrawl symtoms (seizures, agitation).
Side effects including nauzea and vomiting - aspiration in unconscious patients with unprotected airway.
Z drugs
Zopiclone, Zolpidem, Zaleplon
Structurally different but same MOA as benzodiazepines
Tolerance
Tolerance:
Chronic administration leading to decrease in effect
(hence increasing dosage or frequency to achieve the same effect)
Benzodiazepines quick tolerance to sedative effects (alpha 1); Slow tolerance to anxiolytic (alpha2.3) & anticonvulsive effects
Mechanism:
- desensitisation of GABA receptors
- sensitisation of NMDA glutamate receptors
- Neuroadaptive processes
Dependance
Dependance: Compulsive taking due to rewarding/pleasant experience.
Can be physical - withdrawl symptoms; Psychological - craving; Genetic - alcohol related
Withdraw
As a result of physical dependence
syptoms include: anxiety/depression; insomnia, pain, stiffness, muscle aches, convulsions
therefore to avoid withdrawl symptoms, maximum 4wks of treatment
Indication for prescribing Anxiolytics/Sedatives
- Potentially uncomfortable medical procedures (Endoscopy)
- Acute alcohol withdrawl (sudden interrupted supply, anxiety/aggitation; tremor; nauzea/vomiting; sweating; palpitations; convulsions, life threatening. Librium 1-2wks)
- Insomnia - Caution in prescribing sedatives/hypnotics to elderly (falls, confusion); Sleep hygiene; Melantonin in children
- Generalised anxiety states - Guided self help; CBT; beta blockers + SSRI for somatic symptoms - sympathetic system related (tachycardia, palpitations, sweating and tremor)
- Prolonged seizures - Lorazepam IV 4mg or rectal diazepam if IV not available