Benzodiazepines Flashcards
Define Anxiety.
An unpleasant state of tension, apprehension, and uneasiness… It is a fear that arises from an unknown source.
What are the physical manifestations of anxiety?
Sympathetic activation, e.g., tachycardia and sweating.
Do episodes of mild anxiety warrant treatment?
No.
Does severe, chronic, and debilitating anxiety warrant treatment?
Yes.
What names do anti anxiety medications have?
Anxiolytic drugs.
Minor tranquilizers.
What secondary effect do anxiolytics have besides their primary action?
Sedative effect.
What is the term for drugs that induce sleep?
Hypnotics.
Explain.
Benzodiazepines are generally safer because their effects plateau before reaching life-threatening CNS depression.
Compare Drug A and Drug B.
Drug A quickly causes deep CNS depression; risky. (e.g., barbiturates and alcohol).
Drug B is safer as its effects are gradual and higher doses are needed for serious CNS depression (e.g., benzodiazepines).
Which class of drugs is most commonly used for treating anxiety? Why?
Benzodiazepines.
They are safer and more effective than older classes of medications (barbiturates).
What neurotransmitter receptors do benzodiazepines target?
GABA receptors.
How many benzodiazepine receptor subtypes are there?
There are two main types: BZ1 and BZ2.
Which subunit is associated with BZ1 receptors?
α1
Which subunit is associated with BZ2 receptors?
α2
What effect do benzodiazepines have on the affinity of GABA for its receptor?
They enhance GABA binding to its GABA-A receptor.
Where are benzodiazepine receptors located?
Parallel to GABA receptors.
What is benzodiazepines’ mechanism of action?
Benzodiazepines bind to their own specific receptors that are adjacent to GABA-A receptors.
This potentiates the binding of GABA to its own receptor.
This increases chloride ions moving into cells, causing membrane hyperpolarization, reducing action potentials.
Do benzodiazepines bind to the same site that GABA binds to the receptors?
No.
What are the adverse effects associated with benzodiazepines?
Drowsiness and confusion (most common).
Ataxia at high doses, negatively affecting motor coordination (avoid driving).
Cognitive impairment in the form of decreased long-term recall of new knowledge.
Which patients need to take precautions when using benzodiazepines?
Liver disease patients.
Acute-narrow-angle glaucoma patients.
Alcohol and other CNS depressant consumers.
What activities do benzodiazepines NOT exhibit?
No antipsychotic or analgesic activity.
They also don’t affect the autonomic nervous system.
Which specific GABA-A receptor subunits are targeted by benzodiazepines for their effects?
α1, α2, α3, and α5 subunits.
Which GABA-A receptor subunit is associated with sedation, amnesia, and hypnosis?
α1.
Which GABA-A subunits are associated with anxiolytic and muscle relaxant effects?
α2 and α3.
Which GABA-A subunit is associated with memory impariment?
α5 subunit.
What factors determine the effect of benzodiazepines?
Dose and subsequent selectivity.
What therapeutic actions do benzodiazepines exhibit?
- Anti-anxiety.
- Sedative.
- Anterograde amnesia.
- Anticonvulsant.
When are benzodiazepine anxiolytic?
At low doses (α2 subunit).
When are benzodiazepines sedative and hypnotic?
All have some sedative properties; some can produce hypnosis at higher doses (α1 subunit).
Which subunit is associated with anterograde amnesia in benzodiazepine use?
α1 subunit.
Which subunit is associated with anticonvulsant activity in benzodiazepine use?
α1 subunit.
When do benzodiazepines exhibit a muscle relaxing effect?
At high doses (α2 subunit).
How are benzodiazepines classified?
Based on the duration of action:
1. Long-acting.
2. Intermediate-acting.
3. Short-acting.
List long-acting benzodiazepines.
Clonazepam.
Chlordiazepoxide.
Diazepam.
Flurazepam.
Quazepam.
List intermediate-acting benzodiazepines.
Alprazolam.
Estazolam.
Lorazepam.
Temazepam.
List short-acting benzodiazepines.
Oxazepam.
Triazolam.
What is the duration of action of long-acting benzodiazepines?
1-3 days.
What is the duration of action of intermediate-acting benzodiazepines?
10-20 hours.
What is the duration of action of short-acting benzodiazepines?
3-8 hours.
Why are the half-lives of benzodiazepines important?
Their half-lives (i.e., duration of action) determine the therapeutic usefulness.
Do individual benzodiazepines show big differences in their relative anxiolytic, anticonvulsant, and sedative properties?
No (They show small differences in their relative properties).
Which types of anxiety are benzodiazepines used for?
Generalized anxiety disorder.
Social anxiety.
Performance anxiety.
Post-traumatic stress disorder.
Why shouldn’t benzodiazepines be used long-term?
They cause addiction.
Why are longer-acting benzodiazepines preferred for treating patients who require treatment for prolonged periods of time?
Low risk of addiction.
Why do benzodiazepines have a small potential for tolerance when used to control anxiety compared to sedative and hypnotic effects?
Lower dose is used for anxiety.
When does tolerance usually set in with benzodiazepine use?
When used for more than two weeks, due to decreased GABA receptor density.
Why should benzodiazepines be avoided with alcohol consuming patients?
Benzodiazepines potentiate the alcohol effective, causing additive CNS depression.
Which substances do benzodiazepines share cross-tolerance with?
Ethanol.
Chlordiazepoxide.
Which benzodiazepine is effective for short-term and long-term treatment of panic disorders?
Alprazolam.
What serious risk is associated with alprazolam when it is used to treat panic disorders?
Withdrawal reactions occur in about 30% of sufferers.
Which benzodiazepine is used to treat skeletal muscle spams, such as the ones that occur in muscle strain and degenerative disorders like multiple sclerosis and cerebral palsy?
Diazepam.
Which class of benzodiazepines are used for amnesia?
Shorter-acting agents.
When are short-acting benzodiazepines used to induce amnesia?
Before unpleasant procedures, such as endoscopic, bronchoscopic, dental procedures as well as angioplasty.
What type of sedation do shorter-acting benzodiazepines cause (when used to induce amnesia)?
Conscious sedation.
Which benzodiazepine is used as an injection-only inducer of anesthesia?
Midazolam.
Which benzodiazepines are used to treat grand-mal epileptic seizures and status epilepticus?
Diazepam.
Lorazepam.
Which benzodiazepines are used to acutely manage alcohol and barbiturate withdrawal and seizures due to cross-tolerance?
Chlordiazepoxide.
Clorazepate.
Diazepam.
Oxazepam.
What does the sleep cycle consist of?
Deep sleep (slow, long).
Rapid eye movement (REM) (faster).
What are the characteristics of rapid eye movement (REM) phase of the sleep cycle?
Rapid random eye movement.
Low muscle tone.
Vivid dreams.
Heart rate, cardiac pressure, cardiac output, arterial pressure, and breathing rate become irregular.
Are all benzodiazepines useful as hypnotic agents?
No.
How do benzodiazepines affect sleep?
Make one fall asleep faster.
Increase stage 2 of non-REM sleep (i.e., REM sleep and slow wave sleep duration is decreased).
Which benzodiazepines have a strong hangover effect?
Long-acting benzodiazepines.
Why are non-benzodiazepine hypnotic drugs (such as zolpidem, and zaleplon) are preferred as hypnotic drugs over benzodiazepines?
They do not affect sleep stages.
Which long-acting benzodiazepine is most commonly prescribed for sleep disorders?
Flurazepam.
Which intermediate-acting benzodiazepine is most commonly prescribed for sleep disorders?
Temazepam.
Which short-acting benzodiazepine is most commonly prescribed for sleep disorders?
Triazolam.
Which benzodiazepine receptor do benzodiazepines affect when used to treat sleep disorders?
BZ1 receptor.
Flurazepam, a benzodiazepine used to treat sleep disorders, has an active metabolite, resulting in long half-life.
How does this affect its therapeutic profile?
Shortens sleep onset and reduces awakenings.
Extends total sleep time.
Minimally causes rebound insomnia.
However, it leads to daytime drowsiness and drug buildup.
Which type of sleep disorder is the benzodiazepine temazepam most effective for?
Patients who experience frequent wakening; useful for insomnia caused by the inability to stay asleep.
When should temazepam be given when it is used to treat sleep disorders?
1-2 hours before the desired bedtime as the peak sedative effect sets in n1 to 3 hours after an oral dose.
This is done so the onset of action is delayed and the time it takes for the patient to fall asleep is not affected.
Which type of sleep disorder is the benzodiazepine triazolam most effective for?
Helping patients with insomnia (difficulty in going to sleep) to fall asleep.
How quickly can tolerance develop with triazolam use?
Within a few days.
What can happen when triazolam is discontinued?
Rebound insomnia.
What strategy is recommended to prevent tolerance for triazolam?
Take triazolam intermittently, not daily, to prevent tolerance.
For what maximum duration should triazolam be prescribed?
Not for more than two weeks.
What property of benzodiazepines allows for their rapid and complete absorption?
Lipophilicity.
Through which bodily system are most benzodiazepines metabolized?
By hepatic microsomal enzyme system.
Name two benzodiazepines suitable for patients with liver dysfunction.
Lorazepam.
Oxazepam.
Why might the clinical effect of benzodiazepines not align with their half-life?
Their clinical effect is terminated by redistribution, not just excretion.
Should benzodiazepines be given to pregnant or breastfeeding women? Why or why not?
No, they should not; as they can cross the placenta and are excreted in breast milk.
What can prolonged use of high doses of benzodiazepines lead to?
Psychological and physical dependence.
List some withdrawal symptoms from abrupt discontinuation of benzodiazepines.
Confusion.
Anxiety.
Agitation.
Restlessness.
Insomnia.
Tension.
Rarely, seizures.
Which type of benzodiazepines are more likely to cause abrupt and severe withdrawal symptoms?
Short half-life benzodiazepines like triazolam.
How do less potent benzodiazepines, such as flurazepam, that are slowly eliminated affect sleep after discontinuation?
Induce less abrupt and severe withdrawal reactions.
What is the function of flumazenil?
Flumazenil acts as an antagonist to GABA-A receptors and reverses the effects of benzodiazepines.
How is flumazenil administered?
Intravenously.
Describe the onset and duration of action of flumazenil.
Rapid onset and a short duration of action.
Why is flumazenil not typically used for treatment?
Its short action does not align with the longer action of most benzodiazepines; it’s mainly used for diagnosis.
What are the risks associated with using flumazenil in dependent patients?
May precipitate withdrawal symptoms in dependent patients or cause seizures if benzodiazepines were used to control seizures.
