General Pharmacology: Basic Concepts

General Pharmacology

• General pharmacology is the study of how the body works with drugs.
• It's divided into pharmacokinetics and pharmacodynamics.

Pharmacokinetics

• Pharmacokinetics is the study of how the body affects drugs (ADME):
  • Absorption: How drugs enter the body
  • Distribution: Where drugs go in the body
  • Metabolism: How the body breaks down drugs
  • Excretion: How drugs leave the body

Pharmacodynamics

• Pharmacodynamics is the study of how drugs affect the body.

Passage of Drugs Across Cell Membranes

• Drugs pass through cell membranes through:
  • Passive transport:
    • Simple diffusion: Movement of drugs through water pores or lipid membranes
    • Filtration: Movement of drugs through capillary endothelium and glomeruli.
  • Special transfer:
    • Active transport: Requires energy to move drugs across membranes
    • Pinocytosis: Cell engulfs the drug.

Simple Diffusion

• Simple diffusion occurs through water pores or lipid membranes.
• Factors affecting simple diffusion include:
  • Concentration
  • Molecular weight
  • Solubility in water
  • Lipid solubility (high oil/water partition coefficient)
  • Ionization

Ionization

• Ionization affects lipid solubility and drug passage.
• Ionization depends on pH and pKa.
• pKa is the pH at which 50% of the drug is ionized.
• Henderson-Hasselbalch equation determines the degree of ionization.
• Acidic drugs become more non-ionized in acidic environments.
• Basic drugs become more non-ionized in basic environments.

Rules

• Acidic drugs become more non-ionized in acidic pH (e.g., aspirin in the stomach).
• Basic drugs become more non-ionized in basic pH (e.g., amphetamine in the intestines).

Filtration

• Filtration is the passage of drugs through capillary endothelium and glomeruli.
• Factors affecting filtration include:
  • Blood flow
  • Binding to plasma proteins
  • Molecular weight (<500)
  • Osmotic and hydrostatic gradients

Special Transfer (Active Transport and Pinocytosis)

• Active transport requires energy.
• Pinocytosis is where the cell engulfs the drug.

Absorption

• Absorption is how drugs enter the body.
• Routes of administration include:
  • Parenteral (IV, IM, SC)
  • Oral
  • Sublingual
  • Inhalation
  • Topical
  • Rectal

Factors Affecting Absorption

• Drug-related factors:
  • Water and lipid solubility
  • Degree of ionization
  • Valency
  • Nature
  • Preparation and dosage form
• Patient-related factors:
  • Routes of administration
  • Systemic circulation
  • Absorbing surface
  • Specific factors (e.g., gut motility, gastric emptying)
  • Other drugs

C-Specific Factors for Oral Absorption

• Gastric emptying
• Gut motility
• pH
• Food and other drugs (e.g., milk, tea, cholystyramine)

Bioavailability (f)

• Bioavailability is the fraction of administered drug that reaches systemic circulation unchanged.
• Intravenous doses have 100% bioavailability (f=1)
• Bioavailability is calculated: (AUC of route) / (AUC of IV route) x 100

First-Pass Effect

• Drug metabolism before reaching systemic circulation reduces concentration.
• Gut first pass involves enzyme/hormone/protein interactions.
• Hepatic first pass occurs in the liver (e.g., nitroglycerin, lidocaine).

Overview of general pharmacology, including pharmacokinetics (ADME) and pharmacodynamics. Discusses drug absorption, distribution, metabolism, excretion, and mechanisms of drug passage across cell membranes like passive transport and active transport.