Ex1 Benzo Slides Flashcards
Receptors effected by Benzos
a1 GABA-A
a2 GABA-A
a1 GABA-A Receptor is responsible for
Sedation, amnesia, anticonvulsant effects. Most prominent
a2 GABA-A Receptor is responsible for
CNS mediated skeletal muscle relaxant effects and anxiolysis
Benzos decrease wakefulness by inhibition of ______ in the _______
RAS - reticular activating system
Brain stem
Inhibition in the ______ causes _____ effect
RAS
Sedative/hypnotic effects (drowsy/sleep)
Effects of Benzos on CNS
Decrease CMRO2, CBF
Increase seizure threshold
Protect against cerebral hypoxia (Midazolam > diazepam)
Benzo effect on Ventilation
Mild depression of ventilation
Decreased Vt and MV (dose dependent)
Mildly elevated CO2
Apnea occurs in _____% after Benzo administration in dose starting at _____ mg
20; 2
Exceptions to Benzos - ventilation
Flatter CO2 curve. NOT shifted.
Sensitive patients: chronic lung disease, obese, elderly
Special population of patients should receive what dose of Benzos?
1/4 dose and titrate to effect (better to avoid Benzos altogether)
Benzo effects on CV system
Decreased SVR
Benzos will result in _______ blood pressure due to ______
Decreased
Decreased SVR
Drugs used to reduce HR/BP which accompanies intubation
Opioids, beta antagonists, lidocaine
Most common side effects of Benzos
Fatigue, drowsiness
Other: dependence
Important side effect of benzos
Withdrawal syndrome - life threatening, irritability, insomnia, tremors, seizures, death
Long acting Benzo withdrawal will occur after _____ days, while short acting will occur after _____ days
2-5 days
1-2 days
After cessation
T or F: benzodiazepines do not induce microsomal enzymes
True
Benzos should be avoided in who?
Pregnant individuals (teratogenic) Procedures identifying seizure foci
Benzos will create a _____ effect when combined with opioids, propofol, barbiturates, ETOH
Synergistic
Which medications will cause a synergistic effect when given with benzos?
Opioids, propofol, barbiturates, ETOH
What combo of Rx is considered “cardiac stable” when given with benzos?
Opioids
Important structure on midazolam
Imidazole ring
Midazolam in lipid soluble form has a pH of?
> 4
Midazolam in water soluble form has pH of?
< 4
Open ring form
PK of midazolam
6.15
What does midazolam depend on in order to main closed ring/active form?
pH > 5 = 99% is in active form (closed ring)
Midazolam- responsiveness to ______ is preserved
Vasomotor responsiveness to CO2
Increased CO2=increased CBF
Midazolam Sedation Dose - PO
0.5 mg/kg PO 30 min prior to induction in peds
Midazolam sedation dose IV
1-2.5mg IV bolus
Induction of GA - midazolam dose
Induction: 0.1-0.3 mg/kg
Why does diazepam remain in body for such a long time?
Undergoes enterohepatic recirculation
Diazepam metabolites undergo ______
Glucuronidation
E1/2 of Diazepam
21-37h
Delayed clearance and prolonged E1/2t for diazepam may be due to
Inhibition of CYP450 by other substances
Diazepam metabolization is notable for
Desmethyl metabolite - active
E1/2t = 48-96h
What is responsible for biphasic pattern of sedation in Diazepam?
Desmethyl metabolite
Skeletal muscle effects of Diazepam
Muscle relaxant - SPINAL (centrally) mediated
What muscular effect will occur with chronic administration of diazepam?
Tolerance to relaxant effect
Diazepam dosing - PO
10-15mg peaks 1h
Diazepam dosage IV
0.05-0.15 mg/kg
Titrate - start low, go slow
Induction dose Diazepam
0.3-0.5mg/kg
Rate potency of Diazepam, Lorazepam, Midazolam
Lorazepam > midazolam > diazepam
Rate duration of action: diazepam, lorazepam, midazolam
Diazepam > Lorazepam > midazolam
Flumazenil duration of action
30-60 min
Re-sedation or infusion may be required
Dose of Flumazenil
0.2 mg IV reverses CNS effects in 2 minutes
Maximum flumazenil dose
1mg IV
Titrate 0.1 mg each time
Flumazenil is a _______ of the GABA A receptor
Competitive antagonist
Benzos that have venous irritation and why?
Diazepam, lorazepam Propylene glycol (to enhance water solubility)
Why isn’t lorazepam used for seizures?
Slow onset
