Anti-anxiety Pharmacology Flashcards Preview

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Flashcards in Anti-anxiety Pharmacology Deck (28)
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1
Q

What are the barbiturate drugs?

A

“-barbital; -pental”

Phenobarbital, pentobarbital, thiopental, secobarbital

2
Q

What is the mechanism of barbiturates?

A

Facilitate GABAa action by increasing duration of Cl- channel opening and thus decreasing neuron firing

(barbiDURATes) = (increase DURATion)

3
Q

Why have barbiturates been phased out of us and benzodiazepines been phased in?

A

Both work to sedate and lower anxiety, however high amounts of barbiturates can be FATAL, whereas benzodiazepines level off and overdose is not fatal

4
Q

Name the benzodiazepines.

A

“-am” + clorazepate + chlordiazepoxide (Librium)

“-am” = diazepam (Valium), lorazepam (Ativan), triazolam, temazepam, oxazepam (generic), midazolam (Versed), clonazepam (Klonapin), alprazolam (Xanax)

5
Q

Are benzodiazepines lipophilic or hydrophilic?

A

They are lipophilic. Benzodiazepines are taken orally, and since they are lipophilic they can cross the blood-brain barrier, as well as cross the placenta and enter breast milk. A mother taking benzodiazepines must be careful.

6
Q

What is the shortest-acting benzodiazepine?

A

Midazolam with a half-life of 1-7 hours. Its sedation is short.

Midazolam is used during medical or surgical procedures (endoscopy, bronchoscopy) and premedication prior to anesthesia - its full effect occurs in 20-30 minutes, and a few hours later, the effects wear off fully!!

*Be careful because it has higher addictive potential!

7
Q

How do you dose benzodiazepines?

A

Sparingly! Benzodiazepines reach peak blood levels VERY quickly and last a long time - they have cumulative effects such as increasing drowsiness, so you need to dose them sparingly

8
Q

How are benzos eliminated?

A

Entirely through hepatic mechanisms! Most common ACTIVE METABOLITE of benzodiazepines is desmethyldiazepam (nordiazepam) with a half-life of >40 hours –> cumulative effects which can really affect the elderly (older livers don’t metabolize/clear well - standard dose in elderly is HALF)

*If people have liver problems, benzos are very problematic because they can accumulate.

9
Q

What is the mechanism of a benzodiazepine?

A

Facilitates GABAa action by increasing the frequency of Cl- channel opening –> inhibitory

10
Q

Which drugs bind to the GABA receptor?

A

GABA, benzodiazepines, flumazenil, zolpidem (non-benzo hypnotic), barbiturates

They all bind to different sites on the receptor, so they are all synergistic!!

11
Q

What are the clinical uses of benzodiazepines?

A
  • Anxiety reduction, accompanied by some depressant effects of psychomotor (reaction times) & cognitive functions
  • At doses that lower anxiety, BZs can cause disinhibitory effects such as euphoria, impaired judgment and loss of control

Side effect: dose-dependent ANTEROGRADE amnesia - you can’t remember events occurring during drug’s duration of action

12
Q

Which BZs are used for status epilepticus?

A

Diazepam (Valium) & Lorazepam (Ativan) - smaller dose than that given for anxiety is used to stop a seizure - crazy!

Clonazepam (Klonapin) also has some anticonvulsant effects.

13
Q

Which BZs are used for general anesthesia?

A

Diazepam (Valium), Lorazepam (Ativan), and Midazolam (Versed)

14
Q

Which BZ is used to stop a muscle spasm?

A

Diazepam (Valium) - stops the muscle spasm and also relaxes the muscle

15
Q

Tell me about BZs and respiratory depression.

A

At hypnotic doses in healthy patients, BZs have a comparable effect on respiration to changes that occur during natural sleep. (lower respiration to levels normal for sleep)

However, if patients have compromised lung function (pulm disease or asthmatic), even at therapeutic doses, BZs can produce significant respiratory depression - problem!

16
Q

When is cardiovascular depression present with BZs?

A

At levels higher than that necessary for sleep (more than hypnotic dose)

*NOTE: in patients with hypovolemic states, heart failure, and other diseases that impair CV function, even normal doses can –> cardiovascular depression

17
Q

What is the drug that instantly reverses BZ effects?

A

Flumazenil (competitive inhibitor of BZ that binds directly to BZ site on GABAa receptor)

Flumazenil antagonizes actions of BZs and the newer hypnotics zolpidem, zaleplon, and eszopiclone, but NOT the barbiturates.

*Flumazenil has short half-life, about 1 hr, so sedation commonly occurs bc BZs still working (half life about 10 hours) - must give repeated doses of flumazenil!

18
Q

Although BZs are better for short-term use, some of them have long-term uses for __ and ___.

Name the BZs used for long-term management.

A

GAD (generalized anxiety disorder) & panic disorders.

  • Alprazolam (Xanax) - GAD, panic disorder, agoraphobia
  • Lorazepam (Ativan) - panic disorder
  • Clonazepam (Klonopin) - GAD and social phobia
19
Q

What are the advantages of BZs?

A
  • Rapid onset
  • Relatively high therapeutic index & availability of flumazenil for treatment of overdose
  • Low risk of drug interactions based on liver enzyme induction
  • Minimal effects on cardiovascular and autonomic functions
20
Q

Disadvantages of BZs?

A
  • Risk of dependence
  • Depression of CNS functions (additive when administered with other drugs, including antihistamines, anticholinergics, and ethanol)
  • Amnesic effects
21
Q

BZs are used to treat alcohol withdrawal to prevent what from occurring? Which BZs are used in this regard?

A

Delirium tremens is the harmful phenomenon which occurs during severe alcohol withdrawal.

The following BZs are used:

  • Diazepam (Valium) - longer-acting, administered in progressively decreasing doses
  • Lorazepam (Ativan) - parenteral use to suppress DTs
22
Q

How can you tell when a patient is coming close to toxic levels of benzodiazepines?

A

Toxicity will present as severe lethargy, not responding, moving very slowly, and very confused - similar to gross symptoms of ethanol intoxication (behavioral disinhibition)

23
Q

Abrupt cessation of benzos can precipitate withdrawal symptoms. What are the withdrawal symptoms?

A

States of increased anxiety, headaches, insomnia, and CNS excitability that may progress to convulsions.

*Short half-life BZs cause more severe withdrawal signs than longer half-life BZs, which are eliminated more slowly and achieve gradual withdrawal.

24
Q

What is BuSpar?

A

Buspirone (BuSpar) is a newer, non-GABAergic anxiolytic drug - it has selective anxiolytic effects without causing marked sedative, hypnotic, or euphoric effects

25
Q

What is the mechanism of BuSpar/Buspirone?

A

Partial agonist at brain 5-HT1a receptors, though also has affinity at brain dopamine D2 receptors

26
Q

When is BuSpar/buspirone used?

A

BuSpar is used in generalized anxiety states (and doesn’t have amnesic effects like BZs), but less effective in panic disorders.

Anxiolytic effects of BuSpar may take > 1 week to show, making drug unsuitable for acute anxiety states.

BuSpar isn’t effective in blocking acute withdrawal syndrome resulting from abrupt cessation of BZs bc it doesn’t act through GABA

BuSpar patients show no rebound anxiety or withdrawal signs on abrupt discontinuation - yay!

27
Q

Differentiate the drug interactions of Benzodiazepines and BuSpar.

A

Benzodiazepines - no drug interactions!!

BuSpar - inhibitor of CYP3A4 - but therapeutic window is so short and useful that you can deal with that

28
Q

How are beta-blockers used in anxiety & which ones in particular are used?

A

Beta-blockers are used to control the physical symptoms of anxiety (trembling and sweating).

Particularly useful in short periods of time when patient is facing anxiety-producing event (social phobia, giving speech, attending a meeting).

Propranolol and atenolol are the beta-blockers used.