Induction Agents (2)

Question 1

What neurotransmitters do most inhibitory neurons in the brain and spinal cord use?

Answer 1

GABA or glycine

Question 2

What neurotransmitter do most excitatory neurons in the brain use?

Answer 2

Glutamate

Question 3

What is the purpose of an IV induction agent?

Answer 3

Move the patient from a state of consciousness to a state of unconsciousness

Question 4

Moving from a state of consciousness to unconsciousness should happen how?

Answer 4

Rapidly, smoothly, without dysphoria, reversibly, reliably, and in an autonomically stable fashion (no current agent meets all these requirements)

Question 5

What chart describes the stages of anesthesia and is used to assess the depth of general anesthesia?

Answer 5

The Guedel chart (created in 1937)

Question 6

In general when GABA receptors are stimulated there is a ________ in neuronal activity

Answer 6

Decrease

Question 7

What receptor is inotropic, and associated with binding sites for benzodiazepines, propofol, and barbiturates?

Answer 7

GABA-A

Question 8

What type of channel are GABA-A channels

Answer 8

Ionotropic chloride channels

Question 9

What type of channels are GABA-B and what do they effect?

Answer 9

Metabotropic, when activated, GABA-B receptors cause potassium channels to open, allowing positively charged potassium ions to flow out of the neuron making it hyperpolarized

Question 10

What type of channels are GABA-C channels and where are they located?

Answer 10

Ionotropic chloride channels, found primarily in the retina

Question 11

All anesthetics except ketamine and etomidate (barbiturates have little or no effect) stimulate what receptors

Answer 11

Glycine

Question 12

All anesthetics except ketamine stimulate what receptors?

Answer 12

GABA

Question 13

Most excitatory neurons in the brain use glutamate as their neurotransmitter. What channels does glutamate modulate?

Answer 13

Sodium channels

Question 14

What does NMDA stand for?

Answer 14

N-methyl-D-aspartate

Question 15

What type of receptor is the NMDA receptor?

Answer 15

Excitatory glutamate receptor

Question 16

Barbiturates work on what receptor and what subunit?

Answer 16

GABA-A (beta subunit)

Question 17

Barbiturates are metabolized by what?

Answer 17

CYP2C9 and 3A4

Question 18

Barbiturate metabolites are:

Answer 18

Almost all inactive, water soluble, and excreted in the urine

Question 19

Barbiturates accelerate what related to blood?

Answer 19

Heme production; by stimulating D-aminolevulinic acid synthetase (acute porphyria risk)

Question 20

If injected intra- arterially what risk do barbiturates have?

Answer 20

Venous thrombosis risk

Question 21

Patients treated with barbiturates for seizure disorders metabolized drugs ___ x faster than expected (especially muscle relaxants)

Answer 21

2 x

Question 22

Barbiturates have what GI risk/side effect

Answer 22

PONV risk

Question 23

What drugs can cause exacerbations of Porphyria?

Answer 23

Barbiturates (in rare cases some antibiotics, birth control pills, ketamine, and etomidate)

Question 24

What is Porphyria?

Answer 24

rare group of disorders that affect the body’s ability to produce heme. These patients are deficient in enzymes within the heme biosynthetic pathway.

Question 25

What is the rate limiting enzyme in heme synthesis?

Answer 25

ALA (aminolevulinic acid)

Question 26

How do you pronounce Porphyria?

Answer 26

poor fear ya

Question 27

What genetic factors are involved with Porphyria?

Answer 27

Non sex linked autosomal dominant, variable expression (chromosome 11) (Variable expression describes a range of symptoms that can occur in people with the same genetic condition)

Question 28

What are triggers of Porphyria?

Answer 28

Drugs are the most important trigger but other triggers can include infection, fasting, stress, menstruation and hormonal fluctuations

Question 29

Symptoms of Porphyria:

Answer 29

Symptoms usually occur as attacks that develop over several hours or days ~ Abd pain (severe) most common symptom ~ Cause, vomiting, constipation, pain in the back arms and legs, muscle weakness, urinary retention, palpitations, confusion, hallucinations, seizures

Question 30

Why can barbiturates cause a Porphyria attack?

Answer 30

barbiturates accelerate heme production, so it can accelerate the Porphyria process

Question 31

Methohexital onset:

Answer 31

15-30 seconds

Question 32

Methohexital Peak:

Answer 32

within 1 minute

Question 33

Methohexital E1/2T:

Answer 33

3-6 hr

Question 34

Methohexital VD:

Answer 34

2 L

Question 35

Methohexital Protein Binding:

Answer 35

75%

Question 36

Methohexital PKA:

Answer 36

Ph 10 - 11 of 1% solution

Question 37

Methohexital excretion:

Answer 37

Renal

Question 38

Methohexital metabolism

Answer 38

Hepatic oxidation via CYP2C9 and 3A4

Question 39

Methohexital DOA:

Answer 39

5-10 min

Question 40

Methohexital Class / structure:

Answer 40

~ Sedative/hypnotic/barbiturate ~ 6 carbon ring with O at C2 (oxybarbiturate) branched chain at C5 (hypnotic properties) and methyl group on N (decrease in seizure threshold)

Question 41

Methohexital MOA:

Answer 41

Acts on GABA-A (Beta subunit) increasing the duration of Cl- channels being open (hyper polarizes the neuron)

Question 42

Methohexital Dose:

Answer 42

Dose: Induction: 1 - 1.5 mg/kg IVP or 50-120mg (avg 70mg) at 10mg (1ml of 1% solution) over 5 seconds Maintenance: 20-40mg IVP q4-7min PRN; or 3ml/min (1gtt/sec); PEDS: induction dose- 6.6-10mg/kg IM once (5% conc); rectal 25mg/kg using 1% soln

Question 43

Methohexital SE:

Answer 43

SE: hypotension and tachycardia may occur post induction dose; histamine release, coughing, hiccoughing, movement, laryngospasm ↑PONV

Question 44

Methohexital Cautions:

Answer 44

~Long hangover/impaired judgment ~Decreases seizure threshold (ECT) ~Hyperalgesia with lower doses ~Can induce enzymes --> accellerate metabolism of other drugs ~CONTRAINDICATED in pts at risk for porphyria ~Intra-arterial injection- venous embolism

Question 45

Etomidate, Ketamein and Propofol onset time:

Answer 45

30-60 seconds

Question 46

Etomidate DOA:

Answer 46

3-5 min

Question 47

Etomidate Peak:

Answer 47

Within 1 min

Question 48

Etomidate E1/2T:

Answer 48

2-5 hours

Question 49

Etomidate VD:

Answer 49

Large 2.5 - 45. L/kg

Question 50

Etomidate Protein binding:

Answer 50

75%

Question 51

Etomidate PKA:

Answer 51

4.2 WB (99% non-ionized at physiologic pH)

Question 52

Etomidate excretion:

Answer 52

2% excreted unchanged, 85% renal, 13% in bile

Question 53

Etomidate class/structure:

Answer 53

Sedative/hypnotic, imidazole derivative (aromatic N ring) -predominately R (+) isomer for anesthetic effect (5x more potent than S(-) isomer)

Question 54

Etomidate MOA:

Answer 54

Binds to GABA-A (beta subunit) enhancing affinity for neurotransmitter GABA increasing its duration which increased dependent chloride channel opening thus hyperoplarizing the neuron.

Question 55

Etomidate SE:

Answer 55

SE: NO ANALGESIC EFFECT; can increase EEG activity (esp. in patients with seizure history) CV: MINIMAL CV effects, slight fall in PVR Resp: min depression of CO2 response GI HIGH INCIDENCE FOR PONV (30 - 40%) "vomidate"

Question 56

Etomidate Catuions:

Answer 56

Cautions: Pain on injection site d/t propylene glycol, **INHIBITS enzyme 11 beta hydroxylase (adrenocorticall suppression [lasting 4 - 8 hours]; acute porphyrias; Relatively hight margin of saftey (30-fold difference: effective dose vs. lethal dose)

Question 57

Etomidate metabolism:

Answer 57

hepatic ally by ester hydrolysis to ethyl alcohol