Clinical Chem Therapeutic Drug Monitoring

gastric juice

Orally administered drug must encounter the low pH in ________ and digestive enzymes.

bioavailability

the fraction of initial administered dose of the drug that reaches its intended site of action or the systemic circulation

drug absorption

transportation of the unmetabolised drug from the site of administration to the body circulatory system

drug elimination

irreversible removal of an administered drug from the body, or from the plasma/blood, via either

hydrophilic drugs

directly excreted by kidneys

hydrophobic drugs

metabolic biotransformation before excretion

route of administration
rate of absorption
drug distribution within the body
rate of elimination

4 considerations of drug monitoring

intravenous

The most effective route of administering drugs is ______ because it is the most direct and bioavailability is at 100%

passive diffusion
carrier-mediated membrane transport
nonspecific drug transporters

3 mechanisms of drug absorption:

dissociation, solubility, diffusion

gastrointestinal drug absorption is dependent on:

_______ of the drug from its administered form

______ of the drug in gastrointestinal fluid

its ______ across the gastrointestinal membrane

changes in intestinal motility
pH
inflammation
coadministration of certain foods or drugs
age, pregnancy or other pathologic conditions

absorbance rate in small intestine can be altered by:

the stomach has thick mucous layer and short transit time thus limiting drug absorption
Moreover, small intestine has the largest surface area for absorption and the membranes are more permeable

Rate of absorption is different in stomach compared to small intestine, why?

Drug distribution

transfer of the unmetabolised drug from one location in the body to another after absorption

protein concentration
pH
metabolic abnormalities
presence of other chemicals

protein binding is influenced by:

blood perfusion
blood & tissue binding proteins
regional pH
permeability of cell membranes
body water composition
fat composition
diseases

drug distribution is impacted by:

Phase 1: introduction of functional group
phase 2: conjugation of the drug molecule with another molecule

What are the two metabolic pathways of hepatic drug biotransformation?

cytochrome P450

What enzymes are involved in phase 1 of hepatic drug biotransformation?

The drug molecules become water soluble, allowing renal and biliary excretion

What happens after phase 2 of hepatic drug biotransformation occurs?

renal excretion

free fraction of the drugs or its metabolites is filtered in the kidneys, and excreted in the urine

feces, enterohepatic

biliary excretion is where the liver actively secretes ionised drugs into bile to be:

eliminated in ______; or

reabsorbed as part of the _______ cycle