Pharmacology: Basic Concepts

Pharmacology

• It is the study of the interaction of chemical agents with biological systems
• These chemical agents can be endogenous or xenobiotic substances

Endogenous Substances

• These are synthesized within the body
• Examples include hormones and neurotransmitters

Xenobiotic Substances

• These are synthesized outside the body
• Examples include drugs and toxins

Pharmacology Divided

• Pharmacokinetics describes what the body does to the drug.
• Pharmacodynamics describes what the drug does to the body.

Four Primary Aspects of Pharmacokinetics (ADME)

• Absorption refers to the movement of a drug into the bloodstream.
• Distribution involves the spread of the drug to various body sites.
• Metabolism is the process by which the drug is chemically altered.
• Excretion is the removal of the drug from the body.

Biological Transport

• Drugs must cross biological membranes to reach their targets within the body
• Drugs need to be transported to be absorbed, distributed, metabolized, and excreted

Cell Membrane

• It is primarily composed of a lipid matrix and proteins.
• Lipids are arranged in a bilayer, providing a barrier to water-soluble substances.
• Proteins act as structural components, receptors, ion channels, and enzymes.

Types of Drug Transport

• Passive diffusion
• Facilitated diffusion
• Active transport
• Pinocytosis

Passive Diffusion

• It is the movement of drugs from an area of high concentration to an area of low concentration
• It does not require energy (ATP)
• It follows Fick's Law of Diffusion, where the rate of diffusion is proportional to the concentration gradient, surface area, and permeability of the membrane

Key Considerations for Passive Diffusion

• Lipid solubility: Lipid-soluble drugs diffuse more easily across cell membranes.
• Drug size: Smaller molecules tend to diffuse more readily than larger ones.
• Ionization: Non-ionized drugs are more lipid-soluble and diffuse better than ionized drugs.

Filtration

• It involves the movement of drugs through aqueous pores in the membrane.
• It depends on the size of the drug molecule.
• It is significant for very small drugs (e.g., water, urea, and some ions).

Carrier-Mediated Transport

• It involves specific carrier proteins that bind to drugs and facilitate their movement across membranes.
• It includes two types: facilitated diffusion and active transport.

Facilitated Diffusion

• It requires a carrier protein but does not require energy.
• It moves drugs down their concentration gradient.
• It can be saturated and may be inhibited by other drugs that compete for the same carrier.

Active Transport

• It requires a carrier protein and energy (ATP) to move drugs against their concentration gradient.
• It is saturable and can be inhibited by other drugs.
• It includes primary active transport (uses ATP directly) and secondary active transport (uses the electrochemical gradient of another molecule).

Secondary Active Transport

• It uses the electrochemical gradient of one ion (typically Na+) to transport another molecule

Two Types of Secondary Active Transport

• Symport (Co-transport): Both the ion and the drug move in the same direction across the membrane.
• Antiport (Counter-transport): The ion and the drug move in opposite directions across the membrane.

Pinocytosis

• It involves the engulfment of fluids or small particles by the cell membrane.
• The cell membrane invaginates, forming a vesicle that encloses the substance, and then the vesicle is internalized into the cell.
• It is important for the transport of very large molecules (e.g., proteins).