Anxiolytics

Question 1

___: describes the category of drug whose original or most common use and intended therapeutic effect is to control or prevent anxiety or mental disorders whose primary feature is anxiety.

___: a drug which depresses CNS function, leading to a calming or relaxed state.

___: a drug which produces drowsiness and facilitates the onset and maintenance of a state that resembles natural sleep, and from which the patient can be aroused.

___: a drug which produces insensibility (general anesthesia - unconsciousness) from which the patient cannot be extricated without its removal.

Answer 1

Anxiolytic: describes the category of drug whose original or most common use and intended therapeutic effect is to control or prevent anxiety or mental disorders whose primary feature is anxiety.

Sedation: a drug which depresses CNS function, leading to a calming or relaxed state.

Hypnotic: a drug which produces drowsiness and facilitates the onset and maintenance of a state that resembles natural sleep, and from which the patient can be aroused.

Sedative vs Hypnotic

(Sedatives are usually given during daytime hours,and although they may make the patient drowsy, they usually do not produce sleep. A hypnotic is a drug that induces sleep)

Anesthetic: a drug which produces insensibility (general anesthesia - unconsciousness) from which the patient cannot be extricated without its removal.

Question 2

BZDs are useful in treating many types of anxiety disorders including anxiety that accompanies some forms of __ and __.

• Longer-acting BZDs (like ___) are often preferred in patients with more chronic forms of anxiety.
• Anxiolytic effects of BZDs are subject to less ___ than the sedative or hypnotic effects.
• Most BZDs have some ____ activity.
• ____ is useful in the chronic treatment of epilepsy, whereas diazepam and lorazepam are useful in terminating __-__ epileptic seizures and status epilepticus.
• ___ withdrawal can precipitate seizure activity and BZDs are often administered to ___ these seizures.
• ____ is useful in treatment of skeletal muscle spasms as occur in muscle strain, and in the treatment of spasticity from degenerative disorders, such as multiple sclerosis and cerebral palsy.
• BZDs are useful ____ agents, although most have ___ or __ effects.
• The 3 most commonly prescribed BZDs for sleep disorders are:
  1. ____ - long-acting
  2. ____ - intermediate-acting
  3. ____ - short-acting

(The florist team ran a triathalon)

BZDs can cause:

• Reduction in sleep ___
• Suppression of ___ sleep.
• Decreases in all components of sleep except Stage ___.
• Development of ____ to sleep effects with continued use.

MOA

• BZDs are potent potentiators of ____ inhibitory neurotransmission.
• BZDs are not ____ agonists at GABA-A receptors, nor do they ___ neuronal or extraneuronal uptake of GABA.

Instead, in the presence of GABA, BZDs enhance GABA-induced ____ currents resulting in ____. The net effect is decreased neuronal activity.

• BZDs have no ___ activity.
• They are believed to reduce ___ by selectively inhibiting neuronal circuits in the limbic system.
• They are thought to relax ____ by increasing pre-synaptic inhibition in the spinal cord.

The __ __-___ is the factor that decides which benzo is prescribed.

BZDs have a ___ therapeutic index and almost never produce fatal consequences by themselves. BZDs work quickly. Individuals who take massive doses in attempts at suicide generally ___ __ and ___ 24-48 hrs later. The exception is ___ and BZD co-administration, in which death via respiratory failure is of concern.
__ and __ = a deadly cocktail

• __ and __ are often prescribed together
• BZPs can enhance the ___ “high” but they also enhance the sedative and respiratory depressant effects of these drugs
• In the last 15 years, there has been a 400% increase in __ + ___ combo deaths.

Answer 2

BZDs are useful in treating many types of anxiety disorders including anxiety that accompanies some forms of schizophrenia and depression.

• Longer-acting BZDs (like diazepa) are often preferred in patients with more chronic forms of anxiety.
• Anxiolytic effects of BZDs are subject to less tolerance than the sedative or hypnotic effects.
• Most BZDs have some anticonvulsant activity.
• Clonazapam is useful in the chronic treatment of epilepsy, whereas diazepam and lorazepam are useful in terminating tonic-clonic epileptic seizures and status epilepticus.
• Alcohol withdrawal can precipitate seizure activity and BZDs are often administered to suppress these seizures.
• Diazepam is useful in treatment of skeletal muscle spasms as occur in muscle strain, and in the treatment of spasticity from degenerative disorders, such as multiple sclerosis and cerebral palsy.
• BZDs are useful hyponotic agents, although most have sedative or calming effects.
• The 3 most commonly prescribed BZDs for sleep disorders are:
  1. Fluorazapam - long-acting
  2. Temezepam - intermediate-acting
  3. Triazolam - short-acting

“The florist team ran a triathalon”

BZDs can cause:

• Reduction in sleep latency
• Suppression of REM sleep.
• Decreases in all components of sleep except Stage 2
• Development of tolerance to sleep effects with continued use.

MOA

• BZDs are potent potentiators of GABA-ergic inhibitory neurotransmission.
• BZDs are not direct agonists at GABA-A receptors, nor do they inhibit neuronal or extraneuronal uptake of GABA.

Instead, in the presence of GABA, BZDs enhance GABA-induced chlorine currents resulting in hyperpolarization. The net effect is decreased neuronal activity.

• BZDs have no antipsychotic activity.
• They are believed to reduce anxiety by selectively inhibiting neuronal circuits in the limbic system.
• They are thought to relax muscle by increasing pre-synaptic inhibition in the spinal cord.

The elimination half-life is the factor that decides which benzo is prescribed.

BZDs have a high therapeutic index and almost never produce fatal consequences by themselves. BZDs work quickly. Individuals who take massive doses in attempts at suicide generally fall asleep and awaken 24-48 hrs later. The exception is alcohol and BZD co-administration, in which death via respiratory failure is of concern.
Opiods and BZDs = a deadly cocktail

• Opiods and BZDs are often prescribed together
• BZPs can enhance the opioid “high” but they also enhance the sedative and respiratory depressant effects of these drugs
• In the last 15 years, there has been a 400% increase in opioid + BZD combo deaths.

Question 3

• *Non BZD GABA-ergic Drugs:
  1. ____ (Ambien)
  2. ____ (Lunesta)**
• Not benzo’s, but bind to ___ ___ on GABA-A receptors (___>> a2, a3, but not a5) and increase GABAergic synaptic transmission.
• Effects are similar to BZDs, but are structurally unrelated to BZDs (e.g. zolpidem is an imidazopyridine derivative).
• Sedative/Hypnotics (minimal ___ activity)
• Metabolized by liver, t1/2 = 2-3 hrs.

Answer 3

• *Non BZD GABA-ergic Drugs:
  1. Zolpidem (Ambien)
  2. Eszopiclone (Lunesta)**
• Not benzo’s, but bind to BZD receptor on GABA-A receptors (alpha-1>> a2, a3, but not a5) and increase GABAergic synaptic transmission.
• Effects are similar to BZDs, but are structurally unrelated to BZDs (e.g. zolpidem is an imidazopyridine derivative).
• Sedative/Hypnotic activity (minimal anxiolytic activity)
• Metabolized by liver, t1/2 = 2-3 hrs.

Question 4

Buspirone (Buspar)

• ____ wks before anxiolytic effects observed (so not prescribed for ___).
• Anxiolytic without ___, __ and ___ ____ properties.
• Minimal tolerance or ___ liability
• Fairly ___ half-life

____ partial agonist (no BZD binding/interaction) D3 agonist.

S/E

Tachycardia, nervousness, dizziness, headache, light-headedness and GI distress.

Answer 4

Buspirone (Buspar)

• Two wks before anxiolytic effects observed (so not prescribed for panic).
• Anxiolytic without hypnotic, sedative and muscle relaxant properties.
• Minimal tolerance or abuseliability
• Fairly short half-life

5-HT1A partial agonist (no BZD binding/interaction) D3 agonist.

S/E

Tachycardia, nervousness, dizziness, headache, light-headedness and GI distress.

Question 5

Stress activates the_____ axis which, in concert with other physiological responses, coordinates our normal behavioral response to our environment.

Answer 5

Stress activates the Hypothalamic Pituitary Adrenal (HPA) axis which, in concert with other physiological responses, coordinates our normal behavioral response to our environment.

Question 6

Barbituates:

An __, __, ___ and ___. (AAAH)

• Not prescribed anymore for __ disorders
• They have a similar MOA as BZD (allosteric modulators), but the big difference is that at ___ doses, they are GABA mimetic (can activate GABA-A receptors in the absence of GABA, which produces excessive inhibition, and can cause ___ suppression).

Acute, massive barbiturate overdose results in ___ depression or ___ failure. The toxic effects are greatly potentiated by __ and other sedative-hypnotics.

• If the dose is not lethal, the patient may survive for many hours or days. Under these conditions, they will often become _____, with slow___, cyanosis, and greatly diminished ____.
• Maintenance of adequate respiration and circulation are the most important considerations in the treatment of acute poisoning.

In summary, barbiturates have a relatively ___ therapeutic index and have largely been replaced by ___ and other classes of sedative/hypnotic drugs.

Answer 6

Barbituates:

An anesthetic, anxiolytic, anticonvulsant, hypnotic. (AAAH)

• Not prescribed anymore for anxiety disorders
• They have a similar MOA as BZD (allosteric modulators), but the big difference is that at high doses, they are GABA mimetic (can activate GABA-A receptors in the absence of GABA, which produces excessive inhibition, and can cause respiratory suppression).

Acute, massive barbiturate overdose results in respiratory depression or renal failure. The toxic effects are greatly potentiated by alcohol and other sedative-hypnotics.

• If the dose is not lethal, the patient may survive for many hours or days. Under these conditions, they will often become comatose with slow respiration, cyanosis, and greatly diminished reflexes.
• Maintenance of adequate respiration and circulation are the most important considerations in the treatment of acute poisoning.

In summary, barbiturates have a relatively low therapeutic index and have largely been replaced by BZDs and other classes of sedative/hypnotic drugs.