Absorption Flashcards
What factors determine given drug’s ability to cross biological membrane
size, degree of ionization, concentration gradient, lipid solubility,
Mechanisms drugs cross biological membranes
Passive diffusion (aqueous via aquaporins and lipid soluble drugs directly diffusing), Active transport, Endocytosis, Facilitated diffusion
Most important mechanism for drugs to cross biological membranes
lipid soluble drugs diffusing across membrane
Enteral Routes
Oral and rectal
Parenteral Routes
IV, Inhalational, subcutaneous, imtramuscular, transdermal, sublingual, buccal, etc
Oral Route (adv/dis)
systemic effects, variable bioavailability, encounters enterohepatic circulation, man manipulate rate of absorption, food delays absorption
Rectal
Systemic effects, can use for those who are vomitting, unconscious, post GI surgery, uncooperative, low pts acceptance, variable bioavailability, less efficient metabolism than oral
IV route
100% bioavailable, most rapid/direct route, high potential for toxicity, can introduce infectious agents, difficult reversal of effect
IM
approach bioavailability of IV, Can use depot forms or oil suspensions for slower/sustained absorption, pain/necrosis if high pH, microbial contamination
Inhalational (systemic)
volatile gases; high bioavailability but can be addicting
subcutaneous
systemic, generally approaches 100% bioavailability, slower, constant absorption rate, limited dose volume, only for non-irritating drugs
Sublingual
systemic, high bioavailability, rapid onset, avoids first pass metabolism, good for lipid soluble/potent drugs
transdermal
systemic, avoids first pass metabolism, avoid ADR related to hepatic actions, potential for unexpected accumulation/toxicity, need nonsensitizing/nonirritating yet potent d rug
Local routes
Aural, nasal, throat, vaginal, ocular/conjunctival, inhalational
Inhalational (local)
(particles) increase local topical effects in lung/lower systemic effect, effects depend on particle size
Bioavailability
extent of unchanged drug reaching systemic circulaiton; determined by [AUC (from route)/AUC (
IV)]
What form of the weak acid/base drug crosses membranes?
unionized form (AH, B)
Ion trapping
Have two compartments with different pHs separated by membrane –> ionized form of the drug gets trapped on one side of membrane. Total drug concentration greater on side where ionization is greater
What kind of solution will trap a weakly acidic drug?
weak base
Barriers in body with tight junctions
GI, Blood brain barrier, placenta, renal tubules
Characteristics of drug that can easily cross membranes
small, uncharged, high lipid solubility, has large concentration gradient
What does plasma protein binding do to a drug
Creates protein-drug complex that cannot diffuse/cross membrane; increases half-life, decrease Vd, decrease ability to enter blood brain barrier or distribute to tissue (affects distribution/metabolism/excretion)
Protein-binding displacement
Give second drug that will bind to plasma protein and cause displacement of first drug
When you should be concerned about protein-binding displacement interactions
Narrow therapeutic index of displaced drug, displacing drug started in high doses, Vd of displaced drug small, response to drug occurs more rapidly than redistribution
Vd
volume of distribution–extend to which drug is distrubuted
relationship between Cp and Vd
inverse; more in plasma means less distributed to tissues
Volumes of water compartments in body
Plasma/blood - 3-5 L Extracellular water = 12-15L Total body water= 42 L Other compartments (sequestering) = >50 L
High Vd
less drug in plasma, more in tissue
Low Vd
more drug in plasma
Variation in Vd due to…
body size, fat vs lean composition, changes in protein binding
relationship between loading dose and Vd
LD = CpxVd
How to determine effect of dose on Cp
Cp = Dose/ Vd
Where is drug if Vd= 13
drug mostly in extracellular space
