Pharmacokinetics Flashcards
Absorption
the process of moving a drug into the bloodstream so it can reach its target
Intravenous delivery
dependable, immediate systemic circ delivery, can be traumatic
Intramuscular delivery
good and somewhat rapid absorption, can cause bruising, absorption can be unpredictable
Subcutaneous delivery
delivered below epidermis/dermis, good and somewhat rapid absorption, can cause bruising, absorption can be unpredictable
Oral delivery
easy, less predictable absorption, relatively slow onset
Topical delivery
easy, non-invasive, very slow absorption
Respiratory delivery
very rapid absorption, can minimize systemic effects, bioavailability is dependent upon owner’s technique and particle size
Suppository delivery
good absorption, avoids first pass metabolism, unpleasant delivery
Epidural delivery
regional and immediate block, requires technical proficiency
Most drugs diffuse by what process?
simple passive diffusion
Fenestrations
small openings
Pinocytosis
“cell drinking,” small particles brought into the cell through invaginations
Carrier-mediated transport
Active transport and facilitated diffusion
Active transport
requires energy to transport substance
Facilitated diffusion
no energy required, transported down concentration gradient
What type of cells provide additional protection against drugs passing through the blood brain barrier?
glial cells (e.g. astrocytes)
Fick’s Law of Diffusion
the rate of drug passage across membranes is proportional to its concentration gradient, diffusion coefficient, and lipid/water partition coefficient
V’ = D * A * deltaC/T
V’ = rate of diffusion across permeable membrane
D = diffusion coefficient of drug
A = surface area of membrane
delta C = difference in concentration across membrane
T = thickness of membrane
Ionization
process by which a neutral molecule splits into charged ions when exposed in a solution
Membranes are more/less permeable to nonionized/ionized forms of a drug
more; nonionized (lipid soluble)
The amount of drug in the ionized form is dependent on what two factors?
pKa and pH on either side of the membrane; when pH of the medium = pKa, the drug exists in 50% ionized form and 50% unionized form
pKa
negative logarithm of acidic dissociation constant
Henderson-Hasselbalch equation
describes the ratio of ionized to nonionized drug; determines the proportion of a substance that is ionized at any given pH
pH = pKa + log[A-]/[HA]
nonionized form = lipid soluble
ionized form = water soluble
Weakly acidic drugs are ionized at what type of pH?
alkaline - will be less lipid soluble
acidic drugs (e.g. barbiturates, aspirin) are better absorbed in acidic environments (b/c nonionized)
Weakly basic drugs are ionized at what type of pH?
acidic (will be less lipid soluble)
basic drugs (e.g. opioids) are better absorbed in basic environments (b/c nonionized)
Two properties of the ionization of a drug
- it is pH-dependent
- it determines its lipid solubility
Ion trapping
if there is a difference in pH between two compartments separated by a membrane, weak acids will accumulate in a basic compartment and weak bases in an acidic compartment; drug trapped on side of membrane with higher ionization
Functional groups of drugs determine whether acidic or basic
Amine - basic
Carboxylic acid - acidic
Factors affecting absorption
- molecule size of drug (small >>> absorption)
- particle size (> 1 molecule); larger <<< absorption
- physical form of drug - gas >>> absorption
- area of absorptive surface
- greater vascularity = greater absorption
The major driving force for drugs to move into the vasculature is _________
the concentration gradient of the (unbound) soluble drug
