Exam 1! Flashcards by Kappa Epsilon Pi Chapter

Define Pharmacokinetics

what the body does to the drug

- way to measure Cp (plasma concentration vs t)

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_______ determines the dosing interval and dosing frequency

pharmacokinetics

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what are the 4 major processes that contribute to PK

ADME

Absorption, distribution, metabolism, elimination

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IV push vs IV Infusion

IV Push/IV Bolus: one time, rapid injection into bloodstream

IV Infusion: slow “drip” into vein over set period of time to deliver a constant amount of therapy

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IV Bolus Dose Equation for PK: is ?

Cp = Cp0 e^(-kt)

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Ideas behind the one-compartment model?

well-stirred
fluid input and output rates are the same and constant
constant volume

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one-compartment model - taking sample of liquid is like taking a sample of what in the human body?

blood plasma

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After IV Bolus dose - plasma concentrations often decrease ________

exponentially

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___ is the ratio of flow rate (Q) to the volume of the compartment (V)

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how are dose, Vd and Cpo related?

dose = (Vd)(Cpo)

Cpo = dose/Vd

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Vd reflects the _________ distribution of the drug

extravascular

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Cp decreases more quickly when k is ______

large… duh elimination constant rate is large = more of the drug gone faster..

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k is __________ of drug concentration and dose

independent

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what way/equation should I use for finding k in class when given a graph/table of data? (easiest one…)

linear regression line of the natural log of Cp
eq'n: ln(Cp) = ln(Cpo) - kt
(eq'n similar to y = mx + b)
m (slope) = k
intercept = Cpo

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how many half-lives does it take for the >95% of the drug to be eliminated from the body

5 half-lives!

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For a one-compartment model with IV bolus dosing - the elimination rate constant (k) is ______ proportional related to the half-life

INVERSELY (duh - b/c k = 0.693/half life)

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if Vd gets smaller (and clearance stays the same) - how are k and 1/2 life affected

bigger k; smaller half life

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what are the two main clearance (CL) equations to know (hint they are really simple equations…)

CL = (k)(Vd)
CL = (Dose/AUC)

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Protein Binding:

Free (or Unbound drug!) are able to do “3 special things” that bound drugs can’t do…. what are those 3 activities

free drugs CAN:

exit capillaries to reach extravascular sites of action
be filtered by kidney
be metabolized by liver

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can drug bound to protein cross the capillary wall?

NOPE!

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what are the 3 major proteins that bind to drugs

albumin; a1-acid glycoprotein; lipoproteins

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why don’t we worry about the binding rates for protein binding to drugs?

rate of binding/unbinding is SOO fast - don’t worry about it;

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what is the fraction unbound (fu) equation

free drug/total drug

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what kind of drugs does albumin bind to?

weakly acidic drugs, hormones, free fatty acids

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which protein (for protein binding) is the most abundant plasma protein

albumin

a1-acid glycoprotein aka ________ aka ______

AAG; orosomucoid

a1-acid glycoprotein primarily binds to what kind of drugs?

weakly basic drugs

what notable disease states will affect albumin levels

liver and kidney

what notable disease states will affect a1-acid glycoprotein levels

- pregnancy - burns - HIV

Lipoprotein examples

HDL and LDL...

what kind of drugs does lipoprotein bind to?

lipophillic/hydrophobic ones, duh

what disease states may affect lipoproteins

heart disease

what are the metabolic process phases in the Liver

Phase 1 and 2

what metabolic process occur in phase 1 in the liver

oxidation; reduction; cyclization; CYPs

what metabolic process occur in phase 2 in the liver

glucuronidation; acetylation; conjugation

for most drugs, the _____ is the major site of metabolism

LIVER

blood goes back to the heart from the liver via _______

inferior vena cava

2 main blood supplies of the liver

portal vein and hepatic artery

portal vein brings blood to liver from

spleen, pancrease, intestines

blood supplies to the liver - difference in content for portal vein or hepatic artery

portal - nutrient rich/O2 poor | hepatic - O2 rich/ nutrient poor

what is the functional unit of the liver

lobule

E = Hepatic extraction ratio - what is the definition of E?

E is the amount of drug that entered the liver but was removed by metabolism

what are the units for E? (hepatic extraction ratio)

there are none!

Clearance of Liver - is related to E (hepatic extraction ratio) how?

Cl(h) = Q x E

High E Drugs - what effects it most? Q, Cl(h), E?

Q - blood flow (bc/ Cl(int) and f(u) soooo large that they are excluded from the Cl(h) equation) aka rate limiting step controls it all

Low E Drugs - what effects it most? Q, Cl(int), f(u)?

Cl(int), f(u); (bc/ Q soooo large that it is excluded from the Cl(h) equation) aka rate limiting step controls it all

What is the normal hepatic blood flow value?

1500 ml/min

High E drug example in class

Lidocaine

when given orally, _____ E drugs have a high hepatic first-pass effect and low oral bioavailability (F)

high

Low E drug example in class

Phenytoin

4 main renal processes of elimination

1 - glomerular filtration 2 - tubular secretion 3 - tubular reabsorption 4 - urinary excretion

is the processes passive, active, or both? | Glomerular filtration

passive

is the processes passive, active, or both? | tubular secretion

both

is the processes passive, active, or both? | tubular reabsorption

both

is the processes passive, active, or both? | urinary excretion

passive

Glomerular filtration Rate (GFR) is typically about ________ mL/min

120-125

Glomerular Filtration: uni- or bi- directional

Uni!

Glomerular Filtration: | can ionized drugs be filtered?

yes

Glomerular Filtration: | can unionized drugs be filtered?

yes

Glomerular Filtration: | mostly (small or large) molecules can be filtered (approx size?)

small! < 500 Da

Glomerular Filtration: | can protein bound drugs be filtered?

no!

Glomerular Filtration: | can protein drugs be filtered?

Ionization state of drug in renal tubule is determined on what two things?

Urine pH; Drug pKa

Passive reabsorption of a drug in renal system is more likely to happen if the drug is _______

unionized

Arterial blood flow rate to kidney is _____ mL/min

1000

Typical urine flow rate?

1 mL/min

If the renal clearance is < 125 mL/min....what does that be about net tubular action?

low number = low clearance = more (net) REABSORPTION!

If the renal clearance is > 125 mL/min....what does that be about net tubular action?

high number = high clearance = more (net) SECRETION

how is the lithium's renal clearance interesting? (has a pretty low clearance rate - why?)

it is charged - like sodium - it gets reabsorbed in the renal tubule (like sodium gets reabsorbed)

If a drug is REabsorbed renally - how does that affect half life

increases it (duh)

why does metformin have such a large clearance? (talking about renally)

a lot of metformin gets secreted to the renal tubule and none of it gets reabsorbed...

If a drug is metabolized by the liver and has a clearance value close to 1500 mL/min (aka close to the blood flow the liver) the drug is (low or high E)?

high E!