Administration, distribution, metabolism and elimination of drugs Flashcards
ILO 4.12a: have knowledge of the basic principles of pharmacology
what routes of drug administration are enteral via the gut?
5
oral
rectal
nasogastric
nasointestinal
PEG - percutaneous endoscopic gastronomy
what route of drug administration are parenteral via not the gut?
6
transdermal
transmucosal
intravenous IV
intramuscular IM
subcutaneous SC
inhalation
what are the advantages of oral drug administration?
4
convenient, portable, painless
non-invasive
cost effective
patient can self administer
what are the disadvantages of oral drug administration?
4
slow onset
may be inefficient
variable absorption - food interactions, GI disease
first-pass metabolism
what is first-pass metabolism?
blood from GI tract drains to hepatic portal vein which drains to liver
liver metabolises drug which passes through liver once then enters systematic circulation and target tissues
what 2 things can the liver do to a drug?
inactivate proportion of drug - more needed to et desired clinical effect
activate proportion of drug - makes an active form from an inactive drug - less needed by oral route
what are the advantages of intravenous and intramuscular drug administration?
3
very rapid onset
predictable plasma levels
no first pass metabolism
what are the disadvantages of intravenous and intramuscular drug administration?
5
allergic reactions more severe
short duration of action
requires trained staff to administer
higher drug cost
painful
what are the advantages of transdermal and subcutaneous drug administration?
4
no first pass metabolism
allergic reactions often very localised
prolonged action
can be self-administered
what are the disadvantages of transdermal and subcutaneous drug administration?
3
very slow onset
drug cost higher
effect will vary from person to person and site to site
what is bioavailability?
proportion of an ingested drug that is available for clinical effect
what is bioavailability modified by and affected by?
2 (3,3)
modified by pharmaceutical factors
* dosage
* formulation
* route of administration
affected by physiological factors
* destruction in the gut
* poor absorption
* first pass metabolism
what is drug distribution and how does it occur?
the movement of a drug to and from the blood and various tissues
drug is dissolved in the blood and transported bound to plasma proteins
what does the speed of diffusion into tissues depend on?
4
blood flow in the area
membrane characteristics
pH
active secretion of the drug into the tissues
what is the single and two compartment model?
2
single compartment model - drug behaves as if it is evenly distributed around body
two compartment model - drug behaves as it is in equilibrium with different tissues in the body
what is metabolism and where dooes it occur?
metabolism prepares the drug for elimination from the body
occurs in the liver but some processes occur in the gut wall, kidneys, lungs, blood plasma
where are drugs excreted from?
6
renal excretion of water soluble metabolites - urine
liver metabolism and excretion - bile
lungs - inhaled gases and volatile fractions of other drugs
small proportions as sweat, saliva, tears
what are the three stages of renal excretion?
glomerular filtration
reabsorption
secretion
what problems can cause excretion probelms? what should be adjusted?
2(2,2)
renal disease
* chronic renal failure
* drug doses must be reduced
liver disease
* liver failure
* drug doses must be reduced
what is plasma half life?
time taken to eliminate half the drug
what are the first order kinetics in relation to drug clearing?
2
drug elimination increaes as drug concentration increases
excretion is by passive diffusion only
what are the zero order kinetics in relation to drug clearing?
3
drug elimination is at a fixed rate and irrespective of drug concentration
excretion is by active processes
can lead to drug accumulation if saturation exceeded
what happens if drugs are dosed too frequently or infrequently?
2
too frequent - results in plasma levels that may be toxic
too infrequent - results in sub-therapeutic plasma levels and no clinical effect
what is the dosage for paracetamol overdose and where does metabolism occur? what can overdose cause?
safe dosage of 4g over 24 hours
metabolism occurs in the liver
can cause liver damage, failure, acute hepatoxicity