Pharmacokinetics + Pharmacodynamics Flashcards
What is the bioavailability for drug administered via IV?
100%
Doesn’t have to be metabolised or absorbed
How do you calculate bioavailability?
AUCoral / AUCIV
What is bioavailability affected by?
Absorption:
- formulation
- age
- food
- vomiting/malaboprtion
- previous surgery
.
First pass metabolism:
- metabolism before reaching systemic circulation
What are the four processes involved in pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
Pharmacodynamics vs pharmacokinetics
- pharmacodynamics: what the drug does to the body
- pharmacokinetics: what the body does to the drug
What is bioavailability?
The proportion of a drug which entered circulation after being introduced to the body to exert an effect
What factors affect therapeutic distribution?
- blood flow
- capillary structure
- lipophilicity + hydrophilicity
- protein binding (albumin + glycoproteins)
Types of protein binding of drugs
- albumin: acidic drugs
- glycoproteins: basic drugs
How do you calculate Vd?
dose / [drug]plasma
Why shouldn’t modified release tablets be crushed/removed from capsules before taking?
- Modified release tablets are designed to release dose in controlled gradual manner over extended periods.
- Crushing tablet will change the release profile
- Given a greater dose in a shorter duration
- possible GI irritation
What is bioequivalence?
The similarity of two medications:
- expansive brand name vs cheap non branded
- both the same drug + have the same effect
What does a smaller + larger apparent Vd suggest?
- smaller Vd: drug is confined to plasma + ECF
- larger Vd: drug is distributed throughout tissues
What factors affect CYP450 enzymes?
Age
Hepatic disease
Blood flow
Chronic alochol
Smoking
Routes of drug excretion
- urine
- sweat
- tears
- breast milk
- faeces
- hair?
Why is the apparent volume of distribution described as apparent?
It is a hypothetical value that assumes the drug is uniformly distributed throughout the body at the same concentration as the plasma
Why is apparent volume of distribution useful clinically?
Drug distribution information
Dosage adjustments
Drug half life predictions
What are the three outcomes of initial drug metabolism in terms of drug activity?
- no change in activity
- activation
- deactivation
What is the clinical significant of drug protein binding in regards to distribution?
- only unbound drug molecules are active + able to distribute + exert their effects
- high protein bound drugs tend to have a smaller Vd > large proportion remains in bloodstream
What is clearance?
What are the units?
Volume of blood cleared per unit time
ml/min
How do you calculate clearance?
Rate of elimination from body/[drug]plasma
Zero order vs first order elimination kinetics
- zero order: same amount is being eliminated per given time | linear
- first order: same proportion is being eliminated per given time | curved line (
How to calculate half life
t1/2 = 0.693 x Vd / CL
What is the half life?
When 50% of drug has been eliminated
t1/2
What types of elimination kinetics do most drugs exhibit?
First order kinetics
Same proportion of drug is eliminated per time
Relationship between rate contrast (k) and clearance
k is proportional to CL
Relationship between rate contrast (k) and Vd
k is inversely proportional Vd
How could you increase the half life?
Decrease clearance
Increase Vd (not really possible)
What exhibits zero order elimination kinetics?
Very high doses of drugs
Alcohol
Salicylic acid
Phenytoin
What is needed to reach the steady state plasma concentration?
4-5 half lives
Why are you still able to pick up traces of recreational or performance enhancing drugs long periods of time after taking?
It takes 4-5 half lives for the conc. to be negligible
This can take a while to occur
How do you calculate the rate of administration?
Maintenance dose x bioavailabilty / t
How do you calculate the maintenance dose?
Clearance x [plasma]that we want
———————————————— x dose interval
Bioavailability
How do you calculate loading dose?
Loading dose = Css x Vd
What is Css?
Steady state plasma conc
What needs to be considered in dosing schedules?
- to be safe
- maintain dose within therapeutic range
- achieve adherence
Why may a drug be preferentially delivered by oral administration?
- slower administration - first pass metabolism needed for pro drugs
- less invasive
- adherence
- can be taken at home
- if target is within the gut
How do you calculate the therapeutic index?
Median toxic / median effective
CYP table
What are the 4 main pharmacodynamic targets?
Receptors
Ion channels
Enzymes
DNA
