IV anes - BZD Flashcards
What is the MOA of BZDs?
Increases the frequency of chloride channel opening by binding to GABA
What causes midazolam to be water soluble at a low ph?
The imidazole ring
What causes diazepam and lorazepam IV to irritate the veins?
Propylene glycol. It is added because diazepam and lorazepam are insoluble in water
What route are diazepam and lorazepam best absorbed?
Orally thru GI tract
Which two BZDs are absorbed well IM?
Lorazepam and midazolam
What happens to the imidazole ring of midazolam at physiologic ph?
It closes which increases its lipid solubility
What are the differences in brain solubility in the three BZDs?
Diazepam is relatively lipid soluble and readily penetrates the bbb
Lorazepam moderately - slow uptake in the brain
What mechanism is responsible for awakening from a BZD?
Redistribution
How long does it take for peak plasma levels when absorbed orally?
1-2h
How protein bound are the BZDs?
90-98%
How are they biotransformed ?
Phase I metabolism
What BZD has active phase I metabolites?
Diazepam
What is the elimination half life of diazepam and why?
30 hours because it has a low hepatic extraction ratio and a large Vd (high lipid solubility)
What is the elimination half life of lorazepam?
15
It’s lower lipid solubility make it have a smaller Vd
It has a low hepatic extraction ratio
Clinical duration is longer due to increased receptor affinity in most patients
What is the elimination half life of midazolam?
2 hours
Even though it has a large Vd, it has a high hepatic extraction ratio
How are the metabolites of BZDs excreted?
In the urine
What condition can lead to prolonged sedation in patients receiving midazolam?
Kidney failure due to the accumulation do the conjugated metabolite - alphahydroxymidazolam
What are the CV effects of BZDs?
Decreased arterial blood pressure, cardiac output, SVR
What are the respiratory effects of BZDs?
Depress the ventilatory response to CO2
What are the cerebral effects of BZDs?
Decrease CMRO2, CBF and ICP
What drugs reduce the metabolism of diazepam?
Cimetidine, erthromycin,
What drug increases the free drug concentration of diazepam?
Heparin by displacing diazepam from protein binding sites
How do BZDs affect the MAC of a volatile anesthetic?
Reduces it by 30%
What is the bioavailability of midazolam from greatest to least?
IV > IM > intra nasal > rectal > oral
