Non-Barb Induction

Question 1

What is the structure of propofol?

Answer 1

2,6-di-iso-propophenol

Oil at room temp, insoluble in aqueous solution, very lipid soluble

Question 2

How is propofol supplied? What food allergy do you worry about?

Answer 2

1.2% egg (worry about egg yolk allergy)
10% soybean oil
2.25% glycerol base solution
*This supports bacterial growth

Question 3

What is in the preservative of diprivan?

Answer 3

Disodium edetate (EDTA)

Question 4

The generic propofol is prepared in sodium metabisulfite, what is the caution with using this?

Answer 4

Caution/avoid in asthmatics because this preparation leads to bronchospasm

Question 5

How does ampofol formulation differ from diprovan/propofol preparation?

Answer 5

Low lipid formula: 5% soy, 0.6% egg lecithin
No preservative needed
More pain with injection

Question 6

What is the reason aquavan (fospropofol) isn’t used often?

Answer 6

Fospropofol is the prodrug of propofol, once it gets to the plasma, it hydrolyzes to propofol. It effects people differently and is therefore very unpredictable, has slower onset, higher VD, and higher potency

Question 7

Propofol MOA

Answer 7

Decrease rate of dissociation of GABA from GABA-A receptor which increases chloride conductance, hyperpolarizing/inhibiting the postsynaptic cell membrane

Question 8

Does propofol depress the spinal cord?

Answer 8

NO

Question 9

Propofol pharmacokinetics: E1/2t? VD?

Answer 9

LARGE VD

E1/2t 0.5-1.5h

Question 10

Propofol- CNS effects

Answer 10

Dec CBF, ICP, CMRO2, CPP, IOP
Myoclonus/muscle twitching, hallucinations
Cerebral protection through antioxidant effects that resemble vitamin E effects
Also, antiemetic and antipruritic effect at low doses

Question 11

Propofol- respiratory effects

Answer 11

Induction dose causes apnea
Dec TV, RR
Dec response to CO2 and hypoxia
PCO2 rises, pH decreases
Bronchodilation (unless it uses that preservative- sodium metabisulfide)
Hypoxic vasoconstriction intact

Question 12

Propofol- CV effects

Answer 12

HUGE decrease in BP (25-40%)
Myocardial depression, vasodilation
Dec SV, CO, SVR
HR unchanged

Question 13

Does propofol potentiate muscle relaxants?

Answer 13

Nope

Question 14

Propofol induction dose? Adult vs. toddler
GA maintenance dose?
Sedation infusion dose?

Answer 14

Induction 1-2.5 mg/kg, up to 3 in toddlers
Kids higher dose bc they have a larger central distribution and higher clearance rate
Elderly need lower dose due to smaller central distribution and lower clearance rate
GA 100-300 mcg/kg/min
Sedation 25-100 mcg/kg/min

Question 15

How is propofol metabolized?

Answer 15

Conjugated in liver to glucuronide and sulfate by CP450 to water soluble compounds, renal excretion, first pass effect
Liver function doesn’t effect rate of metabolism, safe for liver and renal patients!
Mostly inactive metabolites

Question 16

Which of these are chiral compounds: Thiopental, etomidate, ketamine, propofol

Answer 16

All EXCEPT for propofol

Question 17

Etomidate is what drug class?

Answer 17

Carboxylated Imidazole derivative

Imidazole= C3H4N2

Question 18

What solvent is etomidate prepared in?

Answer 18

Propylene glycol solvent (anti-freeze)

Question 19

What is the pH and solubility of etomidate like in solution? In the body?

Answer 19

In solution: pH 6.9, water soluble

In body: pH 8.2 (weak base), lipid soluble

Question 20

Etomidate MOA

Answer 20

Increases affinity of GABA to GABA-A receptor, which increases chloride conductance, hyperpolarizing/inhibiting the postsynaptic cell membrane (same as propofol)

Question 21

Etomidate pharmacokinetics (VD, E1/2t, PB)

Answer 21

Vd 2.5-4.5 (large)
E1/2t 3-5h
High hepatic extraction ratio and clearance (caution in liver patients, prolonged effects)
Highly protein bound (75%)

Question 22

Etomidate: CNS effects

Answer 22

Rapid loss of consciousness after a single dose
Cerebral vasoconstriction leads to decreased CBF, ICP, CMRO2, IOP
Increases EEG activity in epileptogenic foci, myoclonic movements (disinhibiting extrapyramidal system)
Anticonvulsant properties, BUT can be associated with Grand Mal Seizures (caution in pt with hx of seizures)
High N/V

Question 23

Etomidate: Respiratory effects

Answer 23

Ventilatory response to CO2 depressed minimally
Decrease TV
Increase RR (except big fast dose can lead to apnea)
Hiccups, coughing

Question 24

Etomidate: CV effects

Answer 24

MINIMAL, lacks SNS effects

HR, BP, PAP, CO, SVR, PVR = unchanged

Question 25

Etomidate: Endocrine effects

Answer 25

Prevents conversion from cholesterol to cortisol by inhibiting 2 enzymes (major: 11-beta-hydroxylase, minor: 17-alpha-hydroxylase) Adrenocortical suppression for 4-8h reduces mineralocorticoid and corticosteroid production

Question 26

Etomidate doses: induction, maintenance, sedation, Peds rectal dose?

Answer 26

Induction 0.3 mg/kg Maintenance: 10 mcg/kg/min with N2O and opioid (but inc PONV) Sedation: 5-8 mcg/kg/min Rectal used in Peds: 6.5 mg/kg

Question 27

Does etomidate potentiate neuromuscular blockade?

Answer 27

Yes | Enhances NDMR activity

Question 28

Etomidate metabolism

Answer 28

Liver hydrolysis by hepatic enzymes, plasma esterases or N-dealkylation, to carboxylic acid FAST biotransformation 85% renal, 13% biliary excretion 2% excreted unchanged

Question 29

Which of these non-barb induction agents have analgesia effects? (Ketamine, etomidate, propofol)

Answer 29

KETAMINE

Question 30

Ketamine class

Answer 30

``` Phencyclidine derivative (PCP) Non-barb induction agent ```

Question 31

Ketamine is a racemic mixture of which enantiomers?

Answer 31

Equal parts R and S enantiomers | S enantiomer is a more potent analgesic, faster metabolism, lower incidence of emergence delirium

Question 32

Ketamine MOA?

Answer 32

Interacts with: NMDA (gluamate receptor): Activates NMDAR resulting in Na and Ca ion influx and K efflux Opioid (mu, delta, kappa, sigma) receptors Monoaminergic (involves descending inhibitory pathways) Muscarinic antagonist Ca channels

Question 33

Ketamine metabolism?

Answer 33

Hepatic enzymes ACTIVE metabolite: norketamine (not a significant clinical effect), hydroxilated to hydroxynorketamine Conjucated to water soluble, urinary excretion Clearance effected by liver blood flow

Question 34

Ketamine pharmacokinetics

Answer 34

Large Vd (3 L/kg) High lipid solubility Rapid onset- 30 sec, short duration, max effect for 1 min, effect terminated by redistribution E1/2t 2-3h

Question 35

Ketamine: CNS effects

Answer 35

Crosses BBB Dissociative state caused by depressed neuronal function in association areas of cortex and thalamus while stimulating limbic/hippocampus (caution with psych patients) Amnesia (less than benzos), nystagmus (rapid eye movement), pupil dilation, salivation, lacrimation, myoclonic activity Increases CBF, metabolic rate/ CMRO2, ICP, IOP Emergence reactions: dreaming, out of body sensation, illusions, fear

Question 36

Ketamine: respiratory effects?

Answer 36

Minimal, no CO2 response alteration Bronchial smooth muscle relaxation Increases PVR (avoid in pulmonary hypertension) Increases salivation

Question 37

Ketamine: CV effects?

Answer 37

Sympathomimetic NMDA effect inc BP, HR, CO Inc myocardial work and O2 consumption Inhibits reuptake of NE Myocardial DEPRESSANT, especially in sick people with decreased NE stores

Question 38

Ketamine doses for premedication (sedative/analgesic), induction, maintenance?

Answer 38

Premed: 0.2-0.5 mg/kg Induction 1-2 mg/kg IV, 4-8 mg/kg IM Maintenance: 1-2 mg/kg/h (PO 6 mg/kg)

Question 39

Ketamine contraindications?

Answer 39

``` Inc ICP Open eye injury CAD (for sole anesthetic) Vascular aneurysm Uncontrolled HTN/ pulm HTN Psych diseases ```

Question 40

Dexmedetomidine (precedex) is ____ soluble (water/lipid)

Answer 40

Water

Question 41

Dexmedetomidine drug class?

Answer 41

Alpha-2 adrenergic agonist

Question 42

Where does precedex produce hypnosis and anagesia?

Answer 42

Hypnosis in locus ceruleus | Analgesia in spinal cord

Question 43

Precedex CNS effects?

Answer 43

``` Dec CBF (no change in ICP/ CMRO2) Dec MAC of volatile agents and opioid requirements Depress thermoregulation (depress shivering if hypothermic) ```

Question 44

Precedex CV effects?

Answer 44

Dec HR, SVR, BP (bolus can inc BP and dec HR) Potential for severe bradycardia, heart block, systole Dec catecholamine levels during GA

Question 45

Precedex respiratory effects?

Answer 45

Minimal change in RR Moderate dec in TV No change in CO2 responsiveness (good for COPD pts) Upper airway obstruction possible

Question 46

Precedex metabolism?

Answer 46

Rapid through conjugation, N-methylation, hydroxylation Metabolites cleared in urine and bile Highly PB - 90% E1/2t 2-3h Inhibits CYP-450 (can interfere with opioid clearance)

Question 47

Precedex dose?

Answer 47

1 mcg/kg bolus over 10-15 min followed by 0.2-1 mcg/kg/h

Question 48

What is the precedex reversal?

Answer 48

Atipamezole, it is a specific and selective alpha-2 antagonist that will rapidly and effectively reverse sedative and CV effects of precedex