Pharmacokinetics 1 Flashcards
Which 4 processes constitute a drug becoming therapeutic?
- Pharmaceutical process
- Pharmacokinetic process
- Pharmacodynamic process
- Therapeutic process
Which 2 mechanisms constitute a drug coming into the body?
- Absorption
- Distribution
Which 2 mechanisms constitute a drug coming out of the body?
- Metabolism
- Elimination
What are the 3 routes of administration?
- Focal
- Enteral
- Parenteral
Where does absorption of an oral drug occur and what is the normal transit time?
- Small intestine
- 3-5 hours
What types of drug can use passive diffusion transport?
- Lipophilic drugs
- Weak acids/bases
What does a long transit time allow for when a drug is transported using passive diffusion?
Gives more time for more of the drug to be absorbed due to the maintenance of equilibrium
What transport molecule does facilitated diffusion use and what are its two types?
- Solute Carrier Transporters (SLC)
- Organic Anion Transporters (OATs)
- Organic Cation Transporters (OCTs)
Where are solute carrier transport proteins most abundant?
- GI epithelia
- Hepatic epithelia
- Renal epithelia
What is secondary active SLC transport? Give an example
- Transport given by pre-existing electrochemical gradients
Fluoxetine - co-transported with Na+ ion
Penicillin - co-transported with H+ ion
Name 3 factors that can affect drug absorption
- GI surface area/length
- Drug lipophilicity/pKa
- SLC expression density
- Blood flow
- GI motility
- Food/pH
What is first pass metabolism?
Metabolism that occurs before the drug has entered the systemic circulation
What are the 2 families of enzymes involved in first pass metabolism in the gut wall and liver
- Cytochrome P450s
- Conjugating Enzymes
How can first pass metabolism be avoided?
Use of different routes - parenteral, rectal, sublingual
What is oral bioavailability?
The fraction of a defined dose of drug given orally that reaches the circulation unchanged
What is used as the 100% value to compare to in working out oral bioavailability?
IV bonus dose
What is the equation for oral bioavailability and where does its value always lie?
Amount reaching systemic circulation / total IV dose
- Value is always between 0 and 1
Name 3 drug distribution factors
- Drug molecule lipophilicity/hydrophilicity
- Capillary permeability (OATs/OCTs)
- Degree of drug binding to plasma/tissue proteins
How is the therapeutic window/ratio calculated?
Maximum Tolerated Dose / Minimum Effective Dose
- Area between effective and toxic concentrations
What is the effect of fast and slow release drugs on the therapeutic window?
Fast Release - have to be careful not to exceed toxic concentration
Slow Release - difficult to maintain level within therapeutic window
Which 3 fluid compartments are involved in drug distribution?
- Plasma
- Interstitial
- Intracellular
What happens when drug distribution is increased in interstitium/intracellularly?
- Decreased plasma drug concentration
- Increased volume of distribution (Vd)
Define volume of distribution (Vd)
Theoretical volume which the drug is distributed over if occurring instantaneously (time = 0)
What is the unit of volume distribution (Vd)?
Litres or litres/kg
How is volume of distribution (Vd) calculated?
Total Drug Dose / Plasma Drug Concentration when time=0
How do small and large volume of distribution values relate to penetration?
Small Vd = low penetration of interstitial/intracellular
Large Vd = greater penetration of interstitial/intracellular
How can volume of distribution (Vd) values be indicative of fluid compartments?
Values are indicative of compartments
E.g. 8L is similar to plasma volume
30L is similar to total water volume
Name 3 factors that can affect volume of distribution (Vd)
- Changes in regional blood flow
- Hypoalbuminimea
- Changes in body weight
- Drug interactions
- Renal failure
- Narrow therapeutic window
