Pharmacokinetics Flashcards
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.
If you have a weak basic drug, how do you promote excretion?
Decrease pH. This increases the amount go H+ available to form the ionized drug. Ammonium chloride drops pH.
Designing a dose regimin curve
- Magnitude of therapeutic and toxic effect depends on drug dose
- Method of absorption and rate of metabolism affects how often the drug should be taken
- Cost, side effects and toxicity affect how long the drug should be taken for
What does MEC stand for?
minimum effective concentration (minimum # of receptors needed to be effective)
What does MTC stand for?
minimum toxic effect
What is therapeutic range?
in between minimum toxic concentration in the body and min. effective concentration
What is the difference between TR and TI?
therapeutic range is for drug concentration whereas therapeutic index is w/ respect to effect
What are the non-dosing factors that impact response?
- Patient compliance
- drug interactions
- disease
- age
- genetics
What is patient compliance?
3/4 of individuals are non-compliant with their medications
What is primary compliance?
People are compliant in filling out their prescription
What is secondary compliance?
If the drug is actually taken
What factors prevent people from taking medication?
Side effect, cost, inability to open package, physical appearance of drug
How does age affect ADME?
- as a child, pH of stomach is 4 and not 2. This means, drugs may not break down as readily and may accumulate to a toxic point.
- children have thinner skin -> ointments may absorb too much and become systemic
METABOLISM: fully functional after 1.5 years of age
EXCRETION: kidney function is only at 20% as a kid, and it works less efficiently in the elderly
