PK/PD Flashcards
What is zero order kinetics?
Rate of drug elimination is INDEPENDENT of concentration…Same amount is eliminated per hour. (Very few drugs - ASA, ethanol, phenytoin…)
What is first order kinetics?
Rate of drug elimination is DEPENDENT on concentration…half lifes. (most drugs)
What is therapeutic index?
The desired range of drug concentration. Calculated - Lethal dose for 50% (LD)/Effective dose for 50% (ED)
Which drugs require TDM for narrow TI?
Lithium, digoxin and carbamazepine
What are some drugs that require TDM for SE/ADRs?
Phenobarbital, Vancomycin, Aminoglycosides, Dilantin, Flucytosine
What is pharmacokinetics?
The study of the ACTION of the drug in the body (Absorption, Distribution, Metabolism, Elimination)
What is pharmacodynamics?
The study of the drug’s EFFECT on the biochemical and physiological functions of the body.
What is absorption?
How much of the drug and how fast it leaves the site of administration. Described as “bioavailability” or “F”. (F 1.0=100%)
What is bioequivalence?
Where two drugs have the same active ingredients, identical in strength, dosage form, route of administration AND F.
What are the efflux transporters?
Pgb, MRP2, BCRP
What are the influx transporters?
OATP, PEPT, OAT/OCT
Antacids can cause a DDI with which meds?
Itraconazole (capsules), ketoconazole, posaconazole, atazanavir, dasatinb, erlotinib and Fe. (All need an acid environment.)
Digoxin can cause a DDI with which med?
Amiodarone (Cordarone) because it inhibits the movement of Digoxin into the circulation and can cause toxicity.
Fluorquinolones, tetracycline and levothyroxine can cause a DDI with which di- or tri-valent cations?
Ca++, Fe++, Mg++ and Al+++ (Counsel - give supplements 2 hours pre or post or it will effect bioavailability.)
What happens in the first phase of distribution?
Drug moves from site of administration to blood.
What happens in the second phase of distribution?
Drug moves from the blood to tissue.
What is volume of distribution (Vd)?
The estimated volume (size of compartment) needed to account for the total volume of drug in the body if it were the same concentration throughout.
Which drugs typically have a low Vd?
water soluble drugs (stay in blood)
Which drugs typically have a high Vd?
lipophilic drugs (distribute to tissue)
What happens in Phase I metabolism?
oxidation/reduction via an enzyme system (primarily CYP450). Enzymes give a functional group to prepare the drug for Phase II.
What is the most common CYP450 (Phase I) enzyme?
CYP3A4 (36% of meds)
Which drug is of concern in 2C9 polymorphism?
Warfarin
What is a genetic polymorphism?
The patient’s enzyme is changed and drug concentration can go up because the drug does not recognize it for binding.
What happens in Phase II metabolism?
Conjugation reactions (by nonmicrosomal enzymes)add a compound to the drug to make it more hydrophilic.
What are the Phase II enzymes?
UGT (most common), SALT, NAT, MT enzymes
What influences drug elimination from breastmilk?
Lipid solubility
Plasma concentration
MW (>500 favors elimination)
Protein binding (lower protein bound are “free” in plasma and more readily eliminated)
Estimates of GFR
CrCl using Cockcroft-Gault (adults)
24 hours urine
Cockcroft-Gault Equation (CrCl)
[(140-age) x kg]/72 x Cr = ml/min (then, multiply x 0.85 if female)
What is a normal CrCl for males?
> 120 ml/min
What is a normal CrCl for females?
> 110 ml/min
CrCl - use actual body weight or IBW?
If underweight or NOT >20% over IBW, use actual weight. If >20% over IBW, use a range of IBW-actual.
Formula: IBW (males)
50 + 2.3 (inches > 60)
Formula: IBW (females)
45.5 + 2.3 (inches > 60)
CrCl - consideration if >65 yrs, thin or frail and Cr < 1.0
use Cr=1.0
“Order” for CrCl calculation
- kg, height, age, male/female, Cr
- lbs –> kg
- Calc IBW using height
- Is actual body weight >20% over IBW? If so, calculate ABW.
- Ask, “Cr <1.0. older than 65 and thin/frail? Use Cr=1.0
Plug in numbers to equation. - If female, multiply x 0.85
Formula: ABW
[(Actual body weight - IBW) x 0.4] + IBW
A strong inhibitor increases AUC by how much?
5x (can cause toxicity!)
A moderate inhibitor increase AUC by how much?
2x
A weak inhibitor increases AUC by how much?
1.25-<2
