Steps of drug absorption
slowed by product formation such as sustained release, enteric coating
slowed by acidic pH for weak acids, water insolubility, large particle size
slowed by decreased gastric emptying, increased ionized drug, fast SB transit time
4. first pass metabolism
enzyme saturation, P450 or PGP inhibitors result in less first pass metabilis and increased bioavailability
Why do you change disintigration of meds?
extend duration of effect (pharma)
improve compliance (take less pills)
improve patient satisfication (less peaks and troughs)
extend patent ($$)
Does lipid solubility increase or decrease how well a drug is absorbed from the gut?
lipid soluble drugs are MORE easily absorbed!!
first pass metabolism
pre-systemic - changes that occur before drugs reach the systemic circulation
enzymes on gut lumen (metabolism before enters portal blood)
enzymes in the liver (metabolism before enters IVC)
first in enterocytes then hepatocytes
from the moment it enters the gut until it enters systemic
absorb in SB - go to portal circulation and liver - some kicked out - amt that goes to heart + systemic circulation
orignially identified because of its role in the development of multidrug resistance during chemo
efflux transported located in the plasma membrane which translocates its substrates from the inside of the cells to the ouside
"flipase" , extruder
kick things out or prevent them from getting in
everywhere on protected surfaces - brain, gut, testes, ovaries - kick things out and prevent them from getting in
associated with P glycoproteins - kick things back into gut lumen - anywhere in the body
on surface of GI tract
men have more alcohol dehydrogenase at a younger age
men metabolize alcohol better than women
Why does sublingual bypass first pass metabolism?
mouth and anus are connected to systemic not portal!!
i.e. nitroglycerin has a high first pass!!
Why do antibiotics induce drug toxicity?
bacteria in the microbime can degrade drugs
antibiotics can cause toxicity because if you get rid of them less is metabolized in gut and you have toxicity
Why don't we use Ipecac?m
20 min to vomit can be a long time now
only removes toxins in stomach tht fit through holes
a lot of complications! respiratory depression, increased vagal tone, aspiration, trauma
things stick in large SA
don't get into body and enhances elimination
adsorbs many toxins - prevents absorption and enhances elimination (enteroenteric and enterohepatic)
2x more effective than lavage
need high charcoal:drug ratio!
passive diffusion - how pill gets through - reverse concentration gradient and drag drugs OUT
How do you get out drugs that are too small or not charged right for charcoal or lavage?
golytely - stool aggressively
forceful diarrhea to pull out
fluid and electrolytes!
huge molecule holds water in the gut and has electrolytes so you don't lose a ton
decreased GI transit time
not associated w any clinically significant fluid or electrolyte alteriates
what is the role of P glycoprotein?
prevents access of certain drugs from getting into the blood from the gut
Increasing the lipid solubility of a drug has what effect on it's absorption from the GI tract?
it increases it
Why do many oral abx alter digoxin pharmacokinetics?
some normal bacteria have the ability to metabolize digoxin
some abx interact w P-glycoproteins