Unit 1: Drug Biotransformation Flashcards
Molecules with a ______ charge are usually reabsorbed
Neutral
Which organ excretes most drugs?
Kidneys
Other drugs that are often reabsorbed are ________, aka “_______”
Lipophilic or “protein bound”
What process changes drugs to allow for excretion?
Metabolism
Name the factors that affect the rate of excretion from the kidneys:
1.
2.
- Blood flow to the kidneys
2. GFR (glomerular filtration rate)
What helps to get rid of drugs that are protein-bound?
OAT or OAC
Organic anion transporters
Organic cation transporters
Remember: Lipophilic drugs can easily be ______ and therefore prevent excretion
Reabsorbed
General changes during drug metabolism:
1.
2.
3.
4.
- Active drug —> active metabolite
- Active drug —> inactive metabolite
- Pro-drug —> active drug
- Active drug —> toxic metabolite
Drug metabolism occurs in how many phases?
Phase I and Phase II
Most biotransformation occurs when?
Between absorption into circulation and elimination
What does Phase I do?
Converts drug to more polar metabolite
Name some processes for Phase I:
Oxidation
Hydrolysis
Reduction
What is the overall effect of Phase I on a drug?
Enhances water solubility
Why do we need Phase II?
To further polarize metabolites so the kidney can excrete them.
Phase 2 processes add something to the drug to make it
Inactive
Polar
More readily excretable
Name processes involved in Phase 2:
Acetylation
Methylation
Glucuronidation
Where do phase I and phase II processes generally occur?
Rough endoplasmic reticulism
Name 2 key enzymes in phase I reactions
P450 oxidoreductase
Cytochrome P450
Where are the enzymes housed which perform oxidative drug metabolism?
In the smooth ER
Abbreviations for Cytochrome P450
P450
CYP
What genetic factors are important to remember with the CYP450 mechanism?
CYP2D6 for caucasians (deficient in some)
CYP2C19 for caucasians and Japanese (completely absent for some)
Name most important family in CYP450 mechanism?
CYP3A4: responsible for 50% of drug metabolism by liver
Effect of a CYP inducer:
Speed up metabolism of other drugs —> decreases effectiveness
Effect of CYP or P450 inhibitor:
Blocks enzymes that metabolize other drugs —> increases potential for toxicity
Phase II reactions are
Faster or Slower?
than P450 catalyze reactions
FASTER
Diseases that affect drug metabolism
Anything that affects the liver: hepatitis, cirrhosis
Cardiac disease or renal disease that affects blood flow to liver
Hypothyroidism: increases half life of some drugs
Hyperthyroidism does the opposite
Phase I enzymes are involved in the biotransformation of ____% of prescription drugs
75%
