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What are the 3 A's of pharmacokinetics?
- (bio) availability
What factors affect the time it takes for a drug to get to the target?
- transfer across membranes
What factors affect the amount of time that a drug is available in the body?
- excretion out of the cell
- metabolism (liver)
- excretion from body (kidneys)
What does ADME stand for?
The rate of delivery and distribution of a drug is dependent on what 3 things?
- cardiac output
- regional blood flow
- tissue volume
In what parts of the body is Phase 1 delivery slower?
In what parts of the body is Phase 1 delivery faster?
What factors affect phase II delivery?
- lipid solubility
- binding to plasma proteins
- rate of metabolism/elimination
What is the most common cause of Warfarin problems?
- plasma protein binding
- plasma proteins act as a reservoir of the drug
- also the reason you may need a loading dose
Albumin is a?
What is an example of a drug that has a high rate of redistribution?
- lipid soluble anesthetics
- nitrous oxide
What regions of the body are hardest to treat with drugs? And why?
- CNS, CSF, brain
- because of BBB and tight junctions that are made to prevent toxins from getting in
- reason why brain cancer is so hard to treat..
_____ soluble drugs are better at getting across biological membranes?
What are some examples of teratogenic drugs and why are they teratogenic?
- Vitamin A
- because they are very lipid soluble, they can cross the placenta
T/F: Certain tissues have a higher affinity of drug uptake than others.
T/F: some drugs are eliminated completely unchanged.
true, but very few
When you add glucuronic acid to something during metabolism, it becomes more ____ soluble?
Which are more easily excreted- polar or nonpolar?
How can we make a lipid soluble drug more polar so that it can be more easily excreted?
- Phase 1 metabolism: hydroxylation
- Phase 2 conjugation: attach a water soluble molecule
What will enterohepatic recycling cause?
- prolonged drug effects
- --> oral contraceptives work this way
What is the primary mechanism of excretion?
- (biliary or renal excretion)
Renal excretion decreases how much per year in adulthood?
What are the 3 mechanisms that can occur in the kidneys with respect to excretion? (different paths to be taken)
- glomerular filtration
- tubular secretion
- passive tubular reabsorption
How do we measure renal function?
GFR (glomerular filtration rate)
T/F: exogenous or endogenous substances that are freely filtered by the glomerulus can undergo tubular secretion and tubular reabsorption.
Which are expensive and time-sensitive compounds that are used to test GFR- exogenous or endogenous?
exogenous (like EDTA)
What is the ideal endogenous compound used to test GFR?
Name another endogenous marker used to determine GFR (besided SCr).
Which ROA is best for large volumes or for high MW drugs?
What are 2 disadvantages of IM injections?
- they interfere with diagnostics
- can't be used with anticoagulants
What is the safest ROA?
What is the fastest ROA?
What is the most risky ROA?
the ability of a drug to absorb water from the air is called ______?
What is a cocrystal?
- helps control solubility
- can be found in insulin products
- fairly new area of product dev.
T/F: some drugs can have up to 20 polymorphs.
What drug had an unexpected polymorph spontaneously form and had to be removed from market?
How a molecule packs together in a crystal or more than one crystalline modifications is called ______?
What factors can cause the formation of a new polymorph?
- presence of water
- solvent type
- rate of cooling
- particle size
- method of filtering or drying
What drug was an example of having two different polymorphs, the anhydrous crystal and the hydrate?
triamcinolone (Kenalog inj)
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