Metabolism and Excretion Flashcards
Describe drug metabolism
When drugs are metabolized, they are chemically altered by enzymes into new molecules called metabolites.
Metabolism can increase or decrease the onset, duration of action, and toxicity of a medication
What is the goal of metabolism
More water soluble so they can be excreted by the kidneys
Where does metabolism mostly occur
Can occur in every biological tissue but mostly in the smooth endoplasmic reticulum of cells in the liver
What is first-pass metabolism
metabolism by the liver following oral administration and is important in determining whether a drug can be orally administered
What is the large family of enzymes responsible for metabolizing a large amount of drugs
Cytochrome P450 (CYP450)
How many human CYPs have been isolated so far
50
What is the major CYP subfamily expressed in the human liver?
CYP3As
What are Single Nucleotide Polymorphisms (SNPs) and how are they expressed
Minor mutations in proteins that can result in metabolic activity changes.
When SNP variations exist in the individual CYP enzyme, they are named by an asterisk and a number showing the order in which each SNP was identified
Describe Phase 1 Metabolism
Nonsynthetic Rxns.
-involve oxidation, reduction, and hydrolysis reactions
-rxns introduce or unmask polar groups that, in general, improve water solubility and prepare drug molecules for further metabolic reactions.
-can result in metabolites with greater or lesser pharmacological activity
-Many phase I metabolites are eliminated and others move on to Phase II.
Describe Phase II Metabolism
Synthetic Rxns
Something is added to the drug to synthesize a new compound. Goal is to add something to make it more polar, making it more water soluble and easier to excrete.
Describe First Order Metabolism
Characterized by a half-life, the time period over which the drug concentration will decrease by half.
Therefore, blood levels decrease by 50% in one half-life, 75% in two half-lives, and 87.5% in three half-lives
Describe Zero-Order Metabolism
Enzymes act near to their maximal metabolic capacity and metabolize a constant amount of drug each hour.
What is a prodrug
inactive compounds that rely on metabolism to become active
What determines which drug will be metabolized first if there is competition between drugs and enzyme
When several drugs are metabolized by a single enzyme, each drug will be metabolized in proportion to the affinity for each of the drug–enzyme interactions
What does grapefruit juice due to the CYP3A4 enzyme
inhibits CYP3A4 and can sometimes markedly increase blood levels of drug in patients consuming grapefruit juice.
What is excretion?
Locations at which drugs can pass from inside the body to outside. Include some sites that are familiar as sites of absorption, such as lungs, skin, and intestines.
What are the unique sites of excretion where drug is only excreted and not absorbed
Kidneys and Gallbladder
The production of urine begins where
glomerulus
What is ultrafiltration
a process in which substances in the plasma pass through small holes, or pores, into the glomerular capillary
Which part of the nephron primarily has the active transport systems needed to reabsorb important molecules
Proximal tubule. Important for endogenous reabsorption of ions, amino acids, and glucose
What are the 3 types of active transport in the biliary excretion system
organic anion, organic cation, and bile acid transport
What is an example of a drug excreted through the bile acid transport
digoxin
What is enterohepatic cycling
when drug is excreted in the bile, absorbed from the intestines, and then excreted in the bile again
decreases the amount of drug that is actually excreted and extends the time that a drug remains in the body.
Besides kidney and gallbladder, name a few other ways drugs can be excreted
breathing (ethanol, NO2), skin, saliva, breast milk
