Commit d1cda1e4 authored by Rachel Clipp's avatar Rachel Clipp
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Added references for nrepinephrine and phenylephrine and updated the endocrine...

Added references for nrepinephrine and phenylephrine and updated the endocrine and drugs methodology.
parent 6358bbc7
......@@ -515,7 +515,7 @@ NC @cite ensinger1992relationship" </span>|<span class="success"> 69 | "[174, 19
Minimal Increase @cite ensinger1992relationship" </span>|<span class="success"> 136 | "[83, 99]
Minimal Increase @cite ensinger1992relationship" </span>|<span class="success"> 100 </span>|
The infusion of phenyephrine was validated for the plasma concentration and the effects on heart rate and systolic and diastolic pressure. The values were examined for four different infusion rates. They are shown in Table 10.
The infusion of phenylephrine was validated for the plasma concentration and the effects on heart rate and systolic and diastolic pressure. The values were examined for four different infusion rates. They are shown in Table 10.
| Drug | Infusion Rate (ug/(kg min)) | Experimental Plasma Concentration (ug/L) | Computed Plasma Concentration (ug/L) | "Experimental Heart Rate Change
(beats/min)" | "Computed Heart Rate Change (beats/min)" | "Experimental Systolic Blood Pressure (mmHg)" | "Computed Systolic Blood Pressure (mmHg)" | "Experimental Diastolic Blood Pressure (mmHg)" | "Computed Diastolic Blood Pressure (mmHg)"
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......@@ -7,7 +7,7 @@ Overview
Abstract
--------
The %Endocrine System is a basic system implementation of endocrine signaling. There are currently two hormones included in the %Endocrine system: epinephrine and insulin. The effects of epinephrine are modeled by leveraging the [pharmacodynamics](@ref DrugsMethodology) model. The insulin model is under construction, and when it is finished, insulin will have a regulatory effect on the concentration of glucose in the blood. Functionality that is in the development stage now will enable future releases of the endocrine system to affect:
The %Endocrine System is a basic system implementation of endocrine signaling. There are currently three hormones included in the %Endocrine system: norepinephrine, epinephrine, and insulin. The effects of norepinephrine and epinephrine are modeled by leveraging the [pharmacodynamics](@ref DrugsMethodology) model. The insulin model is under construction, and when it is finished, insulin will have a regulatory effect on the concentration of glucose in the blood. Functionality that is in the development stage now will enable future releases of the endocrine system to affect:
- Metabolic function
- %Renal function
- Ion regulation
......@@ -31,7 +31,7 @@ Hormone values are initialized where necessary during reset. There are no condit
There is no system-specific function for Preprocess in the %Endocrine System.
### Process
During Process, epinephrine is released. This release is augmented in response to exercise and/or stress. The rate of insulin synthesis is calculated and insulin is added to the system.
During Process, norpeinephrine and epinephrine are released. The release represents the basal production rate of the two hormones. The epinephrine production rate is scale to represent the sympathetic response associated with exercise and/or stress. Norepinephrine production is inversely proportional to the epinephrine production to represent the parasympathetic response. The rate of insulin synthesis is calculated and insulin is added to the system.
### Post Process
There is no system specific function for Post Process in the %Endocrine System.
......@@ -66,6 +66,11 @@ Epinephrine is released by the adrenal medulla at a basal endogenous rate of app
Two stimuli, exercise and acute stress, can modify the epinephrine release rate.
### Norepinephrine
Norepinephrine is released as part of the body's parasympathetic response. The norepinephrine clearance rate is estimated to be 22-27 (mL/kg-min) in @cite Johnston2004pharmacokinetics; however, this is in critically injured head trauma patients. We calculated a basal production rate based on this value, resulting in approximately 0.009 (&mu;g/kg-min) as a mass normalized production rate. Norepinephrine is currently released directly into the bloodstream. The basal concentration rate and those for different infusion rates were tested and validated using the data found in @cite Ensinger1992relationship. The clearance and production rates were adjusted slightly to meet this validation data. More information on the validation can be found in (@ref DrugsMethodology) and (@ref BloodChemistryMethodology).
Two stimuli, exercise and acute stress, can modify the norepinephrine release rate. The norepinephrine release is considered to be inversely proportional to the epinephrine release rate during this circumstances. The epinephrine release was validated as noted below.
#### Exercise
The increase in epinephrine release as a function of above-basal exercise was developed using data in @cite stratton1985hemodynamic and @cite tidgren1991renal. We assume that the epinephrine clearance rate is constant; therefore, the fractional increase in epinephrine concentration described in @cite stratton1985hemodynamic and @cite tidgren1991renal can be assumed to be due to a similar fractional increase in release rate. Using that assumption, we fit a logistic function to the basal-normalized epinephrine steady-state concentrations during exercise presented in @cite tidgren1991renal. The release modifier varies from 1 to 19.75, as shown in Figure 1, meaning that the epinephrine release rate will be 19.75 times the basal release rate with maximal exercise. The model is implemented by first computing the above-basal metabolic rate and then using the generic logistic function with the appropriate parameter values to compute the release rate multiplier.
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Methodology Sources and References
@article{Martinsson1986analysis,
doi = {10.1007/BF00607955},
issn = {14321041},
journal = {European Journal of Clinical Pharmacology},
number = {4},
pages = {427--431},
pmid = {3743618},
title = {{Analysis of phenylephrine in plasma: Initial data about the concentration-effect relationship}},
volume = {30},
year = {1986}
}
@article{Hengstmann1982pharmacokinetics,
author = {Hengstmann, J.H. and Goronzy, J.},
issn = {00282162},
journal = {European Journal of Clinical Pharmacology},
pages = {335--341},
title = {{Pharmacokinetics of 3H-Phenyephrine in man}},
volume = {21},
year = {1982}
}
@article{Johnston2004pharmacokinetics,
author = {Johnston, Andrew J. and Steiner, Luzius A. and O'Connell, Mark and Chatfield, Dot A. and Gupta, Arun K. and Menon, David K.},
doi = {10.1007/s00134-003-2032-4},
isbn = {0013400320},
issn = {03424642},
journal = {Intensive Care Medicine},
number = {1},
pages = {45--50},
pmid = {14586494},
title = {{Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients}},
volume = {30},
year = {2004}
}
@article{Ensinger1992relationship,
author = {Ensinger, H. and Stein, B. and Jager, O. and Grunert, A. and Ahnefeld, F. W.},
doi = {10.1097/00003246-199209000-00011},
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