Anxiolytics

Question 1

Phenytoin is metabolized by what CYP enzyme?

It induces what CYP enzyme?

Answer 1

metabolized - CYP2C9/10

induces - CYP3A4

Question 2

Which statins are not metabolized by CYP enzymes?

Answer 2

pravastatin - none

rosuvastatin (CYP2C <10% ; CYP2C19 minor)

Question 3

What is the level of response, airway, & CV support from minimal sedation?

What type of drugs is an example of minimal sedation?

Answer 3

Anxiolytics

• Response: responds normally to verbal commands
• Airway: maintained
• CV support: not needed

Question 4

Describe the pathways involved in axiety and how diazepam works to relieve this anxiety.

Answer 4

• basolateral amygdala complex (BLA) receives negative emotional signals from the thalamus
  
  • activates central nucleus (CeA) via excitatory projections
  • inhibits CeA via inhibitory GABAergic interneurons
• CeA (a2-containing GABA_A) receptors
  
  • outputs to brainstem & hypothalamus
  • Diazepam inhibits these outputs, which reduces the manifestations of anxiety

Question 5

hypnotic effects are mediated by what subunit?

Answer 5

a1 containing GABA_AR

Question 6

anxiolytic effects are mediated by what subunit?

Answer 6

a2 and a3 subunit containing GABA_AR

Question 7

Most benzos bind to waht subunit containing GABA_AR?

What about Z-drugs?

Answer 7

• Benzo - a(1,2,3,5)
• Z-drugs - a1
  
  • much more selective

Question 8

Effects of Benzodiasepines?

AE?

Answer 8

• Effect
  
  • reduce anxiety (limbic)
  • promote sleep (VPLO)
  • Induce muscle relaxation (supraspinal motor area)
  • anti-convulsive (AED)
• AE
  
  • decreased motor skills & confusion
  • anterograde amnesia (hipocampus & cortical area)
  • cardiovascular
  • respiratory
  • tolerance
  • sedation

Question 9

Describe the cardiovascular & respiratry effects of benzodiazepines

Answer 9

• cardiovascular
  
  • oral administration - very little
  • IV can produce hypotension & cardiac arrest
• respiratory effects
  
  • oral administration - very little
    
    • clinicaly significant only when combined with other CNS depressants
    • can be a proble in pt. with resp disorders
      
      • COPD, OSA

Question 10

What are the benzodiazepines?

Answer 10

• alprazolam
• chlordiazepoxide
• diazepam
• lorazepam

Question 11

What is the order of treatment for generalized anxiety disorder?

Answer 11

1. supportive / cognitive behavioral / biofeedback / relaxation training
2. pharmacology
   
   1. SSRI or SNRI or buspirone - delayed onset action (form long-term management)
   2. benzodiasepines - immediate, stabilization for severe anxiety

Question 12

Which benzodiazepines are most commonly used for anxiety?

Answer 12

alprazolam

lorazepam

Question 13

What is the major mechanism of action for benzodiasepines?

Answer 13

potentiate the actions of the inhibitory neurotransmitter, GABA, in the CNS

Question 14

What are the CNS effects of GABA?

Answer 14

• GABA
  
  • induces inhibitory post-synaptic potentials
  • hyperpolarize the membrane
  • prevent hte axon from reachign threshold for firing
  • reduce the synaptic potential produced by excitatory amino acids

Question 15

Synapses on what part of neuron are often excitatory?

What about inhibitory?

Answer 15

• Dendritic synapses - often excitatory
• Cell body synapses - often inhibitory

Question 16

What are the binding sites on GABA_A Receptors?

Answer 16

• GABA binding site
  
  • opened via binding of an agonist
• Benzodiasepine binding site
  
  • activation GABA_A R with
    
    • a1 subunit underlie hypnotic effects
    • a2 subunit underlie anxiolytic effects
• Barbiturate binding site
• Ethanol binding site
• Anesthetic binding site

Question 17

What is the difference in how barbiturates & benzodiazepines impact the GABA Cl^- channel?

Answer 17

benzo - increase frequency of opening

barb - increase duration of opening

Question 18

What is the BZ antagonist?

Answer 18

flumazenil

competitive antagonist of benzodiazepines

Question 19

What are the indications for flumazenil?

Answer 19

• reverse sedative effect of benzodiazepines after anesthesia
• reverse benzodiazepine overdose
• NOT effective in reversing the effects of other CNS depresants
• May precipitate withdrawl

short half life compared to some BZ - may need repetitive doses

Question 20

What are the toxic signs of benzodiazepines?

Answer 20

• drowsiness
• ataxia
• difficulty with speech (dysarthria)
• decreased reflexes (areflexia)

Question 21

Tolerance develops to what effects of benzodiazepines?

Answer 21

• Tolerance
  
  • anticonvulsant effects
• Little / no tolerance
  
  • andiolytic effects
  • hypnotic effects
• cross tolerance with other CNS depressant drugs

Question 22

BZ are what schedule drug?

Answer 22

schedule IV

Question 23

What are the withdrawl symptoms seen with BZ?

Answer 23

• general anxiety or symptom recurrence
• autonimic-like symptoms
  
  • tachycardia, trembling, abdominal issues, systolic hyperension, sweating
• flu-like symptoms
  
  • muscle aches, malaise
• sensory disturbances
• seizures & delirium - after long-term, high-dose usage

Question 24

Benzodiazepines are contraindicated with what other drugs?

Answer 24

• sedative hypnotics
  
  • barbiturates
  • other hypnotics
  • general anesthetics
  • ethanol
  • antihistamines
  • anticholinergics
• opiates

Question 25

Benzodiazepines are what category with relationto pregnancy? This means what?

Answer 25

D or X CI - pregnancy, labor & delivery, breast feeding

Question 26

cimetidine has what effect on benzodiazepines?

Answer 26

inhibits drug metabolism (CYP3A4)

Question 27

What long acting BZ participate in both phase 1 & phase 2 metabolism?

Answer 27

* chlorazepate * chlordiazepoxide * diazepam * flurazepam

Question 28

What short acting BZ participate in both phase 1 & phase 2 metabolism?

Answer 28

alprazolam midazolam troazolam

Question 29

What short acting BZ participate in only phase 2 metabolism?

Answer 29

lorazepam oxazepam temazepam

Question 30

What type of metabolism occurs in phase 1? Phase 2? What patients experience a decrase in phase 1 elimination?

Answer 30

* Phase 1 - * oxidation * reduction * hydrolysis * Phase 2 * conjugation pathway decreased phase 1 reactions for drug elimination can occur in patients with liver disease & in geriatric patients

Question 31

What BZ would you use in a patient with liver dysfunction?

Answer 31

lorazepam | (oxazepam, temazepam)

Question 32

Other than BZ, what drug is used to treat anxiety?

Answer 32

buspirone

Question 33

What are the indications to prescripbe buspirone? MOA? AE Time until effectiveness?

Answer 33

* Buspirone * Indication * **generalized anxiety disorder** * no effective for other types of aniety disorders * MOA * partial agonist at the 5-HT_1A receptor * AE * dizziness & lightheadedness * tachycardia, palpitations * nervousness or restlessness * GI distress * tingling or prickling sensation * takes 1-2 weeks to produce antianxiety effect

Question 34

What are the advantages of using buspirone over BZ to treat anxiety?

Answer 34

little sedation or euphoric effect no rebound anxiety or withdrawl symptoms doens't potentiate the effects of other CNS depressants

Question 35

What drugs are used for people who have a fear of public performance?

Answer 35

* non-selective beta blocker * propranolol (B1 & 2) * if has COPD or Asthma * metoprolol (B1 selective)