1 - Pharmacokinetics Flashcards
(52 cards)
absorption
movement of the drug from site of admin to plasma
distribution
movement of hte drug from plasma to tissues
metabolism
biotransformation of the drug
excretion / elimination
movement of the drug and metabolites out of hte body
Relationship of IAV admin and absorption
IV meds do not require absorption
Other than IV meds, what admin route does not have an absorptive phase?
Any drug delivered directly to target tissues, such as an antifungal topical applied to infected tissue
What are the enteral routes of admin?
oral, sublingual, rectal
What are the parenteral routes of admin?
IV, IM, Sub-Q
Identify the types of membrane crossing
What substances can move directly through the cell membrane?
small lipid solubles
What particles can move through porous gateways in the cell membrane?
Ions or small polarized drugs
What is Fick’s law of simple diffusion?
Flux = (C1 - C2) * [(area * permeability coefficient) / (thickness)]
Fick’s law relates the factors that effect the rate of simple diffusion. Going from high concentration to low concentration, we devide the area by thickness and multiply it by a permeability coefficient.
e.g. if a small amount of medicated paste is on a small part of the skin, the surface is thin and diffusion is quick. If it is on the heel of the foot, it will diffuse slower.
What factors effect absorption?
* diffusion (see Fick’s law)
* dissolution: the rate at which a substance diffuses (e.g. from tablet form into liquid that can contact membranes)
* blood flow [more = better absorption]
* surface area for absorption [more = better absorption]
* contact time [more = better absorption]
* pH and pKa
* expression of P-glycoprotein [less = better absorption]
Most drugs are ___ acids or ____ bases.
Most drugs are weak acids or weak bases.
When are acidic drugs neutral? In what kind of solution is this most likely? If a drug is a weak acid, what are environments when it can cross a biological membrane?
Acidic drugs are in their un-ionized forms they are attached to an H+ ion. This is most likely in an acidic solution.
Acidic drugs are likely to cross the biological membrane …
pK a/b
pKa is the dissocition constant of an acid. It is the pH where:
amount ionized = amount non-ionized.
amount lipid soluble = amount water soluble
amount can move across bio-membrane = amount that can’t
When is an acidic drug with pKa of 2 able to cross the bio-membrane?
Any body area with pH below 2.
Fill
pKa/pKb chart
Is a drug with a pKb of 2 more likely to be absorbed in the stomach or small intestine? Why?
The small intestine, because it is a more basic environment.
What is a P-glycoprotein?
Where in the body is it highly epressed?
Multidrug transmembrane transporter protein that removes drugs from their absorption enviornment and decreases absorption.
It is highly expressed in the Liver, Kidneys, Placenta, Intestine, and Brain Capillaries
Describe P Gylcoprotein role in the following tissues:
Liver
Kidney
Placenta
Intestine
Brain Capillaries
Liver - transports into bile for elimination
Kidney - pumps drug into urine for extretion
Placenta - transports drug back to maternal circulation
Intestine - transports drug back into intestinal lumen
Brain Capillaries - pumps drug back in blood, limiting access to the brain
Bioavailability
Fraction of administered drug that makes it to circulation
How do you calculate bioavailabity?
Using the plasma concentration curve for concentration over time. Bioavailability equals AUC (oral) divided AUC (injected) x 100. AUC = Area under the curve
What are factors influencing bioavailability?
First Pass (Hepatic) Metabolism
Solubility of the drug/balance of aqeuous and lipid solublity
Chemical Stability/Instablity
Nature of the drug formulation (particle size, which salt, etneric coating
