Pharmacokinetics Flashcards
Difference between PK and PD?
PK: what the body does to a drug
PD: what the drug does to the body
Components of PK
Absorption
Distribution
Metabolism
Excretion
What happens in passive distribution?
Movement of drugs from area of high concentration to low concentration
What happens in active transport?
Drugs are moved across the gut wall via transporter proteins - requires energy
Drug absorption pathway when given orally vs IV
Oral –> stomach –> small intestine –> hepatic portal vein –> liver –> systemic circulation
IV –> systemic circulation
Disintegration vs dissolution
During which is the active ingredient released?
Disintegration - when a drug is broken into smaller pieces
Dissolution - when a drug dissolves; this is when active ingredient is released
Dosage forms fastest to slowest rate of absorption
IV SL ODT IR tablet ER tablet
What is a “micronized” medication? What is the benefit?
Drug with very small particle diameters
Increased dissolution rates over other oral formulations of the same drug
What is bioavailability?
The extent to which a drug is absorbed into the systemic circulation
What is considered a high bioavailability?
70% or higher
What is considered a low bioavailability?
10% or lower
Bioavailability calculation
100 x (AUC extravascular/AUC intravenous) x (Dose intravenous/Dosse extravascular)
What is drug distribution?
The process by which drug molecules move from systemic circulation to the various tissues and organs of the body
What factors favor greater drug distribution?
High lipophilicity
Low molecular weight
Unionized status
Low protein binding
If a medication is highly protein bound, what will make it’s distribution higher?
Low albumin (higher percentage of drug will be unbound from albumin and able to move extravascularly)
Corrected calcium formula and when not to use it
Reported calcium + [(4-albumin) x 0.8]
Do not use if measuring free calcium
Corrected phenytoin formula and when not to use it
Total phenytoin measured
(0. 2 x albumin) + 0.1
Do not use if measuring free phenytoin
Volume of distribution equation
concentration of drug in plasma
What is Volume of distribution (Vd)?
how large an area in the patient’s body the drug has distributed into
***theoretical value
What does metabolism do?
Converts original drug form into a form that can be eliminated
Facilitates elimination
Primary sites for drug metabolism
Gut and liver
High levels of enzymes
What is first-pass metabolism - what effect does it have on drug concentration in the body?
Hepatic metabolism of a drug before it reaches the systemic circulation
Reduces bioavailability
What are phase 1 and phase 2 reactions involved in in enzyme metabolism?
Phase 1: oxidation, reduction, hydrolysis; makes molecule more reactive and hydrophilic
Phase 2: conjugation
What is excretion
irreversible removal of drugs from the body
How to increase excretion of a weak base through the urine? Weak acid?
Weak base - make urine more acidic
Weak acid - make urine more basic
Clearance equation
Concentration
What is first order pharmacokinetics?
Where a constant PERCENTAGE of drug is removed per unit of time
Graph is a curved line
What is zero order pharmacokinetics?
constant AMOUNT of drug is removed per unit of time, no matter how much drug is in the body
Graph is a straight line
What is Michaelis-Menten Kinetics?
saturable, non-linear Kinetics
Max rate of metabolism is Vmax
Increase in dose leads to disproportionate increase in drug concentration at steady state
Doubling the dose may lead to more than double the serum concentration
Elimination rate constant (ke) definition and equation
Fraction of drug eliminated (cleared) per unit of time
Cl
—–
Vd
Half-life (t1/2) equation
ke
How many half-lives does it take to reach steady state?
~5
How to calculate loading dose
F
