METHOXYFLURANE

Chemistry - An inhalant general anesthetic agent, methoxyflurane occurs as a clear, mobile liquid.
It has a characteristic fruity odor. Methoxyflurane is very slightly soluble in water and miscible withalcohol or olive oil. At 20°C, methoxyflurane's specific gravity is 1.420-1.425.

Storage, Stability, Compatibility

Store at room temperature in tight, light-resistant containers.
Protect from freezing. Methoxyflurane is very soluble in rubber and soda lime. Avoid contact withpolyvinyl chloride (PVC) plastics as they can be extracted by methoxyflurane.
Methoxyflurane contains an antioxidant (BHT) which may accumulate in the vaporizer causing ayellow to brown discoloration. Do not use discolored solutions. Discolored vaporizer and wick maybe cleaned with diethyl ether (all ether must be removed before reuse).

Pharmacology - METHOXYFLURANE

While the precise mechanism that inhalent anesthetics exert their general anesthetic effects is not precisely known, they may interfere with functioning of nerve cells in the brainby acting at the lipid matrix of the membrane. Some key pharmacologic effects noted withmethoxyflurane include: CNS depression, depression of body temperature regulating centers, increased cerebral blood flow, respiratory depression, hypotension, vasodilatation, and myocardialdepression (less so than with halothane) and muscular relaxation.

Uses, Indications

Methoxyflurane's is used as an inhalent anesthetic. Its use is apparently diminishing due to its potential for causing nephrotoxicity, slow onset of action (a short-acting barbiturate is often used as an induction agent), and prolonged recovery time. However, it does produce some muscle relaxation and analgesia, even at relatively low concentrations.

Pharmacokinetics - METHOXYFLURANE

Methoxyflurane is rapidly absorbed from the alveoli, but it has a comparatively slow onset of activity. It is rapidly distributed into the CNS and crosses the placenta.
Approximately 35% of a dose is eliminated via the lungs and approximately 50% is metabolized inthe liver; substantial amounts of inorganic fluoride is formed which are excreted by the kidneys.
Minimal Alveolar Concentration (MAC; %) in oxygen reported for methoxyflurane in variousspecies: Dog = 0.23; Cat = 0.23; Horse = 0.22; Human = 0.16. Several factors may alter MAC(acid/base status, temperature, other CNS depressants on board, age, ongoing acute disease, etc.).

Contraindications, Precautions, Reproductive Safety

Methoxyflurane should be used cautiously, if at all, in patients with preexisting renal or hepatic disease. It should be used with caution(benefits vs. risks) in patients with increased CSF or head injury, or myasthenia gravis.
Studies are not definitive, but methoxyflurane may cause teratogenic effects; other inhalentanesthetic agents may be safer alternatives. If methoxyflurane is used during delivery or C-section, oxygen may need to be given to newborns after delivery.

Adverse Effects, Warnings

The most concerning adverse effect associated with methoxyfluraneis its potential for causing nephrotoxicity, particularly with prolonged procedures in patientspredisposed to nephrotoxicity.
While methoxyflurane potentially may cause hepatotoxicity, this apparently occurs rarely and maybe associated with hypoxic episodes. Nevertheless, it should be used with caution in patients withpreexisting hepatic dysfunction.
Overdosage, Acute Toxicity - Overdosage or acute toxicities may cause circulatory depressionand hypotension, cardiac arrhythmias, bradycardia, prolonged respiratory depression, emergencedelirium, or malignant hyperthermic crises.

Drug Interactions

Because of methoxyflurane's potential for causing nephrotoxicity, it shouldnot be used concurrently with other nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, cisplatin, NSAIDS, penicillamine, rifampin, tetracycline).
While methoxyflurane sensitizes the myocardium to the effects of sympathomimetics less so thanhalothane, arrhythmias may still result. Drugs included are: dopamine, epinephrine, norepinephrine, ephedrine, metaraminol, etc. Caution and monitoring is advised.
Non-depolarizing neuromuscular blocking agents, systemic aminoglycosides, systemiclincomycins should be used with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur.
Concomitant administration of succinylcholine with inhalation anesthetics may induce increasedincidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and in susceptiblepatients, malignant hyperthermia as well.