Drug Absorption and Distribution Flashcards
What are some factors affecting drug absorption?
solubility
chemical stability
lipid to water partition coefficient
degree of ionisation
How does lipid water partition coefficient affect drug absorption?
a large partition coefficient shows that the drug is readily absorbed in a lipid membrane
What form of drug readily diffuse across the lipid bilayer?
unionised forms of a drug
What does the degree of ionisation depend upon?
the pKa of the drug and local pH
What is the equation used to calculate the proportion of ionised and unionised drug?
Henderson-Hasselbach
pKa - pH = log(HA/A)
Where does the majority of drug absorption occur?
the intestine - even for weak acids
What types of drug are poorly absorbed?
strong acids and bases
When are acidic drugs less ionised?
in an acidic environment
When are basic drugs less ionised?
in a basic environment
What are the gastrointestinal factors that affect absorption?
the GI motility pH at the absorption site blood flow to the stomach and intestines the way the tablet is manufactured physiochemical interactions - i.e. rate of absorption is modified by calcium rich foods
What is the oral availability?
the amount in the systemic circulation/amount administered
What is systemic availability?
the amount in the systemic circulation/amount absorbed
What affects systemic availability?
first-pass metabolism
What are the possible routes of drug administration?
oral inhalational sublingual transdermal IV rectal Intramuscular
What are the advantages and disadvantages of oral administration?
\+convenient \+good absorption -inactivation through first pass -absorption variable -GI irritation
What are the advantages and disadvantages of sublingual administration?
+bypasses portal system
+ avoids gastric acid
- infrequent route
- few preparations available
What are the advantages and disadvantages of rectal administration?
+ by passes portal system
+ avoids gastric acid
- infrequent route
- people are squeamish
What are the advantages and disadvantages of IV administration?
\+ rapid onset \+ continuous infusion \+ complete availability \+ route for drugs that cause local tissue damage - sterile preparation - risk of sepsis - high levels of drug at heart
What are the advantages and disadvantages of intramuscular administration?
\+ rapid onset of lipid soluble \+ slow prolonged release - painful - tissue damage - absorption variable
What are the advantages and disadvantages of inhalational administration?
+ suited to lungs
+ good for volatile agents
+ good for local effect
What are the advantages and disadvantages of topical administration?
+ ideal for local effect
What form of drug can pass between interstitial, intracellular and plasma water?
unbound and unionised
What form of drug can pass between transcellular water and fat?
unionised
What is the equation for the volume of distribution?
Vd=dose/plasma conc.
What does a Vd less than 5L imply?
drug is retained in the vascular compartment or too large to cross capillary wall i.e. haparin
What does a Vd less than 15L imply?
the drug is restricted to the extracellular water - i.e. permanently charged compounds - tubocurarine
What does a Vd greater than 15L imply?
distribution throughout total body water or concentration in certain tissues i.e. ethanol - lipid soluble drugs
