Pharmacokinetics | Drug Clearance
Drug Clearance
In this section, the speaker discusses drug clearance and how it is defined. They also explain the relationship between clearance and elimination, as well as the primary organs responsible for drug elimination.
Definition of Clearance
- Clearance is defined as the rate of elimination of a particular drug over the plasma concentration of the drug.
- Clearance is equal to the rate of elimination divided by the concentration of the drug within the plasma.
- Clearance can be further defined as the volume of plasma that's cleared of a drug per unit time.
Relationship Between Clearance and Elimination
- Elimination is a combination of metabolism and excretion, primarily performed by liver and kidneys respectively.
- Dysfunction in these organs can lead to decreased clearance, which can cause an accumulation of drugs in the body.
Other Organs Involved in Clearance
- Lungs, gastrointestinal tract, breast milk, saliva, and lacrimal secretions are other organs involved in clearing drugs from the body.
- However, liver and kidneys are clinically relevant for pharmacokinetics.
Effects of Organ Dysfunction on Drug Clearance
In this section, we learn about how organ dysfunction affects drug clearance.
Renal Dysfunction
- If someone has renal dysfunction, clearance will decrease because their ability to clear or eliminate drugs through urine will decrease.
- This can lead to an accumulation of drugs in the body if they are primarily cleared by kidneys.
Hepatic Dysfunction
- If someone has liver dysfunction:
- The clearance will decrease because their ability to metabolize and inactivate drugs will decrease.
- This can lead to an accumulation of drugs in the body if they are primarily cleared by the liver.
Clearance and Half-Life
In this section, the speaker explains how clearance is not just dependent on the rate of elimination and drug concentration in the plasma but also on volume of distribution times a particular constant. The speaker then goes on to explain how half-life affects clearance.
Clearance and Half-Life Relationship
- Clearance is inversely proportional to half-life. A long half-life will decrease clearance while a short half-life will increase clearance.
First Order Enzymatic Kinetics
- Most drugs operate under first order enzymatic kinetics where the fraction of drug that we eliminate per unit time is constant. Half-life is very important in first order enzymatic kinetics.
Rate of Elimination and Fraction of Drug Eliminated
- For drugs operating under first order enzymatic kinetics, the rate of elimination can vary but the fraction of drug eliminated per unit time remains constant.
Importance of Half-Life in First Order Enzymatic Kinetics
- In first order enzymatic kinetics, we can use the concept of half-life to determine how quickly a drug will be eliminated from the body since it is constant for that fraction per unit time.
First Order Enzymatic Kinetics
This section discusses the concept of first-order enzymatic kinetics and how it relates to drug concentration and rate of elimination.
Exponential Graph
- The graph for first-order enzymatic kinetics is exponential.
- This means that the fraction of drug removed per unit time is constant.
- The half-life is constant every single hour, removing 50% of the drug.
Drug Concentration and Rate of Elimination
- In first-order enzymatic kinetics, drug concentration and rate of elimination are directly proportional.
- Increasing the concentration of a drug will increase its rate of elimination.
- This is because there are enzyme sites available for the drug to bind onto and be metabolized.
Zero Order Enzymatic Kinetics
This section discusses zero-order enzymatic kinetics and how it differs from first-order enzymatic kinetics.
Exponential Graph
- The graph for zero-order enzymatic kinetics is not exponential.
- The only thing that's constant in zero order is the rate of elimination, not the half-life.
Drugs Undergoing Zero Order Enzymatic Kinetics
- Phenotone (PHT), ethanol (E-T-O-H), and aspirin (A-S-A) are drugs that undergo zero-order enzymatic kinetics.
- The half-life is variable in zero order, unlike in first order where it's constant.
Rate of Elimination
- In zero order, the amount of drug eliminated per unit time remains constant regardless of its concentration.
- Administering more drugs does not change this fact.
Pharmacokinetics
In this section, the speaker explains pharmacokinetics and how drugs are eliminated from the body.
Drug Elimination
- At time 0, there is 100 milligrams of a drug in the body.
- The rate of elimination is 25 milligrams per hour.
- The graph of drug concentration versus time is linear, indicating zero-order kinetics.
- Zero-order kinetics means that the rate of elimination is constant and independent of drug concentration.
Steady State and Half-Life
- Steady state occurs when the amount of drug entering the body equals the amount being eliminated.
- Half-life is important for determining how long it takes to reach steady state and how long it takes to eliminate a drug from the body.
Clearance and Half-Life
In this section, the instructor discusses the relationship between clearance and half-life of a drug. The impact of renal disease on clearance is also discussed.
Clearance and Renal Disease
- A patient with renal disease will likely experience decreased clearance of a drug.
- As clearance decreases, the half-life of the drug increases, which can lead to potential side effects if the drug cannot be cleared from the body.
- When administering a drug to a patient with renal disease causing decreased clearance and an increase in half-life, dosage should subsequently decrease as well.
Half-Life and Steady State Concentration
- It takes approximately four to five half-lives for a drug to reach steady-state concentration.
- If the half-life for an infusion is 12 hours, it would take at least 48 hours (4 x 12 hours) to reach steady-state concentration via continuous infusion.
Dosages and Regimens
In this section, the instructor introduces dosages and regimens of drugs.
Dosage Adjustments
- Dosage adjustments are necessary when administering drugs to patients with altered pharmacokinetics due to factors such as age or organ dysfunction.
- The goal is to achieve therapeutic concentrations while minimizing toxicity.
Regimens
- Drug regimens refer to how often a medication is administered over time.
- Different regimens may be used depending on factors such as desired effect, duration of action, and potential side effects.