Benzodiazepines Flashcards
Five principle pharmacologic effects of benzodiazipine
- Anxiolytic
- Sedative and hypnotic
- Anterograde amnesia
- Spinal cord muscle relaxant
- Anticonvulsant activity
pH of midazolam
3.5
pK of midazolam
6.15
midazolam metabolism is slowed by:
CYP inhibitor
midazolam elimination is not altered by
Renal failure (eliminatin t1/2, clearance, Vd)
What are the two metabolites from midazolam?
1-hydroxymidazolam
4- hydroxymidazolam,
Which midazolam metabolites more of concern? Why?
1-hydroxymidazolam.
It has half of the effect of midazolam, needs to be further broken down.
midazoam was oxidized into 1-hydroxymidazolam during phase 1, conjugated during phase 2 for elimination
Which drugs will inhibit CYP450 activity for midazolam? What does it cause?
cimetidine, erythromycin,calcium channel blocker, antifungals
Causes unpexted CNS depression
What CNS effect does midazolam have?
Does ICP during intubation increase or decrease or?
neuroprotective?
what happens if long term gtt stopped?
Midazolam respiratory effect
Larger than what dose causes resp depression?
Airway effect>
midazolam CV effect
greater than what dose causes hotn?
How does it affect intubation response?
midazolam preop dosage and onset times
midazolam induction dose
midazolam side effects
midazolam contraindications
reaction b/w diazepam and water
Insoluble in water (propylene glycol, sodium benzonate)
• Painful on injection
How well is diazepam absorbed in GI?
Rapidly absorbed in GI
Diazepam Vd
Large Vd reflecting extensive tissue uptake of lipid soluble drug
- Patients with a large BMI will have larger Vd
- Crosses the placenta – fetal concentrations > mother
How well does diazepam bind to protein?
Extensively protein bound (albumin)
• Cirrhosis and renal insufficiency result in increased unbound diazepam with increased side effects
Two metabolites of diazepam
- Desmethyl Diazepam – metabolized more slowly than parent drug and half as potent – may cause return of drowsiness at 6-8 hours. Elimination half-life 48-96 hours?! Can accumulate in plasma with chronic use
- Oxazepam
(• Temazepam)
elimination half life of diazepam
>40hrs
diazepam age and half-life relationship
near-linear
diazepam PK in elderly altered by:
Slow drug absorption
Increased percentage of adipose tissue
Decreased plasma proteins
Decreased hepatic blood flow and metabolism
Decreased cardiac output
Prolonged circulation = slower onset, remains in CNS longer
diazepam ventilation effect
In sedative doses, produces minimal depressive effects on ventilation:
- Exaggerated when combined with opioids or alcohol
- COPD may cause prolonged depression of ventilation
diazepam hemodynamic effect
Even when administered for induction of anesthesia, minimal decreases in BP, CO, SVR are seen (similar to natural sleep)
- Addition of nitrous oxide not associated with adverse cardiac changes
- Concomitant use of fentanyl results in decreased BP and SVR
diazepam clinical application
Preoperative medication
- Largely replaced by midazolam in children
- Management of delirium tremens
- Skeletal muscle relaxation properties useful for:
- Rare patient with tetany
- Lumbar disc disease
anticonvulsant use of diazepam
dose?
seizure caused by what?
0.1 mg/kg IV effective in abolishing seizure activity produced by lidocaine, delirium tremens and status epilepticus
side effect and complication of diazepam
Overdose can be managed if CV and pulmonary systems are supported and other drugs such as ETOH are not present
contraindicatio of diazepam
Most common adverse effects are:
- Unexpected respiratory depression and over sedation
- They should be avoided in patients with acute porphyrias
Compare onset of lorazepam with midazolam and diazepam
Also tell me the IV onset, peak time
how long does antegrade amnesia last
when is maximum plasma concentration reached?
Slower onset of action than midazolam or diazepam
• Maximum plasma concentrations 2-4 hours after oral admin
• Antegrade amnesia may last up to 6 hours with minimal sedation (PO)
• Onset 1-2 minutes IV; peak effect 20-30 minutes
How is lorazepam metabolized in liver?
Are there active metabolites?
conjugated with glucuronic acid in the liver
- inactive metabolites
- less likely to be influenced by alteration in liver fxn, age or drugs that inhibit cyp450 (e.g. cimetidine)
duration of effect of Lorazepam
6-10 hrs
half time of lorazepam
14 hrs
How is lorazepam used clinically?
Postoperative sedation of intubated patients
- Delayed emergence
- Amnestic effects may last several days
- May delay weaning from ventilator
Reversal agent for benzodiazepines
Flumazinel
What type of reversal agent is flumazenil?
Selective antagonist
Dosage of flumazenil
- Initial dose .2mg IV (typically reverses effects in 2 minutes)
- Further doses of .1 mg IV given at 60 second intervals
- .5-1.0 completely abolish the therapeutic effect of benzos
- Unresponsive patients who do not respond to 5 mg of Flumazenil mostly likely have other issues
What type of patients is not recommended to receive flumazenil?
Not recommended for patients being treated with antiepileptic medication for seizure control
Can flumazenil reverse abruptly? Why?
No. Due to its weak intrinsic agonist effect
Flumazenil is not associated with what?
- acute anxiety
- hypertension
- tachycardia
- increased neuroendocrine response (release of steroids etc.)
Do you change MAC requirement d/t flumazenil? Why?
not alter anesthetic requirements of MAC. B/c gas and flumazenil work on different receptors
