Pharmacokinetics I (cont.) Flashcards
What is the range of pH in the stomach?
1.9-2.6
Differences in the pH of body fluids can lead to drug _______ in certain compartments.
trapping
*lead to changes in absorption and/or elimination
What is the range of pH in the intestine
6.4-7.6
What is the range of pH in the urine
5.0-8.0
In lower pH, will weak acid be charged or uncharged?
Uncharged (HA), which will allow it to cross membrane
What is the range of pH in the breast milk
6.4-7.6
same as intestine
What four aspects affect distribution of drugs?
- size of organ
ex: skeletal muscle: large organ hard to fill vs brain: small organ fills quickly - blood flow: well-perfused organs will achieve high tissue concentrations (e.g. brain, heart, kidneys, liver)
- solubility (e.g. highly lipid soluble drugs like high lipid content like the brain)
- binding (e.g. plasma protein binding)
Which organs fill quickly with drugs, large or small?
Small organs fill quickly
How does blood flow affect distribution of drugs?
Well-perfused organs will achieve high tissue concentrations
e.g. brain, heart, kidneys, liver
How does solubility affect distribution of drugs?
Highly lipid soluble drugs like high lipid content (like the brain)
Give an example of binding effects on distribution of drugs?
plasma protein binding
Drugs are distributed in multiple phases, what are these?
First phase drugs
- distributed to “high flow” areas (heart, liver, kidneys, brain)
Later phase drugs
- distributed to “low flow” areas such as bones, fat, and skin
Example of coated tablet:
Misoprostol outer mantle which allows for what?
- replenishes GI-protective COX-1 prostaglandins
- the second layer (enteric coating) delays NSAID release until the lower GI tract)
- do not give to pregnant women, induces smooth muscle contractions
The rate of movement of a drug across a barrier (membrane) is governed by Fick’s law which considers all of the following except:
a - route of delivery
b - surface area
c - drug permeability coefficient
d - thickness of the barrier
e - concentration on both sides of the barrier
a - route of delivery
Propantheline ______ GI Transit; hence more absorption
decreases
*acts to slow down contractions through gut
Metoclopramide ______ GI Transit; hence less absorption
increases
*acts to speed up contractions to move things through gut
Drug delivery to which set of organs is faster:
1 - heart, liver, kidney, and other well-perfused organs
2 - muscle, skin, fat
1 - heart, liver, kidney, and other well-perfused organs
It is the free fraction of drug that distributes from blood to other tissues. As such, distribution may be ____ by drug binding to plasma proteins.
limited
*particularly to albumin for acidic drugs and to alpha-1 acid glycoprotein for basic drugs
What are a few reasons that drugs may accumulate in tissues in higher concentrations than the free concentration in plasma?
- pH gradients
- binding to intracellular constituents
- partitioning into lipid
What is apparent volume of distribution (Vd)?
- relates the amount of drug in the body to the concentration (C) of drug in the plasma (extracellular portion of blood)
- the volume that relates the amount of drug in the body to the plasma concentration (units of volume)
Vd = amount of drug in the body (mg)/plasma drug concentration (mg/L)
*the larger the value of Vd, the greater distribution of drug into tissues/body
Vd (volume of distribution) may be affected by the individual person. For example, a lipophilic drug that has affinity for fat would be predicted to have a ______ volume of distribution in an obese person.
larger
What two general things does a low Vd indicate?
- drug does not have high affinity for tissues
and/or - drug is extensively bound to plasma proteins
What can Vd be used to calculate? Give the equation
the dose of drug that needs to be administered to achieve a desired plasma concentration
Dose = Vd * Cp
Vd = volume of distribution Cp = plasma concentration
What is charcoaid?
activated charcoal used to treat acute poisoning/overdose; should be given within one hour of drug intake
Blood-Brain Barrier
What about the capillary barrier limits paracellular diffusion
Tight junctons as opposed to fenestrations
Blood-Brain Barrier
What does a high TEER indication?
index of permeability
higher value, more restrictive vessel is going to be for drug to cross it
Blood-Brain Barrier
Are ATP-binding cassettes (ABC) efflux or uptake transporters?
efflux
- P-glycoprotein
- multidrug resistance proteins
- breast cancer resistance protein
Blood-Brain Barrier
Are Solute Carriers (SLC) efflux or uptake transporters?
uptake
- organic anion transporting polypeptides
What is the function of the BBB?
- maintain homeostasis
- restrict access to toxic xenobiotics/metabolites
