Session 9 Flashcards
What are the advantages of topical administration?
Concentrates the drug at the site of action, less of it is absorbed by the systemic circulation.
Give examples of sites of administration
Oral, inhaling, topical, IV, IM, rectal, transdermal patches
Define oral bioavailability
Proportion of drug given orally (or any route except IV) that reaches the circulation unchanged
How is oral bioavailability measured?
By area (depends on first pass metabolism and gut absorption) and rate (depends on pharmaceutical factors)
How can oral bioavailability be calculated?
AUC oral/AUC injected x 100
What is the first pass effect?
When the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption (generally related to the liver and gut wall).
How can you avoid the first pass effect?
Parenteral administration (e.g. IV, IM, subcutaneous)
Rectal (note drainage to both portal and systemic systems)
Sublingual (e.g. use of glyceryl trinitrate in angina)
Define volume of distribution.
How is it obtained?
Theoretical volume into which the drug is distributed if this occurred instantaneously.
By extrapolation of plasma levels to zero time
When is protein binding interaction important?
When the object drug: is high bound to albumin, has a small volume of distribution and has a low therapeutic ratio
What is a class I drug?
An object drug. Used at a dose lower than number of albumin binding sites
What is a class II drug?
A drug that is used at doses greater than number of binding sites, and thus displaces the Class I drug.
Describe 1st order kinetics
The rate of elimination of the drug is proportional to the drug level. Constant fraction of the drug is eliminated per unit time. There is a definable 1/2 life
Describe 0 order kinetics.
The rate of elimination is a constant.
Describe the graphs of both 1st and 0 order kinetics against time
1st order –> linear when log y axis plotted against time
0 order –> straight line when linear y axis scale plotted against time
When does drug metabolism display 1st order or 0 order kinetics?
High doses –> 0 order
Low doses –> 1st order
Describe drug elimination
Mixed function oxidases (liver microsomal enzyme) consists of cytochrome P450 reductase. Main CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 3A4. Low substrate specificity. Inducible and inhibitable.
Describe renal excretion
The free fraction of drug is filtered. Drugs can be actively secreted by the tubules (e.g. penicillin secreted by proximal tubule. Passive reabsorption of drug is dependent on pH. Only the non-ionised moiety is lipid soluble and crosses membranes easily.
What is the pK value indicative of?
The pK of a drug is the pH at which half of it is ionised and half of it is non-ionised.
Describe the treatment of overdose of weak acids (e.g. aspirin).
Forced alkaline diuresis
What would you do if you were prescribing to someone with renal failure?
- If drug is excreted by kidneys, half lives of drug are longer. Lower maintenance dose of the drug
• Longer half lives also means longer time to reach a steady state (remember it takes 5 half lives to reach equilibrium).
• Loading dose can be altered. - Protein binding can be altered
