Metabolism + Excretion Flashcards
How does enzyme saturation effect the rate of removal of a drug + what order is this
Makes it constant (a further increase in enzyme conc. does not effect rate of removal)
0
What drug follows 0 order kinetics
Ethanal if alcohol dehydrogenase is saturated
Define half-life
Time taken for a conc. to reduce by a half
What is half-life in the context of drug elimination
Elimination rate from plasma
Why dow e measure elimination rate from plasma
Easy to measure
Define bioavailability
Fraction of administered drug that reaches the systemic circulation un-altered
Why do IV drugs have bioavailability (F) of 1
100% of the drug reaches circulation
Why would oral drugs have F<1
Incompletely absorbed or undergo first pass metabolism
How does bioavailability effect prescriptions
If drug has F=0.1 than we need an oral dose of 10*0.1
How is bioavailability measured
AUC oral/ AUC IV
What factor effects rate of distribution of water-soluble drugs
Rate of passage across membranes
What factor affects rate of distribution of lipid soluble drugs
Blood flow to tissues that accumulate the drug
Why is extent of drug distribution important
Determines total amount of drug that has to be administered to produce a particular plasma conc.
How is extent of drug distribution measured
Volume of distribution (Vd)
Vd = total amount of drug in body/plasma conc.
What does a low Vd indicate
Drug is confined to circulatory volume
What does a high Vd indicate
Drug is mostly distributed in total body water
Define clearance
Volume of blood or plasma cleared of drug per unit time
What is the plasma conc. of a drug with a high Vd
Low
How is rate of elimination related to Vd
Rate of elimination is inversely proportional to Vd
Formula for Rate constant of elimination
K= CL/Vd
Consequence of a CL of 0
Drug would not be removes and plasma conc. would remain at equilibrium indefinitely
Formula for clearance for IV drugs
Dose/AUC for IV
Formula for clearance for oral drugs less than 1
Dose x F/AUC
Why do we use repeated drug doses
Maintain constant drug concentration in blood
What is Css
Steady State - balance between drug input and elimination
Difference in Css between injection and infusion
Injection - Rapid increase then rapid decrease before another dose is given
Infusion - Increase gets gradually slower until it reaches a peak and then decreases
How many half-live are needed to reach 95% of Css IV infusion
4-5
Consequence of a drug with slow elimination
Takes a while to reach steady state and will accumulate high plasma conc. before elimination rate rises to match drug infusion
Consequence of a drug with a high Vd
Delay in reaching Css as half life depends on Vd
When is Css achieved for IV infusion
When rate of elimination = rate of infusion
Rate of elimination = CL x Css
How can we calculate plasma clearance
CL = Rate of infusion / Css
How can we calculate Css
Rate of infusion/CL
Formula for Dose
Dose = Bioavailability/Time interval
What happens to the rate of administration when steady state is reached
Rate of administration = rate of elimination
Formula for rate of elimination
Rate of elimination = CL x drug conc.
D x F/t =?
D x F/t = CL x Css
Css =( Dxf/t)/CL
Effect of drug with long half life on Css
Takes longer time to reach Css
How can we overcome a long half life causing a long time to reach Css
Give a high initial dose to load the system and shortens time to steady state
Formula for loading dose
Css x Vd
How can the steady state be maintained after the loading dose
Css = D x F/t x CL
