Flashcards in Diazepam Deck (30):
What is the trade name of Diazepam?
What is the drug classification of Diazepam?
What are the clinical uses of Diazepam?
-benzo of choice for DT's and LA induced Seizures
-Induction and maintenance of GA
-Spinal cord mediated -muscle relaxation
What is the MOA of Diazepam?
-Enhances affinity of GABA to GABAa receptors
-GABA is primary inhibitory neurotransmitter of the CNS
-GABAa receptor stimulation produces Increased opening of Cl channels. Influx of chloride produces hyperpolarization of the POSTsynaptic cell membrane
-Acts as anxiolytic by inhibiting synapses in the LIMBIC system, which has high [ ] of GABA receptors
How is Diazepam metabolized?
-by Liver CYP450 enzyme CYP3A4
-oxidation via N-demthylation to the 3 metabolites
-conjugated to glucuronic acid prior to renal excretion
-Converted to 3 metabolites: desmethyldiazepam, oxazepam, and temazepam
Tell me about Desmethyldiazepam.
-oxidized, conjugated and excreted in the urine
-metabolized at a slower rate
-slightly lower potency than diazepam
-likely cause of drowsiness: "hangover effect" 6 - 8 hours after initial administration of diazepam
How is Diazepam excreted?
in urine as oxidized metabolites or as glucuronic acid with a clearance rate of 0.2 - 0.5 ml/kg/min
What is the E 1/2 time of Diazepam?
20 - 50 hours (per Dr. E 21 - 37 hours, increases with Age)
What is the E 1/2 time of Desmethyldiazepam?
48 - 96 hours
What is the redistribution info of Diazepam? Why?
Due to its high degree of lipophilicity, diazepam and its metabolites are redistributed to peripheral tissues with a distribution half-life of 10 - 15 minutes
What is the volume of distribution of Diazepam?
-highly lipid- soluble, resulting in rapid uptake into the brain and subsequent redistribution to peripheral tissues
-Vd = 0.7 - 1.7 L/kg
IS Diazepam protein bound?
98% Protein Bound! principally Albumin
What are the common side effects?
-Fatigue, Dry mouth, ataxia, dizziness, nausea, muscle weakness, prolonged somnolence
Does Diazepam effect CV and respiratory status?
produces minimal effects on CV status (SVR, BP, CO; < 20% decrease) and on respiratory status
What can occur cardiovascularly if Diazepam is given in Large doses?
can decrease BP and SVR
What are the contraindications to the use of Diazepam?
-Hypoalbuminemia secondary to hepatic or renal dx will increase the unbound fraction of Diazepam
What increases E 1/2 time?
increases with age and can be 5x normal in pts with hepatic disease
What drug will prolong the effects of diazepam?
What produces a synergistic sedative effect when given with Diazepam?
when used in combination with other CNS depressants, including alcohol, inhaled anesthetics, opioids, and alpha-2 agonists
What is the induction dosage of Diazepam?
0.3 - 0.6 mg/kg IV (per Dr. E, 0.5 - 1 mg/kg IV)
What is the preop anxiety/premedication IV dosage of Diazepam?
2.5 - 10 mg IV, given in 0.5-2 mg increments (per Dr. E, 0.2 mg/kg!)
What is the PO dose that is recommended for Diazepam?
5 - 15mg (Dr. E says 10-15mg)
What is the antagonist of Diazepam in case of OD?
Is Diazepam lipid soluble?
Highly lipid soluble with prolonged duration of action (not as potent and stays around longer!)
How is Diazepam commercially prepared?
-in organic solvents including propylene glycol and benzyl alcohol
-viscous, pH 6.6 - 6.9
What is important to consider when giving Diazepam in an IV or IM injection?
IT IS PAINFUL IV and IM injection
If given orally, what is it about absorption?
Rapidly absorbed from GI tract
What is the DOA based on?
DOA is NOT based on receptor interaction; rather it is determined by rate of metabolism and elimination
Which is more potent and longer acting, Diazepam or Desmethyldiazepam?
Desmethyldiazepam: more potent and long acting metabolite!
--you need one week to clear the drug if chronically used!