Pharmacokinetics Flashcards
Define half life:
Time taken for the concentration of a drug to reduce to half the concentration at administration (i.e time taken for 50% of the drug to be metabolised)
Define volume of distribution
The volume required to contain the drug in the body at the same concentration as the plasma
When does plasma concentration equilibriate?
When the rate of injection and elimination are equal
When is a steady-state plasma concentration acheieved?
After 3 or 4 half lives, hence why loading doses of drugs are often given to speed this up.
Clinically, why is the half life of a drug important?
It determines the interval/ frequency of drug administration
Define bioavailability
The amount of drug that enters systemic circulation and is available at the drugs site of action
What factors can affect bioavailability?
First pass metabolism
Incomplete absorption
Do ocular topical drugs undergo first pass metabolism?
No, they are absorbed by the nasal and nasopharyngeal mucosa directly into the systemic circulation, so they avoid the first pass metabolism in the liver. Hence topically applied ocular drugs can have marked systemic side effects.
What are the two types of kinetics that drugs can exhibit?
First order kinetics
Zero order kinetics
What is first order kinetics?
This is when the rate of a drug is directly proportional to the dose (amount of drug present)
What is zero order kinetics?
Drug dynamics show saturation at higher concentration of the drug i.e. at higher concentrations the rate cannot be increased any further with further increase in the drug because there are no more receptors/enzymes etc
How is drug absorption related to lipid solubility?
Lipid solubility increase the rate of absorption because the drug can diffuse directly through the cell lipid membrane
Do Polar or non-poalr substances diffuse easily?
Non-polar substances
What factors affect the rate of diffusion through a cell lipid membrane?
Ionised state (ie. polar vs non-polar) Lipid solubility Size of molecule pH Route of administration Bound to proteins
How does food in the gut affect absorption of tetracyclines?
Presence of food in the gut will form insoluble salts with magnesium and calcium
If a drug is bound to protein (eg albumin) in the plasma, will the absoprtion be affected by changes in protein level?
No, unless >90% of the drug is carried by binding to protein/albumin, changing protein levels will not have an effect on the distribution of the drug
Are protein-bound drugs freely available to act on tissues?
no
Are acidic on alkalitic drugs more likely to bind with albumin?
Acidic
What is a1 acidic glycoprotein?
A protein that can bind drugs such as propanolol
How does a1 acidic glycoprotein affect propanolol concentrations?
A1 acidic glycoprotein concentrations can be increased in certain conditions such as inflammation, which means that it binds more propanolol therefore less of the free drug is available (AKA reduced action of propanolol)
What factors are known to alter protein binding levels?
Hypoalbuminaemia (Albumin <25g/l)
Increase of other high affinity binding proteins
Last trimester of pregnancy (increased circulating volume dilutes albumin)
Renal failure
Where does drug excretion usually occur?
Mostly in urine, sometimes bile
What are the two phases of drug metabolism?
- Oxidation (cytochrome P450)
2. Conjugation
Where is Cytochrome p450 located?
Liver and some in eye
