Insights gleaned from pharmaco-genetic dissection and modelling of cardio-respiratory neural networks

Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...

The neural regulation of respiration is a meticulously coordinated process primarily controlled by the respiratory centers located within the brainstem. These centers, composed of specialized neurons, transmit nerve impulses that control the contraction and relaxation of our respiratory muscles.
Respiratory Centers in the Brainstem
Two primary areas comprise the respiratory center: the medullary respiratory center in the medulla oblongata and the pontine respiratory group in the pons. The...

Physiological pharmacokinetic models, often called flow-limited or perfusion models, typically assume a swift drug distribution between tissue and venous blood, creating a rapid drug equilibrium. This premise is based on the idea that drug diffusion is extremely fast, and the cell membrane presents no barrier to drug permeation. In this scenario, where no drug binding occurs, the drug concentration in the tissue equals that of the venous blood leaving the tissue. This greatly simplifies the...

Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...

The neurogenic control of respiration coordinates various neural networks and pathways to regulate breathing rate and depth, meeting the body's oxygen and carbon dioxide exchange requirements. This system adapts to physiological and environmental conditions, ensuring optimal breathing patterns.
Central Control
The brainstem is the primary site of central control, hosting respiratory centers:

Pharmacodynamic (PD) responses describe the interaction between a drug and its biological target, culminating in a physiological effect. These responses can be classified into different types: continuous variables, such as blood glucose levels; categorical outcomes, like survival rates; and time-to-event metrics, such as disease progression. Understanding and modeling PD responses are critical for optimizing drug efficacy and safety.PD models describe the relationship between drug concentration...