drug elimination Flashcards by Marissa Bobay

define drug elimination

irreversible removal of drug from the body by all routes

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2 things that elimination includes

metabolism
excretion

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define drug excretion

removal of the intact drug

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excretion method for nonvolatile drugs

renal excretion

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excretion method for volatile drugs

lungs -> expired into air

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6 routes of drug excretion

biliary (liver)
lungs
saliva
breast milk
feces
kidney

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salivary excretion is for drugs with _____

high saliva to plasma ratio

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what is the most important characteristic that drugs need to possess to cross biological membranes

lipophilicity

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excretion method for most drugs that are not absorbed

feces

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where do drugs excreted via biliary route go to next

feces

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what is the most important route of elimination

renal excretion

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3 processes that renal excretion involves (& location)

glomerular filtration (bowman’s capsule)
tubular reabsorption (distal tubule)
tubular secretion (proximal tubule)

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characteristics of a drug that determine its excretion via biliary route

chemical structure
polarity
molecular size

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clearance measures _____ without identifying _____

drug elimination from body without identifying individual process

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clearance technical definition

volume of plasma/body fluid that is cleared of all drug per unit time

ml/min or L/hr

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clearance has nothing to do with _____

the amount of the drug

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what 2 organs are able to clear drug out of the plasma

liver
kidney

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equation for total clearance

= rate of elimination / [drug in plasma]

(ml/min)

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renal excretion equation

= filtration + secretion - reabsorption

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3 factors of a molecule that determine glomerular filtration

molecular size
molecular shape
charge

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what is the “restrictive filtration” size range for glomerular filtration

will filter all drugs < 20 kDa

will selectively filter drugs 20 - 60 kDa

will NOT filter drugs > 60 kDa

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drugs are ONLY filtered across glomerulus if _____

they are unbound (free)

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gold standard to measure renal clearance & why

inulin

bc it is ONLY filtered (no reabsorption or secretion)

active tubular secretion mechanism

translocation of drug from plasma -> urine

mediated by OAT, OCT, or P-gp efflux transporters

why is tubular secretion considered an "active" process, & what is the consequence of this

bc it uses carrier molecules & requires a supply of energy can be competitively inhibited

penicillin tubular secretion can be competitively inhibited by _____, which _____

probenecid decreases penicillin's renal clearance

handling of drugs bound to plasma proteins in glomerular filtration vs tubular secretion

GF: drug bound to plasma protein is not filtered due to size TS: drug is stripped off of protein so it can be excreted

2 reasons a drug in glomerular filtrate is reabsorbed from tubules into peritubular capillaries

drug has lipophilic characteristics there is a positive concentration gradient between the tubule & peritubular capillary

acidic urine favors reabsorption of _____

weak acids

alkaline urine favors reabsorption of _____

weak bases

hepatobiliary excretion mechanism

drug absorbed across GI tract into portal circulation -> drug uptake by hepatocytes -> excretion of drug/metabolite into bile -> bacterial deconjugation & reabsorption of drug

mechanism of drug uptake by hepatocytes

uptake by transporters -> drug transformed into metabolite -> metabolite transported into bile canaliculi OR effluxed out of hepatocyte into blood by ATP

what are the 2 primary determinants for drug/metabolite excretion into bile

molecular weight (needs to be pretty high) drug needs to have a strong polar group

what is the size threshold for biliary excretion in humans

> 500 Da

examples of drugs that undergo enterohepatic recycling (excretion into bile)

hormones (estrogen) morphine 6-glucuronide estradiol glucuronide abx (doxycycline)

where do glucuronide metabolites excreted into bile go next, and what happens there

duodenum microbes that produce beta-glucuronidase enzyme deconjugate the metabolite -> frees the parent compound that is then reabsorbed

what can affect biliary drug elimination

-liver disease / injury -age (neonate or geriatric) -drug competition for same carrier protein

example of drug whose chronic administration can affect biliary elimination

phenobarbital

example of drugs whose co-administration can speed up enterohepatic recycling

ion exchange resins & drugs like abx & estrogens

factors that affect pulmonary elimination of drugs

-respiration rate -pulm blood flow -water (aqueous) solubility -cardiac output -volatility

factors that INCREASE rate of drug loss via pulmonary elimination

-increased RR -increased pulm blood flow -low aqueous (water) solubility -increased CO (cardiac output) -increased volatility

characteristics of a drug that easily passes into breast milk

-high [drug in maternal blood] -low plasma protein binding -high lipid solubility (lipophilicity)

what types of drug get trapped in breast milk, & why

weak bases/alkaline drugs (such as barbiturates) bc breast milk pH is acidic, so an alkaline drug will ionize in the breast milk & be unable to return to system

factors of drug that affect breast milk elimination of drugs

-[drug in maternal blood] -plasma protein binding -lipid solubility (lipophilicity) -pKa (ionization constant) of drug in maternal blood

excretion of drugs via sweat & saliva depends on _____

(minor route) diffusion of non-ionized drug species

some drugs partitioned in saliva can be _____

tasted in mouth even after IV administration

presence of ion-exchange resin will _____ clearance of an estradiol

increase

avg molecular weight of a drug w strong polar group

350 Da

molecular weight of glucuronic acid (which is added to MW of a drug that undergoes glucuronidation)

200 Da

total body clearance equation

total body clearance = plasma clearance x body weight

renal clearance equation

renal clearance = total body clearance x % drug excreted in urine (in decimal form)

if renal clearance = GFR, what is true about the drug behavior in the nephron

the drug is only filtered

if renal clearance > GFR, what is true about the drug behavior in the nephron

the drug is filtered and actively secreted

if renal clearance < GFR, what is true about the drug behavior in the nephron

the drug is filtered and reabsorbed systemically

what promotes fecal elimination of a drug undergoing enterohepatic recirculation

administering an ion-exchange resin

the enzyme produced by the bacteria in the gut has the ability to do what to a drug, & what is the name of this enzyme

regenerate the drug from conjugated metabolite beta-glucuronidase