Intro to Drug Metabolism Flashcards
Which principle describes: what does the drug do to the body
Pharmacodynamics
What is the goal behind the minimum effective concentration (MEC)?
To keep concentration above it
When does onset occur in terms of the therapeutic window?
The moment concentration reaches MEC
When does termination occur in terms of the therapeutic window?
After concentration goes down and just dips below MEC
What is the therapeutic window?
Area between toxicity and MEC
Which principle describes: what does the body do to the drug?
Pharmacokinetics
Which occurs first, pharmacokinetics or pharmacodynamics?
Pharmacokinetics
Which principle describes: How the body absorbs, distributes, and eliminates the drug
Pharmacokinetics
Which principle describes: Plasma concentration (dose) needed to produce effect-
Pharmacodynamics
What are some other terms used interchangeably with metabolism?
Biotransformation & Inactivation
Do all drugs undergoing metabolism inactivate the drug itself?
No, not all
Some actually get activated like L-Dopa to dopamine
Some stay active and transform to another active form like diazepam to oxazepam
Metabolism of drugs make it more (hydrophilic/hydrophobic)
Hydrophilic
Metabolism of drugs make it more (hydrophobic/hydrophilic)
Hydrophilic
Once a drug is metabolized, where is it eliminated?
Kidneys & GI tract
Where is the primary location of metabolism?
Liver (hepatic)
What is found in phase I rxns?
p450
Which rxn requires energy?
Phase II
What is found in phase II rxns?
Conjugation rxns
Which rxn does NOT require energy?
Phase I
Once metabolized, what exactly is being removed?
- Parent (starting) compound
2. Metabolites
Which phase makes the compound more hydrophilic?
Both phase I & II
What specific rxns occur in phase I?
- Hydroxylation
- Dealkylation
- N-oxidation
What specifically do phase II rxns add to the compound?
Endogenous substrates (glucuronides, sulfates & acetates)
What is a pro-drug? How does it cycled through?
Inactive form; bioactivated via enzymatic action
Can a drug go thru phase II then phase I?
Yes
Can a conjugated form of a drug be more active than the parent drug?
Yes (example = morphine glucuronide)
What is the first pass effect?
Metabolism of RX before absorption
Concentration of RX is greatly reduced before it reaches systemic circulation
What is bioavailability?
Signifies how much intact drug reaches general circulation
When does decreased bioavailability occur?
- Drug isnt absorbed
- Drug is inactivated by enzymes, acid, bacteria
- Drug is inactivated by p450 as it passes thru liver
Describe the Entero-hepatic recycling
- Conjugated drug is secreted in bile
- Hydrolysis occurs (makes drug more lipophilic)
- Drug is reabsorbed from GI tract
- Drug duration is prolonged
What rxn occurs in the entero-hepatic recycling to make drug more lipophilic?
Hydrolysis
Hydrolysis rxns in the entero-hepatic recycling makes the drug more….
lipophilic
Where exactly is cytochrome P450 found?
ER of liver (GI tract and other tissues as well)
What rxns do the P450 enzymes participate in?
Oxidation
Nomenclature example: CYP3A4
What is the 3?
Enzyme family
Nomenclature example: CYP3A4
What is the A?
Enzyme sub-family
Nomenclature example: CYP3A4
What is the 4?
Individual enzyme/family member
How many different families are there of P450 in humans? Different isoforms?
At least 18 different families
About 50 different isoforms
What are some examples of inhibitors of biotransforming enzymes?
- Grapefruit
- Cimetidine
- Ketoconazole
Which age group has slower metabolism?
Very young and very old
Which gender has faster metabolism?
Males
