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N524 Summer Pharm > Non-Barb Induction > Flashcards

Non-Barb Induction Flashcards

1
Q

What is the structure of propofol?

A

2,6-di-iso-propophenol

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

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2
Q

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

A

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

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3
Q

What is in the preservative of diprivan?

A

Disodium edetate (EDTA)

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4
Q

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

A

Caution/avoid in asthmatics because this preparation leads to bronchospasm

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5
Q

How does ampofol formulation differ from diprovan/propofol preparation?

A

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

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6
Q

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

A

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

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7
Q

Propofol MOA

A

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

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8
Q

Does propofol depress the spinal cord?

A

NO

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9
Q

Propofol pharmacokinetics: E1/2t? VD?

A

LARGE VD

E1/2t 0.5-1.5h

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10
Q

Propofol- CNS effects

A

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

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11
Q

Propofol- respiratory effects

A 
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
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12
Q

Propofol- CV effects

A

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

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13
Q

Does propofol potentiate muscle relaxants?

A

Nope

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14
Q

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

A

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

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15
Q

How is propofol metabolized?

A

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

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16
Q

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

A

All EXCEPT for propofol

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17
Q

Etomidate is what drug class?

A

Carboxylated Imidazole derivative

Imidazole= C3H4N2

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18
Q

What solvent is etomidate prepared in?

A

Propylene glycol solvent (anti-freeze)

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19
Q

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

A

In solution: pH 6.9, water soluble

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

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20
Q

Etomidate MOA

A

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

21
Q

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

A

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%)

22
Q

Etomidate: CNS effects

A

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

23
Q

Etomidate: Respiratory effects

A

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

24
Q

Etomidate: CV effects

A

MINIMAL, lacks SNS effects

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

25
Q

Etomidate: Endocrine effects

A

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

26
Q

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

A

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

27
Q

Does etomidate potentiate neuromuscular blockade?

A

Yes

Enhances NDMR activity

28
Q

Etomidate metabolism

A

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

29
Q

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

A

KETAMINE

30
Q

Ketamine class

A 
Phencyclidine derivative (PCP)
Non-barb induction agent
31
Q

Ketamine is a racemic mixture of which enantiomers?

A

Equal parts R and S enantiomers

S enantiomer is a more potent analgesic, faster metabolism, lower incidence of emergence delirium

32
Q

Ketamine MOA?

A

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

33
Q

Ketamine metabolism?

A

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

34
Q

Ketamine pharmacokinetics

A

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

35
Q

Ketamine: CNS effects

A

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

36
Q

Ketamine: respiratory effects?

A

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

37
Q

Ketamine: CV effects?

A

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

38
Q

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

A

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)

39
Q

Ketamine contraindications?

A 
Inc ICP
Open eye injury
CAD (for sole anesthetic)
Vascular aneurysm
Uncontrolled HTN/ pulm HTN
Psych diseases
40
Q

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

A

Water

41
Q

Dexmedetomidine drug class?

A

Alpha-2 adrenergic agonist

42
Q

Where does precedex produce hypnosis and anagesia?

A

Hypnosis in locus ceruleus

Analgesia in spinal cord

43
Q

Precedex CNS effects?

A 
Dec CBF (no change in ICP/ CMRO2)
Dec MAC of volatile agents and opioid requirements
Depress thermoregulation (depress shivering if hypothermic)
44
Q

Precedex CV effects?

A

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

45
Q

Precedex respiratory effects?

A

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

46
Q

Precedex metabolism?

A

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)

47
Q

Precedex dose?

A

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

48
Q

What is the precedex reversal?

A

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

N524 Summer Pharm (8 decks)

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