Pharmacology: Pharmacokinetics Flashcards
What are the factors affecting rates of drugs in - drugs out?
Absorption Distribution -------------------------------- Metabolism Excretion
What is first pass metabolism?
Metabolism of the drug carried out by the gut and liver - drugs absorbed by the gut pass into the portal circulation to the liver
What is the bioavailability of a drug?
How is it calculated?
The amount of drug that reaches the systemic circulation
Amount of drug reaching systemic circ / total amount administered
IV bioavailability =1
What is the oral bioavailability of a drug?
How is ti calculated?
A fraction used to determine the optimal route for a drug to be given to reach its therapeutic conc.
F = amount getting in by oral route / amount getting in by IV route
What factors affect the distribution of a drug?
- Lipophilicity - the more lipophilic the greater amount will leave plasma into fattier tissues
- Degree it binds to plasma proteins - high binding will reduce entry into other tissues and also lower free conc
- Degree it binds to tissue proteins - will decrease plasma conc, also lower free conc
- Volume of tissue and density of drug binding sites
What are the major fluid compartments?
Give values for each
- Intracellular fluid 25L
- Extracellular fluid 12 L
- Plasma (part of EC) 3L
What is the volume of distribution?
How is it calculated?
Vd = total amount of drug in body / plasma conc at time 0
The larger the value the more the drug diffuses throughout all the body compartments
How are drugs metabolised?
Largely metabolised by the liver:
- Phase 1 metabolism/ oxidation, reduction is carried out by CYP450s
- Phase 2 conjugation/ hydrolysis
Metabolism involves increase ionic nature of drugs so renal excretion is easier
How are drugs eliminated?
The metabolites are largely eliminated by the kidney via passive glomerular filtration or active tubular secretion. Excretion out of the plasma is offset by diffusion back across the tubule. Changing of the ionic nature by the metabolism also means drugs are more likely to be transported by the organic anion and cation transporters.
What factors affect renal excretion of drugs?
- renal blood flow
- plasma protein binding
- tubular urinary pH (affect the proportion of weak acids/ bases diffusing back into blood stream)
Renal disease states will have significant affects on the above factors
What is clearance?
Rate of elimination of a drug.
Clearance is measured as the volume of plasma that is completely cleared of the drug per unit time.
What factors affect clearance?
Acronym - Her Royal Highness
H- Heart
R- Renal
H- Hepatic
How do you calculate the half life?
T1/2 = 0.7 x Vd / CL
What does first order kinetics mean?
The rate of metabolism and elimination is dependent on the conc of the drug so if the conc of drug is low then the rate of metabolism is also low.
What does zero order kinetics mean?
Drug clearance is saturates so the CYPs are working at max capacity. This is relevant because the CYPs and transporters are not specific and therefore it can take a lot of time to process them and therefore the rate of clearance slows down.
Very few drugs exhibit zero order kinetics at therapeutic doses however with polypharmacy there can be competition for the same CYP.
