Chapter 7. Inhalation Anesthetics

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Chapter 7. Inhalation Anesthetics

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• ???????
• R1 ? ?

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Inhalation anesthetics

• First universally accepted general anesthetics
• - nitrous oxide, chloroform and ether.
• Ethyl chloride, ethylene, and cyclopropane were
  also used
• - particularly popular fast induction
• - but toxicity and flammability led to
  their withdrawal from the market
• Methoxyflurane and enflurane are no longer used
  toxicity efficacy
• 1) Methoxyflurane the most potent
  inhalation agent
• but vasopressin-resistant, high
  output, renal failure
• 2) Enflurane nonpungent odor and
  nonflammable at clinical concentration
• but depresses myocardial
  contractility, sensitizes the myocardium to
• epinephrine, increases the
  secretion of CSF resistance to CSF outflow
• Five inhalation agents continue to be used in
  clinical anesthesiology
• nitrous oxide, halothane, isoflurane,
  desflurane, and sevoflurane.

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Inhalation anesthetics

• The course of general anesthesia
• 1) Induction (????)
• 2) Maintenance (????)
• 3) Emergence (????)
• Inhalation anesthetics are particularly
  useful in the induction of pediatric
• patients it may be difficult to start
  an iv line.
• adults prefer rapid induction with
  intravenous agents.
• regardless of the patients age,
  anesthesia is often maintained with
• inhalation agent
• emergence depends primarily upon the
  pulmonary elimination of agents

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Inhalation anesthetics

• Pharmacokinetics (???)
• ? relationship between a drugs dose,
  tissue concentration,
• and elapsed time
• ? how a body affects a drug
• Pharmacodynamics(???)
• ? the study of drug action, including
  toxic responses
• ? how a drug affects a body
• Clinical pharmacology of individual agents
• Nitrous oxide, Halothane, Isoflurane,
  Desflurane, Sevoflurane

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Pharmacokinetics of Inhalation anesthetics

• Although the mechanism of action of inhalation
  anesthetics remains unknown, it is assumed that
  their ultimate effect depends on attainment of a
  therapeutic tissue concentration in the central
  nervous system.
• There many steps, between the administration of
  an anesthetic from a vaporizer and its deposition
  in the brain

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Pharmacokinetics of Inhalation anesthetics
7
Pharmacokinetics of inhalation anesthetics
-Factors affecting inspiratory concentration(FI )

• 1) fresh gas flow rate(FGF rate)
• 2) volume of the breathing
  system(breathing circuit volume)
• 3) any absorption by the machine or
  breathing circuit(circuit
• absorption)
• the higher the FGF rate, the smaller the
  breathing system
• volume, the lower the circuit absorption
• ? the closer the inspired gas concentration
  will be to the
• fresh gas concentration
• ? the faster induction, recovery times

8
Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 1. Uptake
• 2. Ventilation
• 3. Concentration

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 1. Uptake
• ? FA/FI lt1.0
• ????? uptake? ???, FA ? ??? FI ? ??????.
  ??? ????? uptake? ?? FI gt FA ? ??? FA/FI lt1.0
  ? ??.
• ? Anesthetic agent? uptake? ??? ,
• alveolar concentration? ???? ??? ????
• ? FA/Fi? ??
• ? gas? concentration? ? partial pressure?
  ????? ????.
• alveolar partial pressure? blood?
  anesthetic partial pressure? ????
• ??? brain tissue concentration? ?????
  ????? ?? ????.
• ? Anesthetic agent? uptake? ??? ,
• inspired concentration(Fi)? alveolar
  concentrations(FA),? ??? ???
• ? induction? ??? ????

10
Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• Anesthetic uptake factors
• 1) solubility in the blood
• 2) alveolar blood flow
• 3) difference in partial pressure between
  alveolar gas and
• venous blood
• Uptake ? x Q x (PA-PV) / barometrc pr.
• (Q cardiac output)

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 1) solubility in the blood (???)
• ? Insoluble agents(N2O)? soluble
  agents(halothane) ?? blood? ? ???
• ? N2O ? FA? Halothane? FA?? ? ?? ???-gt
  induction? ???
• ? Partition coefficients(?????)
• relative solubilities of an anesthetic
  in air, blood, and tissues
• ? ?????? ??? ?(??? ?????)?? ???? ?????
  ???
• ? ??? ???? ???? ????.
• (ex.isoflurane(? 1.4) ?????? blood?
  isoflurane??? alveolar?
• isoflurane ???? 1.4? ? ?????
  ???)
• ? blood/gas partition coefficient? ??.
• ? ?? ??? blood??? solubility? ?????
  ????
• pulmonary circulation? ?? ?? ???
  ??(uptake)? ???.
• solubility? ?? alveolar partial
  pressure ? ? ??? ??? induction? ? ?
• ???.

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 2) alveolar blood flow
• ? in the absence of pulmonary shunting equal
  to cardiac output
• ex) cardiac output ? ? anesthetic uptake
  ?, alveolar partial
• pressure ??? ????, induction? ????.
• ? insoluble agent? alveolar blood flow? ??? ??
  ?? ???
• ? soluble agent??? low cardiac output ? ??,
  ????? ??? ???
• ? ???? ???? soluble agent? overdosage?
  ????? ??

13
Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 3) difference in partial pressure between
  alveolar gas and venous blood
• - tissue uptake? ??
• (tissue uptake? ??? Alveolar to venous
  partial pr.difference? 0)
• -tissue uptake ????
• 1) tissue solubility of the agent(
  tissue/blood partition coefficient)
• 2) tissue blood flow
• 3) difference in partial pressure
  between arterial blood and the
• tissue

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• - tissue? solubility? blood flow? ?? 4?? group??
  ????
• 1. vessel-rich group ex) brain, heart, liver,
  kidney, endocrine organ
• 2. muscle group ex) skin, muscle
• 3. fat group
• 4. vessel-poor group ex) bone, ligament,
  teeth, hair, cartilage
• Vessel-rich group?? ??? blood? tissue
  perfusion? ? ????
• Vessel-poor group?? ??? blood? tissue
  perfusion? ? ???? ???.

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• Initial rise of rate of FA/FI
• ?? induction? uptake? ???? ventilation? ??
  FA/FI? ???? ??
• ?ventilation increase FA/FI
• ?alveolar/venous partial pr. difference?
• ?uptake ? ???? ?? FA/FI??? solubility? ????
  ?? level?? ??

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• -? tissue group? ?? ?? ?? ??? ??? ???? ?

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 2. Ventilation
• pul. blood stream? ??? ????? ????? ?????
  alveolar concentration? ????.
• (ventilation? ????? ???
• ? soluble agent??? FA/ FI ? ????? ?????)

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• 3. Concentration
• Concentration Effect
• inspired anesthetic concentration?
• ?alveolar concentration? FA/FI ?

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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• Anesthetic gas? 50???
• 10/9011
  40/6066
• Anesthetic gas concentration? 4? ???
  alveolar concentration? 6? ???

Anesthetic gas 80
O2 20
Anesthetic gas 20
O2 80
Gas 10
O2 80
Gas 40
O2 20
?
?
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Pharmacokinetics of inhalation anesthetics
-Factors affecting alveolar concentration(FA )

• Second gas effect
• ? ?? ?? ???? ?? ??(????)? solubility? ?? ????
  ????? ????? ??? ??? ??? ?? ??? ???? ??
  ????(????)? ?? ??? ????? ?? ???? ??? ???? ??
• 1 of second gas
  1 of second gas (1.7) 1
  of second gas
• uptake of half of the
  N2O absorbed
  gases replaced
• 
  
  by added ventilation
• 
  
  
  0.4 of second gas

O2 19
N2O 80
O2 19(31.7)
N2O 40(66.7)
O2 19
N20 40
O2 7.6
N2O 32
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Pharmacokinetics of inhalation anesthetics-Factor
s affecting arterial concentration(Fa )

• Ventilation/perfusion mismatch
• alveolar anesthetic partial pr.? arterial
  anesthetic partial pr.? ??? ????? ??? arterial
  partial pr.? ?? end-expiratory gas?? ??. ? ???
• ? venous admixture
• ? alveolar dead space
•   ? nonuniform alveolar gas distribution
•   ? ventilation/perfusion mismatching? ??
• -gtalveolar- arterial difference ?
  ????.
• V/Q mismatching?(ex.Atelectasis,emphysema,pn
  eumonia)
• ?alveolar partial pr.?,alterial partial pr.
  ?
• ?? poorly soluble agent?? alveolar gas?
  arterial blood pr.??? ?
• ?

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Pharmacokinetics of inhalation anesthetics-Factor
s affecting elimination

• Recovery from anesthesia? brain tissue??
  anesthetic concentration? ????? ???.
• Anesthetics can be eliminated by
• 1) biotransformation alveolar partial pr.?
  ???? ??? ???.
• Methoxyflurane?? ???? ??? ??? ???? soluble
  anesthetics? elimination? ?? ???
• 2) transcutaneous loss diffusion through
  the skin insignificant
• 3) exhalation
• Induction? ????? ???? Recovery? ?????.
• - Rebreathing? ?? Elimination
• - high Fresh gas flows
• - low Anesthetic-circuit volume
• - low absorption by the
  Anesthetic-circuit
• - decreased Solubility
• - high CBF(Cerebral Blood Flow)
• - increased Ventilation

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Pharmacokinetics of inhalation anesthetics-Factor
s affecting elimination

• Diffusion hypoxia
• on recovery from anesthesia with N2O ? room
  air?? ?????
• ????? ?? ??? N2O? ???? ?? ?? ????
• Diffusion hypoxia ? ???.
• 1. Directly affect oxygenation by
  displacing O2
• 2. diluting alveolar CO2 ? respiratory
  drive ??
• ??? ???? ???? N2O?? ?? ?? 100 O2?
• 510?? ?????.

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Pharmacodynamics of inhalation anesthetics-Theori
es of anesthetic action

• Pharmacodynamics(???)
• ? the study of drug action, including toxic
  responses
• ? how a drug affects a body
• General anesthesia
• 1) reversible loss of consciousness
• 2) analgesia of the entire body
• 3) amnesia
• 4) muscle relaxation
• ? ???? ?? altered physiological state
• General anesthesia? ???? ??
• 1) inert elements ( ??? ?? ex) xenon )
• 2) simple inorganic compounds ( ?? ??? ex)
  nitrous oxide)
• 3) halogenated hydrocarbons ( ???? ???? ex)
  halothane )
• 4) complex organic structures ( ?? ?? ???
  ex) barbiturate )

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Pharmacodynamics of inhalation anesthetics-Theori
es of anesthetic action

• ?? ??? ?? ?? ? ???
• 1) Agent-specific theory  
• 2) Unitary hypothesis
• 3) Critical volume hypothesis
• 4) Fluidization theory of anesthesia

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Pharmacodynamics of inhalation anesthetics-Minimu
m Alveolar Concentration(MAC)

• MAC (Minimum alveolar concentration)
• ? ?? surgical incision? ?? standardized
  stimulus? ??? ??? 50 ? ???
• ? ?? ?? ?????? alveolar
  concentration.
• ? MAC is a useful measure
• brain partial pressure? ??
• agents?? potency? ???? ?? ???.
• experimental evaluation? ??? ??? ??.
• ? Mac value? ?? ?? ?? ??? ?? ?? ??? ?? ???
• ex) 0.5 MAC? N2O (53)? 0.5 MAC? Halothane
  (0.37)? mixture? CNS?
• depression??? 1.0 MAC?
  isoflurane(1.7)? ?? ????.
• ? ?? MAC?? CNS? depression??? ??? Myocardial
  depression??? ??? ??
• ex) 0.5 MAC? Halothane? 0.5MAC? N2O ?? ?
  ???? Myocardial depression
• ? ????.

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Pharmacodynamics of inhalation anesthetics-Minimu
m Alveolar Concentration(MAC)

• ? MAC? dose-response curve?? ? ?? ????. ?
  ED50,( median effective dose)
• ? 1.3 MAC? surgical incision? ?? standardized
  stimulus? ??? ??? ???, ? 95 ??? ??? ??? ??? ???
  ? ? ?? ?????? alveolar concentration ??
• ? MAC Awake 0.3 0.4 MAC
• ? Physiological and pharmacological variables?
  ?? MAC?? ???. ??? ???? ?? 10?? ??? ????? MAC? 6
  ? ????? ????.
• ? MAC? ??, ??, ??????? ????.

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Pharmacodynamics of inhalation anesthetics-Minimu
m Alveolar Concentration(MAC)
29
Clinical pharmacology of inhalation anesthetics

• 1. Nitrous oxide ( N2O) ( N2Olaughing gas)
• 1) physical properties
• ? ???? ??? ??? inorganic anesthetic gas
• ? ??, ??
• ? ??? ?, ??? ? ?? O2 ??? ??? ?? ??
• ? ??, ????? gas??? ??, ?? ????? ?????
• ??? ??
• ? N2O? ??? ??

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Clinical pharmacology of inhalation anesthetics

• 2) effect on organ systems
• A. Cardiovascular system
• - N2O stimulate the sympathetic nervous
  system
• in vitro, N2O? ?? ??(myocardial
  contractility)? direct depress
• but, in vivo, N2O? catecholamines?
  ?? stimulation ? ???
• ? ? arterial blood pressure ? cardiac
  output ? heart rate ? ??? ??? ??
• ? ?? ???
• - N2O? Myocardial depression? unmasked
  ????
• ? coronary artery diseases ? ?? ??
• ? severe hypovolemia ? ??
• ? BP ? ? myocardial ischemia
• - pulmonary vascular smooth muscle?
  constriction
• ? pulmonary vascular resistance ?
  -gt Rt. Ventricular end-diastolic pr. ?
• - endogenous catecholamine level ? ?
  epinephrine induced arrhythmia? higher

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Clinical pharmacology of inhalation anesthetics

• B. respiratory
• - N2O? CNS stimulation, pulmonary stretch
  receptors activation
• -gt increase respiratory rate (
  tachypnea)
• decrease tidal volume
• net effect -gt minimal change in minute
  ventilation and resting arterial CO2 level
• - Hypoxic drive
• ? ?? carotid bodies ?? ?? peripheral
  chemoreceptor? ?? ????
• arterial hypoxia? ????
  ventilatory response
• ? ?? ?? ?? N2O? ???? hypoxic drive? ??
  depression? ? ??.
• C. cerebral
• ? increasing cerebral blood flow
  cerebral blood volume
• -gt mild elevation of
  intracranial pressure
• ? increase CMRO2 ( cerebral oxygen
  consumption )
• ? MAC??? N2O level? ???? dental surgery
  ? ?? minor procedures?? analgesia
• ??? ? ? ??.

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Clinical pharmacology of inhalation anesthetics

• D. neuromuscular
• - not provide significant muscle
  relaxation
• - not a triggering agent of malignant
  hyperthermia
• E. Renal
• - N2O ? renal vascular resistance ? ?
  renal blood flow ?
• glomerular filtration rate(GFR)
  urinary output ?
• F. hepatic
• - N2O ? hepatic blood flow ? but other
  volatile agent? ?? ????.
• G. gastrointestinal
• - N2O is cause of postoperative nausea
  vomiting
• (? activation of the chemoreceptor
  trigger zone and the vomiting center in
• the medulla)

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Clinical pharmacology of inhalation anesthetics

• 3) Biotransformation toxicity
• - emergence(????)?? N2O is eliminated by
  exhalation ???
• 
  diffuses
  out through skin ??
• 
  
  biotransformation 0.01??
• - N2O? Vitamine B12??? cobalt ??? ????
  ??? ????? Vitamine B12?
• ???? enzyme? ??
• ? ? Myelin??? ??? methionine
  synthetase
• ? DNA??? ??? thymidylate
  synthetase ? ??
• ? N2O? ?? ??? ??
• ? ? Bone marrow depression(
  ex) megaloblastic anemia )?
• ? Neurological
  deficiencies ( ex) peripheral neuropathie?
  pernicious anemia)
• ??
• - teratogenic effect ???? ??
• - Polymorphonuclear leukocytes?
  chemotaxis? motility? ??
• ? infection? ?? immunological
  response? ????

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Clinical pharmacology of inhalation anesthetics

• 4) contraindication
• ? air embolism
• ? pneumothorax
• ? acute intestinal obstruction,
• ? intracranial air ( ex) dural closure?
  pneumoencephalus? ??
• tension pneumocephalus)
• ? pul. air cyst
• ? intraocular air bubble
• ? tympanic membrane grafting
• ? Pulmonary HTN?? ??
• ( N2O? pulmonary vasculature
  resistance ?

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Clinical pharmacology of inhalation anesthetics

• 5) drug interactions
• - N2O? MAC?? ??? ???? ?? ??? ??? more
  potent
• volatile agents? ?? ??
• - N2O? neuromuscular blockade? ????? ???,
  ??? ????
• (volatile agents)? ??? ???
• - vaporizer? ???? ??? N2O? ??? ??? ?????
  ???
• ??? ? ? ??.

36
Clinical pharmacology of inhalation anesthetics

• 2. Halothane
• 1) physical properties
• ? ????? halogenated alkane
• ? ???
• ? ????
• ? ?? ??

37
Clinical pharmacology of inhalation anesthetics

• 2) effects on organ systems
• A. cardiovascular
• ? dose-dependent reduction of
  arterial blood pressure
• ? Halothane? coronary artery
  vasodilator ??? Systemic arterial pressure ?
• ? coronary blood flow ?
• ? ????? ???? aortic arch? carotid
  bifurcation ? baroreceptor? ????
• vagal stimulation? ????? ?????
  heart rate? ????
• ??? halothane? ? reflex? ??? ??,
  sinoatrial node conduction? ??? ??,
• ? Junctional rhythm?? bradycardia?
  ??
• ? ?? ???? ?? ?????? ??
• ? ????? ????
• ? Halothane? ?? ??? cardiac arrhythmia?
  ?? ? ? ??? Halothane? ???
• epinephrine? arrhythmogenic
  effects? ?????? epinethrine? ?? ?? ? ?

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Clinical pharmacology of inhalation anesthetics

• B. respiratory
• ? Halothane? ??? ?? ??? ??
• ? ??? ???? ??? tidal volume? ??????
  ???
• ? alveolar ventilation? ????, resting
  PaCO2? ???
• ? Halothane? ventilatory effect? central
  mechanism (medullary depression)?
• peripheral mechanism (intercostal
  muscle dysfunction)???
• ? pre-existing lung disease? ?? ??
  ????, surgical stimulation? ?? ???
• ? Hypoxic drive? 0.1 MAC ??? Halothane?
  ???? ??? ??? ? ??.
• ? Halothane? a potent bronchodilators
• (? Halothane? Airway reflex ??,
  bronchial smooth muscle ?? ??)
• ? Halothane? mucociliary function ?
  ? postoperative hypoxia atelectasis??

39
Clinical pharmacology of inhalation anesthetics

• C. cerebral
• - cerebral vessels? dilating
• ? cerebral vascular resistance? ,
  CBF ?
• ( arterial blood pressure? ???? CBF?
  ???? ??? autoregulation? ?
• ???.)
• - ????? ???? intracranial pressure ???
  Halothane???
• Hyperventilation? ??? ??? ??? ??
• D. neuromuscular
• - ???? ?????, non-depolarizing
  neuromuscular-blocking agents (NMBA)?
• ????
• - malignant hyperthermia? ??

40
Clinical pharmacology of inhalation anesthetics

• E. renal
• - Halothane? renal blood flow,
  GFR(glomelular filtration rate), urinary output
  ?
• (? Halothane? arterial blood pressure?
  cardiac output ? ????? ?? )
• - GFR???? renal blood flow??? ? ?? ???
  filtration fraction? ???
• ? ?? Preoperative hydration
• F. hepatic
• - cardiac output? ?? ?? ?? hepatic
  blood flow? ????
• - hepatic artery vasospasm? ?? ???.
• - fentanyl, phenytoin, verapamil ??
  ??? ?? ??? ???? ????.

41
Clinical pharmacology of inhalation
anesthetics

• 3) biotransformation toxicity
• ? halothane ?
  (liver) trifluoroacetic acid?
  ???
• 
  cytochrome P450(2EI)
• ? ??? ????? disulfiram ???? ?? ???
  ? ??.
• ? postoperative hepatic dysfunction?
  viral hepatitis, impaired hepatic perfusion,
• hepatocyte hypoxia, sepsis,
  hemolysis, benign postoperative intrahepatic
• cholestasis, drug induced
  hepatitis?? ?? ?????,
• ? halothane hepatitis? ?? ???.
• ? Halothane hepatitis is increased
  risk at
• halothane ??? ??
  ???? ?? ?? ??? ??
• ??? ??? ??
• halothane ???
  ??? ???? ?? ??
• ????? halothane
  ??? ?? Hx()? ??

42
Clinical pharmacology of inhalation anesthetics

• 4) contraindication
• ? Halothane? ??? ???? ?? ?? ? ??? ???? ???
  ?
• ?? ?? ?
• ? intracranial mass lesion? ?? ?? ??
• ? intracranial hypertension? ?????
• ? hypovolemic pt.
• ? severe cardiac disease ( ex) aortic
  stenosis )
• ? epinephrine? ???? ??? ??
• ? Pheochromocytoma? ?? ??

43
Clinical pharmacology of inhalation anesthetics

• 5) drug interactions
• ? Halothane? ß- adrenergic blocking
  agent(propranolol)? Ca
• channel blocking agent(verapamil)? ??
  ??? ??
• ? myocardiac depression? ??? ????
• ? Tricyclic antidepressants, MAO
  inhibitor
• ? fluctuations in blood pressure
  arrhythmias
• ( but not absolute
  contraindication)
• ? Halothane? aminophylline?? ???
• ? ??? ventricular arrhythmias ??

44
Clinical pharmacology of inhalation anesthetics

• 3. Isoflurane
• 1) physical properties
• ? nonflammable volatile anesthetic
• ? pungent ethereal oder
• ? Enflurane? chemical isomer??, ??
  ??? ??? ?? ??
• 2) effects on organ systems
• A. cardiovascular
• ? mild cardiac depression
• but carotid baroreflex? ?? heart
  rate ??? ??, cardiac output? ???
• ? ß-adrenergic stimulation
• ? skeletal muscle blood flow?,
  systemic vascular resistance ?arterial blood
  pressure ?
• ? Isoflurane? ??? ??? ???? ??
• ? heart rate ?, arterial blood
  pressure ?, norepinephrine? plasma level ?
• ? dilates coronary arteries

45
Clinical pharmacology of inhalation anesthetics

• B. Respiratory
• ? respiratory depression (resembles that of
  other volatile anesthetics)
• -gt minute ventilation? ??
• ? 0.1MAC?? ??? Isoflurane? hypoxia?
  hypercapnia? ?? ???
• ? ?? ??? ????
• ? good bronchodilator
• C. Cerebral
• ? gt1.0 MAC CBF intracranial
  pressure?
• ( but, Halothane??? ? ???
  ???,Hyperventilation? ?? ???
• ? ? ??. )
• ? ?? ??? ?? O2???? ????
• ? 2.0 MAC? ?, electrically silent
  electroencephalogram(EEG)? ???
• ? EEG suppression? cerebral ischemia?
  brain protection

46
Clinical pharmacology of inhalation anesthetics

• D. neuromuscular
• - relax skeletal muscles
• E. renal
• - renal blood flow ?, glomerular filtration
  rate ? , urinary output ?
• F. hepatic
• - Total hepatic flow ?
• - Hepatic oxygen supply better maintained
  than with Halothane
• ( ? Isoflurane???? hepatic artery
  perfusion? hepatic venouse O2
• saturation? ???? ??)

47
Clinical pharmacology of inhalation anesthetics

• 3) biotransformation toxicity
• ? trifluoroacetic acid? ???
• ? serum fluoride fluid level? ??? ? ???,
  ???? ???? ???.
• 4) Contraindications
• Isoflurane? ??? ?? ??? ??.
• 5) Drug interactions
• ? Epinephrine? 4.5 µg/kg ?? ???? ????
• ? nondepolarizing NMBAs? Isoflurane? ?? ???

48
Clinical pharmacology of inhalation anesthetics

• 4. Desflurane
• 1) physical properties
• ? Isoflurane? ?? ??? ??
• ? Vapor pressure? ??
• ? 20 ? ?? 681 mmHg ? ? ?? ??? ??
• ? low solubility in blood and body
  tissues -gt ultrashort duration
• -gt very rapid wash in and wash
  out of anesthetic
• ? Moderate potency

49
Clinical pharmacology of inhalation anesthetics

• 2) effects on organ systems
• A. cardiovascular
• ? ????? ?? ??? Isoflurane? ??
• ? ?? ??? systemic vascular
  resistance? ? arterial blood pressure ?
• ? cardiac output ?? or ?? ??(12
  MAC??)
• ? heart rate, central venous
  pressure, pulmonary artery pressure moderate
  rise
• ? ???? ??? ?? ?? desflurane? ???
  ??? heart rate, BP,
• catecholamine level? ????
  ????? ??.
• ? ????? ?? ??? fentanyl, esmolol,
  clonidine ?? ????? ??.
• ? coronary blood flow? ???? ??.

50
Clinical pharmacology of inhalation anesthetics

• B. respiratory
• ? tidal volume ? respiratory rate ?
• ? Alveolar ventilation ? ? resting PaCO
  2 ? ? ventilatory response ?
• ? pungency and airway irritation during
  desflurane induction
• ? salivation, breath-holding,
  coughing, laryngospasm??
• C. Cerebral
• ? directly vasodilates the cerebral
  vasculature, increasing CBF intracranial
  pressure
• ? cerebral metabolic rate of
  oxygen(CMRO2) ? ? cerebral vasoconstriction
  increase in CBF
• ? cerebral oxygen consumption ?
• ?during periods of
  desflurane-induced hypotension, CBF is adequate
  to maintain

51
Clinical pharmacology of inhalation anesthetics

• D. neuromuscular
• dose-dependent?? ???? ??? ?? ?? ??
• E. renal
• no evidence of any nephrotoxic
  effects
• F. hepatic
• no evidence of hepatic injury

52
Clinical pharmacology of inhalation anesthetics

• 3) biotransformation toxicity
• ? minimal metabolism
• ? insignificant percutaneous loss
• ? CO poisoning ????
• disposing of dried out
  absorbent or use of calcium hydroxide ? minimize
  the risk
• 4) Contraindications
• ? severe hypovolemia
• ? malignant hyperthermia
• ? intracranial hypertension
• 5) drug interactions
• ? potentiates nondepolarizing
  neuromuscular blocking agents
• ? Epinephrine? 45 µg/kg?? ??? ?????
  ?? ??????.
• ? associated with delirium in some
  pediatric patients

53
Clinical pharmacology of inhalation anesthetics

• 5. sevoflurane
• 1) physical properties
• ? nonpungency rapid increase in alveolar
  anesthetic concentration
• ? excellent choice for smooth rapid
  inhalation induction
• ? rapid emergence than isoflurane
• ? greater incidence of delirium in some
  pediatric pt. (? faster emergence)
• ? treated with 1.02.0 µg/kg of
  fentanyl

54
Clinical pharmacology of inhalation anesthetics

• 2) effects on organ systems
• A. cardiovascular
• ? mildly depresses myocardial contractility.
• ? systemic vascular resistance arterial
  blood pr. ?
• ? prolong the QT interval
• B. respiratory
• depresses respiration , vagus n.??
  bronchospasm ??

55
Clinical pharmacology of inhalation anesthetics

• 3) biotransformation toxicity
• ? Liver microsomal enzyme P-450(2E1)? ?? ??
• ? inorganic fluoride nephrotoxicity
• but ????? significant renal
  dysfunction?? ??? ??.
• ? Barium hydroxide lime?? soda lime? ??
  Alkali? ??? Sevoflurane? ??? ???
• ???? ?? ???.
• (??? ????? Compound A,
  fluorometal-2, 2-difluoro-1-vinylether)
• ? Compound A? ?? ??? ????? ?
• - Respiratory gas temperature? ??
• - Low-flow anesthesia
• - ??? barium hydroxide ??? (Barakyme)
• - Sevoflurane? ?? ??
• - ?? ?? ?? ??? ? ??

56
Clinical pharmacology of inhalation anesthetics

• ? Hydrogen fluoride? ??? ??? ??? Acid
  burn? ??? ? ??
• 4) Contraindications
• ? Severe hypovolemia
• ? malignant hyperthermia
• ? intracranial hypertension
• 5) Drug interactions
• ? potentiates NMBAs
• ? catecholamine-induced arrhythmia????
  ??