BZD Flashcards
5 main effects BZD
Anxiolytic
Sedation
Anterograde Amnesia
Anticonvulsant
Spinal cord mediated muscle relaxation
BZD replaced barbiturates. What were the BZD benefits that led to this change
Benzos: have less tolerance, less abuse, fewer side effects, do not induce hepatic enzymes therefore less drug interactions.
BZD MOA
Facilitates action of GABA at GABA A chloride ionophore.
Enhance affinity of receptor for GABA
Enhanced opening of Cl- Channels
Hyperpolarization of postsynaptic membrane
Alpha 1 Effects
sedative, amnestic, anticonvulsant.
Alpha 1 locations
Cerebral cortex, cerebellar cortex, thalamus
Alpha 2
Anxiolytic, skeletal muscle
Alpha 2 location
hippocampus and amygdala
What other things bind to GABA A receptors
Barbs, etomidate, prop, ETOH
Why is it important to know what other substances bind to GABA A receptor
They all have synergistic effects. Increased OD
BZD eeg effects
All decrease alpha activity
What effect does altering alpha wave have
Very relaxed, deepening into meditation.
Which BZD cannot cause isoelectric brain waves
Versed cannot make brain waves isoelectric
Name drug classes that have synergistic effects with BZD
Alpha 2 agonists, opioids, alcohol, inhaled anesthetics
BZD effect on clotting
Inhibits platelet aggregating factor. Inhibits conformational shape change of platelets from smooth to pseudopod
What effect of versed lasts the longest
The amnesia lasts longer than the sedation.
How is versed diluted
It is not diluted as it is water soluble
What is versed pH
3.5
At what pH is imidazole ring opened and what does this mean
Imidazole ring is open at pH <3.5. This is the water soluble/pronated form.
At what pH is imidazole ring closed and what does this mean
The imidazole ring is closed at pH >4.0. This makes the ring close and become lipid soluble. It is able to reach the brain.
Versed onset
1-2 mins
Versed peak effect
5 mins
Duration of versed
Short duration d/t lipid solubility and rapid redistribution
Versed E 1/2 time
2 hours. Doubled in elderly
Versed Vd:
1-1.5 L/kg (large)
Greater vd in elderly and obese
What is the active metabolite of versed? What percent of active versed does this metabolite exert
1-hydroxymidazolam
1/2 the activity of Versed
What can cause decreased metabolism of BZD
Inhibition of P-450 enzymes
What are some meds that inhibit CYP-450
Tagamet, calcium channel blockers, erythromycin, anti-fungal, fentanyl
Versed metabolism compared to lorazepam? Diazepam?
Clearance 5x faster than lorazepam/10x faster than diazepam
Versed CNS effects
-Decreases CMRO2 and CBF
-Unable to produce isoelectric EEG
-Potent anticonvulsant (even in status)
-Preserves vasomotor response to CO2, high CO2 dilates vessels/low CO2 constricts.
-no change in ICP if decreased cranial compliance (won’t cause further increase of ICP)
Versed pulmonary effects
-Decreases hypoxia drive (ventilation) worsened in COPD. Transient apnea with rapid iv esp if using opioids.
-depressed swallowing reflex
-decreases upper airway activity (increased aspiration risk)
Versed CV effects
Dose dependent increased HR/decreased BP
This allows CO to stay same.
Versed sedation dose
Kids: 0.25-0.5 mg/kg PO
Onset 20-30 mins
Adults: 1-5 mg IV
onset: 5 mins
Versed Induction dose
0.1-0.2mg/kg IV over 30-60 seconds
Versed Maintenance dosing
Uncommon d/t quick onset/offset. Would require many IV bags to keep up.
It supplements prop, opioids, VA. Decreasing VA needed.
Versed post op dose
1-7 mg/ hr IV.
Delayed awakening d/t active metabolite accumulation.
Can interfere with immune/T cells with use for 2-3 days.
Valium onset
1-5 mins
Valium E 1/2
20-40 hours. This makes it better option for post op sedation.
How does Valium’s duration and E 1/2 compare to Versed
Valium has a shorter duration of action and a longer E 1/2.
The longer E 1/2 makes Valium a poor choice for day surgery d/t prolonged awakening r/t long E 1/2
Which active metabolite of Valium is more potent
Desmethyldiazepam is nearly as potent as diazepam. It lasts (48-96 hrs)
CNS effect Valium
Decreased CMRO2 and CBF
Can achieve isoelectric brain wave (versed could not)
Potent anticonvulsant (DT, status, lido tox seizures)
Pulmonary effects of diazepam (Valium)
Minimal ventilation effects
Slight decrease in Vt
Increases PaCO2 after 0.2 mg/kg (worsened by simultaneous use with opioids, ETOH or either COPD)
*ventilatory suppression effects nullified by surgical stimulation
Which BZD would be appropriate for COPD pt and why?
Valium would be most appropriate
Versed decreases hypoxic drive which is further worsened in COPD pts.
Valium CV effects
Minimal decreases in BP/CO/SVR even with induction doses.
Great for cardiac surgery induction
Decreases BP with opioid use
Valium neuromuscular effects
Decreases tonic effect of spinal neuron: skeletal muscle tone decreased, develop tolerance to muscle relaxant effects.
No action at NM junction
Valium induction dosing
0.5-1.0 mg/kg
Decrease dose by 25-50% in elderly, liver disease, presence of opioids.
How does lorazepam (Ativan) compare to Versed and Valium in regards to amnesia/sedation
Ativan is a more potent amnestic and sedative than both of these drugs
Ativan preparation
Requires polyethylene glycol since it is insoluble in water
How does the onset of action of Ativan compare to other BZD
Slower onset of action d/t being less lipid soluble (takes longer to enter CNS)
Slower metabolic clearance
Ativan is great for what use
Post op sedation d/t slower metabolic clearance
Ativan dose and peak
1-4 mg IV
Peak 20-30 mins. Not good for induction great for maintenance and post op sedation
Ativan E 1/2
14 hours
Glucoronidation is slower than hydrolysis
Metabolism of Ativan
Glucoronidation therefore less dependent on hepatic enzymes. Less affected by drugs that alter hepatic functions e.g. cimetidine (Tagamet)
Reversal agent for BZD
flumazenil (Romazicon)
1.4 imidazobenzodiazepine derivative
How does flumazenil (Romazicon) work
Competitive antagonist for BZD receptor.
Prevents/reverses all agonist activity of BZD
Dose of flumazenil
0.2 mg IV and titrate to consciousness
Repeated in 0.1 mg q 1 minute to 1 mg total
Reversal within 2 minutes doses to reverse sedation? Abolish therapeutic effect?
0.3-0.6 mg to reverse sedation
0.5 mg-1.0 mg to abolish therapeutic dose
Why is it important to continually monitor patient after successful reversal of BZD via flumazenil
If the patient OD on Versed, which is fat soluble, they can resedate due to the fat stores of the medication.
Unconscious overdose with no change after 0.5-1.0 mg flumazenil would lead one to suspect what
The OD was not BZD related and most likely Opioid.
Continuous infusion dose of flumazenil
0.1-0.4 mg/hr
Side effects of flumazenil
No known side effects.
Contraindications of flumazenil
Patient on BZD for seizures
Antiepileptic seizures.
Can precipitate acute withdrawal seizures.
