Drug Metabolism & Excretion Flashcards
what are the 2 types of biotransformation rxns?
1) non synthetic
2) synthetic
addition or uncovering of COOH, NH2, O, OH, and/or SH
non synthetic biotransformation
(oxidation, reduction, hydrolysis, phase 1)
addition of group from endogenous cofactor
synthetic biotransformation
( conjugation, phase 2)
which type of enzyme is the sole contributor to phase 2 metabolism of drugs?
transferases
the insertion of oxygen into drugs or side products will cause them to become more ______ and less ______.
hydrophilic; lipophilic
the cytochrome p450 microsomal system is bound in the ________.
smooth er
in a monooxygenase system requiring O2, how many of the oxygens go to the drug?
1; the other forms water
what are the components of the P450 system
- smooth er
- cytochrome p450
- NADPH cytochrome P450 reductase
- molecular oxygen
- NADPH
which three cytochrome p450 families are responsible for most drug oxidation?
- CYP1
- CYP2
- CYP3
which type of enzyme catalyzes alcohol and aldehyde oxidation?
dehydrogenases
which type of enzyme catalyzes purine oxidation?
xanthine oxidases
which type of enzyme catalyzes monoamine oxidation?
type A and B oxidases
monoamine oxidation inhibitors are used as ?
antidepressants
what is the most common phase 2 enzyme?
UDP-glucuronyl transferase
what are the 4 main factors that affect drug metabolism?
- plasma protein binding
- localization of drug in tissues
- liver disease
- drug-drug interactions
an increase in cytochrome P450 proteins _____ drug metabolism
induces
what are the 5 miscellaneous factors affecting drug metabolism?
- age
- diet
- disease
- other drugs
- environmental chemicals
when toxic metabolite intermediates form and bind to proteins, it causes what?
cell death
what are the 4 principal excretion routes?
- renal
- biliary
- pulmonary
- miscellaneous (saliva, sweat, tears, etc)
which principal excretion route is most common/ most important?
renal
what are the 4 routes of renal excretion?
- glomerular filtration
- active tubular secretion
- passive reabsorption
- active tubular reabsorption
what is the daily filtration rate for glomerular filtration?
180 L/day
what is the criteria for a drug to undergo glomerular filtration?
- not too big
- not bound to plasma proteins
(not affected by lipid solubility or environmental pH)
active tubular secretion is carried out by which types of transporters?
- organic anion transporters (OATs)
- organic anion transporter peptides (OATPs)
- organic cation transporters (OCTs)
active tubular reabsorption is inhibited by ?
uricosuric drugs
active tubular reabsorption is important for the conservation of ?
endogenous compounds such as uric acid
passive reabsorption requires the ______ form of a drug
non-ionized
the extent of drug ionization is dependent upon which 2 factors?
- pKa
- urinary pH
biliary excretion can be impaired by ?
liver disease
biliary excretion usually follows phase ___ in liver
2
pulmonary excretion is important for ____ and _____.
gases; volatiles
simplified diffusion into expired air
pulmonary excretion
the elimination rate of pulmonary excretion depends on?
- respiration rate
- pulmonary blood flow
- solubility of drug in blood
to increase phenobarbital excretion, the urine needs to be ________
alkalinized
(increases fraction in ionized form)
to increase amphetamine excretion, the urine needs to be ________
acidified
(increases fraction in ionized form)
