inhalational agent

1. PHARMACODYNAMICS OF INHALED
ANESTHETICS
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2. Minimal Alveolar Concentration (MAC)
 The MAC of an inhaled anesthetic is defined as that
concentration at 1 atm that prevents skeletal muscle
movement in response to a supramaximal painful
stimulus (surgical skin incision) in 50% of patients
 A unique feature of MAC is its consistent measure of
potency and varying only 10% to 15% among individuals
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3.  The immobility produced by inhaled A. is mediated
principally by the effects of these drugs on the
Spinal cord, and
Only a minor component of immobility results from
cerebral effects
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4.  The use of equally potent doses (comparable MAC
concentrations) of inhaled anesthetics is mandatory for
comparing the effects of these drugs, not only at the
spinal cord but at all other organs
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5. Factors That Alter MAC
 MAC values for inhaled anesthetics are additive.
For example, 0.5 MAC of nitrous oxide plus 0.5 MAC
isoflurane has the same effect at the brain as does a 1-
MAC concentration of either anesthetic alone
 A 1-MAC dose prevents skeletal muscle movement in
response to a painful stimulus in 50% of patients,
whereas a modest increase to about 1.3 MAC prevents
movement in at least 95% of patients
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6. Comparative minimum alveolar
concentration (Mac) of inhaled anesthetics
MAC (%, 30 to 55 Years Old at 37°C, PB 760 mm Hg)
Nitrous oxide 104
Halothane 0.75
Enflurane 1.63
Isoflurane 1.17
Desflurane 6.6
Sevoflurane 1.80
Xenon 63-71
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7. Impact of physiologic and
pharmacologic factors on MacIncreases in MAC Decreases in MAC No change in MAC
Hyperthermia Hypothermia Anesthetic metabolism
Drug-induced increases in central nervous
system catecholamine levels
Increasing age Chronic alcohol abuse
Cyclosporine Preoperative medication Gender
Hypernatremia Drug-induced decreases in central
nervous system catecholamine levels
Duration of anesthesia (?)
α-2 Agonists PaCO2 15 to 95 mm Hg
Acute alcohol ingestion PaO2 >38 mm Hg
Pregnancy Blood pressure >40 mm Hg
Postpartum (returns to normal in 24 to
72 hours)
Hyperkalemia or hypokalemia
Lithium Thyroid gland dysfunction
Lidocaine
PaO2 <38 mm Hg
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8. Mechanism of Immobility
 MAC is based on the characteristic ability of inhaled drugs
to produce immobility by their actions principally on the
spinal cord, rather than on higher centers
 The observation that immobility during noxious stimulation
does not correlate with electroencephalographic activity
reflects the fact that cortical electrical activity does not
control motor responses to noxious stimulation
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9. Mechanism of Anesthesia-Induced
Unconsciousness
 Two separate phenomena
1. General anesthesia is a process requiring a state of
unconsciousness of the brain – the mechanism is still not
known
2. Immobility in response to a noxious stimulus - These
effects are mediated by the action of volatile anesthetics
on the spinal cord
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10. Meyer and Overton theory
 According to these concepts, phospholipids were
considered to be the primary targets of anaesthetic action
 Modification of their physical properties then produced
secondary effects on enzymes, receptors and ion
channels.
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11. • Inhalational anesthetics were believed to initially dissolve
in membrane phospholipids and change their physical
properties
Fluidity, volume,
Surface tension or lateral surface pressure, and
Thus modify the degree of order or disorder within the
membrane
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12.  Alterations in the physical properties of boundary lipids
were considered to have secondary effects on membrane
proteins, resulting in conformational changes, which
modified their activity.
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13. Protein theories of anaesthesia
 Recent evidence suggests that inhalational agents may
primarily interact with receptor proteins, producing
conformational changes in their molecular structure,
which affect the function of ion channels or enzymes.
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14. Ionotropic and Metabotropic Receptors
 Neurotransmitters signal through two families of
receptors, designated as ionotropic and metabotropic
receptors.
 Ionotropic receptors are also known as ligand-gated ion
channels because the neurotransmitter GABA binds
directly to ion channel proteins
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15.  This interaction causes the opening (gating) of the ion
channels, thus allowing the transmission of specific ions
(chloride ions), with resulting changes in membrane
potentials
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16. • The binding of neurotransmitters (acetylcholine) to
metabotropic receptors causes an activation of those
guanosine triphosphate binding progestins (G-
proteins) associated with the receptors, and
These G-proteins act as second messengers to
activate other signaling molecules, such as protein
kinases, or potassium or calcium channels
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17. Inhibitory ligand-gated and voltage gated
channels (Glycine and GABA receptors)
• Glycine receptors are major mediators of inhibitory
neurotransmission in the spinal cord and mediate part of
the immobility produced by inhaled anesthetics.
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18. Glutamate (NMDA, AMPA, and Kainate
Receptors)
 Glutamate receptors include G-protein-coupled receptors
and the ligand-gated receptors (NMDA, AMPA, and
Kainate)
 NMDA receptors likely are important mediators of the
immobilizing effects of inhaled anesthetics.
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19.  AMPA receptors mediate the initial (fast) component of
excitatory postsynaptic transmission and are likely targets
for volatile anesthetic-induced immobility
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20. Sodium Channels
 Inhaled anesthetics can inhibit the presynaptic terminal
release of neurotransmitters, particularly glutamate (the
intravenous administration of lidocaine decreases MAC).
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21. 1,1,1,-tri fluro-2-bromo-
2chlorethane
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22.  Halothane was not chemically inert and prolonged
usage of this agent damage metal rubber and
some plastic component of the anesthetic circuit
 Halothane is susceptible to spontaneous oxidation
and photochemical decomposition
Requiring storage in tinted glass bottle (amber glass
bottle) containing 0.01% thymol ( it renders its stability)
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23.  Colorless liquid, relatively pleasant smell, non
irritant , decomposed by light in to hydrochloric
acid (HCL), hydrobromic acid (Hbr), chloride (CL-
), bromide (Br-).
 Potent with a MAC of 0.75%.
 Carbon fluoride is responsible for non-
flammable and explosive nature.
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24. Induction
 The potency and relative lack of irritation favor the use
of halothane for rapid smooth inhalation induction of
anesthesia especially when it is administered together
with 60-70% N₂O.
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25.  Halothane has a relatively low blood gas solubility
coefficient of 2.5 and thus
 Induction of anesthesia is relatively fast in pediatrics
However it may take at least 30min for the alveolar
concentration to reach 50% of the inspired conc.
This is slower than for Enflurane or Sevoflurane
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26.  As with all volatile anesthetics it is customary to use the
techniques of administration of a higher partial pressure
of anesthetic (PI) than the alveolar concentration (PA)
(over pressurization)
Induce halothane anesthesia with concentration 2-3× higher
than the MAC value .
 The inspired value can be reduced when a stable level
of anesthesia has been achieved.
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27.  For halothane MAC is almost
-1.1% in neonate.
-0.9% in infants.
-0.9% at 1-2 years.
-0.75% at 4-5 years.
-0.65% at 80 yrs.
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28. • Recovery from halothane is slower compared to
newer drugs( induction is also slower) because of its
higher tissue gas coefficient
 During awakening after halothane anesthesia
patient remain drowsy for several hours.
Because of the reactive metabolite bromide
This is due to higher solubility in brain, muscle and fat
when compared to other volatile agents.
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29.  The greater solubility of halothane in those tissues
increase the amount of halothane that accumulate
during anesthesia
 Increase the time it takes to clear halothane from
those compartments after administration is
discontinued
Re-Distribution
Delayed awakening
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30. Cardiovascular effects
 Potent direct myocardial depressant effect
 The most prominent circulatory effect of halothane is dose
dependent arterial hypotension
 Decreased HR and coronary blood flow
 Slow conduction to AV node lead to Bradycardia
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31. 1/18/2019 31AMARE H

32.  During controlled ventilation halothane is associated with
dose dependent depression of COP by decreasing
myocardial contractility (vasodilatation) thus there is
reduction of ABP.
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33.  The hypotensive effect of halothane is augmented
by reduction in HR
Antagonism of bradycardia with atropine usually
leads to increased arterial BP
 The reduction in myocardial contractility and low
HR leads to reduction in myocardial oxygen
demand and coronary blood flow
So halothane is advantageous in patients with
coronary artery disease.
Because of reduced oxygen demand caused by low
HR and decreased contractility.
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34. • The depressant effect of halothane on COP is
aggravated in the presence of β-blocker
• Inadequate anesthesia or exogenous administration
of CA’s increases myocardial sensitization leading
to myocardial dysarrythmia and also cardiac arrest
• During local infiltration with adrenaline containing
local anesthetic, caution should be taken
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35. -Over dosage of halothane causes
bradycardia and hypotension ,so treat with
atropine and discontinue halothane.
Guidelines
Avoid hypoxemia and hypercapnia
Avoid concentration of adrenaline greater
than 1:100,000
Avoid a dosage in adults exceeding 10ml of
1:100,000 adrenaline in 10 min. or
30ml/hr.
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36. Respiratory Effects
 Alveolar hypoventilation (hypoxia) and
arterial hypercapnia occurs in a dose
dependent manner during halothane
anesthesia in a spontaneously breathing
patient so patient breathing should be
assisted or controlled.
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37. 1/18/2019 37AMARE H

38. • Non irritant, pleasant to breath during induction of
anesthesia
• The respiratory pattern associated with halothane
anesthesia is characterized by rapid shallow
respiration.
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39. 1/18/2019 39AMARE H

40.  In awake individual hypercapnia does not
occur because even small increase in
arterial CO₂ stimulates the respiratory
drive to increase minute ventilation.
 Halothane and other volatile anesthetics
abolish physiologic mechanism that
protect against hypercapnia
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41.  Rapid loss of pharyngeal and laryngeal reflexes might
lead to risk of aspiration.
 Inhibition of salivary and bronchial secretion.
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42. 1/18/2019 42AMARE H

43.  PaCO₂ increases as the depth of
anesthesia increases and patient becomes
hypoxic(PaCO2 increase PaO₂ decrease)
 Decrease in mucociliary function which
may persist several hours after halothane
anesthesia.
This may contribute to post op. hypoxia and
atelectasis
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44. 1/18/2019 44AMARE H

45. CNS
 Cerebral vasodilatation
 Increase CBF
 Increase ICP
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46. Other systems
 Potentiate action of NDMR by direct
relaxation of skeletal muscle.
 Trigger malignant hyperthermia.
 Post op. shivering is common in old age
(this increase O₂ requirement ⇒300% and
result in hypoxemia unless O₂ is
administered)
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47.  GI motility is inhibited – paralytic illus
 PONV are seldom severe.
 Decrease HBF this is proportional to COP.
 Hepatic artery vasoconstriction
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48. Biotransformation
 Major route of elimination is lung 80%
 10-20% is bio-transformed in the liver
 Small amount diffuse out through skin
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49.  Hepatic biotransformation occurs through
the cytochrome P450 system resulting in
the release of bromide and chloride ion
and the formation of fluorine containing
compounds mostly trifluoroacetic acid
 Many believe that the hepatic
complication of halothane results from its
biotransformation
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50. Emergence
 Awakening is prompt but may take several hours because
of higher solubility of halothane in brain, muscle, fat
increase accumulation
 Clearing time is increased after discontinuation
 PONV
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51. Halothane hepatitis
 Defined as the appearance of liver damage within 28
days of halothane exposure in a person in whom other
known causes of liver disease have been excluded.
 Approximately 20% of halothane is metabolized in liver by
the oxidative pathway, the end product excreted in urine.
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52.  The major metabolites are bromine,
chlorine, trifluoroacetic acid and
trifluoroacetyl-ethanol amide.
 A small proportion of halothane may
undergo reductive metabolism,
particularly in the presence of hypoxemia
and when the hepatic microsomal
enzymes has been stimulated by enzyme
inducing agents such as phenobarbitone
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53.  Reductive metabolism may result in the
formation of reactive metabolite
 Chlorine when absorbed or contact with dry
soda lime and will get broken down to BCDFE
(2-bromo-2-chloro-1,1-difluoroethene) which
has organ toxicity in animal models
Halothane hepatitis
 The product of reductive metabolic
pathway are more toxic than those
produced by oxidative pathway.
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54.  In mild cases halothane increase enzyme of liver, but in
several cases halothane hepatitis and liver necrosis
 Incidence is 1:35,000
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55.  This is supported by the fact that the risk
of post operative liver dysfunction is
increased in the presence of
Obesity which increase hypoxia and greater
storage of halothane
Hypoxemia
A short interval b/n administrations of
the drug
Enzyme induction produced by drugs e.g.-
phenobarbitone, phenytoin
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56. • The incidence of hepatic toxicity is high in
obese middle age women but less in
pediatric (halothane is the drug of choice
in pediatrics)
• As a result of this concern the committee
on safety of medicine has made the
following recommendations in respect
halothane.
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57. 1. A careful anesthetic history should be
taken to determine previous exposure and
any previous reaction to halothane.
2. Repeated exposure to halothane with in
a period of three months should be
avoided unless there are over riding
clinical conditions.
3. A history of jaundice or pyrexia after
previous exposure to halothane is an
absolute C/I to its future use in that
patient.
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58. Precaution
• Space occupying lesion
• Pheochromocytoma
• MHT
• History of PPH,APH, hypovolaemic
• Unexplained liver dysfunction
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59. Indication
• Induction of anesthesia in children
• Maintenance of anesthesia
• In air way obstructions
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60. Advantage Disadvantage
-rapid and smooth
induction
-poor analgesia
-effective in low conc. -CA’s induced arrhythmia
-Minimal stimulation of
salivary and bronchial
secretions
-post op. shivering
-bronchodilation -liver toxicity
-Muscle relaxation -slow recovery
-relative rapid recovery,
cheap
-Halothane hepatitis
-less stable1/18/2019 60AMARE H

61. • Dose – induction-2-3% in adult
-1-2% child
- maintenance-0.8%-1.5%
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62. 1/18/2019 62AMARE H

63. 1/18/2019 63AMARE H

64. Amare H.
INHALATIONAL ANAESTHESIA - 2
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65. Isoflurane
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 Isoflurane is a halogenated methyl ethyl ether that has a
pungent, ethereal odor
• Structural isomer of enflurane
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66. 1/18/2019 66
 Its intermediate solubility in blood, combined with a high
potency,
Permits rapid onset and recovery from anesthesia using
isoflurane alone or in combination with nitrous oxide or injected
drugs, such as opioids.
 Balanced anesthesia ?
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67. 1/18/2019 67
• It has great popularity for a variety of reasons
Virtual absence of serious hepatic toxicity
Minimal biotransformation
Ease of administration
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68. Induction
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• Rapid inhalational induction because of low blood gas
solubility
• It is potent
• Does not increase trachea-bronchial secretions
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69. Cardiovascular effects
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• Minimal depression of the CV system
• In contrast to halothane & Enflurane, COP is generally
maintained during isoflurane anesthesia by increasing
HR
• Decrease ABP by
-direct myocardial depression
-peripheral arterial vasodilatation
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70. 1/18/2019 70
• It causes selective coronary vasodilatation and
decrease coronary vascular resistance
Concerns regarding its use in patients with ‘coronary steal’
• Increase HR in young patients
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71. Central nervous system
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 Decreased cerebral metabolism
 Low conc. No change on CBF
 Doesn’t produce seizure
 ICP increase in spontaneously breathing patient but
this effect is eliminated when the patient is
hyperventilated
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72. 1/18/2019 72
• Some cerebro protective effects during ischemia or
hypoxemia
• Drug of choice for neuro-surgery
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73. Respiratory system
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• Like all VAA blunted hypoxic drive leading to
hypercapnia and V/Q mismatching – CO2 narcosis
• Bronchodilator
• Alteration in gas exchange because of
-decreased pulmonary compliance.
-decreased FRC.
-impairment of hypoxic pulmonary
vasoconstriction.
AMARE H

74. The effect of volatile anesthetics on respiratory system
resistance in patients with COPD – MAC 1.1
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75. Other systems
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• Skeletal muscle relaxation – volatile induction and
laryngoscope with out muscle relaxation
• Relaxation of uterus like halothane - PPH
• Decreased hepatic blood flow but hepatic oxygen
supply better maintained than halothane and liver
function minimally affected
• Enhance the action of GABA
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76. Biotransformation
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• Only small amounts are metabolized(0.2%)
• The quantities of this metabolites are insufficient to cause
significant cell injury or toxicity
 Emergence- is prompt after discontinued
-PONV like other IAA
 Complication-increase HR
-trigger MHT
-lack significant cxn. Safe drug
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77. Incidence of liver injury
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• Halothane > enflurane > isoflurane > desflurane and
• Correlates with the extent of their oxidative metabolism
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78. 1/18/2019 78
Advantage Disadvantage
Rapid induction and onset High cost, trigger MHT
Minimal biotransformation with
little risk of hepatic or renal
toxicity
Pungent odor- coughing,
breath holding
CV stability Coronary vasodilatation with
the possibility of the coronary
steel syndrome
Muscle relaxation Need expensive vaporizer
AMARE H

79. Drug Clearance
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• Volatile anesthetics may interfere with the clearance of
drugs from the plasma
Decreased hepatic blood flow or
Inhibition of drug-metabolizing enzymes
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80. Desflurane
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• Desflurane is a fluorinated methyl ethyl ether that differs
from isoflurane by just one atom: a fluorine atom is
substituted for a chlorine atom on the ethyl component
of isoflurane
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81. This fluorination brings about several effects
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1. It decreases blood and tissue solubility (the blood: gas
solubility of Desflurane equals that of nitrous oxide)
2. It results in a loss of potency (the MAC of Desflurane is
five times higher than isoflurane)
3. Results in a high vapor pressure
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82. Desflurane …
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 The vapor pressure of Desflurane approaches 1 atm at
23°C making controlled administration impossible with
a conventional vaporizer.
• A Desflurane vaporizer is an electronically controlled
pressurized device that delivers an accurately metered
dose of vaporized Desflurane into a stream of fresh
gases passing through it.
AMARE H

83. Desflurane …
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• Carbon monoxide can be generated under certain
conditions and may accumulate in the breathing system
when in contact with soda lime
• The MAC of Desflurane (6.5% in adults) is the highest of
any modern fluorinated agent
• It is non-flammable under all clinical conditions
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84. Desflurane …
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• Desflurane has the lowest blood: gas solubility, similar to
nitrous oxide.
• Desflurane offers a theoretical advantage in long
surgical procedures by virtue of decreased tissue
saturation.
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85. Central nervous system effects
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• Reduces cerebral metabolic rate for oxygen (CMRO2)
to a similar extent as isoflurane.
• Desflurane above 1 MAC produce mild increases in ICP
secondary to mild increase in CBF 2ndary to decreased
Cerebral vascular resistance.
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86. Desflurane …
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• Abolishes cerebral auto regulation at 1.5 MAC.
• Alone amongst the agents it increases CSF production
• Suppresses EEG activity and there is no evidence of
epileptiform activity.
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87. Cardiovascular effects = Desflurane …
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• Similar to those of isoflurane although possibly less
pronounced
• There is a dose-dependent reduction in myocardial
contractility, cardiac output, arterial blood pressure, and
systemic vascular resistance
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88. Systemic vascular resistance – desflurane
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89. Desflurane …
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• Unlike isoflurane, Desflurane may stimulate the
sympathetic nervous system at concentrations above
1 MAC.
• Sudden and unexpected increases in arterial blood
pressure and heart rate might occur
AMARE H

90. The effects of increasing concentrations (MAC) of halothane,
isoflurane, desflurane, and sevoflurane on cardiac index (L/min)
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91. Respiratory system effects = Desflurane …
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• Desflurane causes dose-related respiratory depression
• Tidal volume is reduced and respiratory rate
increases,
• At induction, high concentrations are irritant and may
provoke coughing or breath-holding.
AMARE H

92. Desflurane …
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• Provoke Laryngospasm, excessive secretions and
apnea.
• Do not have a marked bronchodilator effect and in
cigarette smokers it is associated with significant
bronchoconstriction.
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93. Metabolism & toxicity = Desflurane …
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• Desflurane is resistant to metabolism (0.02%) and serum
fluoride levels do not rise even after prolonged
administration
• The potential for Desflurane to cause renal or hepatic
toxicity is small given its minimal bio-transformation.
• near-absent metabolism to serum trifluoroacetate,
makes immune-mediated hepatitis extremely unlikely.
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94. Neuromuscular effects = Desflurane …
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• Marked depressant effect at the neuromuscular
junction
• Prolongs neuromuscular blockade by both non-
depolarizing and depolarizing relaxants.
• Triggers malignant hyperpyrexia
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95. Sevoflurane
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 First released for clinical use in Japan in 1990.
 A polyfluorinated isopropyl methyl ether
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96. Sevoflurane …
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• MAC ranges from 3.3 in infants to 2.5 in older children,
1.8 in adults and 1.3 in elderly patients. { 0.7 – 2.0 in
the presence of 65% nitrous oxide}
• Its low solubility, lack of airway irritability and moderate
potency make it particularly useful for ‘gas induction’ in
children.
• Unlike isoflurane it is non-irritant to the airway and can
be given in high concentrations for anesthetic induction
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97. Sevoflurane …
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 The concentration used for induction of anesthesia is
quoted as 5 – 8%.
 Maintenance of anesthesia is usually achieved using
between 0.5 and 3%
 What is the determinant factors for decreasing the
percentage {MAC} of inhalational anesthesia?
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98. Cardiovascular effects = Sevoflurane …
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• Sevoflurane, in common with all volatile agents,
Reduces cardiac output and systemic blood pressure.
• A small increase in heart rate may be observed,
Less pronounced than with isoflurane and Desflurane
• Sevoflurane is associated with a stable heart rhythm
and does not predispose the heart to sensitization by
catecholamine's.
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99. The effects of increasing concentrations (MAC) of halothane,
isoflurane, desflurane, and sevoflurane on heart rate
(beats/minute)
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100. Sevoflurane …
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 Sevoflurane not appear to cause the “coronary steal”
phenomenon in man.
 Dose related decrease in myocardial contractility and
MAP, systolic pressure decreases to a greater degree
than diastolic pressure
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101. Respiratory system effects = Sevoflurane …
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• Sevoflurane causes dose-related respiratory depression.
• Decrease in tidal volume and an increase in respiratory
rate with a net decrease in minute ventilation.
• Produces the same degree of bronchodilation as
isoflurane and Enflurane.
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102. Sevoflurane …
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• Sevoflurane causes the least amount of subjective airway
irritation and inhalational induction can be swift and
effective in the most testing of circumstances.
• At equi-MAC concentrations, respiratory resistance is
reduced by sevoflurane > halothane > isoflurane
AMARE H

103. The effect of volatile anesthetics on respiratory system
resistance in patients with COPD – MAC 1.1
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104. Central nervous system effects = Sevoflurane
…
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• Sevoflurane preserves cerebral auto regulation better
than the other agents
• Has a dose-dependent effect on cerebral blood flow and
intracranial pressure;
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105. Sevoflurane …
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• Sevoflurane above 1 MAC produce mild increases in ICP,
paralleling Its mild increases in CBF
• One potential advantage of sevoflurane is that its lower
pungency and airway irritation may lessen the risk of
coughing and bucking and the associated rise in ICP as
compared to Desflurane or isoflurane.
• It reduces the cerebral metabolic rate for oxygen
(CMRO2) by approximately 50% at concentrations
approaching 2 MAC.
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106. Gastrointestinal & other effects =
Sevoflurane …
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• A higher incidence of nausea and vomiting after
sevoflurane anesthesia. – prophylactic treatment?
• Sevoflurane reduces renal blood flow and leads to an
increase in fluoride ion concentration {12-90umol/l in
anesthesia lasting 1 to 6hrs respectively.} – no evidence
of gross changes in renal function
• In animal models, the drug decreases liver synthesis of
fibrinogen, transferrin, and albumin.
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107. Metabolism and toxicity = Sevoflurane
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• Approximately 5% of a given dose of sevoflurane is
metabolized with cytochrome P-450, a higher proportion
than with isoflurane or Enflurane
• CYP450 may be induced by chronic exposure to ethanol
and isoniazide
• Produces more fluoride ions than Enflurane
• It should be used with caution in patients with renal
dysfunction, but not a universal contraindication for its
use.
AMARE H

108. Sevoflurane …
1/18/2019 108
 Elimination of sevoflurane is rapid, again due to its low
solubility, resulting in a fast wash-out rate
 Unlike halothane, its metabolism does not result in the
formation of trifluoroacetylated liver proteins and
subsequent production of anti-trifluoroacetylated
protein antibodies
AMARE H

109. Special points = Sevoflurane …
1/18/2019 109
 Sevoflurane potentiates the action of co-administered
depolarizing and non-depolarizing muscle relaxants to a
greater extent than either Halothane or Enflurane.
 As with other volatile anesthetic agents, the co-
administration of N2O, benzodiazepines, or opioids
lowers the MAC of sevoflurane.
AMARE H

110. Advantages = Sevoflurane …
1/18/2019 110
 For inhalational induction of anesthesia in children.
In adults, 8% sevoflurane is well tolerated and, provides rapid
induction of anesthesia without adversely affecting
hemodynamic stability.
 For dental procedures as there is a lower risk of cardiac
arrhythmias than with halothane.
 In children with congenital heart disease.
AMARE H

111. Emergency = Sevoflurane …
1/18/2019 111
 Agitation in the early postoperative period has been
noted in young children.
 Self-limiting or may require by Premedication with midazolam
or similar benzodiazepine
AMARE H

112. Enflurane
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• A halogenated methyl ethyl ether which is a geometric
isomer of isoflurane
• Presentation
As clear, colorless liquid {that should be protected from
sunlight} with a characteristics of sweet smell
 The MAC of enflurane is 1.68{0.57 in 70% nitrous oxide}
AMARE H

113. Cardiovascular effects
1/18/2019 113
 Enflurane is a negative ionotrope and it also cause a
decrease in systemic vascular resistance
Decrease in MAP
 Unlike halothane, enflurane produces a slight reflex
tachycardia
 Enflurane is not markedly arrhythmogenic, but does
sensitize the myocardium to the effects of circulating
catecholamine's
AMARE H

114. Respiratory system effects
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• It is a powerful respiratory depressant, markedly
decreasing tidal volume although RR may increase.
• The drug also decrease respiratory response to hypoxia
and hypercapnia
• Enflurane is non-irritant to the RT; it causes
bronchodilatation and no increase in secretion
• The drug inhibits pulmonary macrophage activity and
mucociliary transport
AMARE H

115. Central nervous system effects
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• Same like others on increasing ICP and CBF, but
decrease cerebral oxygen consumption
• The drug may induce tonic/ clonic muscle activity and
may also produce epileptiform EEG traces, especially in
the presence of hypocapnia
AMARE H

116. Other effects
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 Enflurane decreases renal blood flow and glomerular
filtration rate
 The drug reduces the tone of pregnant uterus
 The drug causes a fall in body temperature predominantly
by cutaneous vasodilatation
 Enflurane depress white cell function for 24hr
postoperatively
AMARE H

117. Toxicity & adverse effects
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• Triggering agent for the development of malignant
hyperthermia
• The drug may also cause myocardial dysarrythmia,
particularly in the presence of hypoxia, hypercapnia and
excessive catecholamine secretion
• Shivering occurs mostly in postoperative period – Mgt?
• Hepatotoxicity and renal toxicity after repeated
exposure to enflurane
AMARE H

118. Metabolism
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• 2.4% of the administered drug metabolized by the liver
cytochrome p450, principally by oxidation and
degradation
Plasma fluoride concentration may reach 10 times observed
after use of halothane or isoflurane.
AMARE H

119. Special points
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• Potentiate the action of co-administered non-depolarizing
muscle relaxant
• Caution when using adrenaline like halothane
AMARE H

120. Nitrous oxide
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 It is used for
As an adjuvant to the induction and maintenance of GA
As an analgesic during labour and other painful procedures
 Presentation
As liquid in cylinders at a pressure of 44 bar at 15˚c
The cylinders are French blue and are available in six
sizes {C-J, containing 450-18000 lit, respectively}
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121. 1/18/2019 121
The gauge pressure does not correlate with cylinder
content until all N2O is in gaseous state.
It is sweet-smelling colorless gas and non-flammable,
but supports combustion
The MAC of nitrous oxide is 105 and blood gas partition
coefficient is 0.46{compared to 0.015 for nitrogen} –
Denitrogenation?
AMARE H

122. 1/18/2019 122
• Entonox - 50:50 mixture of oxygen and nitrous oxide and
is produced by bubbling oxygen through liquid nitrous
oxide
• It is available in cylinders which are French blue with
white and blue shoulders in the following four sizes: SD,
D, F, G containing 440 – 5000L respectively.
• The cylinder pressure is 137 bar at 15˚c
AMARE H

123. Cardiovascular effects
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 Nitrous oxide decreases myocardial contractility,
But the MAP is usually well maintained by reflex increase in
peripheral vascular resistance.
 Deterioration in left ventricular function occurs when
nitrous oxide is added to a high dose opioid oxygen
anesthetic sequence, volatile agents, or Propofol
infusion{TIVA}
AMARE H

124. Respiratory system effects
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• The gas causes slight depression in respiration with a
decrease in tidal volume and in increases in
respiratory rate.
• Nitrous oxide is non irritant and does not cause
bronchospam
AMARE H

125. Central nervous system
1/18/2019 125
• Nitrous oxide is a CNS depressant and, when
administered in a concentration of 80%, will cause LOC.
• The gas is a powerful analgesics in a concentration >
20%
• Its administration causes a rise in ICP
• Anti-hypoxic device?
• N2O has no effect on uterine tone
AMARE H

126. Toxicity / side effects
1/18/2019 126
• 15% of patients receiving N2O will experience nausea &
vomiting
• The gas is 35 times more soluble than nitrogen in the
blood, therefore, cause
An increase in air-filled spaces { eg. Pneumothorax, intestine,
air cysts in the middle ear} in the body.
Fink effect{diffusion hypoxia}
AMARE H

127. 1/18/2019 127
• Prolonged use of high concentration of N2O{>6hr} leads
to inactivation via oxidation of the cobalt ion of the
cobalamin {vitamin B12}
The resulting cobalt ion prevents cobalamin from acting as
coenzyme for methionine synthase, which involves in the
synthesis of DNA, RNA, myelin and catecholamine's.
 Pernicious anemia, megaloblastic anemia and
pancytopenia
20% of elderly patients are deficient in cobalamin
AMARE H

128. Special points
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 The concentration effect
 Second gas effect
 66% nitrous oxide in oxygen decreases the MAC of
halothane to 0.29, of isoflurane to 0.5, of sevoflurane to
0.66, desflurane to 2.8 and of enflurane to 0.6.
 The use of nitrous oxide is safe in patients susceptible to
malignant hyperpyrexia.
AMARE H