10.16 Pharmacokinetics Flashcards
_ refers to how the drug affects the body
Pharmacodynamics refers to how the drug affects the body
_ refers to how the body affects the drug
Pharmacokinetics refers to how the body affects the drug
Stages of pharmacokinetics (4)
Drugs must be sufficiently _ to get through membranes and into our blood
Drugs must be sufficiently hydrophobic to get through membranes and into our blood
* Need to cross the epithelium and the endothelium
Bioavailability (F) for IV drug is _
Bioavailability (F) for IV drug is 100% or “1”
Calculate oral availability based on time vs. concentration curve
F= area under the curve (oral) / area under the curve (I.V)
First pass metabolism
First pass metabolism: oral drugs face two hurdles before they get into the bloodstream:
1. Must pass the gut wall
2. Gets metabolized by the liver
Phase I reactions make _ modifications to drugs
Phase I reactions make small modifications to drugs (makes them slightly more polar)
* They are still slightly active upon completion of phase I metabolism
Phase I reactions include:
Phase I reactions include: oxidation, reduction, hydrolysis
Phase II reactions add larger groups;
The main reaction is _
Phase II reactions add larger groups;
The main reaction is glutathionation
* Also glucuronidation, glycination, sulfation, methylation, acetylation
After phase II reactions, drugs are no longer active; they are in a more _ form and can be excreted easily in the _
After phase II reactions, drugs are no longer active; they are in a more hydrophilic form and can be excreted easily in the urine
How does hydrophilicity affect reabsorption in the kidney?
More hydrophilic metabolites are less likely reabsorbed in the kidney; which helps more of the drug get excreted into the urine
The main enzymes involved in phase I reaction are the _ family
The main enzymes involved in phase I reaction are the CYP450 family
How does ethanol affect acetominophen metabolism?
Ethanol activates CYP2E1 –>
Increases the intermediate NAPQI –>
NAPQI is toxic to the liver
What happens if you take omeprazole & cefpodoxime together?
Cefpodoxime is a prodrug that must get activated by the stomach acid’s low pH –> gains a hydrogen in this process and becomes a neutral/absorbable form
When omeprazole is given for acid-reflux, it increases the pH of the stomach and blocks this activation of cefpodoxime
This is an example of a drug that blocks another drug’s absorption
Why should you not take NSAIDs with warfarin?
NSAIDs will compete for albumin –> knocks warfarin off of albumin –> increases free warfarin –> increased bleeding risk
How does probenecid interact with penicillin?
Probenecid blocks the anion transporters that normally transport penicillin across the nephron epithelial cells –> blocks the transport into urine –> accumulation of penicillin in the blood
How does verapamil interact with digoxin?
Verapamil blocks inhibits the clearance enzyme that removes digoxin –> toxicity
Fick’s law of diffusion
Drugs must be _ enough to cross the BBB
Drugs must be hydrophobic enough to cross the BBB
High Vd means:
High Vd:
* Drug can move out of the plasma and distribute to other tissues
* Drug is likely small and hydrophobic
Low Vd:
Low Vd:
* Drug must stay in the plasma
* It is probably large and less hydrophobic
How do we calculate the volume of distribution?
Vd = Q / Cp
Volume of distribution = dose/ plasma concentration
Affect of plasma proteins on Vd?
Plasma proteins like to bind the drug and retain it in the plasma, lowering Vd
