drug metabolism and elimination Flashcards
true or false. only drugs that are free and unbound from plasma protiens can be absorbed
true
albumin binds to what
warfarin and aspirin
albumin binding to aspirin is an example of what
a drug drug interaction
blood flow, organ size affect what
distribution - more blood flow into the organ, the more medication, the bigger the organ , the more blood flow there is, thus more meducation
blood brain barrier
possesses p-glycoprotiens which prevent some drugs from crossing biological membranes
what do p-glycoprotiens do?
they adhere to drugs stopping them from crossing biological membranes
fetal placental barrier
prevents drugs from affecting the fetus
what mechanical barriers have p-glycoprotiens
BBB, fetal-placenta, liver, epithelial
parenteral route distribution
bloodstream –> tissue
oral administration distribution
liver - hepatic portal –> systemic circulation
first pass effect
this means that always the forst part of a drug is going to be metabolized in the liver and is no longer available
how is to bioavilablilty of a drug affected by the metabolism of the liver?
the bioavailability of the drug is reduced
what routes of administration are affected by the first pass affect
oral and rectal
what is metabolism
process by which drugs are biotransformed into water soluble compounds that are easily secreted by the kidneys
the water-soluble metabolites from the liver are what?
inactive
hepatic drug metabolism is crucial for what
terminating the drug action and facilitates the elimination of drug molecules from the body
what converts lipid soluble drugs into water soluble metabolites
metabolism
the kidneys can only excrete what substances
water soluble
what are phase one reactions
theses reactions are hydrolysis, oxidation, reduction
how do phase one reactions work?
they convert non-polar molecules into polar molcules via the addition of a polar funcitonal group
most important phase one reaction
oxidation
cytochrome p-450 enzymes do what
replace a -CH or -NH group in a molecule with an -OH
what enzymes replace a -ch or -nh group in a molecule with an -oh group
cytochrome p450 enzymes
cytochrome p448 enzymes
insert an oxygen atom between two carbons that are connected by a double bond
what enzymes insert an oxygen atom between two carbons that are connected by a double bond
cytochrome p448
what can activites can inhibit cytochrome enzymes
smoking and grapefruit juice
what drugs can induce or inhibit the synthesis of oxidation enzymes - CYP - 450
rifampin and erythromyocin
rifampin
increases the synthesis of CYP enzymes, effecting the metabolism of the medications
what drug causes the increased metabolism and decreased plasma concentration of co-administered drugs
rifampin
what drug can make things like birth control, antidepessants less effective?
rifampin
erythromycin
inhibits the activity of CYP enzymes
what inhibits the activity of the CYP enzymes
erytromycin
aldehyde oxidase and liver alcohol dehydrogenase
can oxidize alcohol
monoamine oxidase
metabolize things like dopamine and serotonin
phase two reactions do what?
they form a highly water soluble metabolite
what drug isnt rendered inactive after phase two conjugation
morphine
glucuronyl transferase
replaces an -oh or -sh group with glucuronic acid
n- acetyltrasnferase
replaces an -oh, -sh, -nh2 group with acetate
sulfotrasnferase
adds a sulfate group replacing -oh
glutathione s-transferase
forms an adduct between the drug and glutathione
forming an adduct means
you are almost adding a molecule onto another
where do the reactions occur in acetaminophen?
sulfation, oxidation, glucuronidation
the oxidation of acetaminophen causes what
it causes the molecule to be unstable resulting in a spontaneous reaction
what does the spontaneous reaction of acetaminophen result in
another phase two reaction of glutathione s-transferase
in the situation of an acetaminophen overdose, what enzyme stops irreversible damage to the liver?
glutathione
NAPQI combined with sulfahydryl causes what
causes cell death
what is administered in acetaminophen overdose
acetylcysteine
what is acetylcysteine
this is a compound that works just like glutathione, it binds to NAPQI and prevents damage to hepatocytes
excretion is done by
kidneys
in order for drugs to be excreted what must the drugs be
must be ionized and polar
true or false, polarity of drugs can be manipulated by shifting pH of urine
true
where do drugs that are more fat soluble excreted through
the intestines
what drugs can experience intra-hepatic absorption
fat soluble
