Lecture 11: General Anesthetics Flashcards

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1
Q

Volatile anesthetics end in which suffix?

A
  • -ane
  • Halothane, enflurane, isoflurane, desflurane, and sevoflurane
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2
Q

What is the Blood:gas partition coefficient and how does it relate to an anesthetics onset of action?

A
  • Defines relative affinity of an anesthetic for the blood compared with that of inspired gas (i.e., blood solubility)
  • Inverse relationship btw blood:gas partition coefficient values and rate of anesthesia onset
  • Agents w/ low blood solubility (i.e., NO, desflurane) reach high arterial pressure rapidly, rapidly equilibriate with brain and have fast onset of action
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3
Q

How does the value of minimum alveolar concentration (MAC) relate to potency?

A

Lower MAC = MORE potent

*Inverse relationship

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4
Q

What does the MAC correspond to on the drug-dose effect curve?

A

ED50

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5
Q

Which inhaled anesthetic may have a toxic side effect of hepatitis (hepatomegaly, jaundice, and liver tenderness) which can present 2 days to 3 weeks after exposure?

A

Halothane

‘H’ for Hepatoxicity

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6
Q

Which toxicity is associated with the inhaled anesthetics, Enflurance and Sevoflurane?

A

Renal toxicity due to fluorinated metabolites

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7
Q

In combination with succinylcholine, inhaled anesthetics may cause what serious adverse reaction?

What is seen with this reaction?

A
  • Malignant hyperthermia
  • Rapid onset tachycardia and HTN
  • Severe muscle rigidity, rhabdomyolysis, hyperthermia, hyperkalemia, and acid-base imbalance w/ acidosis
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8
Q

What is the antidote for malignant hyperthermia?

A

Dantrolene

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9
Q

What is meant by the term “balanced anesthesia?”

A
  • Modern anesthesia relies on the use of combos of IV and inhaled drugs to take advantage of the favorable properties of each drug, while minimizing adverse effects
  • No single available drug can achieve all 5 desired effects of the anesthetic state
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10
Q

Most general anesthetics cause CNS depressions by facilitating activation of which channel and through which receptors?

Some also reduce activity of which receptors?

A
  • Facilitating chloride channel activation (GABAA and glycine-receptors)
  • Some reduce excitatory ion channels (i.e., nAChRs and mAChRs; AMPA, kainite, and NMDA receptors)
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11
Q

Which organs have higher immediate concentrations of anesthetics based on the amount of cardiac output they receive?

A

Brain, heart, liver, kidneys, and splanchnic beds

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12
Q

Clearance from the ________ is the major route of elimination for inhaled anesthetics

A

Lungs

*Some metabolized by liver to varying degrees

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13
Q

Define minimum alveolar concentration (MAC)?

A

- Concentration of inhalation anesthetic that prevents movement in response to surgical stimulation in 50% of subjects (meausre of potency; ED50)

  • This is equal to 1 MAC
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14
Q

Which inhaled anesthetic has a MAC (vol %) >100 and what does this mean for use in surgery?

A
  • Nitrous oxide
  • >100% indicates that if 100% of inspired air is the anesthetic, the MAC value would still be <1 and other agents must be supplemented to achieve full surgical anesthesia
  • You can’t achieve >100% nitrous oxide; you couldn’t achieve 80% either w/o killing the patient!
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15
Q

What is the MAC of: Desflurane, Sevoflurane, Isoflurane, Enflurance, and Halothane?

A
  • Desflurane = 6-7%
  • Sevoflurane = 2%
  • Isoflurane = 1.4%
  • Enflurane = 1.7%
  • Halothane = 0.75%
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16
Q

What are the general effects on the cardiovascular system by inhaled volatile liquid anesthetics?

Specific effects related to halothane, desflurane and isoflurane?

A
  • Decrease MAP in direct proportion to their alveolar concentration
  • Increase right atrial pressure, due to depression of myocardial function
  • Halothane can cause bradycardia
  • Desflurane and Isoflurane can increase HR
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17
Q

Which property of IV anesthetics accounts for their quick onset of action?

A

Highly lipophilic and preferentially partition into highly perfused lipophilic tissues (brain, spinal cord)

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18
Q

What is the most likely MOA of Propofol?

A

Targets GABAA receptors as an agonist and potentiates the Cl- current

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19
Q

Describe the pharmacokinetics of Propofol (i.e., metabolism, rate of onset and recovery)

A
  • Rapidly metabolized in liver (phase I and II rxns) w/ extensive extrahepatic metabolism (i.e., lung may account for elimination of up to 30% of a bolus dose)
  • Rapid rate of onset; 15-30 seconds
  • Rapid recovery, patients able to ambulate quickly (low hangover effect)
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20
Q

What is Propofol mainly used for based on its PK?

A
  • Used in induction and maintenance; properties allow for continous infusion
  • Sedation in ICU
  • Conscious sedation and short-duration general anesthesia in locations outside OR (i.e., interventional rads., ED, and dental offices)
21
Q

Which IV anesthetic has poor solubility in water and is commonly formulated as an emulsion containing soy bean oil, glycerol, and lecithin; making allergic reactions a possibility in susceptible patients?

A

Propofol

22
Q

Which drugs show dramatic increases in context-sensitive half-life with prolonged infusions?

A
  • Diazepam
  • Thiopental
23
Q

Compared to other IV anesthetics which drug produces the most pronounced decrease in systemic BP due to profound vasodilation in both arterial and venous circulation leading to reductions in preload and afterload?

A

Propofol

24
Q

What are the respiratory effects of Propofol?

A

Profound respiratory depression

25
Q

What is Fospropofol and how is it metabolized?

A

Water-soluble PROdrug of propofol that is rapdily metabolized by alkaline phosphatase

26
Q

What are common adverse effects of Fospropofol?

A
  • Paresthesias (including perineal discomfort or burning sensation)
  • Pruitis (including genital, perineal, and generalized pruritus)
27
Q

What are the differences and advantages of using Fospropofol?

A
  • Effects are similar to Propofol, but onset and recovery are prolonged, since prodrug needs to be metabolized
  • Less pain on administration
28
Q

What is the MOA of the IV anesthetic, Ethomidate?

A

Enhances the actions of GABA on GABAA receptors

29
Q

Which patients would it be useful to use Etomidate in, why?

A
  • Those with impaired CV and respiratory systems
  • Causes minimal CV and respiratory depression
30
Q

What are the CNS effects of Etomidate?

A

Potent cerebral vasoconstictor; decreases cerebral blood flow and ICP

31
Q

What is significant about the CV effects of the IV anesthetic, Etomidate?

A

CV system stability is maintained even after bolus injection; minimal change in HR and CO

32
Q

Which IV anesthetic causes adrenocortical suppression by producing dose dependent inhibition of 11β-hydroxylase (necessary for conversion of cholesterol to cortisol)?

A

Etomidate

*Think Etomidate = Endocrine Effects!

33
Q

What is the MOA of Ketamine?

A

NMDA receptor antagonist

34
Q

What is the only IV anesthetic to produce profound analgesia, stimulation of the sympathetic nervous systm, bronchodilation, and minimal respiratory depression?

A

Ketamine

35
Q

What are the effects on the CV system by Ketamine?

A

Increase systemic BP, heart rate, and CO; through centrally mediated sympathetic stimulation

36
Q

Ketamine is not recommended in patients with which pathology, due to what effects?

A
  • Intracranial pathologies
  • Increases cerebral blood flow and ICP
37
Q

What is the MOA of the IV anesthetic, Dexmedetomidine?

Where specifically does it exert these effects?

A

- Alpha-2 adrenergic agonist

- Hyponosis presumably from stimulation of alpha-2 receptors in the locus caeruleus

- Analgesic effects at the level of the spinal cord

38
Q

What are 4 common IV opioid analgesics used as anesthetic adjuncts?

MOA?

A
  • Fentanyl, Sufentanil, Remifentanil, Morphine
  • Agonists at opioid receptors
39
Q

What are the 2 IV Barbituate anesthetics used as adjuncts?

A
  • Thiopental (prototype)
  • Methohexital
40
Q

Which IV Barbituate is preferred for short ambulatory procedures due to its rapid elimination?

A

Methohexital

41
Q

Which anesthetic adjuncts induce CYP450 enzymes?

A

Barbituates —> Thiopental and Methohexital

42
Q

What are the 3 common IV Benzodiazepines used as anesthetic adjuncts?

A
  • Diazepamn
  • Lorazepam
  • Midazolam
43
Q

What is the MOA of IV Benzodiazepines used as anesthetic adjuncts

A

Act on GABAA receptor to increase receptor sensitivity to GABA (agonist) and enhances inhibitory neuotransmission

44
Q

IV Benzodiazepines used as anesthetic adjuncts are commonly used when and why?

Actions can be terminated by which antagonist?

A
  • Perioperative period because of their anxiolytic properties and ability to produce anterograde amnesia
  • Can be terminated by the antagonist flumazenil
45
Q

Which IV Benzodiazepine used as an anesthetic adjunct is water-soluble and considered the drug of choice for parenteral administration?

What else is unique about this specific benzo?

A
  • Midazolam
  • More rapid onset, shorter elimination half life (2-4 hrs) and steeper dose-response curve
46
Q

Benzodiazepines have potent __________ properties; used in the Tx of status epilepticus, alcohol withdrawl, and local anesthetic-induced seizures

A

Anticonvulsant

47
Q

Which IV anesthetic provides CV stability; causes decreased steroidogenesis and involuntary muscle movements?

A

Etomidate

48
Q

Which IV anesthetic is used as a standard induction agent, but must be avoided in porphyrias?

A

Thiopental