Slattery Anxiolytics

Question 1

What drugs have linear dose dependent CNS depression/

Answer 1

BARBITUATES (phenobarbital, pentobarbital, thiopental)

Increase dose too much and you’re more likely to have bad CNS effects

Question 2

What drugs have non-linear dose dependent CNS depression?

Answer 2

BENZODIAZEPINES (dizepam, lorazepam, triazolam, alprazolam)

Going to be hard to get real CNS depression (good or bad) - never going to work as an anesthetic

Question 3

What are the barbiturates that we need to know?

Answer 3

Phenobarbital, pentobarbital, thiopental

Question 4

What are phenobarbital, pentobartbital, thiopental good for?

Answer 4

Hypnosis, seizure control, anesthesia induction

Question 5

What’s the MOA of barbiturates?

Answer 5

Remember… these are phenobarbital, pentobarbital, thiopental

Bind GABAa receptor and increase DURATION that the Cl- channel remains open - increase GABA inhibition

Mnemonic - barbiDURATes increase DURATION of GABA effects

It can also depress excitatory glutamate by binding to the AMP receptor

Question 6

What kind of CNS depression response do barbiturates have?

Answer 6

Linear!
Barbs bind to more than 1 receptor type (GABA and glutamate) –> more CNS depression?

Just be careful with the dosages

Question 7

What barbiturate can be absorbed SO SO fast and used for anesthesia?

Answer 7

Thiopental! It only takes 30 seconds to knock you out

Question 8

What are barbs metabolized by?… What’s going to be maybe not so great about this?

Answer 8

CYP450 in the liver

They also ∆ rate of metabolism of CYP450 –> ∆ metabolism of barbs AND other drugs

Question 9

Is barb liver metabolism slow or fast? How slow/fast?

Answer 9

SLOW! (thiopental is fast though…)
Phenobarbital has elimination half-life of 4-5 days so you better be careful when you’re dosing to avoid CNS depression that you don’t want

Question 10

How are barbs excreted? What’s not so great about phenobarbital excretion?

Answer 10

Kidney!

25% of phenobarbital is excreted UNCHANGED (you need to be careful about dosing)

Question 11

What are you going to do if you patient tries to overdose on phenobarbital?

Answer 11

Remember…. phenobarbital is a weak acid (~7.4) and weak acids are reabsorbed at low pHs

So…. give your patient an IV of sodium bicarbonate (base) and this will make their urine more basic (increase urine pH)

More of the phenobarbital will be excreted if you do this and your patient won’t die

Question 12

What types of tolerance exist for barbiturates (phenobarbital, pentobarbital, thiopental)

Answer 12

PharmacoKINETIC - increase rate of metabolism (remember they change CYP450 enzymes)

PharmacoDYNAMIC - ∆ CNS responsiveness

Question 13

How does sedation work with barbiturates?

Answer 13

Disinhibit punishment suppressed behavior –> impaired judgment/less filter

Decrease psychomotor functions (YOUR PATIENT CAN’T DRIVE!)

Question 14

How are sleep patterns ∆ with barbiturates (phenobarbital, pentobarbital, thiopental)

Answer 14

INCREASED onset of sleep - good

INCREASED stage II sleep (non-REM)

DECREASED stage IV sleep (not so good - this is restorative)

DECREASED REM sleep duration

Question 15

Will barbiturates change CV/respiratory function?

Answer 15

IF YOU HAVE A CV DYSFUNCTION!

Toxic dose –> contractility depressed –> circulatory collapse

Question 16

Why will your myocardial contractility be depressed if you are on a barbiturate and have a CV issue?

Answer 16

GABA is inhibited everywhere at high doses and so it’s going to be inhibited in our heart too - not good

Question 17

What are the benzodiazepines that we need to know?

Answer 17

Diazepam, Lorazepam, Triazolam, Alparazolam

Question 18

What are my bentos going to treat?

Answer 18

Anxiety, insomnia, seizures, muscle relaxant, preanesthetic

Question 19

What do benzos do?

Answer 19

Remember they’re diazepam, lorazepam, trialozapam, alprazolam

Bind GABAa receptor and increase FREQUENCY of Cl- channel opening events

Question 20

What kind of CNS depression do benzos have?

Answer 20

Nonlinear!!! It’s going to take A LOT of drug to make you have CNS depression

Question 21

What benzo is absorbed into CNS super fast?

Answer 21

TRIAZOLAM!

Question 22

Do benzos do anything to liver metabolism enzymes?

Answer 22

NOPE!

So if you have a choice between a benzo or a barb and you’re worried about CYP enzymes you should go with a benzo instead

Question 23

Tell me about benzo metabolites/how it’s excreted

Answer 23

Diazepam has an active metabolite for more than 40 hours - be careful with dosing

Benzos are excreted via the kidney

Question 24

What kind of tolerance develops with benzos?

Answer 24

PHARMACODYNAMIC

Down regulation of brain GABAa receptors

Question 25

What will happen to you sedation wise with a benzo?

Answer 25

Anterograde amnesic effects - can’t remember anything during drug duration of action

Question 26

What are you going to do if you give too much diazepam/lorazepam during anesthesia and you give your patient post anesthetic respiratory depression?

Answer 26

FLUMAZENIL!!!!!

Question 27

What is the MOA of flumazenil?

Answer 27

Benzodiazepine binding site antagonist to help decrease respiratory depression

Question 28

How will benzos contribute to CV function badness

Answer 28

Toxic doses –> myocardial contractility depression –> circulatory collapse

Question 29

Tell me about zolpidem

Answer 29

INCREASE sleep!!!

Bind at benzo binding site on GABAa receptor (only at sleep receptors)

Rapid onset and short duration of action - no sleepiness in the morning

Question 30

What’s busprione

Answer 30

ONLY anxiolytic

Can take a week so you better get on that quick

You can drive

Question 31

Ramelteon

Answer 31

MT1/MT2 melatonin receptor in suprachiasmatic nuclei of brain (master clock)

NOT the same as melatonin (that’s a dietary supplement)