Pharmacology Chapter 1: Drug Therapy Principles

Pharmacokinetics Overview

• Pharmacokinetics encompasses ADME: Absorption, Distribution, Metabolism, and Excretion, critical for understanding drug action and effectiveness.
• Drug bioavailability can be influenced by factors such as formulation (pill vs. liquid) and route of administration.

Absorption of Drugs

• For optimal absorption, routes and formulation matter; for example, small intestine is crucial for oral drugs like Warfarin.
• Food intake, specifically vitamin K-rich food, can interfere with the absorption and effects of anticoagulants.

Drug Distribution

• Warfarin has 99% protein binding affinity, primarily to albumin, limiting the availability of active drug in circulation.
• Drug interactions that affect protein binding significantly influence distribution and efficacy.

Drug Clearance

• Metabolism of Warfarin primarily occurs in the liver via CYP2C9, producing less active metabolites which impact overall drug activity.
• Individual differences in metabolism, influenced by genetics and liver function, lead to variability in drug response and dosing needs.

Excretion of Drugs

• Warfarin metabolites are mainly excreted through urine, with elimination half-life varying among individuals based on genetics and health factors.

Implications for Dosing

• Warfarin dosing is highly individualized, frequently requiring monitoring of INR levels to guide adjustments.
• Initial doses typically range from 2.5 to 5 mg, while maintenance doses vary widely, often hovering between 2 to 10 mg based on patient response.

Pharmacodynamics Concepts

• Pharmacodynamics examines how drugs interact with body receptors and dictate physiological effects.
• Relationships between dose and response illustrate how various plasma levels can influence patient outcomes.
• Different routes of administration offer distinct advantages and limitations, influencing drug absorption and therapeutic outcomes.

Routes of Administration

• Oral (PO): Convenient but variable absorption influenced by food and gastrointestinal factors.
• Intravenous (IV): Immediate effect and full bioavailability, but more complex and riskier for complications.
• Intramuscular (IM): Moderate speed of absorption, providing a balance between PO and IV, but can be painful and has a risk of infection.

Preferred Route of Administration

• The preferred route depends on therapeutic goals, drug characteristics, and patient factors, with IV often favored for rapid effect in emergencies, while oral routes are preferred for long-term management and convenience.