Absorption Flashcards
What is absorption?
Movement of a drug from the site of administration, across membranes, into the bloodstream
What are factors that affect rate of absorption?
Route of administration
Dose (concentration)
Lipid solubility (logP)
Weak Acid/Base drugs
What are route of drug delivery?
Inhaled
Oral
Topical
Transdermal
IV
IM
Subcutaneous
What determines whether or not a drug is ionised or unionised?
The pH of the solution and the pKa of the drug
What is ionisation?
The process whereby an atom or molecule acquires a negative or positive charge
What is the % ionised for an acid?
100/1+antilog(pKa-pH)
What is facilitated diffusion?
Selective gateway allows entry of one group of molecules but excludes all others
What is active transport?
Structurally selective
Energy requiring
Can be against a concentration gradient
Where are p-glycoproteins present?
In the apical cell membrane
What are p-glycoproteins dependent on?
ATP
Where in the body are p-glycoproteins present?
Intestine - prevents absorption
Liver - exceretion into bile
Kidneys - excretion into urine
Brain - prevent entry from blood to brainn
What is the function of p-glycoproteins?
Membrane efflux pump
What does Rifampicin do in treatment of TB?
Increases p-glycoproteins in the intestinal epithelium and reduces absorption of other substances
What does Verapamil do as a Ca2+ channel blocker?
Large enough dose will saturate the P-Glycoproteins and allow other substances to be absorbed more easily
What is bioavailability?
The fraction of a dose that reaches the systemic circulation in a chemically unaltered form
What does F represent in bioavailability?
The fractional availability
Why does incomplete bioavailability occur?
Failure to disintegrate
Chemical, enzymatic or bacterial attack
Failure of absorption and P-GP efflux
First pass metabolism in gut wall or liver
What can cause failure of absorption?
Binding to other molecules in the gut contents
Too polar to undergo passive diffusion
Efflux due to P-GPs
Examples of drug with good and bad oral bioavailability
Valproate - 100% bioavailability
Gentamycin - less than 5% bioavailable after oral consumption
