Anxiolytics Flashcards
Phenytoin is metabolized by what CYP enzyme?
It induces what CYP enzyme?
metabolized - CYP2C9/10
induces - CYP3A4
Which statins are not metabolized by CYP enzymes?
pravastatin - none
rosuvastatin (CYP2C <10% ; CYP2C19 minor)
What is the level of response, airway, & CV support from minimal sedation?
What type of drugs is an example of minimal sedation?
Anxiolytics
- Response: responds normally to verbal commands
- Airway: maintained
- CV support: not needed
Describe the pathways involved in axiety and how diazepam works to relieve this anxiety.
- 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 GABAA) receptors
- outputs to brainstem & hypothalamus
- Diazepam inhibits these outputs, which reduces the manifestations of anxiety
hypnotic effects are mediated by what subunit?
a1 containing GABAAR
anxiolytic effects are mediated by what subunit?
a2 and a3 subunit containing GABAAR
Most benzos bind to waht subunit containing GABAAR?
What about Z-drugs?
- Benzo - a(1,2,3,5)
- Z-drugs - a1
- much more selective
Effects of Benzodiasepines?
AE?
- 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
Describe the cardiovascular & respiratry effects of benzodiazepines
-
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
- oral administration - very little
What are the benzodiazepines?
- alprazolam
- chlordiazepoxide
- diazepam
- lorazepam
What is the order of treatment for generalized anxiety disorder?
- supportive / cognitive behavioral / biofeedback / relaxation training
- pharmacology
- SSRI or SNRI or buspirone - delayed onset action (form long-term management)
- benzodiasepines - immediate, stabilization for severe anxiety
Which benzodiazepines are most commonly used for anxiety?
alprazolam
lorazepam
What is the major mechanism of action for benzodiasepines?
potentiate the actions of the inhibitory neurotransmitter, GABA, in the CNS
What are the CNS effects of GABA?
- 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
Synapses on what part of neuron are often excitatory?
What about inhibitory?
- Dendritic synapses - often excitatory
- Cell body synapses - often inhibitory
What are the binding sites on GABAA Receptors?
- GABA binding site
- opened via binding of an agonist
- Benzodiasepine binding site
- activation GABAA R with
- a1 subunit underlie hypnotic effects
- a2 subunit underlie anxiolytic effects
- activation GABAA R with
- Barbiturate binding site
- Ethanol binding site
- Anesthetic binding site
What is the difference in how barbiturates & benzodiazepines impact the GABA Cl- channel?
benzo - increase frequency of opening
barb - increase duration of opening
What is the BZ antagonist?
flumazenil
competitive antagonist of benzodiazepines
What are the indications for flumazenil?
- 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
What are the toxic signs of benzodiazepines?
- drowsiness
- ataxia
- difficulty with speech (dysarthria)
- decreased reflexes (areflexia)
Tolerance develops to what effects of benzodiazepines?
- Tolerance
- anticonvulsant effects
- Little / no tolerance
- andiolytic effects
- hypnotic effects
- cross tolerance with other CNS depressant drugs
BZ are what schedule drug?
schedule IV
What are the withdrawl symptoms seen with BZ?
- 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
Benzodiazepines are contraindicated with what other drugs?
- sedative hypnotics
- barbiturates
- other hypnotics
- general anesthetics
- ethanol
- antihistamines
- anticholinergics
- opiates
Benzodiazepines are what category with relationto pregnancy?
This means what?
D or X
CI - pregnancy, labor & delivery, breast feeding
cimetidine has what effect on benzodiazepines?
inhibits drug metabolism (CYP3A4)
What long acting BZ participate in both phase 1 & phase 2 metabolism?
- chlorazepate
- chlordiazepoxide
- diazepam
- flurazepam
What short acting BZ participate in both phase 1 & phase 2 metabolism?
alprazolam
midazolam
troazolam
What short acting BZ participate in only phase 2 metabolism?
lorazepam
oxazepam
temazepam
What type of metabolism occurs in phase 1? Phase 2?
What patients experience a decrase in phase 1 elimination?
- 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
What BZ would you use in a patient with liver dysfunction?
lorazepam
(oxazepam, temazepam)
Other than BZ, what drug is used to treat anxiety?
buspirone
What are the indications to prescripbe buspirone?
MOA?
AE
Time until effectiveness?
- Buspirone
- Indication
- generalized anxiety disorder
- no effective for other types of aniety disorders
- MOA
- partial agonist at the 5-HT1A receptor
- AE
- dizziness & lightheadedness
- tachycardia, palpitations
- nervousness or restlessness
- GI distress
- tingling or prickling sensation
- takes 1-2 weeks to produce antianxiety effect
What are the advantages of using buspirone over BZ to treat anxiety?
little sedation or euphoric effect
no rebound anxiety or withdrawl symptoms
doens’t potentiate the effects of other CNS depressants
What drugs are used for people who have a fear of public performance?
- non-selective beta blocker
- propranolol (B1 & 2)
- if has COPD or Asthma
- metoprolol (B1 selective)
