Lecture 8 Flashcards
What is drug absorption?
The passage of drug from the site of administration into the general circulation (topical drugs are an exception to this)
What is rate?
How rapidly does the drug get from its site of administration to the general circulation
What is extent?
How much of the administered dose enters the general circulation
What is bioavailability?
The area under the concentration time curve, expressed as a percentage, symbol F
What are the enteral routes of drug administration?
Oral, Sublingual (placed under tounge), rectal
What are the parenteral routes of drug administration?
Intravenous, subcutaneous, Intradermal, intramuscular, lungs
What are the two most popular routes of drug administration?
Intravenous, Oral
When is intravenous administration and oral administration used?
Intravenous is used when speed and accuracy is important
Oral is used in situations where this is less important as it is more convenient due to the lack of technical skill required to administer to it
What are the advantages to intravenous administration?
Very rapid, Precise control as 100% bioavailable, avoids problems of absorption, or drug break down before entering blood, good for drugs that are too irritating to be taken by month or given by tissue injection
What are the disadvantages to intravenous administration?
Skill is required, as air embolisms can form if incorrectly administered
Careful preparation of injected material is required as it must be sterile and non-particulate
Most hazardous as there is no way to stop the dose once it has been administered
What are the advantages to oral administration?
Safest, most convenient and economic
What are the disadvantages to oral administration?
Slow (1/2 hour - 3 hours till effect)
Unpredictable with regards to rate, extent and reproducibility as it must pass through the various barriers in the brain
What are the four barriers that drugs must pass through if administered orally?
1-Disintergration by stomach acid
2-Dissolution as the drug is dissolved in gut fluids
3-absorption drug must be absorbed by drug
4- Liver metabolism where the drug may be broken down by liver enzymes
What are the factors influencing the oral bioavailability of drugs?
Decomposition in acidic gastric juices
Decomposition by hydrolytic gut enzymes
Degradation by gut microorganisms
Food in the gut may alter absorption rate and amount (interactions or complex formation)
Metabolism by gut wall enzymes
Metabolism by liver enzymes prior to reaching the systemic circulation
What is the rate limiting step in oral drug absorption?
The stomach emptying rate
What are the patient factors which influence absorption?
Stomach emptying rate, intestinal motility, interactions with food
How does the stomach emptying rate affect the rate of drug absorption?
Rate is increased by mild exercise, hunger, metoclopramide
Rate is decreased by hot meals, vigorous exercise, pain, migraine, lanour and drugs
How does the intestinal motility change the rate of drug absorption?
Increased motility due to gastroenteritis and diarrhoea (decreased transit time which is important for drugs with low H2O solubility e.g. digoxin leading to a decrease in bioavailability)
Motility can be decreased by various drugs
How can interactions with food change the rate of drug absorption?
Chelation with metal ions leading to a decrease in bioavailability
What are the two most common mechanisms for excretion of a drug from the body?
Liver biliary secretions which lead to faecal excretion
the more common renal excretion by the kidney
How does capillary permeability affect drug absorption?
Most capillaries are relatively porous resulting in drugs being able to leave the blood regardless of their polarity
However brain capillaries also have a layer of glial cells which form the blood brain barrier, only lipid soluble drugs diffuse across this barrier
How can the solubility of a drug influence its access to bodily fluids?
H2O soluble drugs is restricted to extracellular fluid (14L)
While lipid soluble drugs can move into the intracellular fluid to access almost all bodily fluids
How does drug distribution relate to drug flow?
The tissue that receives more blood must also receive more drug
Rate of distribution to tissues depends on relative blood flow so the heart, lungs, brain, liver and kidney receive drugs rapidly while tissues such as skin,muscle and fat which are poorly perfused receive drugs at a slower rate
