Pharmacokinetics Flashcards
What are the pros and cons of IV administration?
very rapid onset but its invasive and requires training
What are routes of administration?
ingestion - GI tract -> hepatic portal system ->liver -> systemic circulation -> body
some goes to bile -> GI tract - > absorbed/excreted
What are systemic and local routes of administration?
systemic = entire organism exposed to the drug e.d BP lowering drug
local = restricted to one area of organism e.g skin infection
What is enteral and parenteral administration? Why would you use parenteral administration?
enteral = via GI tract - orally
parenteral = everything but GI tract - e.g IV
maybe drug isn’t absorbed/has short half life but needs to get into systemic circulation as quickly as possible,
How do drugs get into the systemic circulation?
bulk flow transfer - e.g in bloodstream in bulk
diffusion transfer - molecule by molecule over short distance
What are compartments and barriers?
compartment = aqeous e.g blood, lymph, ECF
barrier = lipids e.g cell membrane
What does the ratio of ionised to non-ionised form of the drug depend on?
pH of the environment and the pKa of the molecule
What form is aspirin in in the stomach?
aspirin is acidic and has a pKa of 3.4- in stomach pH is 1 (less than pKa of aspirin) so aspirin is persuaded to be non-ionised -readily diffuses across lipid layer -> intestines which is basic so becomes ionised -> much slower absorption
When would you use enteric coated aspirin?
uncoated aspirin for headache - fast absorption
coated for arthritis - resistant to stomach acid -> intestines -slow absorption
What is ion trapping?
e.g aspirin
in stomach its un ioninsed, in blood stream (neutral pH) its both ionised and un-ionised - un ionised form is mopped up by protein -> drug -protein complex -> extends half life of drug
What factors affect drug distribution?
regional blood flow- well perfused tissues = exposed to higher conc. of drug
extracellular binding (plasma proteins) - 50-80% drug bound to protein, albumin can bind to both ionised and un ionised
capillary permeability - fenestrated = more permeable to drugs, continous had=s water filled gap-junctions, discontinous had large gaps
localisation of tissues - fat isn’t usually highly perfused so its very lipophilic- lipophilic drugs localise in fatty tissue e.g brain
What are the main routes of excretion?
liver and kidney (kidney does most of the excretion)
many drugs and metabolites eliminated by kidneys -> converted into water soluble
in liver- large molecular weighted material -> bile -> intestines -> excreted
How do excreted drugs get into the urine?
via active secretion (not ultrafiltration) because you can’t filter large. protein bound drug complexes
Glomerulus-drug-protein complexes are NOT filtered
Proximal Tubule-active secretion of acids and bases
Proximal and Distal Tubules-lipid soluble drugs are reabsorbed Urine is an aqueous environment and if you have secretion from the glomerular filtration of a lipid material or the material has become more lipid by becoming unionised because of the pH of the urine -it has the ability to be reabsorbed
Why might treatment with I.V. sodium bicarbonate increase aspirin excretion?
I.V. Sodium Bicarbonate increases urine pH
Increase in urine pH ionises the aspirin
This makes it less lipid soluble
Less aspirin is reabsorbed in the proximal and distal tubules
Increase in the rate of excretion of aspirin
How does excretion occur int he liver?
Biliary excretion allows the concentration of large molecular weight molecules that are very lipophilic
There are also active transport systems that secrete drugs into bile
The active transport systems are geared for the transport of bile acids and glucuronides into the bile -drugs hitch a ride on this because they are non-polar and have a large molecular weight
Other routes of drug excretion include lungs, skin, GI secretions, saliva, sweat, milk, genital secretions
