Anesthesia

Question 1

zero order

Answer 1

not constant and dependent upon plasma (constant mg/hr)

Question 2

Clearance of drugs with first order kinetics

Answer 2

constant regardless of plasma concentration (%)

Question 3

Phase 1 metabolism

Answer 3

Converts parent drug to more polar

water soluble

Question 4

Phase II metabolism

Answer 4

Conjugate drug with polar moiety

making it more water soluble

Question 5

Distribution of Cardiac Output

Answer 5

VRG= 10% body mass but 75% CO
Muscle = 40% body mass but 19% CO
Fat = 30% body mass but 6% CO
VPG = 20% body mass but 0.5% CO

Question 6

Albumin binds _____ drugs?

Answer 6

Acidic I.e. Barbiturates

Question 7

A1AG bind to _____ drugs?

Answer 7

Basic I.e. Local anesthetics

Question 8

Which diseases decrease Albumin available to bind to drugs?

Answer 8

liver, kidney, CHF, Cancer which increase available drug

Question 9

Which diseases decrease A1AG available to bind to drugs?

Answer 9

trauma, infection, MI, chronic pain

Question 10

Volume of Distribution

Answer 10

total amount of drug in the body/drug blood concentration

– VD 0.7=total body water

Question 11

Propofol Mech. of action?

Answer 11

Presumed interaction with GABA
– Delays the dissociation of GABA from receptors
• Increasing GABA activated opening of chloride ion channels
• Also acts as a sodium channel blocker
– Hyperpolarization of cell membranes.

Question 12

Propofol Pharmacokinetics?

Answer 12

• 95-99% protein binding
• Metabolized via glucoronidation in the liver (up to 30% possibly in lungs
• Renal excretion

Question 13

Dosing Propofol?

Answer 13

Induction - 1.5-2.5 mg/kg (adults) - decrease in elderly
- 2.5-3.5 mg/kg (kids)
Sedation (MAC) - 25-100mcg/kg/min
TIVA - 100-300 mcg/kg/min

Question 14

Propofol effects on Cardio?

Answer 14

SBP ⇓d; MAP ⇓d; SVR ⇓d; HR ⇔

– Profound arterial and venous vasodilation ⇓s both preload and afterload.

Question 15

Propofol effects on RESP and CNS?

Answer 15

RR depressed dose dependent—apnea after bolus
– Reduces airway reflexes

CBF ⇓d; ICP ⇓d; CMRO2 ⇓d; ⇓d IOP

Question 16

What is Propofol infusion syndrome?

Answer 16

Acute refractory bradycardia (kids)
– RBBB is an early sign
– May lead to asystole if one or more:
    • Metabolic acidosis
    • Rhabdomyolisis
    • Hyperlipidemia
    • Enlarged or fatty liver
– Associated with propofol infusion >4mg/kg
for long duration (> 48 hours)

Question 17

Fospropofol

Answer 17

Prodrug of Propofol
Longer onset
6.5 mg/kg (60-90kg)
Perianal paresthesia in 74%

Question 18

Prop key points? - take home?

Answer 18

Awaken due to redistribution
• CV depression slightly > than NaP
• Resp effects similar to NaP but good
bronchodilator
• Does NOT cause hyperalgesia
• Reduces PONV and PDNV
• Good hypnotic
• Burns upon rapid injection in small vein
• Contraindicated with Egg Allergy

Question 19

Etomidate Mech of action and Pharm?

Answer 19

Mechanism of Action
– Rapid onset of sleep--30-60 seconds
– Assumed to enhance the effects of GABA
– Rapid awakening
– 75% protein bound
– Hydrolyzed to inactive metabolites via ester
hydrolysis
– Elimination half life is 75 minutes
– Clearance is 5X faster than Sodium pentothal
– Excretion 85% renal, 15% biliary

Question 20

Etomidate S/E Card, Pulm, CNS

Answer 20

CV effects
– SBP ⇔⇓d; HR ⇔⇑d ; SVR ⇔⇓d
• Pulmonary effects
– Minimal respiratory depression; increased
with opioids.
• CNS effects
– CBF ⇓d, ICP ⇓d, CMRO2 ⇓d

Question 21

Etomidate Induction and maintenance dose?

Answer 21

.2-.4 mg/kg

NO REDOSING!!! Suppresses Adrenals!!!
- Inhibits 11β-hydroxylase and to a lesser extent 17α
hydroxylase

Question 22

What to think about when giving Etomidate?

Answer 22

Beware of
– Myoclunus (spontaneous jerking)
– Adrenal Suppression
• Inhibits 11β-hydroxylase and to a lesser extent 17α
hydroxylase.
– ⇑d PONV versus NaP or Propofol
– No Analgesia

Question 23

_______________ states that the potency of an anesthetic is proportional to its lipid solubility. This suggests a lipophilic site of action.

Answer 23

The Meyer-Overton rule

Question 24

Ketamine works on which receptors?

Answer 24

NMDA; Opioid; Monoaminergic; muscarinic

receptors; & voltage gated Ca+ channels

Question 25

Ketamine Pharmacokinetics?

Answer 25

``` Extremely lipid soluble (5-10X NaP) – Metabolized in liver to norketamine • 1/3 to 1/5 potency Ketamine – Norketamine is hydroxylated and conjugated to H2O soluble and excreted. – Elimination half-life 2-3 hours – Excretion >90% renal ```

Question 26

Ketamine CV, Pulm, & CNS effects?

Answer 26

• CV effects – SBP ⇑d; HR ⇑d ; SVR ⇑d • Pulmonary effects – No respiratory depression; increased with opioids. • CNS effects – CBF ⇑d, ICP ⇑d, CMRO2 ⇑d (probably not good for neuro cases)

Question 27

Ketamine induction dose IV & IM?

Answer 27

Induction of Anesthesia – 1-3mg/kg IV or 4-8mg/kg IM • Adjunctive Analgesic – 0.2-0.5 mg/kg can provide profound analgesia BEWARE OF: – Emergence Delirium • Visual, auditory, proprioceptive, and confusion • Premedicating with Midazolam seems to help

Question 28

Barbiturates Mech. of Action? (what receptors?)

Answer 28

Interact with GABAA (α subunit) receptor • Different from the GABA or the BZD site • Directly activate Cl- ion channels, increase their duration of opening. – Increases the efficacy of GABA • Hyperpolarize postsynaptic cell membranes. – Also block the AMPA receptors (excitatory receptor)

Question 29

Barbiturates elimination and protein bound?

Answer 29

``` NaP 83% protein bound (Albumin) – Highly lipid soluble=rapidly into CNS – Achieve CNS uptake in 30 seconds – Prompt awakening after a single dose – Hepatic metabolism (inactive) and eliminated by kidneys ```

Question 30

Barbiturates CV, Pulm, & CNS effects?

Answer 30

CV effects – SBP ⇓d; HR ⇑d (reflexive) ; SVR ⇓d • Pulmonary effects – Respiratory depression, APNEA, return with slow respers and ⇓d tidal volumes. • CNS effects – CBF ⇓d, ICP ⇓d, CMRO2 ⇓d - neuro protective

Question 31

Barbiturates effect on Renal & pH?

Answer 31

Modest decrease in GFR – Metabolic acidosis ⇑s the effect of barbiturates – Metabolic alkalosis ⇓s the effect of barbiturates – Respiratory acidosis has much less effect

Question 32

Barbiturates Key Points?

Answer 32

``` Awakening due to redistribution • NaP causes dose dependent ⇓ SBP, SVR, CO due to myocardial depression and increased venous capacitance • Potent respiratory depressants • Poor analgesics-may cause hyperalgesia • Contraindicated in Acute Intermittent Porphyria • Can cause histamine release • Avoid SubQ and Intra-arterial injection ```