Drug Absorption/Biotransformation? Flashcards
Pharmacokinetics
examines the movement of a drug over time through the body
Pharmacodynamics
mechanisms of drug action are the processes of Pharmacodynamics
Bioavailability
% of dose that gets into body
Bioequivalence
similarity between two formulations of same drug
Speed of drug onset
how long it takes the drug to begin working
Dosing interval
how often the drug should be given
site of action
whether the drug stays local or acts systemically
what is drug absorption?
the movement of drug molecules across biological barriers (mostly layers of cells) from the site of administration to the blood stream
What affects drug absorption?
rate of release of drug from pharmaceutical preparation
membrane permeability of drug
surface area in contact with drug
blood flow to site of absorption
destruction of drug at or near site of absorption
what determines rate of release of drug from pharmaceutical preparation?
Dosage form additives (excipients) manufacturing parameters delayed release preparations sustained release preparations
Dosage form
solutions - no delay, immediate response
capsules & tablets - delay (dissolution) followed by rapid release
creams, ointments & suppositories - no delay, but slow release
Additives (excipients)
decrease rate of dissolution - binders, lubricants, coating agents
increase rate of dissolution - disintegrants
Variable effects on rate of dissolution - diluents, coloring agents, flavoring agents
Manufacturing parameters
tablet compression - hard tablets dissolve more slowly
tablet shape - round tablets dissolve more slowly
tablet size - large tablets dissolve more slowly
Delayed release preparations
enteric coating - dissolve in intestines, not stomach
sustained release preparations
Reservoir diffusion products - drug diffuses from pill core through membrane shell
Matrix diffusion products - diffuses through matrix in which it is embedded
Matrix dissolution products - released as matrix dissolves
osmotic tablets - pumped out of tablet by osmotic forces
Ion-exchange products - bound to resin exchanges with endogenous ions
Lipophilicity
increases membrane permeability
presence of aliphatic and aromatic structures
absence of polar groups
Ionization
decreases membrane permeability
weak acids in intestines are mostly ionized (intestinal pH ranges from 6.6 to 7.5)
weak bases in stomach are mostly ionized (stomach pH ranges from 1 to 2)
Henderson-Hasselbach equation
pH = pKa + [nonprotonated species/protonated species]
For acids: pH = pKa + log [A-]/[HA]
For bases: pH = pKa + log [B]/[BH+]
when pH is less than pKa,
the protonated forms HA and BH+ predominate
when pH is greater than pKa, the
deprotonated forms A- and B predominate
when pH = pKa then
HA = A- BH+ = B
What parts of the anatomy have a low surface area?
eyes, nasal, buccal cavity, rectum, stomach large intestines
High surface area anatomy
small intestines and lungs
Low blood flow areas of the body
eyes, stomach, large intestines, rectum, subcutaneous tissue
High blood flow areas of the body
small intestines, lungs, muscle, buccal cavity, nasal cavity
what determines whether a drug is destroyed at or near site of administration?
Liver - hepatic enzymes (first pass effect)
colon - intestinal microflora
stomach - digestive enzymes and acids
Considering types of administration what is most safe to least safe?
highest safety is Oral -> SC -> IM -> IV
Routes of administration that would be highly bioavailable to least?
IV is the highest, IM = SC > oral
Onset of action of routes of administration
fastest is IV > IM > SC > oral
Most interaction with food to least?
Oral > IV = IM = SC
Highest volume of drug required to least
Oral = IV > IM > SC
Availability of sustained release dosage forms
Highest with IM > oral > SC > IV
Tolerance to “funky” vehicles
Highest with Oral = IM = SC > IV
Sublingual administration
rapid absorption that bypasses liver
Rectal
great for patient that is vomiting or cannot (will not) swallow medication
