Lecture 1 Flashcards
What is the clinical aim of a drug?
Achieved effective drug concentration at site of action long enough to produce a therapeutic effect
What is the therapeutic index?
Ratio of a drug’s toxic level to the level that provides therapeutic benefits
What is bioavailability?
Proportion of a dose that reaches systemic circulation
What does 100% bioavailability mean?
All of the unchanged drug has reached the site of action
Positives of intravenous injections
- 100% bioavailability - rapid action
Negatives of intravenous injections
- sterile equipment - trained personnel - expensive - potentially painful
Positives of Oral Administration
- safest - most convenient - most cheap
Negatives of oral administration
- always less than 100% bioavailability - destruction by enzymes, pH, bacteria - drugs can complex with food - absorption depends on rate of passage - irritation may cause vomiting - requires patient compliance
Factors affecting passive diffusion
- size of drug molecule - ionisation of drug - lipid solubility
Which drug ionisation is better absorbed?
Unionised drugs
What is the main site of drug absorption?
small intestine
Why is the small intestine the main site of drug absorption?
- large surface area - alkali pH - large blood flow from capillaries
What are the two other sites of drug absorption?
Stomach and colon
How does formulation affect GI absorption
Drug form affects likelihood of entering hepatic portal vein
Do tablets or fine particles better enter the hepatic portal vein
Fine particles
Two factors affecting rate of absorption
- gut motility - splanchnic blood flow
Examples of orally administered drugs with potential problems
- phenomethylpenicillin (pen V) - tetracyclines - aspirin (NSAIDS)
Phenomethylpenicillin (pen v) issue
- absorbed by food - reduced bioavailability when this happens
Tetracyclines issue
Chelate metals so absorption reduced by milk, antacids, and iron preparations
Aspirin (NSAIDS) issue
- irritate the stomach= dyspepsia, nausea, vomiting and diarrhoea - gastric damage
Issues of taking antibiotics and oral contraceptives
- drug interactions - oral contraceptives undergo enterohepatic cycling
first pass metabolism
Degradation of an orally administered drug caused by enzyme metabolism in the liver and gut lumen before the drug reaches the systemic circulation
Why is a high first pass metabolism bad
- orally ineffective - a drug will be broken down before it reaches system circulation
Different routes of administration
- inhalation - transdermal - buccal and sublingual - intranasal - rectal - subcutaneous - intramuscular
Inhalation mechanisms
- absorption depends on particle size - lipid soluble anaesthetics
Transdermal mechanisms
- stratum corneum acts as a rate limiting step - lipophilic - low input rates (slow absorption)
Examples of transdermal drugs
- nicotine patches - HRT (oestrogen/progesterone) - fentanyl patches - ibuprofen gels
Buccal and sublingual mechanisms
Passive absorption, washed away by saliva