4- Drug Metabolism Flashcards
How does the body convert a drug from an active to an inactive form?
Phase I and II reactions (talked about last chapter)
What is first pass extraction?
When drugs are taken orally or rectally, they are taken up by the portal system and metabolized in the liver. This means less drug will be delivered to the blood stream that you put in because an amount of it will be inactivated by the liver.
What type of administration bypasses the first pass extraction?
IV administration of a drug
What does oxidation reactions do to the drug for metabolization?
more hydrophilic metabolites by adding or exposing polar functional groups
Where does conjugation and hydrolysis take place in the liver for phase II reactions?
in both the cytosol and ER
Since neonates don’t have the capacity to conjugate, what do they used to conjugate bilirubin to excrete it?
UDGPT
What happens if a neonate doesnt have UDGPT yet?
They get jaundice.
What is the Multidrug resistant protein 1 ( MDR1)?
ABC family of efflux transporters, actively transports compounds back into the intestinal lumen
What is the Organic anion transporting polypeptide (OATP)?
Help transport drugs from portal circulation into hepatocytes
What is induction?
chronic drug exposure (barbs, alcohol, coffee) creates more enzymes to increase the metabolism of the drug in the next initial dose. This means you need more of the drug to produce the same effects as the initial dose as they are quickly metabolized by the surplus of enzymes.
What is an example of a drug that speeds up its own metabolism via P450 3A4 induction?
Carbamazepine
What is significant about P450 3A4?
It’s responsible for metabolizing more than 50% of prescribed drugs
What is a drug that induces P450 3A4, used in HIV therapy, and induces the metabolism of other drugs?
Rifampin/St. Johns wort
Why is the induction of other drugs bad?
Induction can reduce other drug concentrations below their therapeutic level if standard doses of the drugs are administered
What is inhibition?
Sometimes drugs inhibit enzymes that other drugs use for metabolism. This leads to a toxicity of the drug.
What is an example of an antifungal drug that inhibits P450 enzymes?
Ketoconazole
What are prodrug metabolites?
Prodrug is inactive compounds that are metabolized by the body into their active, therapeutic forms
What are toxic metabolites?
drug metabolites have adverse effect
What is an example of a famous toxic metabolite that injures the liver when the levels exceed the therapeutic range?
Acetaminophen. Excessive accumulation of acetaminophen metabolites that are not conjugated side reacts and causes harm to the liver
What is the role of genetics in drug metabolism?
Certain population exhibit polymorphism mutation in one or more enzymes of drug metabolism, changing the rate of these reactions and eliminating others altogether
What is the role of race in drug metabolism?
Race may be a key consideration in choosing drug treatment or doses.
Ex: P450 2D6 is functionally inactive in 8% Caucasians while in Asians only 1%.
What is the role of age in drug metabolism?
In young children and elderly, they have slow biotransformation reaction. Neonates are not able to carry out all oxidative reaction. Elderly has decline in function
What is the role of diet in drug metabolism?
Both diet and environment can alter drug metabolism by inducing or inhibiting enzyme of the P450 system
What is the role of the patient’s health in drug metabolism?
This is important because much disease state can affect the rate and extent of drug metabolism in the body. Especially liver disease because liver is the main site of biotransformation.
What is an important nolecule that Fe in P450 uses to split the O2 molecule?
NADPH
What are poisons?
poisons are substances that can cause damage, illness, or death to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism
What are toxins?
A toxin is a poisonous substance produced by living cells or organisms that is active at very low concentrations.
