Pharmacokinetics and Drug Absorption, Distribution, Metabolism, Excretion (ADME)

Pharmacokinetics

What the body does to a drug; what happens to a medication after it enters the body.

ADME

Absorption → Distribution → Metabolism → Excretion

Absorption

Movement of a medication into the bloodstream.

Distribution

Movement of medication from the bloodstream → tissues/site of action.

Metabolism

The body chemically changes a medication so it can be eliminated.

Excretion

Removal of medication from the body; final step of pharmacokinetics.

Bioavailability

Amount of medication that reaches systemic circulation.

IV bioavailability

100% — IV medications enter the bloodstream directly.

PO bioavailability

Less medication may reach systemic circulation because PO medications must first be absorbed through the GI tract.

Most oral medication absorption

Small intestine; its large surface area promotes absorption.

Medication formulation & absorption

Liquids/smaller particles generally absorb faster; tablets/capsules more slowly; extended-release medications absorb slowly and should NOT be crushed, chewed, or altered.

Route of administration

Most influential factor for the rate and amount of medication absorbed.

Rate

How quickly a medication enters the bloodstream and begins to work; influenced by route and blood flow to the absorption site.

Passive diffusion

HIGH → LOW concentration; no energy; most common. Think: "goes with the flow."

Facilitated diffusion

HIGH → LOW concentration; uses a carrier protein; no energy. Think: "gets some help."

Active transport

Can move LOW → HIGH concentration; requires a carrier + energy. Think: "active = requires energy."

Distribution — major factors

Blood flow, body fluids, body composition/tissue type, plasma proteins/protein binding, and presence of disease.

Goal of distribution

Achieve a therapeutic concentration at the target site.

Free drug

Active/unbound; can leave the bloodstream, reach tissues, and act at receptors.

Protein-bound drug

Attached primarily to albumin; temporarily inactive/unavailable to tissues.

Albumin

Primary plasma protein involved in medication binding.

Low protein / hypoproteinemia

↓ protein → ↑ free drug → ↑ medication effect → ↑ toxicity risk.

Protein binding as "storage"

Bound medication is gradually released → can prolong medication effect and half-life.

Highly protein-bound drugs given together

May compete for the same binding sites; one can displace another → ↑ free medication → ↑ toxicity risk.

Protein-binding competition — greatest concern

Narrow therapeutic index medications because even a small increase in free medication can cause toxicity.

Highly protein-bound medications — nursing connection

Consider albumin levels, nutritional status, liver function, and other medications.

Metabolism — primary site

Liver.

Other sites of metabolism

Kidneys, GI tract, lungs, skin, and plasma.

Metabolism usually produces

Inactive metabolites and/or more water-soluble forms that are easier for the kidneys to excrete.

Factors affecting metabolism

Age, liver/kidney function, depot binding, enzyme induction, and other medications.

Metabolism too slow

Medication accumulates → ↑ drug levels → ↑ toxicity.

Metabolism too fast

Medication may be eliminated before achieving the desired effect → ↓ therapeutic effect.

Severe liver disease

Slower metabolism → medication stays in body longer → ↑ blood levels → ↑ adverse effects/toxicity → dose or frequency may need adjustment.

Depot binding

Medication binds to an inactive site and is unavailable for metabolism; may be stored in tissues and released slowly, affecting duration of action.

Enzyme induction

Increased enzyme activity can cause medications to be metabolized faster.

Biotransformation

Metabolic process primarily in the liver that helps break down medications for easier excretion.

Prodrug

Inactive when consumed → becomes active after metabolism.

First-pass metabolism

Oral medication is metabolized by the liver BEFORE reaching systemic circulation → some medication is inactivated before reaching its site of action.

First-pass pathway

Oral medication → GI tract → liver → systemic circulation.

Excretion

Removal of medication from the body; final step of pharmacokinetics.

Primary route of excretion

Kidneys.

Other routes of excretion

GI tract/feces, lungs, and skin.

Clearance

Body's ability to remove a medication.

Decreased organ function

↓ clearance → medication accumulation → ↑ toxicity.

Clearance depends on

Kidney/liver function, blood flow/circulation, and characteristics of the medication.

Excretion — nursing focus

Assess kidney/liver function; monitor creatinine + eGFR; watch for medication accumulation/toxicity; dose or interval may need adjustment.

Poor kidney function

↓ kidney function → ↓ medication excretion → ↑ medication levels → ↑ toxicity risk.

Lipid-soluble medication → excretion

Lipid-soluble drug → liver metabolism → water-soluble form → kidney excretion → urine.

Why water-soluble medications matter

Kidneys can more easily filter and eliminate water-soluble medications in urine.

Renal excretion

PRIMARY route; occurs through kidneys; water-soluble drugs excreted in urine.

Hepatic/biliary excretion

SECONDARY route; liver sends some medications into bile → intestine → may be eliminated in stool.

Kidneys vs. liver — excretion

Kidneys = remove drugs in urine; liver = changes drugs and helps remove them through bile.

Kidney/liver dysfunction

Slower clearance → drug accumulation → toxicity. Think: "If the exit is blocked, the drug builds up."

Therapeutic effect

Desired/intended effect of a medication; medication produces the expected response.

Goal of medication therapy

Desired effect WITHOUT toxicity or serious adverse effects.

Evaluating therapeutic effect

"Did the medication do what we wanted it to do—without causing harm?"

Insulin therapeutic-effect example

Hyperglycemia → insulin → blood glucose decreases; nurse checks glucose, improvement in hyperglycemia, and monitors for hypoglycemia.

Therapeutic range

Blood concentration between the lowest effective level and highest safe level.

Below therapeutic range

Medication may not work.

Within therapeutic range

Desired effect.

Above therapeutic range

↑ risk for toxicity.

Peak

Highest medication concentration in the blood; usually drawn AFTER administration.

Trough

Lowest medication concentration in the blood; usually drawn JUST BEFORE the next dose.

Random drug level

Drawn at a specified or unscheduled time to evaluate current medication concentration.

Therapeutic drug monitoring — nursing responsibility

TIMING MATTERS: know when medication was given, know when level should be drawn, coordinate administration with lab draw, review results, and monitor therapeutic effects/toxicity.

Therapeutic effect vs. therapeutic drug level

Therapeutic effect = Is the drug working? | Therapeutic drug level = Is the right amount in the bloodstream?

Gentamicin

IV antibiotic with a NARROW therapeutic range → requires close monitoring.

Gentamicin therapeutic range

5-10 mcg/mL.

Gentamicin >12 mcg/mL

↑ risk for kidney damage + hearing loss.

Gentamicin peak

Drawn ~30 minutes AFTER dose; measures highest concentration and helps determine therapeutic vs. too high/toxic.

Gentamicin trough

Drawn JUST BEFORE next dose; measures lowest concentration and determines whether enough medication remains to treat infection.

Gentamicin levels

Too low → may not treat infection | Just right → therapeutic effect | Too high → nephrotoxicity + ototoxicity.

Half-life

Time required for medication in the bloodstream to decrease by 50%.

Short half-life

Medication leaves faster → may need MORE frequent dosing.

Long half-life

Medication stays longer → may need LESS frequent dosing.

Half-life matters because it determines

How often medication is given, how long it stays in the body, how long elimination may take, and risk for accumulation/toxicity.

Factors affecting half-life

Kidney function, liver function, age, and ability to metabolize/excrete medication.

Impaired kidney/liver function & half-life

Slower clearance → LONGER half-life → medication accumulation → ↑ toxicity risk.

Half-life example

100 mg → 50 mg → 25 mg → 12.5 mg; each step = one half-life.

Blood-brain barrier (BBB)

Protects brain from harmful substances and makes it harder for some medications to reach the CNS.

Medications that cross the BBB more easily

Small + lipid-soluble (lipophilic) + able to use special transport proteins.

CNS medications

Must cross OR bypass the BBB to work.

Intranasal route

Can provide direct access to CNS and also avoids first-pass metabolism.

Intrathecal route

Medication injected directly into CSF → bypasses BBB.

Tissue permeability

How easily medication moves from bloodstream into body tissues to reach its site of action.

Easy tissues to enter

Liver + kidneys.

Hard tissue to enter

Brain/CNS because of BBB.

Poor tissue permeability

Less medication reaches target site → can affect therapeutic effect.

CYP450 enzymes

Primarily found in liver; help metabolize medications.

CYP450 enzyme INDUCER

↑ enzyme activity → ↑ metabolism → ↓ drug level → ↓ therapeutic effect.

CYP450 enzyme INHIBITOR

↓ enzyme activity → ↓ metabolism → ↑ drug level → ↑ toxicity risk.

CYP450 memory trick

INDUCER = metabolism UP → drug level DOWN | INHIBITOR = metabolism DOWN → drug level UP.

CYP450 — nursing connection

If medications affect the same CYP450 enzymes, watch for ↓ therapeutic effects or signs of toxicity.

Pharmacodynamics

How a medication works in the body and the effects it produces.

Dose-response relationship

Relationship between the dose given and the intensity of the response produced.

Increasing medication dose/concentration

Generally activates more receptors → medication effect increases → until maximum effect is reached.

Dose-response helps determine

Minimum amount needed for a response, maximum response possible, and how much the dose must increase to produce the desired increase in response.

Maximal efficacy

Largest effect a drug can produce.

Relative potency

Amount of drug that must be given to elicit an effect; usually of little clinical concern.

Receptors

Located on cells throughout the body; ligands bind to them and create a response.