Cincinnati | Advanced Pharmacology Exam | Questions & Answers
with Complete Solution
Test 1 Study Guide
Pharmacokinetics / Pharmacodynamics- you do NOT have to do any calculations!
• Define and understand the concepts of: pharmacokinetics, pharmacodynamics,
pharmacotherapeutics, toxicology, legend drug vs OTC drug
o Pharmacokinetics: studies absorption, distribution, metabolism, and elimination
of drugs – what body does to the drug
o Pharmacodynamics: studies the actions of the chemical (drug) on the organism –
what the drug does to the body
o Toxicology: branch of pharmacology that deals with the undesirable effects of
chemicals on living systems
o Pharmacogenomics: genetic variations that cause differences in drug response
among individuals/populations
o Prodrug: inactive precursor chemical that must be absorbed, distributed, and
converted to active form of drug
• Pharmacokinetics: understand concepts of Absorption, Distribution, Metabolism,
Elimination
o ADME
▪ Absorption: entry of pharmacologic agent into plasma
▪ Distribution: leaves bloodstream and distributes to
interstitial/intracellular fluids
▪ Metabolism: must be metabolized via liver, kidney, other tissue
▪ Elimination: metabolites eliminated from body via urine, bile, feces
• Understand concepts of pharmacodynamics - Physiologic effect, Mechanism of action
o Passive diffusion = concentration gradient
o Active transport = energy dependent, move drug from lower to higher
concentration
o Endocytosis = transport large molecules by engulfment
• Know what factors impact drug absorption
o Typically weak acids or weak bases
▪ Smaller size → easier to cross membranes
o Solubility
o Blood flow – intestinal blood flow greater than stomach
o pH – especially with H2 antagonists and PPI
, o contact time with absorptive surface
▪ rapid vs slow GI transport
▪ food → delayed absorption
• Concept of bioavailability - relationship between drug route and bioavailabilty
o Bioavailability: fraction of chemically unchanged drug that reaches systemic
circulation
▪ Influenced by…
• First pass metabolism
• Solubility
• Chemical instabililty
• Nature of drug formulation
o First pass (hepatic) metabolism
▪ Drug absorbed across GI tract → enter portal circulation and is filtered
through liver PRIOR to systemic circulation (body)
• If drug has rapid hepatic metabolism in portal circulation →
decreased amount of drug enter systemic circulation
o Area under the curve (AUC): used to calculate bioavailability of a drug
• Physiologic variables in absorption and distribution
o Drug distribution-delivery: process where drug reversibly leaves bloodstream
and enters interstitium and/or cells
▪ Dependent on blood flow, cap perm, plasma protein binding, structure,
hydrophobicity
• Higher blood flow in the heart, brain, lungs, liver, kidney, gut
• Lower blood flow in skeletal muscle and adipose tissue
o Capillary permeability: dependent on capillary structure and chemical nature of
drug
▪ Variance in capillary structure: slit junctions between endothelial cells
allows passage of plasma proteins AND drug molecules
• Not found in blood brain barrier
• Chemical properties of drugs that affect absorption and distribution
o Solubility
▪ Hydrophilic (lipophobic)
• Poorly absorbed!!
▪ Lipophilic (hydrophobic) = cross membranes easier!!!
o Chemical nature – pH and pKa
o Molecular weight
o Partition coefficient
• Concept of volume of distribution (Vd)
o Volume of distribution (Vd): amount of drug in the body compared to the
concentration of drug in blood or plasma
, ▪ If Vd is large = majority of drug is not in plasma → not available to
excretory organs because more is found throughout body
▪ Factors the increase Vd
• Increased half-life
• Extended duration of action
• Blood-brain barrier
o Drugs must pass through CNS capillary endothelial cells OR be actively
transported through
o Lipid-soluble drugs penetrate CNS by dissolving in membrane of endothelial cells
o no slit junctions!!! Ionized or polar drugs cannot pass
• Hydrophilic (lipiphobic) and Lipophilic (hydrophobic)
o Hydrophilic drugs = poorly absorbed r/t not being able to cross lipid-rich
membranes
o Extreme hydrophobic drugs = poorly absorbed r/t insoluble in aqueous body
fluids
o Ideal drug
▪ very HYDROPHOBIC but with some solubility in aqueous solution
▪ highly lipid-soluble drugs transported in fluids via carrier proteins such as
albumin!!!
• Relationship of molecular weight and drug absorption
• Concept of drug transport across membranes- different modes of transport
o Passive diffusion: higher to lower concentration – concentration gradient across
a membrane
o Active transport: energy-dependent – move drug from lower to higher
concentration
o Endocytosis: transports large molecules via engulfment of molecule by cell
membrane and into the cell
• Plasma protein binding
o Generally reversible and non-selective!!
▪ Drug binds where other compounds like bilirubin would normally attach
o Plasma albumin = drug reservoir
▪ Adipose tissue also works as drug reservoir for drugs and hormones
o Class 1 drugs: majority of drugs
▪ Amount of drug < albumin binding capacity
▪ Number of binding sites > available drug (lots of binding sites)
o Class 2
▪ Amount of drug > albumin binding capacity
▪ High proportion of drug in “free” state – not protein bound
, • Factors that influence distribution
• Protein binding of a drug. “bound” vs. “free”
• Concept of first pass effect/ metabolism and how it may effect drug dose or route
o First pass Hepatic metabolism
▪ Drug absorbed in GI tract → enters portal circulation and filters through
liver → then goes to systemic circulation
• If drug undergoes rapid metabolism by liver → decreased amount
of unchanged drug enters systemic circulation!!!!
• Differentiate between Phase1 and Phase 2 metabolism.
o Phase 1: increase polarity and water solubility of the drug
o Phase 2: conjugation – increases solubilituy and facilitates excretion of the
metabolite from the body
▪ Some drugs go through both phases, some only one
o Cytochrome (CYP) P450 System: family of isoenzymes found in cells (especially
in liver and GI tract) important for metabolism of many endogenous compounds
(hormones) and biotransformation of exogenous substances (drugs)
• Drug inducers vs. drug inhibitors
o Inducers: drugs can be inducers of certain CYP isozymes – results in INCREASED
biotransformation of drug
▪ Will see decreased blood concentrations, decreased therapeutic drug
effect
o Inhibitors: inhibition of CYP isozyme activity
▪ Example: many drugs inhibit one or more biotransformation pathways of
warfarin (omeprazole inhibits THREE)
• Difference between Zero order and linear (first order) elimination kinetics
o First order kinetics – most drugs
▪ Metabolic transformation of drugs by enzymes
▪ Rate is directly proportional to concentration of free drug, CONSTANT
FRACTION of drug per unit of time
• Each half life cuts drug concentration by 50%
o At 2 half-lives, its at 75% removed. At 5 half-lives, drug is
basically removed from body.
o Zero order kinetics
▪ Rate of metabolism is constant over time – CONSTANT AMOUNT
of drug metabolized per unit of time