Oral: Benzos

Question 1

MOA

Answer 1

Potentiates binding of GABA to the GABA-A receptor, keeping the Cl- channels open and hyperpolarizing the cell, making it more resistant to excitation

Question 2

Class / 5 Uses

Answer 2

Benzodiazepine / Anxiolytic, Sedation, Anterograde amnesia, muscle relaxation (spinal), anticonvulsant

Question 3

Antagonist

Answer 3

Flumazenil

Question 4

Pharmacokinetics

Answer 4

Generally highly lipid soluble and highly protein bound;

Large Vd

Question 5

Pharmacokinetics: Diazepam (Valium)

Answer 5

rapidly crosses BBB & placenta; 
hepatic conjugation by CYP450 & excreted in urine; 
rapid IV onset (30-60 sec); 
3 active metabolites- most active is desmethyldiazepam w/ E1/2= 48-96 hrs (hangover effect); 
E1/2= 21-37 hours; 
least potent of the benzos;
Pain on injection (propylene glycol); 
Does not effect NMB dose;

Question 6

Side Effects: Diazepam (Valium)

Answer 6

⬇SVR, BP, CO with induction dose;

⬇ CBF & CMRO2, does NOT cause isoelectric EEG, preserves CO2 response but FLATTENS the curve.
Dose dependent ⬇ in RR & TV (synergistic w/ opioids);
Does NOT attenuate SNS response to DVL.
Can cause paradoxical excitation.

Question 7

Contraindications: Diazepam (Valium)

Answer 7

Early pregnancy,
⬇ dose for renal/hepatic impairment (decreased albumin),
use with caution in elderly (⬆sensitivity);
DO NOT give with glaucoma

Question 8

Dose: Diazepam (Valium)

Answer 8

Pre-med: 0.2 mg/kg IV, 10-15 mg PO;
induction: 0.5-1 mg/kg IV;
Anticonvulsant 0.1mg.kg IV

Question 9

Pharmacokinetics: Midazolam (Versed)

Answer 9

rapidly crosses BBB;
Fast onset;
hepatic metabolism by CYP450- excreted in urine;
1 active metabolite = 1-hydroxy-midazolam (1/2 as potent);
E1/2= 1-4 hrs;
DOA = 15-80 min, redose in 5 min.

Question 10

Side Effects: Midazolam (Versed)

Answer 10

⬇ SVR & BP at induction but NO change to CO, otherwise CV stable.

⬇ CBF & CMRO2, does NOT cause isoelectric EEG, preserves CO2 response but FLATTENS the curve.
Dose dependent ⬇ in RR & TV (synergistic w/ opioids);
Does NOT attenuate SNS response to DVL.
Can cause paradoxical excitation.

Question 11

Contraindications: Midazolam (Versed)

Answer 11

Pregnancy,
⬇ dose for renal/hepatic impairment,
use with caution in elderly, synergistic with opioids.
Do not give with glaucoma

Question 12

Dose: Midazolam (Versed)

Answer 12

Pre-med: 1-2.5 mg IV (max 5), 0.5 mg/kg PO (max 20 mg);

induction: 0.1-0.2 mg/kg over 30-60 sec

Question 13

Pharmacokinetics: Lorazepam (Ativan)

Answer 13

hepatic metabolism by CYP450 & 80% excreted unchanged in urine; 
most potent benzo; 
no active metabolites;  
SLOWEST onset of Benzos;
most potent benzo;
Pain on injection (propylene glycol); 
Does not effect NMB dose;  
E1/2= 10-20 hours
DOA = 11-20 hours

Question 14

Side Effects: Lorazepam (Ativan)

Answer 14

⬇SVR, BP, CO with induction dose;

⬇ CBF & CMRO2, does NOT cause isoelectric EEG, preserves CO2 response does NOT flatten the curve.
Dose dependent ⬇ in RR & TV (synergistic w/ opioids);
Does NOT attenuate SNS response to DVL.
Can cause paradoxical excitation.

Question 15

Contraindications: Lorazepam (Ativan)

Answer 15

⬇dose for renal/hepatic impairment,
use with caution in elderly, synergistic with opioids.
Do not give with glaucoma!

Question 16

Dose: Lorazepam (Ativan)

Answer 16

Pre-med 1-4 mg IV; 50 mcg/kg PO (Max 4mg)

Question 17

Class: Flumazenil (Romazicon)

Answer 17

Benzodiazepine antagonist

Question 18

MOA: Flumazenil (Romazicon)

Answer 18

Competes with benzos for binding sites on GABA-A receptor, reversing their effect. Has high affinity for the receptor.

Given to reverse respiratory depression and cardiac effects of benzodiazepines

Question 19

Pharmacokinetics: Flumazenil (Romazicon)

Answer 19

50% PB
Onset = 1-2 min 
DOA = 30-60 min (might need to redose)
Vd = moderate
E1/2t = 1 hour
metabolized by liver and excreted by urine

Question 20

Side Effects: Flumazenil (Romazicon)

Answer 20

dizzy
sweating
HA 
N/V
abnormal vision
agitation
pain on injection
depression
confusion
no change in HR or BP or neuroendocrine response

Question 21

Contraindications: Flumazenil (Romazicon)

Answer 21

DO NOT USE in sz disorder, hypersensitivity

Question 22

Dose: Flumazenil (Romazicon)

Answer 22

0.2 mg IV, wait 2 min then repeat 0.1 mg q 60 sec to a max of 3 mg