Test 1 Part IV Flashcards
saying the clearance of a drug is 2mg/min would be an example of __________________
zero order kinetics
define half life
the time it takes for the total amount of drug in the body to be reduced by 1/2
_________ half lives must elapse before the full effect of a dosing regiment can be seen
4
a drugs half life is dependent on what two factors
Vd and clearance
define bioavailability
the fraction of unchanged drug reaching systemic circulation following administration
what is the bioavailability of any drug administered IV assumed to be?
100%
what decreases the bioavailability of drugs administered PO?
poor absorption across the GI tract
first pass elimination
what are the two main organs that affect the bioavailability of drugs administered PO
liver and GI tract
when is a loading dose utilized
when drugs have long half lives
what is the goal with the loading dose?
to promptly raise blood concentration levels
what is the most important influencing factor with dosing a loading dose?
volume of distribution (Vd)
what is the most important influencing factor with dosing a maintenance dose
clearance
what is the purpose of the mainteance dose?
to keep a steady state of drug in the body. just enough is given to replace what was eliminated since the preceding dose
T/F: rate of administration may be crucial with a loading dose
true
what can be an adverse effect of a loading dose
transient, potentially severe toxicity
what is biotransformation
a process of drug metabolism that alters the chemical structure of a lipid soluble drug to make it water soluble for elimination
only ______________ substances can be excreted in the kidneys
water soluble
byproduct metabolites formed from biotransformation are often _____________ pharmacologically active than the parent drug, but they could also be _____________, _____________, or _______________
less; inactive; more enhanced activity; toxic activity
what is the principle organ of drug metabolism and thus also of biotransformation
liver
what are other areas of drug metabolism besides the liver
GI tract, Lungs, skin, kidneys, brain
the _________________ harbors a lot of micro-organisms that are capable of many biotransformation reactions
lower gut
if there is compromise of the liver, primary site of metabolism for drug A, what can be the result?
significant elevations of plasma levels, which is clinically relevant in drug-drug interactions
drug metabolizing enzymes are found specifically in the ________________ of the liver
endoplasmic reticulum
what are the phases of biotransformation
phase I - oxidative reduction
phase II - conjugation
in phase I of biotransformation, oxidation =
P450 + P450 reductase + NADPH + O2
the oxidation process of phase I biotransformation will consume one molecule of ___________ (reduced) and produce ______________ + _____________
O2; a metabolite; H2O
which phase of biotransformation changes the polarity of the drug
phase I - oxidation
if a metabolite produced from a phase I reaction is sufficiently polar it will be ______________; if not then it will ________________
excreted; undergo phase II reaction
what are the 2 key enzymes involved in the phase I (oxidative reduction) of biotransformation
NADPH-cytochrome P450 oxidoreductase (flavoprotein)
and Cytochrome P450
what would increase the availability of P450s
repeated administration of or exposure to exogenous chemicals
what does CYP (P450) “induced” mean
there is an enhanced rate of synthesis or reduced rate of degradation
what are the results/consequences of being CYP (p450) “induced”
- results in accelerated metabolism and usually in a decrease in the pharmacologic action of the inducer and co-administered drugs
- may exacerbate metabolite mediated toxicity
what environmental/occupational factors have been found to be capable of inducing P450 enzymes
- smoking
- industrial workers
- those that work with insecticides
what drugs have been found to be P450 inducers
- antipsychotics
- various sedative-hypnotics
- anticonvulsants
- rifampin
in general, if a drug is a p450 inducer or inhibitor it is safe to assume what?
all drugs within that class have same action on P450
if something is a P450 inhibitor, what is the result
decreased metabolism
what is the mechanism at which a drug is a P450 inhibitor?
tells the apo protein responsible for making the P450 not to make it –> decreases metabolism
_____________ is responsible for metabolizing over 50% of prescription drugs metabolized in the liver
CYP3A4
P450 is an enzyme, and is specifically a ________________
hemoprotein
if an enzyme is described as microsomal, you know that means what?
they are a part of the Smooth ER and Rough ER
what are the microsomal reactions of a phase I biotransformation reaction
Cytochrome P450 oxidation
what are the non-microsomal reactions of a phase I biotransformation reaction
oxidation and hydrolysis
phase II of biotransformation is called ___________________
conjugation
define what happens in the Phase II (conjugation) biotransformation reaction
metabolic byproducts (not sufficiently polar) of phase I are further conjugated into highly polar molecules by an endogenous substrate
phase II of biotransformation forms drug conjugates, what is the purpose of this?
makes the drug metabolites highly polar, which makes them readily excreted and often inactivated
what endogenous substrates are commonly used in a phase II biotransformation reaction
glucuronic acid, sulfuronic acid, acetic acid, amino acid
where do endogenous substrates for phase II biotransformation reaction come from
diet and often affected by nutrition status
2 drugs may compete for the same endogenous substrate during a phase II biotransformation reaction, what could be the result of this
the faster drug may deplete substrate reserves and impair the metabolism of the slower reacting drug.
if the slower reacting drug has a narrow therapeutic index –> toxicity/death
what is required for a phase II biotransformation reaction to occur
- endogenous substrate
- energy
- transferase
what is the most dominant transferase enzyme found in the cytoplasm for phase II biotransformation reaction
uridine 5’-diphosphate-flucuronosyl transferases (UGTs)
