Anxiolytics and Sedatives Flashcards
Define stress.
a normal re-action to an abnormal experience
What is the limit of time that patients should be taking benzodiazepine for anxiety ? What happens after that ?
2 to 4 weeks. After that, can have rebound effects of anxiety (i.e “emergence or re-emergence of symptoms that were either absent or controlled while taking a medication”)
Describe the trends in prescription of antidepressants and benzos.
Antidepressants have overtaken benzos, because benzos increasingly recognised as being problematic due to addiction and misuse
Identify the main indications for barbiturates.
- (Now obsolete as anxiolytics)
- IV induction agents (“drugs that, when given intravenously in an appropriate dose, cause a rapid loss of consciousness”)
- Anti-convulsant (NOT first line)
Identify the main problems associated with barbiturates.
Dependence / addiction / misuse
Narrow therapeutic index
Identify the main classes of drugs used as anxiolytics.
• Antidepressants • Benzodiazepines • Z-drugs • B-blockers • Other – Melatonin – Sedating antihistamine
How do beta blockers treat anxiety ? Which beta blocker is usually used, and what are the main pros of beta blockers as a treatment cf benzos ?
Manage the somatic symptoms of anxiety (tachycardia, tremors, palpitations, sweating), not the anxiety itself
PROPRANOLOL
Advantages: non-sedative, no dependence or abuse
Identify side effects of Benzodiazepines.
-Dependence / addiction / misuse
-Hangover effect (i.e. if taken at night, “morning and daytime drowsiness”)
– Sexual dysfunction
Describe the main features of Benzodiazepines wrt its absorption and metabolism.
- Highly lipophyllic (cross BBB quickly)
- Well-absorbed orally
- Highly protein bound (95%)
- Hepatic metabolism
- Active metabolites
- Excreted as glucoronide conjugate
Identify the main effects of Benzos.
Have 5 major effects
- Anxiolytic: reduce anxiety (α2 and α3 subunits on GABA receptor)
- Hypnotic: induce sleep (α1) (e.g. in patients with insomnia)
- Reduce muscle tone
- Anterograde amnesia (pros and cons) (e.g. patients with dental anxiety)
- Anticonvulsant effect
What is the problem associated with the anteretrograde amnesia affect of Benzos ?
In order to treat underlying anxiety, they have to be able to remember (e.g. in dental exam, that the procedure is painless)
What is the main difference between different Benzos.
Large number of benzodiazepines, all similar actions, main difference duration of action.
Identify the main administration routes for Benzos.
- Normally given orally or intravenously (IV effect faster, instant)
- Can be given by intranasal or rectal route (if difficult IV access e.g. convulsing patient)
- Not advised to be given intramuscular route (poorly absorbed + painful)
Identify the main benzos, and divide them by length of action.
- Short; lorazepam, temazepam (t1/2 8-12 hours)
- Intermediate: flunitrazepam
- Long acting: diazepamt (t1/2 20-100 hrs)
Describe the structure of the receptor to which Benzos bind.
GABAA receptors
- Pentameric arrangement
- Central ion channel pore (for Chloride)
- 18 possible subunits
- Approximately 30 forms of receptor
- Some subunits are location specific
How do benzos interact with the GABA receptor ?
• Anaesthetics and benzos allosterically activate the GABA(A) receptors
- Sedation mediated via GABA(A) with α1 subunit
- Anxiolysis mediated via GABA(A) with α2 and α3 subunits (benzo binding site is different to GABA binding site)
• Increase the frequency of opening (if ion channel is open, Chloride (extracellular ion) will come inside the cell, hyperpolarise it, and so it is less likely to discharge)
Identify any drugs used as antagonists to benzos.
- Mechanism of action
- Half life
- Side effects
- Administration and dose
FLUMAZENIL
- Mechanism: clinically, competitive benzo antagonist (reverse agonist, binds to receptors and has negative effects on receptor)
- Half life: short compared with benzos (hence may need to repeat dose or set up infusion)
- SE: may precipitate agitation and seizures + N/V
- Dose: IV in 100 mcg increments
Identify any alternatives to Flumazenil in benzo overdose.
• Supportive management (i.e. support airway) better than Flumazenil, because benzos by themselves will tend not to stop respiration (wide therapeutic index), although it can result in respiratory depression, reduce muscle tone and conscious levels
In what situations may benzos result in respiratory arrest ?
In combination with opioids/alcohol etc. (by themselves, wide therapeutic index so may depress respiration but tend NOT to stop respiration)
Z DRUGS
- Mechanism of action
- Effects
- Examples
Z DRUGS
-Mechanism of action: act via benzodiazepine receptors
-Effects: reduces anxiety, generates sleep, probably a bit less muscle relaxation cf benzos
-Examples:
Zopiclone
Zaleplon
Zolpidem
What are the main similarities and differences between Z drugs and Benzos.
- Structurally different
- Very similar pharmacodynamic profile
- Shorter acting than benzodiazepines (but still long-acting)
Define tolerance.
Tolerance: is a physiological state characterized by a decrease in the effects of a drug with chronic administration.
To what extent do patients develop tolerance to the effects of benzos.
Benzodiazepines:
tolerance develops quickly for sedative effects (if giving it for effect on sleep, may have to increase dose for same effects, so tell patient to take whenever they need it, ideally not every night) more slowly for anxiolytic and anticonvulsant effects.
What are the main mechanisms for tolerance ?
- Neuro-adaptive process
- Desensitisation of inhibitory GABA receptors
- Sensitisation of (excitatory) NMDA receptors
- Adaptions take place on different time scale
