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Flashcards in General Anesthetics Deck (38)
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1
Q

General anesthesia

A
altered physiologic state with:
- hypnosis
- analgesia
- amnesia
- immobility
- inhibition of autonomic and sensory reflexes
\+/- muscle relaxation
2
Q

Inhaled anesthetics chem structures

A

Nitrous oxide = inorganic gas

All others: volatile halogenated hydrocarbons/ethers

3
Q

Hydrocarbon anesthetics

A

chloroform
cyclopropane
ethylene
halothana

4
Q

Ether anesthetics

A
Diethyl ether
enflurane
methoxyflurane
isoflurane
fluoroxene
sevoflurane
desflurane
5
Q

Uptake and distribution of gen anesthetics

A

Anesthesia induced when critical concentration reached in the brain
Expressed as partial pressure: Pbr/Fbr
Depth of anesthesia determined by Pbr

6
Q

Concentration gradient - anesthetics

A

1) delivered
2) inspired (P1)
3) alveolar (PA)
4) arterial (Pa)
5) brain (Pbr)

7
Q

FA/FI

A

rate of uptake of an inhaled anesthetic
ratio of alveolar anesthetic concentration/inspired anesthetic concentration
determined by:
- solubility in blood
- partial pressure difference between alveoli and pulmonary venous blood
- alveolar ventilation

8
Q

Solubility of gen anesthetics

A

Expressed as partition coefficients (blood/gas)
Modern agents are less soluble in blood than in gas
Higher the blood/gas solubility, the longer it takes “blood pool” to fill –> the longer it takes until equilibrium reached between alveoli and blood, and eventually brain
Want low solubility to reach brain faster

9
Q

Relative solubility of gen anesthetics

A

Desflurane>nitrous oxide> sevoflurane > isoflurane > halothane

10
Q

MAC (gen anesthetics)

A

Minimal Alveolar Concentration
concentration of an inhaled anesthetic in alveoli at 1 atm that prevents movement in response to a painful stimulus in 50% of patients
~1.2 MAC prevents movement in 95% of patients

11
Q

Factors decreasing an agent’s MAC

A
increased age
low temperature
pregnancy
opioids
other anesthetics/CNS drugs
12
Q

MACs of several agents

A
Nitrous oxide: 105%
Desflurane: 6
Sevoflurane: 1.71
Isoflurane: 1.15
Halothana: 0.75
13
Q

MAC with 70% nitrous oxide

A

desflurane: 2.83
Sevoflurane: 0.66
Isoflurane: 0.5
Halothane: 0.29

14
Q

Meyer-Overton rule

A

MAC inversely correlates with lipid solubility

= the more lipid-soluble the agent, the more potent it is

15
Q

Gen anesthetics MOA

A

Facilitation of inhibition

  • increase GABAa receptor-mediated transmission
  • increased background (leak) K_ conductance

Inhibition of excitation
- reduce glutamate/ACh receptor-mediated transmission

16
Q

Metabolism of general anesthetics

A

Metabolites may be hepato/nephrotoxic
Degree of metabolism may influence rate of decrease in alveolar partial pressure at conclusion of anesthetic

General rule: rate of metabolism of inhaled anesthetics tend to follow solubility in blood

17
Q

Methoxyflurane metabolism

A

40-50% metabolized
chief metabolite: fluoride
Nephrotoxicity/hepatotoxicity

18
Q

Halothane metabolism

A

15-20% metabolized
chief metabolite: trifluoracetic acid
Hepatotoxicity/nephrotoxicity

19
Q

Sevoflurane metabolism

A
3% metabolized
Chief metabolite: fluoride (short lived)
increased degradation by soda lime to a vinyl ether ("Compound A")
Low potential for toxicity
Nephrotoxicity in rats
20
Q

Isoflurane metabolism

A

0.2% metabolized
chief metabolite: trifluoracetic acid
low potential for toxicity

21
Q

Desflurane metabolism

A

0.02% metabolized
resistant to metabolism
high molecular stability; no significant toxicity

22
Q

Nitrous oxide

A

0.0004% metabolized
chief metabolite: nitrogen
? toxicity of free radicles

23
Q

GA effect on CNS

A

reduced cerebral metabolic rate

  • greatest with isoflurane: ?cerebral protection
  • enflurane: epileptic activity in EEG

Cerebral vasodilatation

  • increased cerebral blood flow
  • nitrous oxide: only modest effect (low potency)
24
Q

GA effect on CV system

A

reduced arterial BP due to

  • reduced CO (halothane) and/or
  • reduced total PVR (e.g. isoflurane)
Ventricular arrhythmias (halothane)
- sensitization of myocardium to circulating catecholamines

N2O: mild sympathetic stimulation

  • laughing gas
  • rarely used due to nausea/vomiting
25
Q

GA effect on respiratory system

A

Respiratory depression

  • increased rate and reduced depth of breathing (tidal volume)
  • net effect: reduced alveolar ventilation/ increased PaCO2
  • -> reduction in respiratory response to increased PaCO2

Decreased airway resistance
- advantage for patients with asthma (inhibition of bronchiole smooth muscle)

26
Q

GA effect on kidneys

A

reduced renal blood flow

- low GFR, urine output

27
Q

GA effect on skeletal muscle

A

muscle relaxation

potentiation of effects of nondepolarizing muscle relaxants (greatest with isoflurane)

28
Q

GA effect on uterus

A
Uterine relaxation (halothane and all other volatile agents)
Could lead to prolonged uterine atony/severe blood loss in parturients
Delivery: spinal anesthetic, not general
29
Q

Balanced anesthesia

A

combination of agents to maximize advantages, minimize adverse effects
Combination of iv + potent inhaled drugs
many anesthesiologists prefer to decrease total dose of a potent inhaled drug that a patient receives with any one of a number of iv drugs

30
Q

Thiopental uses/MOA

A

iv anesthetic
barbiturate
Rapid induction of hypnosis (no analgesia)
facilitation of inhibitory NT via GABAa

31
Q

Thiopental pharmacokinetics

A

rapid induction in one “arm-brain circulation time” patient normally wakes up ~5 min after a single bolus injection
when tissues are saturated, elimination and not redistribution determines time of emergenc
t1/2 ~ 11 h

32
Q

Thiopental adverse effects

A
hypotension
- exaggerated with hypovolemia 
- dose reductions necessary in elderly
Respiratory depression
Histamine release
Arterial occlusion possible
33
Q

Propofol uses/MOA

A

iv anesthetic
2,6-diisopropylphenol
sedation, induction, and maintenance of anesthecia (TIVA - total IV anesthesia)
smooth induction, pleasant dreams, rapid, clear-headed wakening
antiemetic
no analgesia

facilitates inhibitory transmission via GABAa

34
Q

Propofol PK

A

rapid induction similar to thiopental, even more rapid awakening (3min after iv bolus)
rapid metabolism in liver, t1/2 ~1 hour
no significant redistribution - useful for infusion

35
Q

Propofol adverse effects

A

pronounced hypotension

  • greater than with thopental
  • marked dose reductions necessary in elderly

Respiratory depression & apnea
injection pain
potential for sepsis - dispensed in egg lecithin/soy bean oil
use formulation soon after opening

36
Q

Ketamine uses/MOA

A

iv anesthetic
PCP derivative
state of “dissociative anesthesia” - patient appears conscious but unable to respond to/process sensory input
little cardiorespiratory depression and maintain airway reflexes
bronchodilating properties
unpleasant dreams common

Induction of anesthesia in trauma/shock
battlefield surgery
analgesia in burn patients
im induction in children

Antagonist at NMDA receptors (a type of glutamate receptor)

37
Q

Ketamine PK

A

rapid induction after iv bolus (slower than thiopental, propofol)
hepatic metabolism
t1/2 ~3 hour

38
Q

Etomidate

A
iv anesthetic
imidazole derivative
minimal effects on hemodynamics - useful for induction of unstable patients
No analgesia
Kinetics/MOA similar to propofol
produces adrenal suppression