Exam 1; Metabolism and Excretion Flashcards
In general, the action of the drug is terminated by what
its metabolism
Which drugs are not terminated by its metabolism
prodrugs; they are inactive when given and are activated in the body
What are four sites of drug metabolism
skin
lungs
kidney
small intestine
What is the main organ (primary site) of drug metabolism
the liver
This is when an oral drug gets absorbed by the small intestine and travels to the liver via the portal system
first pass metabolism
If a drug is rapidly metabolized (nitroglycerin, morphine), it will not what
reach the circulation
The smooth endoplasmic reticulum of the liver cells contains a complex of enzymes referred to as what
cytochrome P450 (CYP)
What is the most significant form of CYP
CYP3A4; involved in more than 50% of the metabolism of drugs we talk about
CYPs catalyze what type of reactions
oxidation reactions
When CYP oxidizes a drug, what occurs?
the drug becomes more polar, which increases water solubility and makes it more readily excreted by the kidney
CYPs can be both induced and inhibited by what
environmental factors
What are some inhibitors of CYP
grapefruit juice
some antibacterials
some antifungals
What are some activators of CYP
phenytan and phenoharbitol
St. Johns
rifampin
What happens to the concentration of the drug upon inhibition or activation of CYP
inhibition of CYP = concentration of drug increases
activation of CYP = concentration of drug decreases
CYP450 is responsible for what percentage of phase 1 reactions
75%
Oxidation of the drug molecule forms what
a polar group like -OH or the removal of a non-polar group
This is the addition of -OH to a molecule
hydroxylation
What are four CYP450 phase 1 reactions besides hydroxylation
N-oxidation
S-oxidation
N-dealkylation
O-dealyklation
What are four non-CYP450 phase 1 reactions
deamination
hydrolysis; esterases
peptidases
phosphatases
What is the purpose of the phase II reactions
“finisher”
add a moiety to the drug (large molecule
What five endogenous molecule groups can be added to a drug during phase II
acetyl group glucuronic acid methyl group sulfate grouo amino acid (like glycine)
What is the primary organ of drug excretion
the kidney
The more polar molecules will or will not be excreted via the kidney
will
the more polar molecule will or will not stay in the urine and be excreted
will
The more non-ionized molecule will or will not be resorbed from urine
will
HA ⇆ H+ - A-
this means what
if you acidify the urine, this will allow the drug to stay in the body
In what other ways can the drugs be excreted
feces
lung
sweat
breast milk
What are three factors that can alter absorption
time of day; before during or after meals
age (older cannot metabolism as readily)
environment (other drugs taken)
What are three factors that can alter distribution of the drug in the body
body size and fat
gender
other drug interactions
What are two enzymes that can be genetically different that can alter metabolism/excretion
CYP450
plasma cholinesterases
This enzyme is necessary for maintaining RBS integrity; deficiency can lead to RBC hemolysis
glucose-6-phosphate dehydrogenase
This acetylator can slow metabolism
procainamide
This acetylator can cause a lupus-like syndrome
hydralazine
What four things can alter metabolism and excretion
age (infants and elderly)
route of administration
star of disease/pregnancy
exposure to drugs (especially those affecting P450)
What are the four phases of new drug testing
animal testing
phase 1-3
This phase of new drug testing is dose dependent effect in normal and healthy humans
phase 1 (after animal testing)
This phase of new drug testing is in a small number of patients with the target disease
phase 2
This phase of new drug testing is in a large number of patients with the target disease
phase three
How long and how much money does it cost for a drug to enter the market
8-9 years
1 billion dollars
This FDA category regarding pregnant women taking drugs is when there is no risk
A
This FDA category regarding pregnant women taking drugs is when there is no risk in animals, but humans have not been tested
B
This FDA category regarding pregnant women taking drugs is when risk cannot be ruled out (humans not tested) but the benefit is greater than the risk
C
This FDA category regarding pregnant women taking drugs is when there is risk but also benefit; the risk = benefit
treat the patient, may worry about the fetus
D
This FDA category regarding pregnant women taking drugs is when there is a severe risk; drug is contraindicated; the risk is more than the benefit
X
