Actions of Foran in details
Foran induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Foran also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. Also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Foran also binds to the GABA receptor, the large conductance Ca2+ activated potassium channel, the glutamate receptor and the glycine receptor.
Foran pharmacology
Foran is an inhalation anesthetic. The MAC (minimum alveolar concentration) in man is as follows:
Age 100% Oxygen 70% N2O
26 ± 4 1.28 0.56
44 ± 7 1.15 0.50
64 ± 5 1.05 0.37
Induction of and recovery from Foran anesthesia are rapid. Foran has a mild pungency, which limits the rate of induction, although excessive salivation or tracheobronchial secretions do not appear to be stimulated. Pharyngeal and laryngeal reflexes are readily obtunded. The level of anesthesia may be changed rapidly with Foran. Foran is a profound respiratory depressant. RESPIRATION MUST BE MONITORED CLOSELY AND SUPPORTED WHEN NECESSARY. As anesthetic dose is increased, tidal volume decreases and respiratory rate is unchanged. This depression is partially reversed by surgical stimulation, even at deeper levels of anesthesia. Foran evokes a sigh response reminiscent of that seen with diethyl ether and enflurane, although the frequency is less than with enflurane.
Blood pressure decreases with induction of anesthesia but returns toward normal with surgical stimulation. Progressive increases in depth of anesthesia produce corresponding decreases in blood pressure. Nitrous oxide diminishes the inspiratory concentration of Foran required to reach a desired level of anesthesia and may reduce the arterial hypotension seen with Foran alone. Heart rhythm is remarkably stable. With controlled ventilation and normal PaCO2, cardiac
output is maintained despite increasing depth of anesthesia, primarily through an increase in heart rate, which compensates for a reduction in stroke volume. The hypercapnia, which attends spontaneous ventilation during Foran anesthesia further increases heart rate and raises cardiac output above awake levels. Foran does not sensitize the myocardium to exogenously administered epinephrine in the dog. Limited data indicate that subcutaneous injection of 0.25 mg of epinephrine (50 mL of 1:200,000 solution) does not produce an increase in ventricular arrhythmias in patients anesthetized with Foran.
Muscle relaxation is often adequate for intra-abdominal operations at normal levels of anesthesia. Complete muscle paralysis can be attained with small doses of muscle relaxants. ALL COMMONLY USED MUSCLE RELAXANTS ARE MARKEDLY POTENTIATED WITH Foran, THE EFFECT BEING MOST PROFOUND WITH THE NONDEPOLARIZING TYPE. Neostigmine reverses the effect of nondepolarizing muscle relaxants in the presence of Foran. All commonly used muscle relaxants are compatible with Foran.
Foran can produce coronary vasodilation at the arteriolar level in selected animal models1,2; the drug is probably also a coronary dilator in humans. Foran, like some other coronary arteriolar dilators, has been shown to divert blood from collateral dependent myocardium to normally perfused areas in an animal model (“coronary steal”)3. Clinical studies to date evaluating myocardial ischemia, infarction and death as outcome parameters have not established that the coronary arteriolar dilation property of Foran is associated with coronary steal or myocardial ischemia in patients with coronary artery disease4,5,6,7.
Pharmacokinetics
Foran undergoes minimal biotransformation in man. In the postanesthesia period, only 0.17% of the Foran taken up can be recovered as urinary metabolites.
References
- DailyMed. "ISOFLURANE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- EPA DSStox. "Isoflurane: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
