Basic Principles of Pharmacology Flashcards
Pharmacokinetics describes…
the relationship between drug
dose and drug concentration in plasma or at the site of drug
effect over time
What processes make up pharmacokinetics?
Absorption, distribution and elimination (metabolism and excrection)
What is the volume od distribution? How to calculate?
The volume of distribution (Vd) is the apparen size of the tank in which a known amount of drug distributes to produce a measured drug concentration once the drug has had enough time to thoroughly mix within the tank.
Volume of distribution = Amount of dose (t) / Concentration (t)
(t) = at a given time
Usually in mg/L
If drug elimination occurs as a first-order process (i.e.,
elimination is proportional to the concentration at that
time), in a tank model, the volume of distribution calculated by will be … over time
constant
The more soluble a drug is in peripheral tissue relative to blood or plasma, the … the peripheral volumes of distribution
larger
Clearence describes …
the rate of drug removal from the
plasma/blood, is defined as the volume of plasma cleared of a drug over a specified time period
What is systemic clearence? And intercompartimental clearence?
Systemic clearance permanently removes drug from the body, either by eliminating the parent molecule or by transforming it into
metabolites.
Intercompartmental clearance moves drug
between plasma and peripheral tissue tanks
What is the difference between clearence and elimination rate?
Clearance is defined in units of flow, that is, the volume completely cleared of drug per unit of time (e.g., L/min).
Clearance is not to be confused with elimination rate (e.g., mg/min).
The elimination rate is not an accurate method of describing the mass of drug removed over time. For example, assuming a first-order process, when plasma concentrations are high, the rate of drug elimination is high. When low, the rate is also low.
Clearance is a better descriptor as it is independent of drug concentration
How clearance can be calculated at the steady state during a continuous infusion?
Clearance= Infusion rate / Css
Css is the plasma concentration at steady state
How the the first-order elimination rate constant can be calculated?
K = CL / Vd
Where CL is clearance with units of volume/time (L/min), Vd is the compartment distribution volume with units of liters (L),
In a physiologic model of clearance, how the total clearance can be obtained?
The total clearance is the sum of each clearance by metabolic organs such as the liver, kidney, and other tissues
To calculate a metabolic organ clearance:
Clearance= Q (Cin −Cout) / Cin
- Q is the blood flow to metabolic organs;
- Cin is the concentration of drug delivered to metabolic organs;
- Cout is the concentration of drug leaving metabolic organs
Obs: The fraction of inflowing drug extracted by the organ [ (Cin−Cout) / Cin ] is called the extraction ratio (ER), so:
Clearance = Q x ER
Describe the relation between hepatic extraction ratio (ER), blood flow and drug metabolism
- For drugs with an ER of nearly 1 (e.g., propofol), a change in liver blood flow produces a nearly
proportional change in clearance.
If nearly 100% of the drug is extracted by
the liver, this implies that the liver has a very large metabolic capacity for the drug. In this case, the rate-limiting step in metabolism is the flow of drug to the liver, and such drugs are
said to be “flow limited.” As a consequence, any reduction in liver blood flow due to circulatory effects of anesthetic agents or changes in circulatory volumes in cases of perioperative bleeding or other situations of excessive fluid loss can be expected to reduce liver-dependent drug clearance. - For drugs with a low ER (e.g., alfentanil), clearance is nearly independent of the rate
of liver blood flow.
For these drugs, clearance is limited by
the capacity of the liver to take up and metabolize drug. These drugs are said to be “capacity limited.” Clearance will change in response to any change in the capacity of
the liver to metabolize such drugs, as might be caused by liver disease or enzymatic induction
What is the zero and the first order kinetics?
With zero-order kinetics, drug is eliminated at a constant rate, regardless of the plasma concentration, following a linear elimination phase as the system becomes saturated.
A simple analogy would be an athlete signing an autograph on a picture. Regardless of the total amount of photographs that must be signed, the athlete can only sign one autograph every 15 seconds. The rate-limiting factor of this analogy and zero-order kinetics is time.
With first-order kinetics, drug is eliminated at a rate proportional to the amount of drug
present at that time.
To utilize the same analogy, now the entire team can sign the photographs. The more hotographs there are to sign, the more athletes can sign. The rate-limiting factor of this analogy and in first-order kinetics is the initial concentration
- In the case of the autographs, if the amount of needed autographed photos exceeds the number of available athletes, the first-order elimination then becomes zero-order
How to calculate de elimination half-life of a drug with first-order kinetic from a compartment?
t1/2 = 0.693 / k
k is the first-order kinetic elimination rate constant
Front-end kinetics
Front-end kinetics refers to the description of intravenous drug behavior immediately following administration.
- How a drug rapidly moves from the blood into peripheral tissues directly influences the peak plasma drug concentration.
The amount of drug that moves to the peripheral tissue commonly surpasses the amount that is eliminated during the first few minutes after drug administration
