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After phase II reactions, drugs are no longer active; they are in a more _ form and can be excreted easily in the _
After phase II reactions, drugs are no longer active; they are in a more hydrophilic form and can be excreted easily in the urine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
As the concentration of drug decreases, the rate of clearance decreases; this describes _ order kinetics
As the concentration of drug decreases, the rate of clearance decreases: first order
As the concentration of drug decreases, the rate of clearance remains constant; this describes _ order kinetics
As the concentration of drug decreases, the rate of clearance remains constant: zero order
In first order the enzyme is (saturated/ not saturated)
In first order the enzyme is NOT saturated
Drug half-life only applies to drugs cleared by _ order kinetics
Drug half-life only applies to drugs cleared by first order kinetics
As Vd increases, clearance _
As Vd increases, clearance decreases
You have to be in the plasma to be cleared/excreted
As Vd increases, clearance decreases, therefore half life _
As Vd increases, clearance decreases, therefore half life increases
Equation for half life
All drugs take _ half-lives to reach steady state concentration
All drugs take 4-5 half-lives to reach steady state concentration
Equation for maintanence dose
Equation for loading dose
Relationship between Kd and potency
Lower Kd = higher potency
What does Kd represent?
Kd = dissociation constant; it is the concentration of [s] that causes 50% receptor accupancy
Non-competitive antagonists are always (reversible/irreversible)
Non-competitive antagonists are always irreversible
Competitive antagonists change (potency/efficacy)
Competitive antagonists decrease potency (curve shifts right)
Non-competitive antagonists change (potency/ efficacy)
Non-competitive antagonists decrease efficacy
Inverse agonists work on receptors that are _
Inverse agonists work on receptors that are constituitively active
* These receptors have agonist-independent activity
* Ex: histamine
Equation for therapeutic index
Equation for margin of safety
A _ therapeutic index makes for a safer drug
A larger therapeutic index makes for a safer drug
