Benzodiazepines

Question 0

Why are benzos are unique among the intravenous anesthestics?

Answer 0

They have a selective antagonist, flumazenil

Question 1

What are the most common benzo’s used?

Answer 1

Diazepam, Lorazepam, Midazolam

Question 2

What are benzodiazepines used for?

Answer 2

Sedative-hypnotics a1
anterograde amnesia
Anxiolysis y
Anticonvulsant ( seziure activity produced by local, alcohol withdrawals, and status epilepticus) a1
muscle relaxation y, happens in higher doses and effect site is in spinal cord

Question 3

physiochemical characteristics of benzodiazepines???

Answer 3

1. All 3 highly lipid soluble
2. high protein bonding 90-98%
3. Midazolam water soluble at PH no pain on injection, once it hits the physiologic PH there is a change in ring structure that renders ring more lipid soluble
4. Lorazepam and Diazepam are made water soluble with propylene glycan —-> pain on injection

Question 4

what are the pharmacokinetics of benzos? Where are the drugs metabolized?

Answer 4

1. Diazepam is metabolized to active metabolites –> prolonged effect of the drug
2. Midazolam is metabolized into one non-active metabolite
3. Metabolism by CYP45

Question 5

What is the reason for short duration of action of midazolam?

Answer 5

High lipid solubility which results in the rapid re-dist of drug from brain to inactive tissue

Question 6

Why should midazolam injection be paced sufficiently?

Answer 6

Although midazolam crosses the blood-brain barrier quickly it take 3-5 min to equilibrate in the effect site—> pace it so that you get a peak effect before giving another dose

Question 7

Why is midazolam good for continuos infusion?

Answer 7

bc it has a shortest context sensitive half life in compare to the rest of the benzos

Question 8

what are the pharmacokinetics of Benzos?

Answer 8

They bind to GABAa receptor btw a and Y subunits and enhance the affinity of GABA for GABA receptor, —> more frequent opening on cl- channels and more hyperpolarization which prevent the subsequent depolarization of the nerve
-midazolam has twice as much affinity of GABA than diazepam

Question 9

Where are the GABAa receptors located?

Answer 9

The ones responsive to benzos are exclusively in post synaptic neurons in cerebral cortex—> benzos have little effect on heart and respiration

Question 10

What are the effects on Benzos on CNS?

Answer 10

1. decrease in cerebral blood flow
2. decrease in cerebral oxygen consumption
3. No or minimal effect on ICP
4. not neuroprotective
5. potant anticonvulsant ( status epilepticus, alcohol withdrawal and local induced seizure

Question 11

What is the effect of benzos on CVS?

Answer 11

1. ONLY IF YOU USE MIDAZOLAM FOR INDUCTION
2. you get a large decrease in arterial blood pressure due to peripheral vasodilation
3. Cardiac output in unchanged
4. Can produce midazolam induced hypotension in hypovolemic patients

Question 12

what are the effects on midazolam on respiratory system?

Answer 12

min resp effect
if given as a bolus for induction you can get apnea in presence of opioids
benzos decrease the vent responce to co2 usually with opioids not when admined alone

Question 13

What are the side effects of benzos?

Answer 13

1. Allergic reaction rare

2. pain on injection with diazepam and lorazepam bc they are not water soluble and have propylene glycol

Question 14

What are benzodiazepams used for?

Answer 14

1. premed 1-2mg iv for anxiolysis, sedative-hypnotic, amnesia
2. induction: 0.1-0.3 mg/kg
   onset of unconsciousness and recovery slower than propofol
   onset of action is facilitated if 50-100 mcg of fentanyl is injected 3-5
   min before induction
3. anti-convulsant :0.1 mg/kg iv of diazepam

Question 15

what is the antagonist of benzos and how much?

Answer 15

flumazenil 8-15 mcg/kg