Chapter 4: Pharmacokinetics Flashcards
Pharmacokinetics
the study of drug movement throughout the body
drugs usually pass through
cells
- because they are too large to pass through channels or pores
most drugs lack
transport systems
what is the general rule in chemistry
“like dissolves like”
Cell membranes are composed primarily of lipids; therefore to directly penetrate membranes, a drug must be _________
lipid soluable (lipophilic)
examples of polar molecules and ions
- quaternary ammonium compounds, pH dependent ionization, pH partitioning
three ways to cross a cell membrane
- channels and pores
- transport systems (p glycoprotein)
- direct penetration
p glycoprotein
transmembrane protein that transports a wide variety of drugs out of the cell
liver
transports drugs into bile for elimination
kideney
pumps drugs into the ursine for excretion
placenta
transports drugs back into the maternal blood
brain
pumps drugs into the blood to limit drugs access to the brain
direct penetration of the membrane
- polar molecules dissolve in polar solvent
- most ions are unable to
absorption
movement of a drug from its site of administration into the blood
rate of absorption determines
how soon the effects will begin
amount of absorption help determine
how intense the effects will be
5 factors affecting drug absorption
- rate of dissolution
- surface area
- bllod flow
- lipid solubility
- pH partitioning
Intravenous (parenteral)
- barrier to absorption:
-absorption pattern:
- Advantages:
- disadvantages
- barrier to absorption: none
-absorption pattern: instant and complete - Advantages: quick, large volume, control, irritants
- disadvantages: cost, fluid overload, error
intramuscular
- barrier to absorption:
-absorption pattern:
- Advantages:
- disadvantages
- barrier to absorption: nothing significant
-absorption pattern: variable (solubility/blood flow) - Advantages: depot, good fro poorly soluble drugs
- disadvantages: discomfort, inconvenience
Oral (enteral)
- barrier to absorption:
-absorption pattern:
- Advantages:
- disadvantages
- barrier to absorption: stomach or intestine epithelial cells and capillary walls
-absorption pattern: highly variable (drug solubility and stability, food, other drugs, GI, pH, gastric emptying, coatings, ect.) - Advantages: easy, convient, safe
- disadvantages: variability, inactivation, swallowing (client, local irritation
Subcutaneous
- barrier to absorption:
-absorption pattern:
- barrier to absorption: no significant
-absorption pattern: similar to IM administration
distribution
movement of drugs through the body
drug distribution is determined by which three factors
- blood flow to tissues
- exiting the vascular system
- entering cells
blood flow determines
the rate of delivery
how do abscesses and effect blood flow
- soild tumors have limited blood supply
Blood Brain barrier
thight junctions between the cells that comprise the walls of most capillaries in the central nervous system
only drugs that are __________ or that habe a ________ can cross the blood brain barrier to a significant degree
lipid soluble
transport system
risk with placental drug transfer
brith defects: gross malformations, low birth rate, drug dependent baby, ect.
what is the most abundant and important plasma protein
albumin
albumin levels in the body influence
drug distribution
albumin
- large molecule that always remains in the bloodstream
- affects drug distribution
- ” protein binding” important factor in pharmacokinetics
drug metabolism is also known as
biotransformation
drug metabolism
defined as the chemical alteration of drug structure
drug metabolism most often takes place in the
liver (Cytochrome P450 system)
5 therapeutic consequences of drug metabolism
- accelerated renal drug excretion
- drug inactivation
- increased therapeutic action
- activation of prodrugs
- increased or decreased toxicity
5 special considerations in drug metabolism
- age
- induction of CYP450 system
- ” first pass” effect
- nutritional status (reduced cofactors)
- competition amoungst drugs
first pass effect
excretion
removal of drugs from the body
factors that modify renal drug excretion
- ph dependent ionization
- competition for tubular active transport
- age
non renal routes o f drug excretion
- breast milk
- bile (enterohepatic recirculation)
- lungs (anaesthesia)
- sweat and saliva
what are the 4 time courses of drug responses
- plasma drug levels
- single dose time course
- drug half life
- drug levels produced with repeated doses
half life
the time required for the amount of drug in the body to decrease by 50%
half life determines
dosing interval ( how often you take the drug)
steady state (plateau) level
4-5 half lives
