The drug system contains the physiologically based pharmacokinetic (PBPK) model and the pharmacodynamic (PD) model. More...

#include <Drugs.h>

Inherits SEDrugSystem, PulseDrugsSystem, and PulseSystem.

Public Member Functions
virtual	~Drugs ()

void	Clear ()

Public Member Functions inherited from SEDrugSystem
	SEDrugSystem (Logger *logger)

virtual	~SEDrugSystem ()

virtual const SEScalar *	GetScalar (const std::string &name)

virtual bool	HasBronchodilationLevel () const

virtual SEScalarNegative1To1 &	GetBronchodilationLevel ()

virtual double	GetBronchodilationLevel () const

virtual bool	HasHeartRateChange () const

virtual SEScalarFrequency &	GetHeartRateChange ()

virtual double	GetHeartRateChange (const FrequencyUnit &unit) const

virtual bool	HasMeanBloodPressureChange () const

virtual SEScalarPressure &	GetMeanBloodPressureChange ()

virtual double	GetMeanBloodPressureChange (const PressureUnit &unit) const

virtual bool	HasNeuromuscularBlockLevel () const

virtual SEScalar0To1 &	GetNeuromuscularBlockLevel ()

virtual double	GetNeuromuscularBlockLevel () const

virtual bool	HasPulsePressureChange () const

virtual SEScalarPressure &	GetPulsePressureChange ()

virtual double	GetPulsePressureChange (const PressureUnit &unit) const

virtual bool	HasPupillaryResponse () const

virtual SEPupillaryResponse &	GetPupillaryResponse ()

virtual const SEPupillaryResponse *	GetPupillaryResponse () const

virtual void	RemovePupillaryResponse ()

virtual bool	HasRespirationRateChange () const

virtual SEScalarFrequency &	GetRespirationRateChange ()

virtual double	GetRespirationRateChange (const FrequencyUnit &unit) const

virtual bool	HasSedationLevel () const

virtual SEScalar0To1 &	GetSedationLevel ()

virtual double	GetSedationLevel () const

virtual bool	HasTidalVolumeChange () const

virtual SEScalarVolume &	GetTidalVolumeChange ()

virtual double	GetTidalVolumeChange (const VolumeUnit &unit) const

virtual bool	HasTubularPermeabilityChange () const

virtual SEScalarNegative1To1 &	GetTubularPermeabilityChange ()

virtual double	GetTubularPermeabilityChange () const

Public Member Functions inherited from SESystem
	SESystem (Logger *logger)

virtual	~SESystem ()

Public Member Functions inherited from Loggable
	Loggable ()

	Loggable (Logger *log)

virtual	~Loggable ()

virtual Logger *	GetLogger () const

virtual void	Debug (std::string const &msg, std::string const &origin=empty) const

virtual void	Debug (std::stringstream &msg, std::string const &origin=empty) const

virtual void	Debug (std::ostream &msg, std::string const &origin=empty) const

virtual void	Info (std::string const &msg, std::string const &origin=empty) const

virtual void	Info (std::stringstream &msg, std::string const &origin=empty) const

virtual void	Info (const std::stringstream &msg, std::string const &origin=empty) const

virtual void	Info (std::ostream &msg, std::string const &origin=empty) const

virtual void	Warning (std::string const &msg, std::string const &origin=empty) const

virtual void	Warning (std::stringstream &msg, std::string const &origin=empty) const

virtual void	Warning (std::ostream &msg, std::string const &origin=empty) const

virtual void	Error (std::string const &msg, std::string const &origin=empty) const

virtual void	Error (std::stringstream &msg, std::string const &origin=empty) const

virtual void	Error (std::ostream &msg, std::string const &origin=empty) const

virtual void	Fatal (std::string const &msg, std::string const &origin=empty) const

virtual void	Fatal (std::stringstream &msg, std::string const &origin=empty) const

virtual void	Fatal (std::ostream &msg, std::string const &origin=empty) const

Protected Member Functions
	Drugs (PulseController &data)

void	Initialize ()
	Initializes system properties to valid homeostatic values. More...

void	SetUp ()
	Initializes parameters for the Drugs Class. More...

void	AtSteadyState ()
	Determines if the engine is stable. More...

void	PreProcess ()
	Substance Preprocess function. More...

void	Process ()
	Substances process function. More...

void	PostProcess ()

void	AdministerSubstanceBolus ()
	Increments the mass of a substance to represent drug injection. More...

void	AdministerSubstanceInfusion ()
	Increments the mass of a substance to represent drug infusion. More...

void	AdministerSubstanceCompoundInfusion ()
	Increases the substance masses for compounds. More...

void	CalculatePartitionCoefficients ()
	Calculate partition coefficients for the PK Model. More...

void	CalculateSubstanceClearance ()
	Calculates the substance mass cleared. More...

void	CalculatePlasmaSubstanceConcentration ()
	Calculates the concentration of a substance in the plasma. More...

void	CalculateDrugEffects ()
	Calculates the drug effects on other system parameters. More...

Protected Attributes
PulseController &	m_data

double	m_dt_s

SELiquidCompartment *	m_aortaVascular

SELiquidCompartment *	m_venaCavaVascular

SELiquidCompartment *	m_muscleIntracellular

SELiquidCompartment *	m_liverVascular

SETissueCompartment *	m_liverTissue

SEFluidCircuitPath *	m_IVToVenaCava

SETissueCompartment *	m_fatTissue

Protected Attributes inherited from SEDrugSystem
SEScalarNegative1To1 *	m_BronchodilationLevel

SEScalarFrequency *	m_HeartRateChange

SEScalarPressure *	m_MeanBloodPressureChange

SEScalar0To1 *	m_NeuromuscularBlockLevel

SEScalarPressure *	m_PulsePressureChange

SEPupillaryResponse *	m_PupillaryResponse

SEScalarFrequency *	m_RespirationRateChange

SEScalar0To1 *	m_SedationLevel

SEScalarVolume *	m_TidalVolumeChange

SEScalarNegative1To1 *	m_TubularPermeabilityChange

Protected Attributes inherited from SESystem
std::stringstream	m_ss

Protected Attributes inherited from Loggable
Logger *	m_Logger

Friends
class	PBPulsePhysiology

class	PulseController

class	PulseEngineTest

Additional Inherited Members
Static Public Member Functions inherited from SESystem
static const SEScalar *	GetScalar (const std::string &name, std::vector< SESystem > systems)

Static Public Attributes inherited from Loggable
static const std::string	empty

Detailed Description

The drug system contains the physiologically based pharmacokinetic (PBPK) model and the pharmacodynamic (PD) model.

Drug transvascular transport is modeled with a physiologically-based pharmacokinetic (PBPK) model, and the physiologic effects on the body are modeled with a low-fidelity pharmacodynamic (PD) model.

Constructor & Destructor Documentation

◆ Drugs()

Drugs::Drugs ( PulseController & data )

protected

◆ ~Drugs()

Drugs::~Drugs ( )

virtual

Member Function Documentation

◆ AdministerSubstanceBolus()

void Drugs::AdministerSubstanceBolus ( )

protected

Increments the mass of a substance to represent drug injection.

The mass of a substance is increased based on the administration of a substance. For a bolus administration, the user specifies a dose (amount), a concentration, and a substance. The calculated mass is then incrementally added to the vena cava over two seconds.

Error:: Error: Unavailable Administration Route

Todo:: Add fluid amount to fluid system

◆ AdministerSubstanceCompoundInfusion()

void Drugs::AdministerSubstanceCompoundInfusion ( )

protected

Increases the substance masses for compounds.

The masses of all substances associated with the compound substance are increased. The mass of each substance is incremented in the vena cava based on the rate specified by the user and a concentration specified in the compound substance file.

Todo:: Enforce limits and remove the fatal error

Error:: Fatal: rate cannot exceed 285 mL/min

Todo:: correct the mass based on what we have left in the bag

◆ AdministerSubstanceInfusion()

void Drugs::AdministerSubstanceInfusion ( )

protected

Increments the mass of a substance to represent drug infusion.

The mass of a substance is increased based on the administration of a substance. For an infusion, the user specifies a concentration and a rate. The calculated mass is then added to the vena cava every time step until the infusion is stopped.

Todo:: sub needs to be const

Todo:: Enforce limits and remove the fatal error

Error:: Fatal: Titration administration cannot be negative

Todo:: Need to add fluid amount to fluid system

Todo:: Support state, and how would a user remove this action?

◆ AtSteadyState()

void Drugs::AtSteadyState ( )

protectedvirtual

Determines if the engine is stable.

When the engine is stable, the CDM makes this call to update the member variable.

Reimplemented from PulseSystem.

◆ CalculateDrugEffects()

void Drugs::CalculateDrugEffects ( )

protected

Calculates the drug effects on other system parameters.

If the substance is a drug with an EC50 value, the effects on heart rate, blood pressure, respiration rate, tidal volume, neuromuscular block level, sedation level, bronchodilation level, and pupillary state are calculated using the current plasma concentration, the EC50, and the maximum drug response.

Todo:: The drug effect is being applied to the baseline, so if the baseline changes the delta heart rate changes.

◆ CalculatePartitionCoefficients()

void Drugs::CalculatePartitionCoefficients ( )

protected

Calculate partition coefficients for the PK Model.

Parameters

vSubstances Coefficients are calculated for the substances in the vector with IonicState.

The partition coefficients are calculated for each substance in the input vector (active substances). To ensure the diffusion is modeled with PK for the substance, a check is performed for Ionic State. If the property is present the coefficients are calculated. They are calculated for all tissue compartments. coefficients are set on the substance compartment effects for use during the diffusion calculation.

Error:: Fatal: Binding Protein not supported

Todo:: How to support oral absorption - should I check if oral administration then use Oral absorption rate otherwise assume 1?

◆ CalculatePlasmaSubstanceConcentration()

void Drugs::CalculatePlasmaSubstanceConcentration ( )

protected

Calculates the concentration of a substance in the plasma.

If the substance has PK properties, the concentration of the substance in the plasma is calculated. PlasmaConcentration = TotalMassInTheBlood / PlasmaVolume. The plasma concentration is then set on the substance. The concentration computation is obviously erroneous. This is a known issue. See pharmacokinetics

◆ CalculateSubstanceClearance()

void Drugs::CalculateSubstanceClearance ( )

protected

Calculates the substance mass cleared.

If the substance has PK properties, the substance clearance is calculated. The renal, liver, and systemic clearance terms are applied to each anatomy compartment per substance. The amount of mass is then removed from the tissue node each time step. The tissue node mass and concentration are then updated. Sets the amount of substance cleared as a compartment effect for each substance.

◆ Clear()

void Drugs::Clear ( )

virtual

Reimplemented from SEDrugSystem.

◆ Initialize()

void Drugs::Initialize ( )

protectedvirtual

Initializes system properties to valid homeostatic values.

Reimplemented from PulseSystem.

◆ PostProcess()

void Drugs::PostProcess ( )

inlineprotectedvirtual

Implements PulseSystem.

◆ PreProcess()

void Drugs::PreProcess ( )

protectedvirtual

Substance Preprocess function.

The AdminsterSubstances, AdministerIVSubstances, and Hemorrhage actions are processed in this step. The masses of the substances associated with these actions are updated as the actions are processed.

Implements PulseSystem.

◆ Process()

void Drugs::Process ( )

protectedvirtual

Substances process function.

For any drugs circulating in the system the renal and hepatic clearance factors and metabolic factors are assigned to the appropriate compartments. The drug effects categories and system level drug effects are calculated and the values are set on the common data model for use in other systems. Drug effects are only calculated if the PD is enabled.

Implements PulseSystem.

◆ SetUp()

void Drugs::SetUp ( )

protectedvirtual

Initializes parameters for the Drugs Class.

Initializes member variables and system level values on the common data model.

Implements PulseSystem.

Friends And Related Function Documentation

◆ PBPulsePhysiology

friend class PBPulsePhysiology

friend

◆ PulseController

friend class PulseController

friend

◆ PulseEngineTest

friend class PulseEngineTest

friend

Member Data Documentation

◆ m_aortaVascular

SELiquidCompartment* Drugs::m_aortaVascular

protected

◆ m_data

PulseController& Drugs::m_data

protected

◆ m_dt_s

double Drugs::m_dt_s

protected

◆ m_fatTissue

SETissueCompartment* Drugs::m_fatTissue

protected

◆ m_IVToVenaCava

SEFluidCircuitPath* Drugs::m_IVToVenaCava

protected

◆ m_liverTissue

SETissueCompartment* Drugs::m_liverTissue

protected

◆ m_liverVascular

SELiquidCompartment* Drugs::m_liverVascular

protected

◆ m_muscleIntracellular

SELiquidCompartment* Drugs::m_muscleIntracellular

protected

◆ m_venaCavaVascular

SELiquidCompartment* Drugs::m_venaCavaVascular

protected

Public Member Functions

Protected Member Functions

Protected Attributes

Friends

Additional Inherited Members

Detailed Description

Constructor & Destructor Documentation

◆ Drugs()

◆ ~Drugs()

Member Function Documentation

◆ AdministerSubstanceBolus()

◆ AdministerSubstanceCompoundInfusion()

◆ AdministerSubstanceInfusion()

◆ AtSteadyState()

◆ CalculateDrugEffects()

◆ CalculatePartitionCoefficients()

◆ CalculatePlasmaSubstanceConcentration()

◆ CalculateSubstanceClearance()

◆ Clear()

◆ Initialize()

◆ PostProcess()

◆ PreProcess()

◆ Process()

◆ SetUp()

Friends And Related Function Documentation

◆ PBPulsePhysiology

◆ PulseController

◆ PulseEngineTest

Member Data Documentation

◆ m_aortaVascular

◆ m_data

◆ m_dt_s

◆ m_fatTissue

◆ m_IVToVenaCava

◆ m_liverTissue

◆ m_liverVascular

◆ m_muscleIntracellular

◆ m_venaCavaVascular