M1 L3: pharmacokinetics 2 Flashcards
drug clearance
process of removing drug from body
thru metabolism and excretion
CL = rate of drug elimination/drug concentration in blood
ml/min or L/hr
describe drug half-life
- eqtn
- definition
- an example
time required to remove 50% of drug from body
t₁₂ = 0.7 x Vd/CL
increased Vd = increased t₁₂
decreased CL = increased t₁₂
Ex:
10milligrams of the substances
Half life is 8 hours
5 milligrams is left
Another 8 hours
2.5
Another 8 hours
1.25
And so on…
Each time you lose half of whatever is left
Vd (volume of distribution)
CL (clearance)
0.7 is the constant
Big distribution = spreading everywhere
Small distribution = is confined (easier to get rid of)
If clearance is fast half life is low
If clearance is slow half life will be high
High volume distribution is high half life
what is 1st order kinetics
- for most drugs, body eliminates a fixed % of drug per unit of time
- elimination is not saturable
Most drugs we have follow this order of kinetics
* Fixed percentage means that x amount will be eliminated according to half life
* Kidney is main player here
* No saturation and everything depends on the drug concentration and therefore the drug half-life
Half life dictates drug loss
what is zero-order kinetics
- Lose drug here with a fixed amount (not fixed percentage)
- All dependent on the maximum amount you can lose
- Mainly thru liver
- Elimination is saturable (as enzymes get saturated)
- You need enzymes to metabolite in liver, at certain point liver can’t make this many enzymes so there will be a saturation
- r8 of drug elimination is independent of drug concentration
- Depends on enzymes, enzyme availability, liver, and liver function not the concentration of the drug
- Alcohol is eliminated by fixed amount: as long as the liver makes the alcohol enzyme alcohol can be excreted
AVAILABILITY OF ENZYMES**
zero order kinetics vs 1st order kinetics
(try drawing this out to remember)
elimination/unit of time:
rate of elimination:
extent of elimination:
main organ:
curve:
t₁₂:
drugs:
- 1st order kinetics
elimination/unit of time: percentage
rate of elimination: variable (depends on drug concentration)
extent of elimination: unsaturable
main organ: kidney
curve: exponential
t₁₂: constant regardless of drug concentration
drugs: most - zero order kinetics
elimination/unit of time: amount
rate of elimination: constant (unrelated to drug concentration)
extent of elimination: saturable
main organ: liver
curve: linear
t₁₂: no true t₁₂
drugs: few (ex: alcohol)
what is the plateau principle
- drugs eliminated by 1st order kinetics
- input = rate of elimination
- time to achieve depends on t₁₂
- takes 5x t₁₂ to reach plateau state
- doubling drug dose doubles concentration - 5x t₁₂ required to reach new plateau
- reducing the dose into half, reduces concentration by half - 5x t₁₂ required to reach new plateau
- when stopping a drug still takes 5x t₁₂ required to clear from body
- You will take medications again at the “half-life” to increase the concentration back to a good amount, but as time goes by and you are continuously doing this you are actually adding more concentration each time so you have to make sure its within the 2 red lines in the graph below (btwn D and 2D). It will reach a static amount they’ll just start showing similar values
- You want to stay in the therapeutic limit
- Usually takes 5 half-lives to maintain the plateau principle
- Zero order does not have this rule
- What if you double the dose: double the amount of concentration in the blood, your still losing 50%
dosage intervals
- depend on t₁₂ and plateau principle
- maintenance doses replace drug lost from the body
- consider inter-individual diff in ADME
calculating drug dosages
use metric sys of measurement
- L/mL } volume
- Kg, g, mg, mcg } weight
dosages for adults
determined by clinical trials
special consideration for obese patients
dosages for children
have diff ADME than adults
kids dose depends on: age, weight, body surface area
1.73 = avg BSA of an adult
child’s dose = (body surface area / 1.73) x adult dose
