Absorption Flashcards
What type of structures are animal cell membranes?
phospholipid bilayers
What is lipophilicity?
lipid solubility of drug; most important characteristic allowing it to diffuse across cell mbs
What factor other than lipophilicity is important in allowing a drug to diffuse across cell mb?
molecular size
How do chemicals cross cell mbs?
- passive transport (simple diffusion)
- filtration (bulk flow)
- facilitated diffusion
- active transport
What is passive transport (simple diffusion)?
chem follows concentration gradient across cell mb; termed transcellular diffusion
What is filtration (bulk flow)?
passive transport through cell junctions due to pressure gradient; termed paracellular transport
what is facilitated diffusion?
also passive transport following concentration gradient, but requires transporter to assist movement across mb
what is active transport?
movement against concentration gradient, requires ATP
What is most common way that drugs cross cell mbs?
passive transport
What on either side of the mb determines direction of diffusion?
concentration gradient
In order for drug mc to passively diffuse across cell mb, it must be…?
lipophilic (lipid soluble)
Pharmaceuticals can be categorized into 2 types of chemicals, influencing their absorption:
- lipophilic organic chemicals
- weak organic acids & bases
What are lipid organic chemicals?
about 25% of drugs are organic molecules w/ varying degrees of lipid solubility
what are weak organic acids & bases?
about 75% of drugs are weak acids & bases; such chems exist in both ionized & nonionized forms in soln, & relative proportion of ionized vs nonionized form depends on pKa of drug & pH of solution; ONLY NONIONIZED FORM OF DRUG CAN PASSIVELY DIFFUSE ACROSS CELL MBS
What can the Henderson-Hasselbach eqn be used to determine?
ratio of nonionized vs ionized form of drug
What is the Henderson-Hasselbach eqn?
Log ([protonated]/[nonprotonated]) = pKa - pH
Remind me what pKa is:
number that measures strength of an acid or tendency of mc to keep a proton.
calculated as negative base-10 log of acid dissociation constant (Ka).
lower pKa value indicates a stronger acid, meaning acid dissociates more completely in water.
protonated form of an acid is?
nonionized (HA)
Protonated form of a base is?
ionized (BH+)
weak acids (HA) donate … to form …
proton (H+), anions (A-)
weak bases (B) accept … to form …
a proton, cations (HB+)
what form of drug can readily penetrate cell mbs?
nonionized
pKa of weak acid or base is …
… pH @ which there are equal amts of protonated form & nonprotonated form
What is nonionized in what?
like is nonionized in like!
(weak base is more nonionized in basic soln & weak acid is more non-ionized in acidic soln)
would benzoic acid (pKa =4, acid) be ionized @ neutral pH?
yes
would aniline (pKa =5, base) be ionized @ neutral pH?
no
What is clinical significance of a drug that is a weak base being 10 times more ionized in breast milk (more acidic) than plasma?
More ionized means more protonated. Clinical significance is concept of “ion trapping”. as nonionized form diffuses into breast milk, more acidic pH causes more of drug to be ionized, & thus “trapped”.
treating mammary gland infection (mastitis) w/ an antimicrobial drug that is a weak base will result in increased drug concentration @ site of infection & increase efficacy.
What is filtration (bulk flow) of a drug?
- drug moves w/ H2O through gap jxns btwn cells due to pressure gradient (ex: blood press)
how big are the gaps btwn most cells?
4 nm
how big are the gaps btwn most blood vessel endothelial cells?
2 nm
how big are the gaps in glomerulus?
70 nm
How big are gaps in CNS?
0 nm
what is the most important characteristic about a drug in order for it to move via filtration (bulk flow)?
size of drug mc
What is the importance of facilitated diffusion of a drug?
- important for nutrients & electrolytes; certain drugs can compete for these systems
- mjr families are the organic anion transporters (OATs) & organic cation transporters (OCTs)
- important for excretion too
How is active transport related to drugs?
- important for excretion: brain, liver, & kidney all have active transport systems
- all are “ATP-binding cassette” (ABC) prots; major families are multi-drug resistance prots (MDRs & MRPs) & breast cancer resistance prot (BCRP)
- names originated from high expression in certain cancer cells, severely limiting chemotherapeutic treatments
- referred to as “lipophilic vacuum cleaners”
