Methoxyflurane
Sun, 11/04/2007 - 10:59 — oxygen
Methoxyflurane
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physical properties
effects on organ system
biotransformation and toxicity
contraindications
drug interactions
physical properties
-MAC value: 0.16 %
-vapor pressure: 22.5 mmHg at 20 degrees celcius
-halogenated methyl ether
-colorless
-sweet, fruity odor
-light senstitive which is stabilized with butylated hydroxytoluene
-non-explosive and nonflammable at clinical concentrations
-most potent inhalational anesthetic
-high lipid solubility leading to absorption within breathing circuit and low vapor pressure reduce rate of induction with methoxyflurane
effects on organ system
Central Nervous System
-decreases CMR02
-increases CBF
-increases ICP
Cardiovascular System
-decreases myocardial contractility
-decreases mean arterial pressure secondary to decreased myocardial contractility
-baroreceptor reflex intact which leads to increased heart rate
Respiratory System
-increased respiratory rate
-decreased tidal volume
-resultant decrease in alveolar ventilation
-elevated resting Pac02
-mild bronchodilating properties
-depressed mucociliary function
Hepatic System
-decreases hepatic blood flow
Renal System
-decreases renal blood flow
-decreases GFR
-may be associated with high-output renal failure (discussed more in detail in biotransformation and toxicity)
Neuromuscular System
-relaxes skeletal muscles
biotransformation and toxicity
-liver microsomal cytochrome P-450 enzyme activity leads to extensive metabolism of methoxyflurane
-oxidative metabolites of methoxyflurane include: free flouride ions and oxalic acid
-both flouride ions and oxalic acid are both considered to be nephrotoxic
-free flouride ions are considered responsible for the vasopressin-resistant high output renal failure
-renal toxicity from methoxyflurane is associated with: peak plasma flouride levels and duration of exposure
-flouride ions directly inhibit renal tubular function which leads to a concentrating defect within the kidneys
Clinical signs of methoxyflurane toxicity:
-polyuria resistant to administration of vasopressin
-increased serum osmolality
-increased serum sodium
-increased creatinine
-increased BUN
-decreased urinary clearance of creatinine
-decreased urinary clearance of urea nitrogen
-urine hypo-osmolality
contraindications
-generally not used due to nephrotoxicity
-if used in healthy patients, exposure should be limited to less than 2 MAC hours
-patients with renal impairment should not be exposed to methoxyflurane
drug interactions
-nephrotoxic drugs (ex. aminoglycosides) may have additive effects leading to renal failure
-enhanced methoxyflurane metabolism with drugs such as: phenobarbital, isoniazid, and ethanol
-increased metabolism of methoxyflurane may lead to higher than expected flouride ions
-methoxyflurane prolongs the effects of nondepolarizing muscle relaxants (NDMR)
Methoxyflurane
Listen to Audio
physical properties
effects on organ system
biotransformation and toxicity
contraindications
drug interactions
physical properties
-MAC value: 0.16 %
-vapor pressure: 22.5 mmHg at 20 degrees celcius
-halogenated methyl ether
-colorless
-sweet, fruity odor
-light senstitive which is stabilized with butylated hydroxytoluene
-non-explosive and nonflammable at clinical concentrations
-most potent inhalational anesthetic
-high lipid solubility leading to absorption within breathing circuit and low vapor pressure reduce rate of induction with methoxyflurane
effects on organ system
Central Nervous System
-decreases CMR02
-increases CBF
-increases ICP
Cardiovascular System
-decreases myocardial contractility
-decreases mean arterial pressure secondary to decreased myocardial contractility
-baroreceptor reflex intact which leads to increased heart rate
Respiratory System
-increased respiratory rate
-decreased tidal volume
-resultant decrease in alveolar ventilation
-elevated resting Pac02
-mild bronchodilating properties
-depressed mucociliary function
Hepatic System
-decreases hepatic blood flow
Renal System
-decreases renal blood flow
-decreases GFR
-may be associated with high-output renal failure (discussed more in detail in biotransformation and toxicity)
Neuromuscular System
-relaxes skeletal muscles
biotransformation and toxicity
-liver microsomal cytochrome P-450 enzyme activity leads to extensive metabolism of methoxyflurane
-oxidative metabolites of methoxyflurane include: free flouride ions and oxalic acid
-both flouride ions and oxalic acid are both considered to be nephrotoxic
-free flouride ions are considered responsible for the vasopressin-resistant high output renal failure
-renal toxicity from methoxyflurane is associated with: peak plasma flouride levels and duration of exposure
-flouride ions directly inhibit renal tubular function which leads to a concentrating defect within the kidneys
Clinical signs of methoxyflurane toxicity:
-polyuria resistant to administration of vasopressin
-increased serum osmolality
-increased serum sodium
-increased creatinine
-increased BUN
-decreased urinary clearance of creatinine
-decreased urinary clearance of urea nitrogen
-urine hypo-osmolality
contraindications
-generally not used due to nephrotoxicity
-if used in healthy patients, exposure should be limited to less than 2 MAC hours
-patients with renal impairment should not be exposed to methoxyflurane
drug interactions
-nephrotoxic drugs (ex. aminoglycosides) may have additive effects leading to renal failure
-enhanced methoxyflurane metabolism with drugs such as: phenobarbital, isoniazid, and ethanol
-increased metabolism of methoxyflurane may lead to higher than expected flouride ions
-methoxyflurane prolongs the effects of nondepolarizing muscle relaxants (NDMR)
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The effects of methoxyflurane on the circulatory system resemble those of diethyl ether.[19] In dogs, methoxyflurane anesthesia causes a moderate decrease in blood pressure with minimal changes in heart rate, and no significant effect on blood sugar, epinephrine, or norepinephrine. Bleeding and increased arterial partial pressure of carbon dioxide (PaCO2) both induce further decreases in blood pressure, as well as increases in blood glucose, epinephrine and norepinephrine
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methoxyflurane
This monograph includes information on the following:
1) Enflurane
2) Halothane
3) Isoflurane
4) Methoxyflurane
5) Nitrous Oxide
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methoxyflurane is rarely
methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with nitrous oxide to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation.
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Methoxyflurane
The biodegradation of methoxyflurane produces inorganic fluoride and dichloroacetic acid (DCAA).
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If used as an anesthetic
If used as an anesthetic gas, does Di ethyl Ether get metabolized via bio transformation?
Bio transformation typically results in intermediate metabolites that may be responsible for toxic after effects, such as inorganic fluoride and bromide ions.
Do only halogenated anesthetic gases (methoxyflurane, halothane, enflurane, desflurane, sevofulrane, isoflurane) undergo bio transformation and result in the production of inorganic fluoride and bromide ions?
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