Isoflurane

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

|preview=

}}{{Infobox drug/maintenance categoriesTemplate:Yesno | drug_name = | INN = | _drugtype =

| _has_physiological_data= | _has_gene_therapy=

| vaccine_type= | mab_type= | _number_of_combo_chemicals={{#invoke:ParameterCount |main |component1 |component2 |component3 |component4|component5|component6 }} | _vaccine_data= | _mab_data= | _mab_vaccine_data= | _mab_other_data=3251FC(F)(F)C(Cl)OC(F)F1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2HPIWKPBJCKXDKJR-UHFFFAOYSA-NTemplate:StdinchiciteTemplate:Stdinchicite1.496<ref name="PubChem">Template:Cite web</ref>48.513.5 mM (at Template:Convert)<ref>Template:Cite journal</ref> | _combo_data= | _physiological_data= | _clinical_data=Template:Drugs.comIsoflurane <ref name="Drugs.com pregnancy">Template:Cite web</ref>B3RespiratoryForane, othersInhalational anestheticN01Template:ATCvet | _legal_data=<ref>Template:Cite web</ref>C1<ref name="Isoflurane SmPC">Template:Cite web</ref>POM<ref name="Forane FDA label">Template:Cite web</ref><ref name="Terrell FDA label">Template:Cite web</ref>Rx-only

| _other_data=2-chloro-2-difluoromethoxy-1,1,1-trifluoroethane

| _image_0_or_2 = Isoflurane.svgIsoflurane-3D-vdW.png | _image_LR =

| _datapage = Isoflurane (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=C1POMRx-only | _ATC_prefix_supplemental=N01Template:ATCvet | _has_EMA_link = | CAS_number=26675-46-7 | PubChem=3763 | ChemSpiderID=3631 | ChEBI=6015 | ChEMBL=1256 | DrugBank=DB00753 | KEGG=D00545 | _hasInChI_or_Key={{#if:1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2HPIWKPBJCKXDKJR-UHFFFAOYSA-N |yes}} | UNII=CYS9AKD70P | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields=changed |Watchedfields=changed |verifiedrevid=443883276}}

Isoflurane, sold under the brand name Forane among others, is a halogenated ether used as a general anesthetic.<ref name="Forane FDA label" /><ref>Template:Cite book</ref> It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane.<ref name="Isoflurane SmPC" /><ref>Template:Cite book</ref> Isoflurane is a inhalational anesthetic given via inhalation.<ref name="Forane FDA label" />

Isoflurane was approved for medical use in the United States in 1979.<ref name="Forane FDA label" /><ref>Template:Cite web</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO24th">Template:Cite book</ref>

Medical uses

Isoflurane is indicated for induction and maintenance of general anesthesia.<ref name="Forane FDA label" />

Isoflurane is always administered in conjunction with air or pure oxygen. Often, nitrous oxide is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane,<ref name="NiedermeyerSilva2005">Template:Cite book</ref> its pungency can irritate the respiratory system, negating any possible advantage conferred by its physical properties. Thus, it is mostly used in general anesthesia as a maintenance agent after induction of general anesthesia with an intravenous agent such as thiopentone or propofol.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name = NBK532957>Template:Cite web</ref>

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated.<ref>Template:Cite magazine</ref> Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABA_A receptor in electrophysiology studies of neurons and recombinant receptors.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> It potentiates glycine receptor activity, which decreases motor function.<ref>Template:Cite journal</ref> It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels.<ref>Template:Cite journal</ref> Isoflurane also affects intracellular molecules. It inhibits plasma membrane calcium ATPases (PMCAs) which affects membrane fluidity by hindering the flow of Template:Chem2 (calcium ions) out across the membrane, this in turn affects neuron depolarization.<ref>Template:Cite journal</ref> It binds to the D subunit of ATP synthase and NADH dehydrogenase.

General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness.<ref>Template:Cite journal</ref>

Adverse effects

Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat.<ref name="Isoflurane SmPC" /> Isoflurane can cause a sudden decrease in blood pressure due to dose-dependent peripheral vasodilation. This may be specially marked in hypovolemic patients.<ref name = NBK532957/>

Serious side effects can include malignant hyperthermia or high blood potassium.<ref name="Forane FDA label" /> It should not be used in patients with a history of malignant hyperthermia in either themselves or their family members.<ref name="Isoflurane SmPC" />

It is unknown if its use during pregnancy is safe for the fetus, but use during a cesarean section appears to be safe.<ref name="Isoflurane SmPC" /><ref name="Forane FDA label" />

Animal studies have raised safety concerns of certain general anesthetics, in particular ketamine and isoflurane, in young children. The risk of neurodegeneration was increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam.<ref name=Mel2007>Template:Cite journal</ref> Whether these concerns occur in humans is unclear.<ref name=Mel2007/>

Elderly

Biophysical studies using NMR spectroscopy has provided molecular details of how inhaled anesthetics interact with three amino acid residues (G29, A30 and I31) of amyloid beta peptide and induce aggregation.<ref name="Mandal-2009">Template:Cite journal</ref> This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer's disease".<ref name="Kuehn-2007">Template:Cite journal</ref>

Anesthetic physical properties

Isoflurane has a Minimum alveolar concentration (MAC) of 1.15 vol %. The blood/gas partition coefficient is 1.4, and the oil/gas partition coefficient is 98.Template:Citation needed Its vapor pressure at Template:Convert is Template:Convert.<ref name="PubChem" />

It is administered as a racemic mixture of (R)- and (S)-optical isomers.<ref>Template:Cite journal</ref> It is non-combustible but can give off irritable and toxic fumes when exposed to flame.<ref name="PubChem" />

History

Together with enflurane and halothane, Isoflurane began to replace the flammable ethers used in the pioneer days of surgery; this shift began in the 1940s to the 1950s.<ref>Template:Cite journal</ref> Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula.<ref>Template:Cite journal</ref>

Environment

The average lifetime of isoflurane in the atmosphere is 3.2 years, its global warming potential is 510 (times greater than carbon dioxide) and yearly emissions as of 2015 were 880 tons.<ref>Template:Cite journal</ref>Template:Update inline

Veterinary use

Isoflurane is used for the induction and maintenance of general anesthesia in horses and dogs.<ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite web</ref><ref>Template:Cite journal</ref><ref>Template:Cite web</ref>

External links

• Template:US patent - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
• Template:US patent - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether as an anesthetic agent