{"id":218,"date":"2019-04-24T15:14:14","date_gmt":"2019-04-24T15:14:14","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=218"},"modified":"2020-09-04T04:31:44","modified_gmt":"2020-09-04T04:31:44","slug":"thiopental","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/drugs\/thiopental\/","title":{"rendered":"Thiopental"},"content":{"rendered":"\n<h4 class=\"inTable wp-block-heading\">Thiopental pharmacokinetic parameters <\/h4>\n\n\n\n<table class=\"wp-block-table has-fixed-layout\"><tbody><tr><td> Clearance (CL) <\/td><td>10 L\/h  <\/td><\/tr><tr><td> Volume of Distribution (Vd) <\/td><td>160 L<\/td><\/tr><tr><td> Elimination Half-life (t1\/2) <\/td><td>10 h <\/td><\/tr><tr><td>Distribution Half-life (t1\/2)<\/td><td>1 h<\/td><\/tr><\/tbody><\/table>\n\n\n\n<h3 class=\"wp-block-heading\">Description<\/h3>\n\n\n\n<p>Thiopental is used in the induction of anesthesia\n and for the control of convulsive states. It is a short acting \nbarbiturate with sedative, hypnotic and anticonvulsant properties. The \nbrain sensitivity to thiopental shows interindividual variability. \nTherefore, the dosage of thiopental needed during surgery shows \nconsiderable individual variations. \n<\/p>\n\n\n\n<p>Thiopental is usually used as an <a href=\"\/pharmacology\/intravenous-bolus\">intravenous injection<\/a>. Therefore, absorption is complete and instantaneous.\n<\/p>\n\n\n\n<p>Thiopental is non polar, lipophilic and only \npartially ionized at plasma pH. As such, its entry into both brain and \nmuscle occurs readily and is perfusion rate limited. Therefore, \nthiopental equilibrates rapidly in highly perfused organs, like the \nnervous system and viscera, while its <a href=\"\/pharmacology\/distribution\">distribution<\/a>\n into less perfused organs like muscle and adipose tissue is \nconsiderably delayed. After bolus injection, termination of the drug \neffect mainly results from redistribution from its site of action (the \nhighly perfused brain) into other tissues (e.g. the poorly perfused \nadipose tissue). Fat is a reservoir for thiopental and the intensity of \nfat uptake accounts for between two-thirds and tree-quarters of the \nadministered dose. In the plasma, thiopental is bound predominantly to \nalbumin (75-90%). Thiopental crosses the placenta easily.\n<\/p>\n\n\n\n<p>Acute thiopental action is limited by redistribution and not by metabolic breakdown. The role of <a href=\"\/pharmacology\/metabolism\">metabolism<\/a> becomes more relevant after <a href=\"\/pharmacology\/repeated-administration\">repeated administration<\/a>\n of high doses of thiopental in neurotraumatology. Thiopental is almost \ncompletely biotransformed in the liver to mostly inactive metabolites, \nwhich are then excreted in the urine. A very small percentage of the \ndose is excreted unchanged in the urine. Metabolic autoinduction can \noccur when patients are treated with high doses of thiopental over a \nprolonged period in the intensive care unit. <\/p>\n\n\n\n<p><p class=\"hiddenTitle\">Chart Pharmacokinetics<\/p>\n<div>\n\n    <div id=\"chartContainer\">\n        <canvas id=\"chart\"><\/canvas>\n        <div class=\"\" id=\"divSliderContainer\"><\/div>\n    <\/div>\n\n    <script>\n\n        let chart;\n        let baseDataChartValues = [];\n        let dataChart = [];\n        let dataChartStoredValues = [];\n        let labelsChart = [];\n\n        let dose = 1000;\n        let baseDose = 1000;\n\n        let mDose = 1000;\n        let baseMDose = 1000;\n\n        let tau = 6;\n        let baseTau = 6;\n\n        let vd = 160;\n        let baseVd = 50;\n\n        let cl = 10;\n        let baseCl = 10;\n\n        let f = 1;\n        let baseF = 0.7;\n        \n        let tInf = 0.1;        \n\n        let drugC = 10;\n        let vInf = 300;\n\n        let ka = 1.5;\n        let tH;\n\n        const maxTime = 24;\n\n        function getPlasmaConcentration(h) {\n            \n            let tInfFormula = tInf;\n\n            if(tInf >= h) tInfFormula = h;\n            \n            let tl = h;\n\n            if(h < tInf) tl = 0;\n\n            let formulaPlasmaConcentration = ((drugC*vInf*tInfFormula)*f*ka\/(vd*(ka-cl\/vd))*(Math.exp(-cl\/vd*tl)-Math.exp(-ka*h)));\n\n            return formulaPlasmaConcentration;\n        }\n\n        \/*\n         *\n         * t1\/2 = ln(2) * (volume of distribution \/ clearance)\n         *\n         *\/\n        function getHalfLife() {\n            tH = Math.log(2)*(vd\/cl);\n            return (Math.round(tH * 100) \/ 100);\n        }\n\n        function updateSlider(updateStored = false) {\n            dataChart = [];\n            if(updateStored) dataChartStoredValues = [];\n\n            for(let i = 0; i <= maxTime; i++) {\n                let concentration = getPlasmaConcentration(i);\n                dataChart.push(concentration);\n                if(updateStored) dataChartStoredValues.push(concentration);\n            }\n\n            chart.data.datasets[0].data = dataChart;\n            chart.data.datasets[1].data = dataChartStoredValues;\n\n            $( \"#slider-f\" ).slider( \"option\", \"value\", tInf);\n            chart.update();\n        }\n\n        let sliderF = '<div id=\"slider-f\" class=\"sliderRange\">' +\n                            '<span id=\"custom-handle-f\" class=\"ui-slider-handle customHandle\"><\/span>' +\n                            '<span class=\"spanUnit\" id=\"\">Tinf<\/span>' +\n                        '<\/div>';\n\n        $('#divSliderContainer').append(sliderF);\n\n\n   \n\n        $(function() {\n\n            let handle = $('#custom-handle-f');\n\n            $( \"#slider-f\" ).slider({\n                orientation: \"vertical\",\n                range: \"true\",\n                min: 0.01,\n                max: 12,\n                step: 0.01,\n                value: tInf,\n                create: function() {\n                    handle.text( $( this ).slider( \"value\" ) );\n                },\n                slide: function( event, ui ) {\n                    tInf = ui.value;\n                    handle.text( ui.value );\n                    updateSlider();\n                }\n            });\n        });\n\n        Chart.pluginService.register({\n            beforeInit: function(chart) {\n\n                for(let i = 0; i <= maxTime; i++) {\n                    labelsChart.push(i);\n                    dataChart.push(getPlasmaConcentration(i));\n\n                    dataChartStoredValues = dataChart;\n                    baseDataChartValues = dataChart;\n                }\n\n            }\n        });\n\n        chart = new Chart(document.getElementById(\"chart\"), {\n            type: 'line',\n            data: {\n                labels: labelsChart,\n                datasets: [{\n                    label: \"Plasma Concentration\",\n                    data: dataChart,\n                    borderColor: colorDatasetMain.borderColor,\n                    fillColor: colorDatasetMain.fillColor,\n                    strokeColor: colorDatasetMain.strokeColor,\n                    highlightFill: colorDatasetMain.highlightFill,\n                    highlightStroke: colorDatasetMain.highlightStroke,\n                    borderWidth: \"1\",\n                    pointRadius: 0,\n                    fill: false\n                }, {\n                    label: \"Plasma Concentration\",\n                    data: dataChartStoredValues,\n                    borderColor: colorDatasetStored.borderColor,\n                    fillColor: colorDatasetStored.fillColor,\n                    strokeColor: colorDatasetStored.strokeColor,\n                    highlightFill: colorDatasetStored.highlightFill,\n                    highlightStroke: colorDatasetStored.highlightStroke,\n                    borderWidth: \"1\",\n                    pointRadius: 0,\n                    fill: false\n                }]\n            },\n            options: {\n                scales: {\n                    xAxes: [{\n                        scaleLabel: {\n                            display: true,\n                            labelString: 'H [hour]'\n                        }\n                    }],\n                    yAxes: [{\n                        scaleLabel: {\n                            display: true,\n                            labelString: 'C [mg\/l]'\n                        }\n                    }]\n                },\n                responsive: true,\n                maintainAspectRatio: false\n            }\n        });\n\n    <\/script>\n\n<\/div><\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical implications<\/h3>\n\n\n\n<p>For induction of anesthesia, the rapid \nredistribution of thiopentoui mal accounts for the short duration of \neffect, while during prolonged administration, the elimination half-life\n of the drug accounts for the longer lasting effect. Anesthetists call \nthis effect the context dependant half-life.\n<\/p>\n\n\n\n<p>Lower thiopental requirements have been reported in \nthe elderly. The lean body mass (LMB) decreases with increasing age. \nCardiac output also decreases with increasing age and is an important \ndeterminant of initial intravascular drug mixing and therefore affects \nthe dose of a drug with rapid onset of effect, such as thiopental when \nadministered by bolus. The dosage of thiopental must also be adapted in \npatients with liver damage and patients with heart failure. \n<\/p>\n\n\n\n<p>Obesity influences the thiopental induction dose;  the dose was significantly less per kg in obese patients, because the  initial volume of distribution is similar between obese and lean  patients, before redistribution occurs. However, for long term  administration of thiopental to treat seizures, the volume of  distribution at steady-state is 3 to 4 times higher in obese compared  with lean patients, probably due to the extreme lipophily of thiopental.  Because of this larger volume of distribution, the elimination  half-life of thiopental is prolonged in obese patients.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Thiopental pharmacokinetic parameters Clearance (CL) 10 L\/h Volume of Distribution (Vd) 160 L Elimination Half-life (t1\/2) 10 h Distribution Half-life (t1\/2) 1 h Description Thiopental is used in the induction of anesthesia and for the control of convulsive states. It is a short acting barbiturate with sedative, hypnotic and anticonvulsant properties. The brain sensitivity to &hellip; <\/p>\n<p class=\"link-more\"><a href=\"https:\/\/sepia2.unil.ch\/pharmacology\/drugs\/thiopental\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;Thiopental&#8221;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":10,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-218","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/218","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/comments?post=218"}],"version-history":[{"count":35,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/218\/revisions"}],"predecessor-version":[{"id":1368,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/218\/revisions\/1368"}],"up":[{"embeddable":true,"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/pages\/10"}],"wp:attachment":[{"href":"https:\/\/sepia2.unil.ch\/pharmacology\/wp-json\/wp\/v2\/media?parent=218"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}