Overview of Clinical Pharmacokinetics

how does lipophilicity affect Vd (volume of distribution)

• increase lipophilicity = increase Vd

  • increase distribution outside of drug space

ADME is a part of

a) pharmacokinetics

b) pharmacodynamics

a) pharmacokinetics

active drug → active metabolite is…

a) phase 1 metabolism

b) phase 2 metabolism

a) phase 1 metabolism

active drug → inactive metabolite is…

a) phase 1 metabolism

b) phase 2 metabolism

b) phase 2 metabolism

what the drug does to your body (i.e. receptor binding) is

a) pharmacokinetics

b) pharmacodynamics

b) pharmacodynamics

how does a chronic agonist affect the body?

• decrease # of receptors

• alter receptor conformation to decrease receptor binding

how does a chronic antagonist affect the body?

• increase # of receptors

• alter receptor conformation to increase receptor binding

full absorption is nearly complete after 1-2 hours except for ________

• SR/DR/ER products

fraction of unchanged drug that reaches the systemic circulation after administration is ….

• bioavailability (F)

amount of active drug in dosage from given is…

• salt fraction

list the factors that can affect bioavailability

• dosage form

• route of administration

• gut perfusion (oral only)

• gut function (oral only)

• presystemic extraction

how does rapid GI transit time effect SR & ER formulations

• decreases bioavailability

  • slow releasing formulations are being digested more than being released into systemic circulation

how does gut perfusion affect absorption

• decreased perfusion = decreased absorption

how does gut function affect absorption

• increased GI transit time (i.e. diarrhea) = decreased absorption

• decreased GI transit time (i.e. constipation) = increased absorption

way(s) to determine if the gut functioning is….

• administer a dose of a medication and check drug concentration

  • ex. acetaminophen → good absorption = good GI function

• check for gastric residual volume (suction back contents of stomach)

  • higher volumes than expected = decreased GI function

drug metabolism/elimination that occurs before the drug reaches the systemic circulation is….

a) presystemic extraction

b) bioavailability

c) first-pass effect

d) salt fraction

a) presystemic extraction

clearance of a drug in liver before systemic circulation is ….

a) presystemic extraction

b) bioavailability

c) first-pass effect

d) salt fraction

c) first-pass effect

T/F: increased lipophilicity is more likely for a drug to be 1 compartment

• false

  • increased lipophilicity= increased distribution = increased chance for 2 compartment

central compartment includes…

• blood volume + rapidly perfused organs (i.e. brain, heart, lungs, liver)

T/F: only free drug is available for therapeutic effect/ movement into tissue

• true

fu (fraction of drug that is unbound) typically does NOT vary with _______

a) plasma protein concentrations

b) drug concentration

c) both of the above

b) drug concentration

how does low plasma protein contractions affect fu?

a) typically does not affect fu

b) decrease fu

c) increase fu

c) increase fu

• low plasma protein = decreased bound = increased fu

how does low plasma protein contractions affect free concentration?

a) typically does not free concentration/ unbound

b) decrease free concentration/ unbound

c) increase free concentration/ unbound

a) typically does not free concentration/ unbound

binding affinity can be affected by what 2 factors?

• pH changes (conformation changes)

• uremia (displacement)

what is considered a highly bound drug?

• fu </= 0.2

relative increase in fu correlates with..

a) highly protein bound drug

b) hydrophilic drugs

a) highly protein bound drug

no elimination occurs in the..

a) first compartment

b) second compartment

b) second compartment

alpha half-life

• time to complete distribution x 3-5

beta half-life

• offset of effect, clearance, steady state x 3-5

T/F: a drug that has been metabolized will always have been made inactive or less toxic

• false

  • not always (i.e. prodrugs / phase 1 metabolism)

only ___ drug will be metabolized

free

how does polarity of a drug affect metabolism

• increased polarity = decreased metabolism (decrease hepatocyte entering)

• increased polarity = increased elimination WITHOUT metabolism

how does highly plasma protein bound drugs affect metabolism

• increased PPB = decreased chance for fast rate of metabolism

the intrinsic ability of the body to remove drug from the blood is known as ______

• clearance

amount of drug removed depends on what 2 factors?

1. plasma concentration

2. clearance

how does extraction ratio affect clearance?

• increased extraction ratio = increased liver ability = increased clearance

SATA: what factors can increase Vd?

a) lipophilic

b) hydrophilic

c) high PPB

d) low PPB

a) lipophilic

d) low PPB

SATA: what factors can decrease Vd?

a) lipophilic

b) hydrophilic

c) high PPB

d) low PPB

b) hydrophilic

c) high PPB

what can be given to a patient to help shorten time to steady state? (faster onset of effect)

• give a loading dose

the fraction of the total amount of drug removed per unit of time is known as the ______

elimination rate constant (K_e)

increasing clearance will (increase/decrease) K_e, while

increasing V_d will (increase/decrease) K_e

• increase clearance = increase k_e

• increase V_d = decrease k_e

T/F: half-life is determined by clearance and volume of distribution

• true

increasing clearance will (increase/decrease) t_1/2, while

increasing V_d will (increase/decrease) t_1/2

increase clearance = decrease t_1/2

increase V_d = increase t_1/2

assume that steady state is reached after ____ to ____ half-lives

3-5

how can you tell steady state on a graph?

• the point at which the peak & trough concentrations are interchangeable

when the (% drug cleared) / (time) does NOT change with drug concentration, it is

a) zero order

b) first order

c) michaelis-mention

b) first order

when the (amount of drug cleared) / (time) does NOT change with drug concentration, it is

a) zero order

b) first order

c) michaelis-mention

a) zero order

which of the following has a straight line on a logarithmic graph of plasma drug concentration vs time

a) zero order

b) first order

c) michaelis-mention

b) first order

what can be found from the slope of a first order reaction on a log-transitioned graph? (straight line)

• K_e = slope of the line

assume that offset occurs after ____ to ___ half lives after discontinuation

• 3-5

drug exposure during the dosing interval is also known as ______

• AUC

for first order reactions, how does absorption and clearance affect AUC?

• increased absorption = increased AUC

• increased clearance = decreased AUC

which of the following medication formulations would have the fastest time to peak concentration after a single dose is given?

a) subcutaneous injection

b) intramuscular injection by rapid push

c) Intravenous injection by rapid push

d) transdermal patch

c) Intravenous injection by rapid push

when considering chronic administration of a pharmacological agonist, which of the following is true?

a) may result in toxicity

b) may result in receptor upregulation

c) may result in increased therapeutic effect

d) may result in decreased binding affinity

d) may result in decreased binding affinity

which of the following factors is typically associated with a greater volume of distribution?

a) high hydrophilicity

b) high plasma protein binding

c) high lipophilicity

d) extensive first pass metabolism

c) high lipophilicity

which of the following factors or patient characteristics would most likely ncrease the volume of distribution for a drug with a Vd of 3L?

a) gastric bypass surgery

b) obesity

c) kidney disease

d) administration of large volumes of IV fluids

d) administration of large volumes of IV fluids