Anxiolytic and Hypnotic Drugs Flashcards
Define anxiety.
An unpleasant emotional state consisting of apprehension, tension, and feelings of danger without a real or logical cause.
What are the physical symptoms seen with anxiety?
Tachycardia.
Tachypnea.
Sweating.
Trembling.
Weakness.
How do benzodiazepines work, including details on their receptor subtypes and mechanism of action?
Benzodiazepines target GABA receptors.
Two benzodiazepine (BZ) receptor subtypes are commonly found in the CNS, designated as BZ1 and BZ2 receptors, depending on whether their composition includes the α1 subunit or the α2 subunit, respectively.
The binding of the benzodiazepine to its site on the GABA-A receptor increases the affinity of GABA to bind to the receptor. The BZ receptor locations in the CNS are parallel to those of the GABA neurons.
Binding of GABA to its receptor triggers an opening of a chloride channel, i.e., an increase in chloride influx, resulting in a hyperpolarization that moves the postsynaptic ptoential away from its firing threshold, thereby inhibiting the formation of action potentials.
So, in other words, benzodiazepines amplify the effect of GABA by increasing the frequency at which chloride channels open, thus enhancing GABA’s inhibitory action on neuronal activity.
Do benzodiazepines bind on the same site on the GABA receptors as gaba itself?
No. Instead, BZs attach to a distinct allosteric binding site on the GABA receptor, which enhances the affinity of the inhibitory neurotransmitter GABA for the receptor, thus amplifying its inhibitory effect.
Do benzodiazepines have antipsychotic activity or affect the autonomic nervous system?
No, benzodiazepines do not have antipsychotic activity, nor do they affect the autonomic nervous system.
Where are GABA-A receptors found in the human body, and what are their subunits?
GABA-A receptors are present in the human body in various isforms, and each one contains a particular type of subunit: α1, α2, α3, and α5.
What effects are produced upon the activation of different GABA-A receptor subunits?
The α1 subunit is associated with sedation, amnesia, and hypnosis.
The α2 and α3 subunits are associated with anxiolytic and muscle relaxant effects.
The α5 subunit is associated with memory impairment.
How does the effect of benzodiazepines vary?
The effect of benzodiazepines depends mainly on the dose and subsequent selectivity.
What is the primary effect of benzodiazepines at low doses, and which subunit do they act upon?
At low doses, benzodiazepines are anxiolytic, primarily acting on the α2 subunit.
What type of amnesia is associated with benzodiazepine use and which subunit does it affect?
Benzodiazepines can cause anterograde amnesia, which is a temporary impairment of memory formation. This effect is linked to the α1 subunit.
What are the sedative and hypnotic effects associated with benzodiazepines, and how do these effects change with higher dosages?
Benzodiazepines are known for their sedative and hypnotic actions; they all possess some sedative properties, and at higher doses, some can produce hypnosis, which is an artificially induced sleep. These effects are associated with the α1 subunit.
In addition to their sedative and hypnotic effects, what role do benzodiazepines play in the treatment of seizure disorders, and which receptor subunit is primarily involved in this action?
Several benzodiazepines have anticonvulsant activity and are utilized in the treatment of epilepsy, including status epilepticus, as well as other seizure disorders.
This therapeutic effect is due to their affinity for the α1 subunit of the GABA-A receptor.
What is the effect of high doses of benzodiazepines on skeletal muscle, and which GABA-A receptor subunit do they primarily interact with to produce this effect?
At high doses, benzodiazepines act as muscle relaxants, alleviating spasticity of skeletal muscle. This effect is primarily mediated through the α2 subunit of the GABA-A receptor.
How are benzodiazepines classified based on their duration of action?
Benzodiazepines are classified into three categories based on the duration of their action:
1. Long-acting.
2. Intermediate-acting.
3. Short-acting.
Why is the half-life of benzodiazepines clinically important?
The half-lives of benzodiazepines are very important clinically because the duration of action of the drug may determine its therapeutic usefulness.
Different durations of action are suitable for different clinical situations and treatment goals.
Do individual benzodiazepines differ significantly in their therapeutic effects?
The individual benzodiazepines exhibit small differences in their relative anxiolytic, anticonvulsant, and sedative properties, which can influence their specific therapeutic uses.
In what types of anxiety disorders are benzodiazepines indicated?
Benzodiazepines should not be used to alleviate normal everyday stress because they are intended for the treatment of severe and continuous anxiety disorders and are not appropriate for the normal fluctuations in stress that people experience regularly.
Benzodiazepines are indicated for severe and continuous anxiety, including generalized anxiety disorder, social anxiety, performance anxiety, and post-traumatic stress disorder (PTSD).
Why should benzodiazepines not be used for long durations?
Benzodiazepines should not be used for long durations because they may cause addiction and lead to dependence.
Why are longer-acting benzodiazepines, such as clonazepam, diazepam, often preferred for prolonged treatment of anxiety disorders?
Longer-acting agents like clonazepam and diazepam are often preferred for prolonged treatment because they are less addictive than short-acting benzodiazepines and are less likely to lead to tolerance.
Why are the anti-anxiety effects of benzodiazepines less subject to tolerance than their sedative and hypnotic effects?
The anti-anxiety effects of benzodiazepines are less subject to tolerance than the sedative and hypnotic effects because a lower dose is typically sufficient to alleviate anxiety, reducing the risk of tolerance development.
What happens when benzodiazepines are used for more than two weeks?
When benzodiazepines are used for more than two weeks, tolerance can occur due to a decrease in GABA receptor density.
What is cross-tolerance in the context of benzodiazepines?
Cross-tolerance exists among benzodiazepines and other central nervous system depressants like ethanol, chlordiazepoxide, meaning tolerance to one can lead to tolerance to the others.
How do benzodiazepines interact with alcohol?
Benzodiazepines potentiate the effects of alcohol, leading to additive central nervous system depression.
What is the efficacy of alprazolam for panic disorders, and what is a notable risk?
Alprazolam is effective for short-term and long-term treatment of panic disorders but may cause withdrawal reactions in about 30 percent of sufferers.
What is diazepam’s role in the treatment of muscular disorders?
Diazepam is useful in the treatment of skeletal muscle spams, which may occur in conditions like muscle strain. It is also used in treating spasticity resulting from degenerative disorders, such as multiple sclerosis and cerebral palsy.
What is the purpose of using shorter-acting benzodiazepines in medical procedures?
Shorter-acting benzodiazepines are used before unpleasant medical procedures, such as endoscopic, bronchoscopic, and certain dental procedures like angioplasty, to induce conscious sedation, helping patients to relax while still being able to respond to stimuli.
Which benzodiazepine is commonly used for the induction of anesthesia and how is it administered?
Midazolam, which is an injectable-only benzodiazepine, is commonly used for the induction of anesthesia.
Which benzodiazepines are considered the drugs of choice for terminating grand-mal epileptic seizures and status epilepticus?
Diazepam and lorazepam.
How do certain benzodiazepines contribute to the treatment of alcohol and barbiturate withdrawal?
Due to cross-tolerance, benzodiazepines such as chlordiazepoxide, clorazepate, diazepam, and oxazepam are useful in the acute treatment of alcohol and barbiturate withdrawal and in reducing the risk of withdrawal-related seizures.
How does an organism’s sleep cycle alternate, and what are the characteristics of REM sleep?
In the sleep cycle, an organism alternates between deep sleep (which has slow, large brain waves) and rapid eye movement (REM) sleep (which has faster brain waves). REM sleep is a unique phase of mammalian sleep characterized by:
- Random movement of the eyes.
- Low muscle tone throughout the body.
- A propensity for the sleeper to dream vividly.
- Quickly changing and often irregular heart rate, blood pressure, cardiac output, arterial pressure, and breathing rate.
Are all benzodiazepines effective as hypnotic agents for sleep disorders?
Not all benzodiazepines are useful as hypnotic agents, although they all have sedative or calming effects, which is an important consideration for their use in sleep disorders.
What effects do benzodiazepines tend to have on the sleep cycle?
A. Decrease the latency to sleep onset, meaning they help individuals fall asleep more quickly.
B. Increase stage II of non-rapid eye movement (NREM) sleep. However, the duration of both REM sleep and slow-wave sleep are decreased.
Why is it important to balance the sedative effects of benzodiazepines at bedtime with their effects upon waking?
It is important to balance the sedative effect needed at bedtime with the hangover effect upon waking because long-acting benzodiazepines can lead to more pronounced hangover effects, which may impair cognitive and motor functions the following day.
Why might non-benzodiazepine hypnotic drugs be preferred for treating sleep disorders?
Non-benzodiazepine hypnotic drugs such as zolpidem and zaleplon are preferable as hypnotics for sleep disorders because they do not significantly alter sleep stages, thereby reducing the likelihood of hangover effects and preserving the natural structure of sleep.
Which benzodiazepines are commonly prescribed for sleep disorders and what is their mechanism of action?
Commonly prescribed benzodiazepines for sleep disorders include the long-acting flurazepam, intermediate-acting temazepam, and short-acting triazolam. Their mechanism of action involves targeting the BZ1 receptor, which contributes to their sedative effects.
Why is flurazepam considered a long-acting benzodiazepine for sleep disorders?
Flurazepam is considered a long-acting benzodiazepine for sleep disorders due to its active metabolite, which has a long half-life. This pharmacological feature contributes to its effects on sleep, such as reducing sleep-induction time, decreasing the number of awakenings, and increasing the total duration of sleep.
What are the potential advantages and disadvantages of using flurazepam?
The potential advantages of using flurazepam include its ability to reduce sleep-induction time and the number of awakenings, as well as increasing the duration of sleep, with little rebound insomnia reported. However, a disadvantage may be daytime sedation and the accumulation of the drug due to its long half-life, which can lead to hangover effects or cumulative sedation.
For which type of sleep disorder is temazepam particularly useful?
Temazepam is particularly useful for patients who experience frequent awakening, as it has an intermediate duration of action. It is beneficial for insomnia characterized by the inability to stay asleep.
When should temazepam be administered in relation to bedtime, and why?
Temazepam should be administered 1 to 2 hours before the desired bedtime. This timing is recommended because the peak sedative effect occurs 1 to 3 hours after an oral dose. However, it is noted that temazepam delays the onset of action and does not decrease the latency to fall asleep.
What characteristic of triazolam’s action makes it suitable for treating certain sleep disorders?
Triazolam has a relatively short duration of action, making it suitable for inducing sleep (decreasing sleep latency) in patients with recurring insomnia, particularly those who have difficulty falling asleep.
What should be considered when prescribing triazolam due to its potency and the risk of tolerance?
When prescribing triazolam, it’s important to consider that tolerance to this potent drug can develop quickly, often within a few days. Withdrawal from the drug can result in rebound insomnia. To avoid tolerance, triazolam should be prescribed for intermittent rather than daily use and should not be used for more than two weeks.
How are benzodiazepines absorbed and distributed in the body?
Benzodiazepines are lipophilic, meaning they can easily dissolve in fats, which allows them to be rapidly and completely absorbed after oral administration and distributed throughout the body.
What is the fate of most benzodiazepines in terms of metabolism?
Most benzodiazepines are metabolized by the hepatic microsomal enzyme system, including cytochrome P450 isozymes, to compounds that are also active, contributing to a longer duration of action.
Why are lorazepam and oxazepam preferred in patients with liver dysfunction?
In patients with liver dysfunction, lorazepam and oxazepam, which are metabolized extrahepatically (outside the liver), are less likely to cause excessive central nervous system (CNS) depression and are therefore preferred for use as preanesthetic sedation in these patients.
How is the effect of benzodiazepines terminated in the body?
The effect of benzodiazepines is not terminated solely by excretion but also by redistribution within the body. This is why sometimes the clinical effect is not directly correlated with the half-life of the drug.
Can benzodiazepines be used during pregnancy and lactation?
Benzodiazepines cross the placenta and are excreted in breast milk, which is why they are generally not recommended for use by pregnant individuals or breastfeeding women.
