Drug Absorption- 3

Question 1

Drug metabolism

Answer 1

Isn’t always a way of elimination. Some drugs need to be metabolized first to work.

Question 2

Interrelationships between pharmacokinetic and pharmacodynamic processes

Answer 2

Drug administration site -> Systemic circulation -> Sites of action/ Elimination sites (biotransformation liver, excretion kidney)/ Tissue reservoirs.

Question 3

A.D.M.E

Answer 3

Absorption
Distribution
Metabolism
Elimination or Excretion

Question 4

Absorption

Answer 4

A combined measure of the rate and amount of drug that moves from the administration site into the bloodstream. Does not account for metabolism or excretion and, thus is NOT a good predicter of a drug’s therapeutic action.

Question 5

Bioavailability (F)

Answer 5

A mathematical measure of the fraction (F) of drug that passes into the bloodstream. For any route of administration, F is measure relative to IV administration of the same dose of the drug.
F= AUCnon-iv/AUCiv X 100%.
Is a better predicter of a drug’s therapeutic action than absorption.Required by FDA and CVM for all new drug approvals.

Question 6

Determinants of Drug Absorption

Answer 6

Drug solubility, drug concentration, local blood flow, total SA, ability of drug to permeate cell membranes- passive diffusion, facilitated diffusion, active transport, pinocytosis & phagocytosis, filtration.

Question 7

Drug Solubility

Answer 7

in order to be absorped, a drug must dissolve into the aqueous phase of ECF, process called dissolution. Dissolution is highly-dependent upon the specific formulation and physical-chemical properties of a drug.
High to low absorption rates: aqueous solutions, aqueous suspensions, oily vehicles, pellets/solids.

Question 8

Drug concentration

Answer 8

the major driving force for drugs to move into the vasculature is the concentration gradient of unbound soluble drug. Increased concentration= increased absorption.

Question 9

Xylazine (ANASED)

Answer 9

classified as a sedative-analgesic agent, central alpha 2 adrenergic receptor agonist.
If you want to give an IM injection at a dose rate of 0.1 mg/kg, what volume formulation (20mg/ml) should be administered to sedate a 500 kg bull?
500kg X .1 mg/kg X 1ml/20mg= 2.5ml

Question 10

Blood flow

Answer 10

for drugs that easily permeate cell membranes, local blood flow can be the rate-limiting step for absorption. Local blood flow can vary markedly for IM vs SC injections.

Question 11

Absorptive area

Answer 11

contact surface area and drug absorption are proportional. Primarily determined by the site (route) of drug administration.
Factors that influence contact area:
PO- small intestines,
SC- loose skin, multiple injection sites, hyaluronidase,
IM- multiple injection sites,

Question 12

Cell membrane permeation

Answer 12

drug passage through cell membranes influences all pharmacokinetic processes (tissue distribution, onset speed, duration, elimination, etc). Primarily involves five processes. Smaller molecules can get thru quicker.
Passive diffusion- facilitated diffusion, filtration, active transport, pinocytosis & phagocytosis.

Question 13

Passive diffusion

Answer 13

is the most common mechanism by which drugs pass through cellular barriers in the body. Requires no energy nor any carriers. Movement is driven by the concentration gradient. The net rate of membrane diffusion is determined by- drug size, lipid, net charge. Smaller is better and fat is good!
Net charge is a critical determinant for membrane diffusion. Acids and bases behave in opposite manners. In most cases, the neutral forms of drugs permeate membranes easily whereas the charged forms do not.

Question 14

Henderson-Hasselbach relationship

Answer 14

the relative concentrations of protonated and non-protonated forms of a drug can be predicted by this relationship- part of passive diffusion.
pH= pK4 + log ( Proton acceptor/proton donor)

Question 15

Facilitated diffusion

Answer 15

like passive diffusion it does not require energy and results in drug movement exclusively down a concentration gradient. Involves a carrier molecule which binds with the drug and hastens the diffusion process. Molecule often demonstrates specificity for structurally related compounds.

Question 16

Filtration

Answer 16

typically refers to drug passage across the vascular wall by passage through small intercellular gaps between endothelial cells. Tissues exhibit marked differences in the “leakiness” or size of capillary endothelial gaps.

Question 17

Active transport

Answer 17

this process requires energy and is capable of moving drugs up and down the concentration gradient. More common than once thought and is largely responsible for urinary and biliary transport of drugs and drug metabolites, the neuronal transport of many neurotransmitters and movement of drugs across the choroid plexus.

Question 18

Principals of drug distribution

Answer 18

drug distribution into any tissue depends on two factors. 1) amount of drug delivered to a tissue:
Drug Delivery= concentration (plasma drug) X volume(blood flow).
2) rate of drug passage through the vascular wall: drug properties, vascular wall leakiness.

Question 19

Tissue blood flow- principles of drug distribution

Answer 19

for highly lipophilic drugs, distribution depends exclusively on tissue blood flow. Changes in cardiac output can alter drug delivery to a tissue. Some drugs undergo “redistribution” for termination of effect.
Thipental: rapid acting IV anesthetic, initially goes to brain, “recovery” occurs by drug redistribution to vessel poor adipose. Caution with emaciated or obese animals.

Question 20

Plasma protein binding- principles of drug distribution

Answer 20

typically involves an ionic interaction between a drug and one or more families of plasma proteins. Effectively reduces the level of “free” drug in plasma.
Drug-protein binding is reversible. The degree of binding is NOT a fixed constant. Drugs may compete for common binding sites and cause mutual displacement.