Absorption and Distribution of Drugs Flashcards
How can a drug pass through a layer of cells?
Passive diffusion
- phospholipid bilayer
- intercellular pores
Pinocytosis, Facilitated diffusion,Active transport (of limited importance for drugs)
Describe ion trapping
Many drugs exist in an equilibrium between the ionised and unionsied forms
Only the unionised forms can diffuse through membranes
Drugs tend to accumulate in areas where ionisation is favoured.
Weak acids tend to be well absorbed from acid environments and weak bases tend to well absorbed from basic environments.
Weak acids will be trapped in basic environments
Weak bases will be trapped in acid environments
What is bioavailability?
the fraction of the total dose administered that reaches the plasma
Factors affecting absorption of drugs from the GI tract
- dispersal/solubility in gut contents
- stability of drug
- lipid solubility
- time available
- concentration
- blood flow
- interaction with food
- first pass metabolism
Possible pharmaceutical interventions
- particle size
- enteric coated tablets
- slow/delayed release preparations
- implantable preparations
Factors affecting transdermal absorption
Lipid solubility Formulation Skin thickness Hydration Blood flow
What is the first pass effect?
The metabolism of orally administered drugs by gastrointestinal and hepatic enzymes, resulting in a significant reduction of the amount of non-metabolized drug reaching the systemic circulation
Variation in plasma protein binding
Competition between drugs Albumin – decreased levels in liver/kidney disease Alpha one acid glycoprotein – increased levels in inflammatory conditions
What is apparent volume distribution?
The notional volume of fluid required to dilute the absorbed dose to the conc found in plasma
AVD = dose/plasma conc
If heavily plasma protein bound AVD = low
If heavily tissue bound AVD = high
