Pharmacokinetics and Pharmacodynamics

What Is Pharmacokinetics?

Pharmacokinetics describes what the body does to a drug. Every drug you give a patient travels through four sequential phases: absorption, distribution, metabolism, and excretion (often remembered as ADME). Understanding ADME is not merely academic—it directly guides how often you give a drug, what dose is safe, and which patients need extra monitoring.

Phase 1: Absorption

Absorption is the movement of a drug from its administration site into the bloodstream. The route of administration is the single biggest factor controlling absorption speed.

• Intravenous (IV): Absorption is immediate because the drug enters the bloodstream directly. Onset is fastest; errors are also hardest to reverse.
• Intramuscular (IM) and subcutaneous (SC): Drug must cross tissue into capillaries; onset is slower than IV.
• Oral (PO): Drug dissolves in the gastrointestinal tract and crosses the intestinal wall into portal circulation. Before reaching systemic circulation, it passes through the liver—a process called the hepatic first-pass effect. The liver may metabolize a significant portion of the drug before it ever reaches its target, reducing the amount of active drug available (bioavailability).

Factors that slow oral absorption include food in the stomach, altered GI motility, and certain medications. pH also matters: acidic drugs absorb better in the acidic stomach; basic drugs absorb better in the alkaline small intestine.

Phase 2: Distribution

Once in the bloodstream, the drug is carried to tissues. Two major factors affect distribution:

1. Plasma protein binding: Many drugs bind to albumin or other plasma proteins. Only the free (unbound) fraction is pharmacologically active. Patients with low albumin (malnutrition, liver disease) have more free drug circulating, increasing both effect and risk of toxicity.

2. Volume of distribution: Highly lipid-soluble drugs cross cell membranes easily and distribute widely into tissues. Water-soluble drugs stay closer to the bloodstream. In older adults, increased body fat and decreased lean muscle mass alter drug distribution significantly.

Phase 3: Metabolism (Biotransformation)

Metabolism converts drugs into forms (metabolites) that are easier to excrete, usually in the liver via cytochrome P450 enzyme systems. Some drugs are given as prodrugs—inactive forms converted to active metabolites in the liver (e.g., codeine to morphine).

Hepatic impairment reduces the liver's ability to metabolize drugs. The result is prolonged drug action and elevated plasma levels, raising the risk of toxicity. Nursing implication: patients with liver disease often require reduced doses and more frequent assessment for adverse effects.

Phase 4: Excretion

Most drugs and their metabolites leave the body through the kidneys in urine. Some are excreted in bile, feces, sweat, or breast milk. Renal function is measured clinically by creatinine clearance or estimated GFR.

Renal impairment slows drug excretion, causing drug accumulation and toxicity. Older adults naturally experience a decline in renal function with age, even when serum creatinine appears normal, because muscle mass (which produces creatinine) also decreases.

Half-life is the time it takes for the plasma drug concentration to decrease by 50%. It takes approximately five half-lives for a drug to be effectively eliminated from the body and approximately five half-lives to reach steady state when dosed repeatedly.

Pharmacodynamics: What the Drug Does to the Body

While pharmacokinetics describes drug movement, pharmacodynamics describes drug effect—the interaction between the drug and its receptor.

Key Pharmacodynamic Concepts

• Peak concentration: The highest plasma level reached after a dose. Peaks that are too high may cause toxicity.
• Trough concentration: The lowest plasma level, measured just before the next dose. Troughs that are too low may result in therapeutic failure.
• Therapeutic window (therapeutic range): The concentration range between the minimum effective concentration and the minimum toxic concentration. Drugs must be maintained within this range to be both effective and safe.
• Therapeutic index (TI): A ratio reflecting the margin of safety between a toxic dose and an effective dose. Narrow-therapeutic-index drugs (e.g., digoxin, warfarin, lithium, aminoglycosides) require careful monitoring because the toxic dose is close to the effective dose.

Dose-Response Curve Concepts

• ED50: The dose that produces the desired effect in 50% of a population.
• LD50: The dose that is lethal in 50% of a population (used in preclinical research).
• A wide gap between ED50 and LD50 indicates a safer drug; a narrow gap signals a high-risk drug.

Special Populations and Nursing Safety

| Population | Key Change | Nursing Action |

|---|---|---|

| Hepatic impairment | Reduced metabolism, more free drug | Monitor for toxicity; expect dose reductions |

| Renal impairment | Reduced excretion, drug accumulates | Monitor labs (creatinine, drug levels); adjust frequency |

| Older adults | Both above plus altered distribution | Start low, go slow; assess for falls, confusion, toxicity |

Safety principle: Always check peak and trough levels for narrow-therapeutic-index drugs before administering the next dose. Hold the dose and notify the prescriber if levels fall outside the therapeutic window. Document your findings and actions.