Benzodiazepines Flashcards
1
Q
Use
A
- sedation
- anxiolysis
- anticonvulsant
- SC mediated muscle relaxation
- anterograde amnesia
- unconsciousness
- resp depression
- *NO analgesia
2
Q
Therapeutic index
A
high- >100
BZ + opioids- <10
3
Q
Mechanism of action
A
- facilitates action of GABA at the alpha subunit
- enhances opening of Cl- channel -> hyper polarization of postsynaptic membrane
4
Q
Diazepam (Valium) pharmacokinetics
A
- very lipid soluble- rapid uptake/redistribution
- large Vd- 1-1.5 L/kg
- CL 0.2-0.5 ml/kg/min
- longest elimination t1/2- 21-37 hrs
- *age correlates with t1/2
5
Q
Diazepam metabolism
A
- hepatic metabolism via oxidative N-demethylation
- 3 active metabolites- desmethyldiazepam, oxazepam, temazepam
- hepatic CL doesn’t change with age d/t increase fatty tissue -> increase Vd
- cimetidine delays hepatic clearance
6
Q
Diazepam anesthetic effects
A
- decreases dose of induction agent
- decreases MAC of inhalation agent
7
Q
Midazolam (Versed) pharmacokinetics
A
- 2-4 x more potent than diazepam
- contain imidazole ring -> water soluble at pH <4
- 96-98% protein bound
- very lipid soluble
- Vd 1-1.5 L/kg
- CL rate 6-8 ml/kg/min
- short elim t1/2 1-4 hrs
- renal failure has minimal effects of t1/2, Vd, CL
8
Q
Midazolam metabolism
A
- hepatic oxidative hydroxylation
- renal glucoronide conjugation
- renal excretion
9
Q
Cardiac response to midazolam
A
minimal
10
Q
Pulmonary effects of midazolam
A
resp depression with 0.15 mg/kg
11
Q
Neuro effects of midazolam
A
decrease CBF, CMRO2
12
Q
Does midazolam cross the U-P membrane?
A
Yes, contraindicated with pregnancy
13
Q
Lorazepam (Ativan) pharmacokinetics
A
- highest potency
- elim t1/2 10-20 hours
- reliable GI/IM absorption
- hepatic metabolism via glucuronide conjugation that is NOT altered by age, disease, H2 blockers
14
Q
Lorazepam dose
A
- 0.5-2.0 mg PO at HS and in AM before surg
- 50 mcg/kg (4 mg max) produce anterograde amnesia for 6 hours
15
Q
BZD reversal
A
flumazenil- competitive antagonist with high affinity of BZD receptor
