Pharmacology - PHARMACOKINETICS (MADE EASY)

Summary

This lecture delves into the fundamentals of pharmacokinetics and pharmacodynamics, essential for understanding drug action. It explains the body's processes of drug absorption, distribution, metabolism, and elimination, highlighting different absorption methods and the impact of factors like lipophilicity and blood flow on distribution. The importance of bioavailability, volume of distribution, and drug half-life in dosing and maintaining therapeutic levels is discussed. The video also covers the liver's role in drug metabolism through phase 1 and 2 reactions, emphasizing the cytochrome P450 enzymes' significance in drug interactions.

Takeaways

• 💊 Pharmacokinetics is the study of what the body does to a drug, including absorption, distribution, metabolism, and elimination.
• 🧽 Absorption occurs through various methods such as passive diffusion, facilitated diffusion, active transport, and endocytosis, influenced by factors like pH, surface area, and blood flow.
• 📊 Bioavailability is the fraction of a drug that enters systemic circulation in its unchanged form, which is not always 100% due to gut and liver metabolism.
• 📈 The Area Under the Curve (AUC) helps in comparing different drug formulations and routes of administration, and is used to calculate bioavailability.
• 🚀 Distribution of a drug is affected by factors like lipophilicity, blood flow, capillary permeability, binding to plasma proteins, and the drug's volume of distribution.
• 🧪 Elimination of drugs primarily occurs through hepatic, renal, and biliary routes, with most drugs following first-order kinetics, while some follow zero-order kinetics.
• ⏳ Half-life is the time required for the drug concentration in plasma to be reduced by half, which helps in predicting the duration of drug action and steady-state concentrations.
• 💧 The kidney is the main route of drug elimination, but lipid-soluble drugs require liver metabolism to become water-soluble for efficient excretion.
• 🔬 Phase 1 and Phase 2 reactions in the liver are crucial for drug metabolism, with Phase 1 making drugs more hydrophilic and Phase 2 involving conjugation reactions.
• 🌀 Cytochrome P450 enzymes, particularly CYP 3A4, 2D6, 2C8, 9, and 1A2, play a significant role in drug metabolism and are involved in many drug interactions.
• 🚫 Drug interactions can occur due to the induction or inhibition of cytochrome P450 enzymes, with mnemonics like 'PCRABS' for inducers and 'GPACMAN' for inhibitors helping to remember them.

Q & A

What is pharmacokinetics and why is it important to understand before studying the mechanism of action of drugs?

Pharmacokinetics refers to what the body does to a drug, including absorption, distribution, metabolism, and elimination. It's important to understand because it helps in predicting how a drug behaves in the body, which is crucial for its efficacy and safety.

What are the four main processes involved in the pharmacokinetics of a drug?

The four main processes are absorption, distribution, metabolism, and elimination. These steps describe how a drug is taken into the body, spread throughout, modified, and finally removed.

How does absorption of a drug typically occur?

Absorption usually happens through passive diffusion, facilitated diffusion, active transport, or endocytosis, depending on the drug's properties and the route of administration.

What is meant by bioavailability and how is it affected by the route of administration?

Bioavailability refers to the extent and rate at which the active ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of action. It is affected by the route of administration, with oral administration often having lower bioavailability due to first-pass metabolism in the liver.

How can the area under the curve (AUC) be used to compare different drug formulations or routes of administration?

The AUC represents the total exposure to the drug over time. By comparing the AUC for different formulations or routes, one can evaluate the relative bioavailability and effectiveness of the drug delivery methods.

What factors influence the distribution of a drug within the body?

Factors influencing drug distribution include lipophilicity, blood flow, capillary permeability, binding to plasma proteins and tissues, and the volume of distribution.

What is the significance of the volume of distribution in drug dosing?

The volume of distribution is a theoretical volume that indicates where the drug is likely to concentrate in the body. It helps in estimating drug dosing, as drugs with a large volume of distribution may require higher doses to achieve the desired therapeutic effect.

What are the two types of drug elimination kinetics and how do they differ?

The two types are first-order kinetics, where the amount of drug eliminated is proportional to its concentration, and zero-order kinetics, where the amount eliminated is constant regardless of concentration. The latter results in a straight-line graph when plotted over time.

How does the liver assist in the elimination of drugs, especially those that are lipid-soluble?

The liver assists by metabolizing lipophilic drugs into more water-soluble substances through phase 1 and phase 2 reactions. This makes them easier for the kidneys to excrete.

What are phase 1 and phase 2 reactions in drug metabolism, and what is their purpose?

Phase 1 reactions aim to make drugs more hydrophilic by introducing or unmasking a polar functional group, often involving oxidation, hydrolysis, or reduction. Phase 2 reactions involve conjugation, adding a polar group to make the drug more water-soluble and easily excretable.

Why are cytochrome P450 enzymes significant in drug metabolism, and which ones are commonly involved in phase 1 reactions?

Cytochrome P450 enzymes are significant because they catalyze the majority of phase 1 reactions, making drugs more water-soluble for elimination. The commonly involved enzymes are CYP 3A4/5, CYP 2D6, CYP 2C8/9, and CYP 1A2.