Test 1 Study Guide
Pharmacokinetics / Pharmacodynamics- you do NOT have to do any calculations!
e 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
Pharmacodynamics: studies the actions of the chemical (drug) on the organism —
what the drug does to the body
Toxicology: branch of pharmacology that deals with the undesirable effects of
chemicals on living systems
Pharmacogenomics: genetic variations that cause differences in drug response
among individuals/populations
Prodrug: inactive precursor chemical that must be absorbed, distributed, and
converted to active form of drug
e 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
e 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
e Know what factors impact drug absorption
o Typically weak acids or weak bases
= Smaller size - easier to cross membranes
Solubility
o
Blood flow — intestinal blood flow greater than stomach
o
pH — especially with H2 antagonists and PPI
o
contact time with absorptive surface
o
= rapid vs slow Gl 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...
e First pass metabolism
e Solubility
e Chemical instabililty
e Nature of drug formulation
o First pass (hepatic) metabolism
= Drug absorbed across Gl tract = enter portal circulation and is filtered
through liver PRIOR to systemic circulation (body)
e 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
e Higher blood flow in the heart, brain, lungs, liver, kidney, gut
e 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
e Not found in blood brain barrier
Chemical properties of drugs that affect absorption and distribution
o Solubility
= Hydrophilic (lipophobic)
e 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
e 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!!! lonized 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
Extreme hydrophobic drugs = poorly absorbed r/t insoluble in aqueous body
fluids
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
Active transport: energy-dependent — move drug from lower to higher
concentration
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
Pharmacokinetics / Pharmacodynamics- you do NOT have to do any calculations!
e 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
Pharmacodynamics: studies the actions of the chemical (drug) on the organism —
what the drug does to the body
Toxicology: branch of pharmacology that deals with the undesirable effects of
chemicals on living systems
Pharmacogenomics: genetic variations that cause differences in drug response
among individuals/populations
Prodrug: inactive precursor chemical that must be absorbed, distributed, and
converted to active form of drug
e 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
e 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
e Know what factors impact drug absorption
o Typically weak acids or weak bases
= Smaller size - easier to cross membranes
Solubility
o
Blood flow — intestinal blood flow greater than stomach
o
pH — especially with H2 antagonists and PPI
o
contact time with absorptive surface
o
= rapid vs slow Gl 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...
e First pass metabolism
e Solubility
e Chemical instabililty
e Nature of drug formulation
o First pass (hepatic) metabolism
= Drug absorbed across Gl tract = enter portal circulation and is filtered
through liver PRIOR to systemic circulation (body)
e 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
e Higher blood flow in the heart, brain, lungs, liver, kidney, gut
e 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
e Not found in blood brain barrier
Chemical properties of drugs that affect absorption and distribution
o Solubility
= Hydrophilic (lipophobic)
e 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
e 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!!! lonized 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
Extreme hydrophobic drugs = poorly absorbed r/t insoluble in aqueous body
fluids
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
Active transport: energy-dependent — move drug from lower to higher
concentration
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
