This is referred to as zero-order kinetics and can result in dangerously high concentrations with continued, unmonitored drug administration. A low cardiac output can also accelerate the uptake somewhat, with reduced perfusion to areas outside the vessel-rich group resulting in less drug needed to be taken up from the alveoli.Alveolar partial pressure, measurable from end-tidal exhaled gas, closely reflects that of arterial blood and, in turn, that of the brain, enabling continuous monitoring of an indirect measure of drug delivery to the target site.After i.v. Distribution. It is the high blood supply more than the lipid solubility that explains this.Conversely, a low cardiac output leads to a higher initial peak concentration, because the drug is mixed with a smaller volume of blood during injection, though it will take longer to reach its target site. When based on these, even the most sophisticated dosage schemes for i.v.
Wherever possible, drug administration should be based on a measured patient response, which will incorporate both of these aspects of its pharmacology.However, such an approach may not always be possible. There is no consensus on which one is “right”, because each method has its advantages and shortcomings. neuromuscular blockers masking signs of anaesthetic depth) or difficult to quantify precisely (e.g. with the whole The target concentration can be attained far more rapidly using an initial loading dose followed by further additional drug in a declining exponential fashion as redistribution to other tissues occurs. Drugs that have a volume of distribution 7 4 L or less are thought to be confined to the plasma, or liquid part of the blood.
Oral bioavailability = area under curveUptake after intramuscular or subcutaneous administration is largely dependent on local blood flow rather than ionization or lipid solubility. The speed with which a drug reaches a particular tissue is largely dependent on its local blood flow, and for analytical convenience, similar tissue types are often grouped together into various ‘compartments’ depending on their blood supply.The capacity of each compartment to act as a reservoir for the drug is determined by a combination of its size and affinity for the drug. You can stump your professor, mentor, or other pharmacokinetic scientists with this little definition.The power behind understanding volume of distribution comes from the explanation.
Well, each of the different volume of distribution parameters refer to either volumes associated with different theoretical compartments or different methods of calculating the volume of distribution.
propranolol). As the duration of infusion continues, redistribution becomes progressively less important and the CST increases, until ultimately it equals the elimination half-life.
As the process continues, the concentration gradient falls, thus progressively slowing the rate of change. Pipe size represents blood flow and tank size the capacity as a drug reservoir.Illustration of a three-compartment model for a lipid-soluble drug. This explains why a smaller dose of induction agent is required in an elderly or shocked patient but may have a slower onset of action, while a young patient may require a much larger dose, yet will start to feel the effects more quickly.Other tissues may also have a high affinity for the drug, but can only take up the drug slowly as they receive a lower proportion of the cardiac output. The degree to which an administered drug reaches the systemic bloodstream is termed its bioavailability (Fig. With a high cardiac output, the effective volume of blood in which the drug is initially diluted is larger, leading to a lower peak concentration. glycopyrrolate), passive GI absorption is negligible.Even after GI absorption, a drug may not reach the systemic circulation. The volume of distribution is a proportionality factor that relates the amount of drug in the body to the concentration of drug measured in a biological fluid. If the volume is between 7 4 and 15 7 L, the drug is thought to be distributed throughout the blood (plasma and red blood cells). Now that you understand the the volume of distribution is a proportionality factor, and not a physiologic value, I can explain why this is important.