Drug Transport & Absorption -Dr. Issar Flashcards
what are types of transport mechanisms
- passive mechanism: simple diffusion
- active mechanisms: active transport
- specialized mechanisms: fascilitated diffusion
what are the types of simple diffusion
- filtration
- ion pair transport
- paracellular
what is a type of active transport
pinocytosis
what is lipid water partitioning
partition coefficient used in
simple diffision happens from high to low:
along concentration gradient.
What is Fick’s law of diffusion
Diff factors that inf the rate of diffusion across the bilayer membrane.
h= membrane thickness and the thicker the membrane the ____ the rate of diffusion.
lesser;
The only thing that changes is ____ gradient and is only dependent on conc of drug at the site and is very small thus follows ____ order diffusion pattern.
diffusion; first
The role of fascilitated diffusion is pretty small in absorption of drugs and follows Michaelis Menten kinetics. Low drug concentrations. Cabs
first
when conc of drug becomes high the Cabs»_space; Km and this follows ___ order diffusion. It doesnt depend on how much drug is at site, it depends on fixed ____
zero; rate
Some characteristics of active transport are
- against conc gradient (low to high)
- requires energy
- can be competitive
- saturable( when you go to high conc can go from 1st order to 0 order rate of transport)
- present in intenstine, kidneys, liver
- constant (0 order) absorption at higher drug conc.
____diffusion is most common with pharmaceutical drugs
Passive
____diffusion has no saturation. But fascilitated diffusion and active transport does have saturation
Passive
what does the extent of ionization of a weak electrolyte depend on
- pKa of the drug
2. pH of the solvent
for weak acids assume that we have a weak acid, HA which ionizes into its counterpart ions. Ratio of nonionized to ____.
ionized
What is ion trapping
If taking an aspirin with pka of 3.2. The aspirin in the non ionized form placed in acidic medium exists mainly as non ionized spcies. Will have a small portion being ionized. This has a tendency to go into blood with pH of 7.4. An acid sitting in alkaline medium gets ______. Majority gets transferred to ionized form and cannot cross and go back onto other side and gets trapped into circulation.
-ionized
Non ionized species on both targets will always be _____
equal
If molecule has ability to ionize and there is differential to pH it will:
move to other side
Weak ____ or acid will ionize to ___ degrees on the respective sides and have ____ drug conc on either side of the membrane and the compartment containing greater proportion of ____ drug will contain greater total drug concentration
base; different; unequal; ionized
when weak base is being ionized it will form its counterpart ions and the ratio flips in the case of a base. In weak acid, non ionized species on top, in the numerator. So in weak base the ratio is ionized species to ____
non ionized (more in stomach it will ionize)
anything thats ionized is hydrophillic and hydrophillic molecules have difficulty going across the _____
membrane.
weak acids in plasma are usually in ___ ____ form
non ionized
for weak base, you will acidify urine by giving ___ ___. Weak base wil be in ionized species and will have difficulty going back and will get excreted.
ammonium chloride
for weak acid you basify it…raise pH of urine. Phenobarb is weak acid and will ionize when pH is much higher and will get _____ out
excreted
Drugs with similar pKa can be affected differently by changes in pH of body fluids. Even though amphetamine has a similar pKa to chlorpromazine, why is there greater amphetamine excretion compared to chlorpromazine?
Bc chlorpramize is more lipophilic in nature. Liphophilicty overrides whatever pKa is doing in pH environment. A lipophilic drug will precede and will still be able to go back and get reabsorbed even if their being ionized.
what is another factor that affects drug elimination?
affinity/binding of the drug to a tissue component
weakly basic drugs can go into breast tissue and get trapped and ionize bec breast milk is ____
acidic
