What is pharmacokinetics?
The study of what the body does to a drug or toxin—how it is absorbed, distributed, metabolized, and excreted.
What are the four main ways small molecules cross cell membranes?
1) Diffusion through lipids, 2) Diffusion through aqueous pores (aquaporins), 3) Carrier-mediated transport, 4) Pinocytosis.
Which passage routes are most important for drugs?
Lipid diffusion and carrier-mediated transport.
Why are aquaporins and pinocytosis less important for small drug molecules?
Aquaporins mainly transport water, and pinocytosis is relevant only for macromolecules like insulin.
What type of substances penetrate cell membranes freely?
Non-polar, lipid-soluble substances.
Why is lipid solubility important?
It determines absorption rate, tissue penetration (e.g., brain), and renal elimination.
Why are many drugs weak acids or weak bases?
Because they can exist in both ionized and unionized forms, allowing variable membrane permeability.
What is the Henderson-Hasselbalch relationship for weak acids?
AH ↔ A- + H+; at low pH, more protonated (unionized) form crosses membranes.
What is the Henderson-Hasselbalch relationship for weak bases?
BH+ ↔ B + H+; at high pH, more unprotonated (unionized) form crosses membranes.
What is pKa?
The pH at which 50% of a drug is ionized; determines how much of a drug is in the unionized form.
Which form of a drug diffuses across lipid membranes?
The uncharged (unionized) form.
What is pH partitioning?
The accumulation of weak acids in high-pH (alkaline) compartments and weak bases in low-pH (acidic) compartments.
How does pH partitioning affect drug distribution?
It causes drugs to concentrate in tissues based on their ionization and local pH differences.
How does urinary pH affect drug excretion?
Acidic urine increases excretion of weak bases and decreases that of weak acids; alkaline urine does the opposite.
How does plasma pH affect CNS drug concentration?
Increased plasma pH draws weak acids out of the CNS, while decreased pH increases their CNS concentration (and neurotoxicity).
What is carrier-mediated transport?
A process involving transmembrane proteins that bind molecules or ions and transport them across membranes via conformational change.
What characterizes carrier-mediated transport?
Saturation kinetics—transport rate plateaus when all carriers are occupied.
Where is carrier-mediated transport important?
Renal tubules, biliary tract, blood-brain barrier, and gastrointestinal tract.
What is P-glycoprotein?
A transport protein found in renal tubules, brain microvessels, and GI tract; eliminates toxins and contributes to multidrug resistance in cancer.
What is the physiological role of P-glycoprotein?
To eliminate environmental toxins and reduce intracellular accumulation of xenobiotics.
Why is plasma protein binding important?
Only the unbound fraction of a drug is pharmacologically active; bound drug is inactive.
What is the main plasma protein that binds drugs?
Albumin, which binds many acidic drugs.
What factors affect plasma protein binding?
Free drug concentration, binding site affinity, and plasma protein levels.
How does plasma protein binding affect elimination?
Extensive binding slows drug metabolism and excretion.
