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Anxiolytics
- caution
Caution surrounding Psychotropics
Effect size of antidepressants for anxiety = 1.2
Effect size of antidepressants for depression = 0.7
Benzos are very common sedatives. In general population, 8% have used benzos in the past year; 2% have used them for over a year.
- types
- uses
- side effects
- adverse drug reactions
- potential for abuse
- withdrawal
- mechanism of action
- pharmacokinetics
Types of benzodiazepines
The big difference of benzodiazepines is length of action.
- diazepam (Valium) - most rapid onset, long acting
- lorazepam (Ativan) - rapid onset, long acting
- alprazolam (Xanax) - fast onset, short-acting, fast offset
- interdose withdrawal leads to feelings of anxiety and high dependency
- clonazepam (Klonopin) - intermediate
- midazolam (Versed) - fast-acting
- triazolam - short
- oprazolam - short
- fluorazepam - long (t1/2 of 100 hours)
- chlordiazepoxide
down-regulation of GABAA receptors occurs a lot
Uses
should be given for at most weeks or months due to potential for dependence and side effects.
- anxiety
- specific and social phobias
- panic disorder
- insomnia (quick acting is best)
- phobias
- chemotherapy-induced vomiting
- treatment of epilepsy
- as a component of anesthesia
- seizures
- alcohol withdrawal
- muscle spasms
- as a diagnostic aid (not sure how)
Side Effects
- sedation
- dizziness, weakness, ataxia
- psychomotor impairment
- cognitive impairment
- anterograde amnesia (used in cancer centres to prevent negative associations from forming
- nausea, slight hypotnesion
- personality changes in less tha 1%, but disinhibition can lead to rage etc
- loss of coordination
- increased traffic accidents
long term use can result in cognitive decreases
Adverse Drug Reactions
- enhanced toxicity of other CNS depressants, ie alcohol, TCAs, barbiturates
Overdose: give flumazinil
Interactions
There are varying effects of alcohol on benzo concentrations.
Synergistic pharmacological interactions occur.
Overuse, misuse, abuse
- people factors:
- multiple drug abuse
- alcohol drug abuse
- need for large doses
- recent abrupt BZP d/c
- drug factors:
- rapid onset, offset
- euphoriant effects
specific tricky drugs:
- Triazolam: rapid onset/offset, euphoriant
- Alprazolam: rapid offset, significant withdrawal effects
- Diazepam: most rapid onset, euphoriant
Withdrawal
Symptoms of BZD withdrawal syndrome:
- insomnia
- anxiety
- GI distress
- diaphoresis
- tremor
- GI distress
- lethargy
- dizziness
- headache
- increased sensory acuity (hearing, visual)
- zappy feelings in your fingers
- seizure
- psychosis
- delirium
risk factors:
- short acting agents
- dose and duration
- rate of discontinuation
- panic disorder or severe Axis II disorder
- concomitant alcohol/substance abuse
lose dose: tachycardia, hypertension, insomnia
high dose: seizures, psychosis
Stopping Treatment
To stop treatment, in general you should taper off with all psychotropics.
Go really slow at the end of the taper (asymptotic)
get patient involved in drafting the schedule
have a treatment plan for break-through emergence of symptoms (PRNs)
switch to long-acting BZP prior to taper (ie clonazapam or diazepam)
Benzo agonists
facilitate GABA action: zolpidem, zaleplon, eszopiclone
antagonists: used in overdose: flumazenil
inverse agonists: act as negative allosteric modulators of GABA receptors
Mechanism of action
Benzodiazepines bind to chloride channels in neurons, causing conformational changes that increase GABA binding and subsequent chloride channel opening. This leads to hyperpolarization and inhibits CNS activity.
Pharmacokinetics
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Phase I capacity decreases with age, meaning half life will be increased in the elderly.
Non-phase I metabilized drugs: lorazepam, o, tamazapam