Benzodiazepines

Question 1

Five principle pharmacologic effects of benzodiazipine

Answer 1

• Anxiolytic
• Sedative and hypnotic
• Anterograde amnesia
• Spinal cord muscle relaxant
• Anticonvulsant activity

Question 2

pH of midazolam

Answer 2

3.5

Question 3

pK of midazolam

Answer 3

6.15

Question 4

midazolam metabolism is slowed by:

Answer 4

CYP inhibitor

Question 5

midazolam elimination is not altered by

Answer 5

Renal failure (eliminatin t1/2, clearance, Vd)

Question 6

What are the two metabolites from midazolam?

Answer 6

1-hydroxymidazolam

4- hydroxymidazolam,

Question 7

Which midazolam metabolites more of concern? Why?

Answer 7

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

Question 8

Which drugs will inhibit CYP450 activity for midazolam? What does it cause?

Answer 8

cimetidine, erythromycin,calcium channel blocker, antifungals

Causes unpexted CNS depression

Question 9

What CNS effect does midazolam have?

Does ICP during intubation increase or decrease or?

neuroprotective?

what happens if long term gtt stopped?

Answer 9

Question 10

Midazolam respiratory effect

Larger than what dose causes resp depression?

Airway effect>

Answer 10

Question 11

midazolam CV effect

greater than what dose causes hotn?

How does it affect intubation response?

Answer 11

Question 12

midazolam preop dosage and onset times

Answer 12

Question 13

midazolam induction dose

Answer 13

Question 14

midazolam side effects

Answer 14

Question 15

midazolam contraindications

Answer 15

Question 16

reaction b/w diazepam and water

Answer 16

Insoluble in water (propylene glycol, sodium benzonate)

• Painful on injection

Question 17

How well is diazepam absorbed in GI?

Answer 17

Rapidly absorbed in GI

Question 18

Diazepam Vd

Answer 18

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

Question 19

How well does diazepam bind to protein?

Answer 19

Extensively protein bound (albumin)

• Cirrhosis and renal insufficiency result in increased unbound diazepam with increased side effects

Question 20

Two metabolites of diazepam

Answer 20

• 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)

Question 21

elimination half life of diazepam

Answer 21

>40hrs

Question 22

diazepam age and half-life relationship

Answer 22

near-linear

Question 23

diazepam PK in elderly altered by:

Answer 23

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

Question 24

diazepam ventilation effect

Answer 24

In sedative doses, produces minimal depressive effects on ventilation:

• Exaggerated when combined with opioids or alcohol
• COPD may cause prolonged depression of ventilation

Question 25

diazepam hemodynamic effect

Answer 25

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

Question 26

diazepam clinical application

Answer 26

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

Question 27

anticonvulsant use of diazepam dose? seizure caused by what?

Answer 27

0.1 mg/kg IV effective in abolishing seizure activity produced by lidocaine, delirium tremens and status epilepticus

Question 28

side effect and complication of diazepam

Answer 28

Overdose can be managed if CV and pulmonary systems are supported and other drugs such as ETOH are not present

Question 29

contraindicatio of diazepam

Answer 29

Most common adverse effects are: * Unexpected respiratory depression and over sedation * They should be avoided in patients with acute porphyrias

Question 30

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?

Answer 30

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

Question 31

How is lorazepam metabolized in liver? Are there active metabolites?

Answer 31

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)

Question 32

duration of effect of Lorazepam

Answer 32

6-10 hrs

Question 33

half time of lorazepam

Answer 33

14 hrs

Question 34

How is lorazepam used clinically?

Answer 34

Postoperative sedation of intubated patients ## Footnote * Delayed emergence * Amnestic effects may last several days * May delay weaning from ventilator

Question 35

Reversal agent for benzodiazepines

Answer 35

Flumazinel

Question 36

What type of reversal agent is flumazenil?

Answer 36

Selective antagonist

Question 37

Dosage of flumazenil

Answer 37

* 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

Question 38

What type of patients is not recommended to receive flumazenil?

Answer 38

Not recommended for patients being treated with antiepileptic medication for seizure control

Question 39

Can flumazenil reverse abruptly? Why?

Answer 39

No. Due to its weak intrinsic agonist effect

Question 40

Flumazenil is not associated with what?

Answer 40

* acute anxiety * hypertension * tachycardia * increased neuroendocrine response (release of steroids etc.)

Question 41

Do you change MAC requirement d/t flumazenil? Why?

Answer 41

not alter anesthetic requirements of MAC. B/c gas and flumazenil work on different receptors