Chapter 78: Pharmacokinetics Flashcards
____ is what the human body does to a drug
Pharmacokinetics
____ is what the drug does to the human body
Pharmacodynamics
Pharmacokinetics involves the study of drug ___, ___, ___ & ____
Absorption
Distribution
Metabolism
Excretion
what the body does to the drug
Absorption is not required when a drug is given ___
intravascularly
Some drugs are extensively metabolized in the liver before reaching the systemic circulation; this is called
first-pass metabolism
Some drugs are transported through the bile back to the gut where they can be reabsorbed; this is called
enterohepatic recycling
Active transport occur when:
drugs are moved across the gut wall via transporter proteins
How does drug absorption occur with oral drugs
stomach –> small intestine –> liver –> systemic circulation
What is drug disintegration
When a solid oral dosage form is ingested and breaks into smaller pieces in the GI tract
What is drug dissolution
When the smaller pieces of ingested drug are broken down and dissolve, releasing the active ingredient
Which drug formulations generally have fast absorption
SL and ODT
Rank the rate of absorption of the following formulations from fastest to slowest:
- IR
- ER
- IV
- ODT
- SL
IV > SL > ODT > IR > ER
Most IR drug formulations dissolve and get absorbed rapidly, but some can be destroyed in the gut, primarily through which chemical process
hydrolysis
Which drug formulation can limit drug degradation in the stomach (acidic) but permits dissolution in the intestine (basic)
Enteric-coated
If a drug has poor absorption, once of the methods used to increase the dissolution rate is to
reduce particle diameter, which increases surface area
Drugs with very small particle diameters for better absorption are referred to as
micronized
The rate of dissolution is described by which equation
Noyes-Whitney
The rate and extent to which a drug dissolves depends on the drug’s ___
solubility
As a drug moves through the GI tract, only ___ drug is absorbed into the bloodstream
dissolved
What is bioavailability
The extent to which a drug is absorbed into the systemic circulation or the % of drug absorbed from extravascular (e.g., oral) relative to intravascular administration (e.g., IV)
A drug with good absorption has high bioavailability ( > __%)
70
A drug with poor absorption has low bioavailability ( < __%)
10
Which two antibiotics have high bioavailability
Levofloxacin and linezolid
T/F: the oral and IV doses of Levofloxacin and linezolid are the same and nearly 100% of the oral dose is absorbed
True
When drugs are converted from IV to PO in the same dose by protocol, it is called
Therapeutic interchange
Bioavailability can be calculated using AUC (the total exposure of drug following administration). What is the equation
F (%) = 100 x (extravascular AUC/IV AUC) x (IV dose/ extravascular dose)
What is the formula to calculate an equivalent dose of a drug when the dosage form is changed
Dose of new dosage form = Amount Absorbed from Current Dosage Form / F of new dosage form
What is drug distribution
drug molecules move from systemic circulation to the various tissues and organs of the body
Factors that favor passage across membranes and greater drug distribution to the tissues:
- high lipophilicity
- low molecular weight
- unionized
- low protein binding
The primary protein responsible for drug binding
albumin
Only the ___ form of a drug can interact with receptors, exert therapeutic or toxic effects & be cleared from the body
unbound (free)
Free phenytoin and ionized calcium only measure the ____ portion, so no adjustment is required for hypoalbuminuria
unbound
With hypoalbuminemia, the corrected level of a highly protein bound drug will be ___ than the total level reported by the lab
higher
Corrected calcium formula
Ca corrected (mg/dL) = calcium (serum) + [(4 - albumin) x (0.8)]
Corrected phenytoin formula
Phenytoin corrected (mcg/mL) = total phenytoin measured / [(0.2 x albumin) + 0.1]
What is Vd
how large an area in the patient’s body the drug has distributed into
Vd formula
Vd = amount of drug in body/concentration of drug in plasma
What are the primary sites for drug metabolism
the gut and liver
Enzyme metabolism involves
Phase I reactions (oxidation, reduction, hydrolysis) & phase II reactions (conjugation)
What is excretion
irreversible removal of drugs from the body
How can you increase excretion of a weak base
acidifying the urine
How can you increase excretion of a weak acid
alkalinizing the urine
What is clearance
the rate of drug removal in a certain volume of plasma over a certain amount of time (the efficiency of drug removal from the body)
Most drug elimination occurs at a
steady state (called the rate of elimination)
Clearance formula
Cl = rate of elimination (mg/hr) / concentration (mg/L)
What is the most reliable measurement of a drug’s bioavailability
AUC
Formula for the clearance for extravascular administration
Cl = F x Dose/AUC
Formula for the clearance for IV administration
Cl = Dose/AUC
What is first-order elimination or first-order kinetics
A constant PERCENTAGE of drug is removed per unit of time (e.g., a 325 mg dose of APAP is eliminated at the same rate as a 650 mg dose)
What is zero-order elimination or zero-order kinetics
A constant AMOUNT of drug (mg) is removed per unit of time, no matter how much drug is in the body
Which drugs exhibit Michaelis-Menten kinetics (aka saturable, or non-linear kinetics)
Phenytoin, theophylline, and voriconazole
Michaelis-Menten kinetics:
At very low concentrations (much less than the Km), the rate of metabolism mimics a ____ process
first-order
Michaelis-Menten kinetics:
At most concentrations approaching and exceeding the Km, the rate of metabolism becomes ___
mixed
Michaelis-Menten kinetics:
At even higher concentrations relative to Km, the rate of metabolism approaches ___ order (e.g., Vmax)
zero
Most drugs follow ____ kinetics
first-order (linear)
In first-order kinetics, at steady state, doubling the dose approximately ___ the serum concentration
doubles
What is the elimination rate constant (ke)
Fraction of the drug that is cleared per unit of time
Ke formula
Ke = Cl/Vd
How would you interpret a ke that is 0.1 h-1
10% of the drug remaining is cleared per hour
The ke can be used to predict the concentration of a drug at any time after the dose. What is the calculation
C2 = C1 x e^(-kt) ke = [ln (C1/C2)]/t
What is the elimination half-life
The time required for the drug concentration to decrease by 50%
Formula for half-life
t1/2 = 0.693/ke
How many half-lives does it take for a drug to reach steady state
~5
__ half-lives are required to eliminate more than 95% of the drug
5
What is steady state
when the rate of drug intake = the rate of drug elimination
Loading dose formula
LD = Desired concentration x Vd / F
