Pharmacokinetics Flashcards
(36 cards)
What does ADME stand for?
Absorption -> gets the drugs into the blood
Distribution -> where it goes in the body
Metabolism -> what happens to it
Excretion -> how it gets out
Where does absorption take place?
stomach, blood, and small intestine
How does absorption happen?
movement of drug from site of administration into the blood (passive diffusion)
What factors influence absorption?
- concentration gradient
- size of the drug (smaller is better, so it can pass the lipid membrane)
- lipid solubility (to pass hydrophobic tail)
How does charge effect lipid solubility and permeability?
Only uncharged molecules can passively diffuse across the lipid bilayer. This is because uncharged particles are hydrophobic, whereas charged particles are hydrophilic.
What is the pH of the stomach and urine?
Stomach: 2
Urine:6
Where does the drug know where to go?
It does not, it circulates through the blood and binds to the receptors that they have affinity for.
What is distribution?
The process by which the drug reversibly leaves the bloodstream.
What are the influencing factors?
- concentration gradient
- size
- lipid solubility
- blood flow
- protein binding
How does blood flow influence distribution?
Blood circulates to drugs to the highest areas first. These are the heart, brain and other vital organs.
2nd = muscles, skin
3rd = fat
How does protein binding influence distribution?
Plasma proteins like albumin attach to the drug at different degrees. This can decrease the therapeutic effect by trapping the drug. Additionally, since the plasma proteins are large, they make the small drug particle large too. This renders the drug pharmacologically inactive.
What is an important consideration when formulating a drug?
Checking how much of the drug could potentially be trapped.
What is metabolism? Where does it occur?
Irreversible biotransformation of the drug. It occurs primarily in the liver, but on rare occasions the lung or gut.
How does metabolism transform the drug?
It makes the drug more polar to make excretion easier through the urine. (urine is mostly water, which is polar)
What is Phase 1 metabolism?
Oxidization, reduction and hydrolysis occurs.
CYP 450 enzymes add or uncover chemical groups to increase solubility (-NH2, -OH, -SH).
Inducers and inhibitors
inducers -> decrease therapeutic effect (alcohol and St. Johns Wart)
inhibitors -> decrease the rate of metabolic activity hence increasing the toxicity of the drug (grapefruit, or antibiotics)
What is Phase 2 metabolism?
Various non-CYP 450 liver enzymes covalently add large, polar, endogenous molecules to the drug.
After metabolism why cant the drug re-absorb?
It is large, polar, charged and has a changed shape.
What is excretion?
Irreversible loss of drug or metabolite from the body
Where does excretion occur?
through the urine, but sometimes in bile, feces and breastmilk.
How does the metabolite move?
Active transport
How do diseases affect ADME process?
GI tract -> vomiting, chrons diastase (decrease absorption)
Circulatory -> heart failure (decreases distribution)
Liver ->hepatitis, liver failure (decreases metabolism)
Kidney -> renal failure (decreases excretion)
How are drug overdoses treated?
If the drug has not been absorbed you can induce vomiting or get the stomach pumped.
If the drug has already been absorbed, it can be forced out by the urine.
If you have a weak acidic drug, how do you promote excretion?
Increase pH. This shifts the eq’m so there is more water soluble form. Sodium bicarbonate raises pH.
