Lecture 1 pharmacokinetics Flashcards
What is Bioavailabilty (F)?
- % of medication that reaches systemic circulation
- IV drugs have a 100% bioavailability
Digoxin tablet: F=0.7
Digoxin elixir F= 0.8
Currently taking 250mcg of tablet. How much elixir is equivalent?
- New dose= (F old med x current dose)/F new med
(0. 7 x 250mcg)/0.8= 218.75 mcg of elixir.
Levothyroxine: Oral tablet bioavailability = 50% PO dose= 100mcg, then IV dose= ?
50mcg
New dose= (F old med x current dose)/F new med
IV dose = (.5 x 100mcg)/ 1 [IV drugs have 100% bioavailabiltiy]
IV dose =50 mcg
List what factors influence a drug’s bioavailibility.
-dissolution and absorption characteristics
-Route (IV vs PO, IM)
-Stability in GI tract
Metabolism prior to blood stream (first pass of the liver)
First Pass Metabolism is:
The vessels that absorb nutrients, fluids and medications from the GI tract take blood directly to the liver for detoxification before joining into general venous circulation back to the heart.
-90% of oral medication is metabolized and destroyed by the liver before it gets into the general circulation.
T/F: only oral medications participate in first pass metabolism in the liver.
True
Loading dose = Vd x Cd
Vd=Volume distribution
Cd=Concentration desired.
Calculate the loading dose of vancomycin (Vd=0.7L/kg) for a 70kg patient. Desired concentration = 30mg/L.
0.7Lx30mgx70kg=1470, round to 1500mg of Vancomycin
Protein binding:
T/F: only drugs bound to albumin are “active”
False.
unbound/free drug = active.
low albumin=more free drug and vice versa.
Acidic drugs bind to Albumin
Basic drugs bind to alpha 1 acidic glycoprotein.
T/F: the fetus is exposed to nearly all medications a mother takes.
True
_____ is the reservoir for lipid soluble drugs
Fat, adipose tissue (3rd compartment)
____ is a family of transporter proteins that are found all over the body including the blood-brain-barrier. Important for medication interactions and drug resistance
P-glycoproteins
Does passive diffusion require a carrier or energy?
Neither.
Passive diffusion O2 or CO2 exchange
T/F: Facilitated diffusion uses a carrier and energy.
False, a carrier only. No energy is expended.
Which one uses both a carrier and energy for transport?
Aqueous Channels
or
Active Transport?
Active Transport.
Aqueous Channels do not use carriers or energy. (electrolytes)
Metabolite:
Anything other than the original drug. The resultant compound after any stage of metabolism
T/F: A prodrug is any substance that enhances the effect of a drug on the body.
False: prodrug = active metabolites.
CYP450 Inhibition=
Will inhibit the enzyme from working properly and DECREASE the rate of elimination of a drug causing more of the drug to remain active.
CYP450 Induction=
Will enhance the capability of the enzyme and therefore accelerate the rate of drug metabolism. May need to redose sooner.
Name some factors that affect drug metabolism
- Genetics
- Environmental and diet (however no convincing data for diet- per Emily)
- Disease factors (Liver/kidney)
- Age and sex (not until age 17 do people have full CYP Enzyme Array)
____ is/are the major organ of drug excretion.
The kidneys
____is/are the major organ of drug metabolism and manufacturer of CYP enzymes.
The Liver
To be eliminated/excreted through the kidneys, a drug needs to be _____.
- polar (charged ions)/hydrophillic
- small
In First order kinetics for drug elimination, the length of half-life is ________.
Constant.
- Elimination is a constant percentage of the remaining med at each interval. (ex. 10% of the remainder at each half-live).
- Graph has a rounded curve.
In Zero order kinetics for drug elimination, the length of the half-life ______.
Decreases as the concentration decreases (each subsequent half life is shorter).
- Constant amount is eliminated each time. (10 units is eliminated at each interval)
- straight line slope
- Zero order kinetics is more common.
Elimination rate (k): fraction or % of the total amount of drug in the body removed per unit of time.
k=Cl/V
Cl=clearance
V=Volume
Natural log=ln
k=ln(C1-C2)/Time
t1/2 = 0.693/k
t=ln (C1-C2)/k
FYI. Know these for calculating half-lives.
It takes _____ half-lives to reach steady state.
5
One sample drawn at 1100am = 13.5mg/L. The second sample drawn at 1600 = 5.8mg/L. K=? t1/2=?
ln(13.5-5.8)/5 hours
ln7.7/5
k=0.408
t1/2=0.693 (0.408)
t1/2=1.7 hour half life
A medication is toxic at 55mg/L. Toxicity happens at concentrations >35mg/L. k=0.12. How long until the patient is below toxic concentrations?
t1/2=0.693(0.12)
t1/2=5.6 hour half life
t=ln(55-35)/0.12
t=ln20/0.12
t=2.99/0.12
t=24.96 rounded to 25 hours to non toxic level.
Pharmacokinetics is:
described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion.
