DD Frech metabolism excretion Flashcards
In general, what are the Phases of metabolism and what occurs during these phases?
Phase I - drug is made more hydrophilic. Phase II - drug is made very water soluble.
Where does Phase I metabolism take place.
Liver smooth endoplasmic reticulum
What type of reactions take place in Phase I metabolism?
Oxidations, reductions, hydrolysis
What types of enzymes participate in Phase I
CYP450, reductases, esterases-amidases
Which phase of metabolism is more susceptible to drug-drug interactions?
Phase I
Which phase of metabolism is more likely to be saturated?
Phase II
Which phase of metabolism is more susceptible to age related changes?
Phase I
What type of reactions take place in Phase II metabolism?
Conjugations
What types of enzymes participate in Phase II
Transferases
What are the 4 things that can happen to a drug during metabolism?
Detoxify, active drug to more active compound, inactive drug to an active compound, make a toxic metabolite
Which phase of metabolism can be induced or inhibited?
Phase I
T or F: Hydrophilic drugs can be metabolized by Phase I reactions.
FALSE. They must be lipid soluble otherwise they will have low specificity.
What does an Amplichip test tell you?
Detects polymorphisms in metabolism - ultrarapid metabolizers and poor metabolizers
Name the 3 highlighted CYP450 dependent drug modifications. (probably want to know these)
Aromatic hydroxylation, aliphatic hydroxylation, oxidative dealkylation
Name the 3 highlighted CYP450 independent drug modifications. (probably want to know these)
Amine oxidation (monoamine oxidase), alcohol dehydration, aldehyde dehydration
Name the 3 highlighted Phase I reduction drug modifications. (probably want to know these)
Azo reduction, nitro reduction, carbonyl reduction
T or F: Phase I esterases are commonly used in the design of pro-drugs.
TRUE
T or F: Phase II metabolism is mature at birth.
FALSE. Generally takes longer to mature than Phase I metabolism
Describe enterohepatic recirculation.
Absorption in intestines?> goes into circulation?> eventually makes it back to liver ?> into bile ?> resealed back into intestines ?> reabsorbed from intestines
What do inducers do?
Produce a qualitative and/or quantitative change/increase in enzyme activity. Generally this is due to an increase in enzyme synthesis, but sometimes induces will also decrease enzyme turnover.
Generally, how long do inducers take to affect metabolism?
48-72 hrs. Remember, most inducers cause increased enzyme synthesis, so they act as transcription factors, which means they will take a little more time to have effect.
Do inducers affect Phase I or Phase II metabolism?
They can affect both, but most are known to affect CYP450 (Phase I)
What do inhibiters do?
Produce a qualitative and/or quantitative decrease in enzyme activity.
Generally, how long do inhibitors take to affect metabolism?
Within hours
Name the mechanism by which metabolism inhibitor can work (4 things).
1.) Inhibit enzyme synthesis 2.) Compete for enzyme active site 3.) Allosterically inhibit enzyme 4.) Destroy or permanently disable enzyme
Do inducers affect Phase I or Phase II metabolism?
They can affect both, but most are known to affect Phase I
What is pharmacokinetic tolerance?
Induction of a drug by its own metabolite.
Diseases of ______ (organ) may have a profound affect on metabolism.
the liver
What type of proteins move molecules out of cells?
P-glycoproteins
Which drug from this unit inhibits p-glycoproteins?
Erythomycin (resulting in prolonged Lipitor levels in circulation)
Which drug from this unit induce p-glycoproteins?
Rifampin and St. John?s Wort (rifampin increases elimination of oral contraceptives)
T or F: Death of bacteria flora can affect hepatoenteric recycling.
Yes, especially if drug absorption is dependent on gut bacterial enzymes.
T or F: Most drugs cross into breast milk.
TRUE. Usually at low levels.
T or F: Milk is more basic than plasma.
FALSE. Milk is usually more acidic
T or F: When choosing a drug during breastfeeding, pick one that is more lipid soluble.
FALSE
T or F: When choosing a drug during breastfeeding, pick one that has higher protein binding.
TRUE. It will stay in the plasma rather than go into your mommy fountains
T or F: If a highly soluble drug is eliminated via lungs, increasing your respiration rate will increase elimination.
TRUE
T or F: If a poorly soluble drug is eliminated via lungs, increasing your respiration rate will increase elimination.
FALSE. Increasing blood flow to lungs increases the elimination of this drug.
Define first order kinetics.
The rate of elimination is proportional to the concentration of drug in the plasma.
How many half lives does it take to be reasonably sure that a drug is out of the body.
4-5
What is steady state?
The state in which plasma concentration is constant. Amount in = amount out. Steady state is generally reached in 4-5 half lives.
Does drug dose change the time it takes to reach steady state?
No. Time to steady state is independent to drug dose. However, drug concentration does influence the plasma concentration (Cp) when steady state is reached.
What factor does change the time to steady state?
Drug half life
If a drug?s half life is 2 hrs, what will be the change in plasma concentration if the drug is not given for 6 hrs?
8 fold fluctuation (2^3) in concentration
Define zero order kinetics.
The amount of drug eliminated per unit time is constant and not dependent on drug concentration.
