2.1.3 CPK and CPD, Elimination Flashcards
What is zero order elimination
Same amount per time
Drug is eliminated at a constant rate e.g. alcohol, 7g eliminated per hour, doesnt matter if there is 100g or 10g it will still only be 7g per hour
What is first order elimination?
Same proprotion of drug per time
e.g. 50% of a drug will be eliminated ever hour, so if there’s 100g of a drug after 1 hour it will be 50g then after 2 hours 25g
What is half-life (t1/2)?
Time taken for half of the concentration of a drug to be eliminated
Independent of conentration - up to saturation point
First order kinetics
What is clearance?
Constant proportion,
Volume of blood cleared per time
e.g. 10% 100mL/min 20% 200mL/min
How do you work out clearance?
How does concentration affect clearance?
Constant proprotion
If there is more drug in the same volume, elimination of the drug increases
Elimination is directly proprotion to 1/Vd, so if Vd is large (low plasma concentration) less elimination ; vive.
How do you work out drug half life?
Higher Vd (spreads out to more tissues, low concentration in plasma) longer t1/2 ; vive.
What is the clinical significance of t1/2, Vd and CL?
Vd- volume that needs to cleared
CL-determines rate of elimination
t1/2 given by these
Elimination determines how much drug needs to be added to get back to therapeutic window
Allows us to calculate dosing in chronic treatment
What order of kinetics do most drugs exhibit?
First order at therapeutic doses
Very high doses leads to saturation causing zero order kinetics
What drugs can exhibit zero order kinetics?
Alcohol (most important example)
Salicylic acid
Phenytoin
What is the issue with zero order kinetics?
Dose change can produce unpredictable changes in [plasma]
T1/2 not calculable
What is steady state plasma (Css)?
Plasma concentration within the therapeutic range
Reached within 4-5 half lives
Why can recreational or performance enhancing drugs be detectable after long periods of time?
Takes a very long time to completely eliminate due to half lives of drugs
How do you calculate Css (steady state drug)?
How can dosing differ between different conditions?
Multiple doses in hypertension vs single in headache
In chronic treatment what is the most common mode of delivery?
Oral (p.o.)
How do you calculate maintenance dose?
What is a loading dose?
Single dose to achieve desired concentration taking into account apparent Vd
Why do we use loading doses?
Rapid onset required or drug with a long half-life
Therapeutic response needed quickly
How do you calucate loading dose?
Clinical example of loading dose, Amiodarone
Amiodarone - very large Vd 66L/kg
If amiodarone is to be used for SVT need loading dose
Long half-life, can remain in body for several months afterwards, can cause medical error if prescribing as may not be considered if it was months ago
Why are dosing schedules important?
Maintain a dose within therapeutic range
Achieve adherence
May need to increase or decrease dose size to get in therapeutic range
How do you know if you have prescribed successfully?
What is selectivity?
Ratio of [drug] that achieves response at one receptor subtype vs [drug] needed at other receptor subtype
Basically how much does the drug prefer one receptor
What is affinity?
Strength of interaction between a drug and its receptor
High affinity means less drug needed to occupy given proportion of receptors and elicit a given response
What is potency?
[Drug] needed to elicit half of the maximal response
EC50
What is efficacy?
The ability to produce the maximal response of a particular system
Give an example of a:
- Full agonist
- Partial agonist
- Inverse agonist
- Neutral antagonist
- Non-competitive antagonist
- Functional antagonist
Full agonist- adrenaline
Partial agonist- buprenorphine
Inverse agonist- propranolol
Neutral antagonist- naloxone
Non-competitive antagonist- alpha blocker
Functional antagonist- depends on what it is opposing
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