Module 3 Pharm Kinetics and Dynamics

What is the difference between intended (therapeutic) and unintended therapeutic effects?

Intended effects are desired (e.g., diphenhydramine blocks histamine → allergy relief). Unintended effects occur in non-target cells (e.g., diphenhydramine crosses BBB → drowsiness).

What are common side effects of opioids?

Respiratory depression (life-threatening), confusion, euphoria, hypotension, bradycardia, itching, urinary retention, constipation.

What is drug absorption?

The process of drug movement from site of administration into the bloodstream. Drugs must be in solution to be absorbed.

How can drugs cross the cell membrane?

Passive diffusion, facilitated diffusion, active transport, or pinocytosis (rare).

What form of drug crosses membranes by passive diffusion?

Non-ionized (lipid-soluble) form crosses easily; ionized (charged, water-soluble) form needs facilitated diffusion or active transport.

What factors impact drug absorption?

Drug formulation (liquid faster than tablet), dose (higher dose faster), route (IV fastest), size (small faster), surface area (large faster), digestive motility, blood flow, lipid solubility, ionization, food/drug interactions.

Which route of administration works fastest?

IV → drug directly into bloodstream (no membranes crossed).

What is the main factor influencing drug distribution?

Amount of blood flow to tissues.

Which organs receive the most blood flow?

Kidneys, brain, GI tract, skeletal muscle.

What are signs of hypoperfusion (low blood flow)?

Organ dysfunction (confusion from low brain perfusion, decreased urine output from kidney hypoperfusion, fatigue, poor healing).

What is blood made of (simplified)?

Plasma (water, proteins), blood cells (RBCs, WBCs, platelets).

What carries drugs in the blood?

Plasma proteins (albumin most abundant). Only unbound (free) drug can leave vessels and act on tissues.

What is drug displacement?

When one drug displaces another from protein binding → ↑ free drug → ↑ effect/toxicity.

What organ is primary site of drug metabolism?

Liver (others: GI tract, lungs, skin).

What is the CYP450 system?

Hepatic microsomal enzymes that metabolize drugs; can be induced (↑ metabolism) or inhibited (↓ metabolism) → major source of drug interactions.

What is the first-pass effect?

Drugs absorbed from GI go through liver first; liver metabolizes some drug before reaching systemic circulation → lowers bioavailability.

What is the primary site of drug excretion?

Kidneys (via urine).

Which substances are easily excreted?

Free drugs, water-soluble agents, electrolytes, small molecules.

If patient has little/no urine output, how does that affect drug excretion?

Excretion impaired → drug accumulates → requires lower doses/less frequent dosing.

What labs assess renal function?

BUN (normal 5–20), creatinine (normal <1.3). Rising creatinine = declining kidney function.

What labs assess liver function?

ALT, AST, ALP, bilirubin.

What does rising creatinine indicate?

Decreasing kidney function; drug clearance impaired → higher risk of toxicity.

What is biliary excretion?

Drug secreted in bile → feces. Problem: bile recirculated (enterohepatic recirculation) → drug action prolonged.

What are signs of renal failure?

Fluid overload (edema, HTN, JVD, crackles), electrolyte buildup (↑K, ↑Phos, ↑Mg, ↓Ca), ↓urine (oliguria, anuria), metabolic acidosis, proteinuria, anemia, uremia.

What are signs of liver failure?

Jaundice, ↑liver enzymes, ↑bilirubin, fatigue, N/V, steatorrhea, clay stools, ascites, encephalopathy (confusion, asterixis), coagulopathy (bleeding), portal hypertension.

What is minimum effective concentration?

Lowest drug level that produces therapeutic effect.

What is toxic concentration?

Level of drug causing serious adverse effects.

What is therapeutic range?

Plasma drug concentration between minimum effective and toxic levels.

What is onset of action?

Time required to produce a therapeutic effect.

What is duration of action?

How long the drug maintains its therapeutic effect.

What is half-life?

Time for drug concentration to drop by 50%. Determines dosing frequency.

What is ED50?

Median effective dose; dose that produces therapeutic effect in 50% of population.

What is LD50?

Median lethal dose; dose lethal to 50% of animals in studies.

What is TD50?

Median toxicity dose; dose toxic in 50% of patients.

What is therapeutic index (TI)?

Measure of drug safety margin = LD50 ÷ ED50. Higher TI = safer drug.

Which drug is safer: TI of 10 or TI of 2?

TI of 10 (wider safety margin).

What is drug potency?

Amount of drug needed to produce a given effect. Lower dose needed = more potent.

What is drug efficacy?

Maximum effect a drug can produce, regardless of dose.

What is pharmacodynamics?

How a drug changes the body; relationship between concentration and effect.

What factors affect dose response?

Body mass, age, sex, genetics, biorhythms, receptor density, second messengers.

What is an agonist?

Drug that binds and activates a receptor (e.g., albuterol binds β2 receptors → bronchodilation).

What is an antagonist?

Drug that binds to receptor but blocks activation (e.g., naloxone blocks opioid receptors).

What is a competitive antagonist?

Reversibly binds to receptor; can be overcome by more agonist.

What is a noncompetitive antagonist?

Irreversibly binds receptor; effect cannot be reversed by more agonist.

Example of partial agonist?

Buprenorphine (Suboxone) → activates opioid receptors partially; weaker effect than full agonist.

What is norepinephrine’s effect on receptors?

Binds α receptors in arteries (vasoconstriction ↑BP) and β receptors in lungs (bronchodilation).