Isoflurane

Isoflurane: Mechanism of Action, Uses, and Side Effects

What is Isoflurane?

Isoflurane is classified under the category of inhalational general anesthetic used during surgeries. It is a halogen (fluoride) containing a highly stable anesthetic drug that undergoes no significant metabolism. It has little or no toxicity towards body tissues. Another advantage associated with the use of isoflurane is that it does not induce cardiac arrhythmias. The drug is said to be beneficial in patients with ischemic heart disease.

Isoflurane Mechanism of Action

Isoflurane operates by inhibiting the following receptors, resulting in the amnesia and sedation required for safe surgical procedures.

  1. Neurotransmitter-gated ion channels such as GABA
  2. Glycine
  3. and N-methyl-d-aspartate (NDMA) receptors in the central nervous system

Inhibition of NMDA-type glutamate and glycine receptors, at the action sites in the spinal cord, results in skeletal muscle relaxation. Isoflurane has little effect on left ventricular function, although it does cause a dose-dependent reduction in systemic vascular resistance due to slight beta-adrenergic activation.

This would result in a drop in ventricular preload and, as a result, a fall in cardiac output, but a rise in heart rate would stabilize this effect. It causes coronary dilation as well as lowering systemic vascular resistance. This might conceivably result in a coronary steal phenomenon, in which blood is diverted away from a fixed stenotic lesion.

Isoflurane’s cardio-protective effect, which comes through ischemia preconditioning, has completely dominated this. The degree of ischemia and reperfusion injury to the heart is reduced as a result of this.

Isoflurane also has an effect on the respiratory system, generating a significant reduction in tidal volumes with a minor rise in respiratory rate, resulting in a reduction in minute ventilation. A rise in PaCO2 is caused by a decrease in minute ventilation.

Isoflurane produces an increase in intracranial pressure and cerebral blood flow at concentrations greater than 1 MAC (minimum alveolar concentration). Despite the increased blood flow, the brain metabolic rate decreases, and 2 MAC concentrations can cause an electrically quiet electroencephalogram.

Isoflurane also reduces renal and hepatic blood flow in a dose-dependent manner, with no clinical influence on renal or hepatic function.

Pharmacokinetics of Isoflurane

In humans, isoflurane undergoes minimal biotransformation. Only 0.17 percent of it consumed can be retrieved as urine metabolites in the post-anesthesia phase.

How to Administer Isoflurane?

A specially constructed variable bypass vaporizer is used to inject isoflurane. Over a wide variety of flow rates and temperatures, this vaporizer has been standardized to provide a specific percentage of gas anesthesia based on the specific volatile vapor pressure.

This is critical to understand since each vaporizer is standardized for a unique volatile anesthetic, and filling a vaporizer with any other volatile anesthetic would result in the volatile anesthetic being delivered incorrectly.

Each agent’s distinct minimum alveolar concentration (MAC), which is utilized as a substitute for the partial pressure of each compound in the brain, is used to administer volatile anesthetics, including isoflurane. The alveolar concentration required to inhibit movement in 50% of patients in response to surgical incision is therefore defined as minimum alveolar concentration.

The MAC is determined by the partial pressure of the agent in relation to the atmospheric pressure. The MAC of isoflurane at sea level is 1.2 percent, which can be expressed as 1 MAC of isoflurane.

It is important to note that halothane and isoflurane have somewhat identical vapor pressures. So, putting halothane in an isoflurane vaporizer or vice versa would have a negligible effect on the amount supplied.

Factors affecting MAC

MAC increases in following conditions

MAC decreases in the following conditions

  • Hypothermia
  • Hyperthermia
  • Acute intoxication
  • Old age
  • Use of IV anesthetics (such as benzodiazepines, ketamine, and dexmedetomidine)

The effect of age, which causes a 6% decrease in MAC per decade of age above the age of 40, is the most striking of all these factors.

Indications of Isoflurane

Isoflurane is a volatile anesthetic accepted by the Food and Drug Administration (FDA) for general anesthesia induction and maintenance. Since 1979, it has been approved for use in the United States.

Isoflurane Side Effects

  • Hypotension due to Peripheral vasodilation
  • Respiratory depression
  • Nausea (pots-operative period)
  • Vomiting (pots-operative period)
  • Shivering (pots-operative period)
Nausea

Contraindications

Use of Isoflurane is contraindicated under the following circumstances:

  • Malignant hyperthermia
  • Hypersensitivity to the drug or other halogenated anesthetics
  • Genetic susceptibility to malignant hyperthermia (patients with a family history of the disease)
  • Perioperative hyperkalemia
  • Pediatric neurotoxicity

Food Interactions

The drug has reportedly shown no drug-food interactions.

Drug Interaction

  • Isoflurane show drug interactions with the following
  • Non-depolarizing muscle relaxants
  • Sympathomimetic
  • Aminoglycosides
  • Sodium oxybate
  • Labetalol
  • Benzodiazepines
  • Acetyl salicylic acid

Is Isoflurane Safe in Pregnancy?

According to FDA Isoflurane is categorized under pregnancy category C drugs. When this medicine was given during organogenesis, animal studies demonstrated embryo-fetal toxicity manifested by greater post-implantation losses and a lower live-birth index. Embryo-toxicity has been discovered in animal research. In human pregnancy, there are no controlled data available. Only if the benefit outweighs the hazard, should this medication be used during pregnancy.

Precautions

Isoflurane, a halogen-containing anesthetic gas, is a possible health danger, and precautions should be taken to minimize exposure during its usage as per Isoflurane MSDS (material safety data sheet). It is a common anesthetic used in research animals.

While this generation of halogenated anesthetics is safer than earlier generations, measures must be taken to limit exposure dangers. Waste anesthetic gas can be inhaled by people who work with isoflurane and other volatile anesthetics.

Isoflurane Brand Names

Following are some brand names containing Isoflurane:

  • Forane by Baxter Laboratories
  • Forane by Abbott
  • Isorane by Abbott

References

https://www.ncbi.nlm.nih.gov/books/NBK532957/
https://www.drugs.com/pro/isoflurane.html
https://go.drugbank.com/drugs/DB00753
https://www.drugs.com/pregnancy/isoflurane.html

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.