Absorption/Distribution Flashcards
What is drug absorption?
Mass transfer process that involves movement of unchanged drug molecules from the site of absorption to the bloodstream
What is the rate limiting step for drug absorption?
Crossing the epithelia or endothelia
What is the rate of absorption related to?
Time
What is the rate of absorption measured by?
Time parameters (ka, tmax)
What is ka?
Absorption rate constant
What is tmax?
time for the drug concentration to reach maximum in the plasm
What is absorption t1/2?
The time for 50% of the administrated dose is absorbed
What is the extent of absorption related to?
Magnitude or amount of the drug reaching to systemic circulation
How is the extent of absorption measured?
Bioavailability (F) of the drug
What are the 4 factors influencing drug absorption from oral admin?
Type of dosage form
Physico-chemical properties of the drug
Physio-anatomic condition of the host patient
Pathologic conditions of the host patient
What are the two main factors of physico-chemical properties of the drug
Aqueous solubility and permeability (log p)
What is the preferred route of administration?
oral
What do lipids and proteins in the blood do for circulating concentration of the drug?
Serve to increase the circulating drug concentration for certain aqueous insoluble drugs
What is permeability also dependent on?
pH (ionization)
What affects aqueous solubility and permeability?
Molecular weight
Ionization constant (pKa)
Solid state form
Particle size
What are charged species restricted to during absorption?
Paracellular pathway
What can drug release from the dosage form be affected by?
Excipients and manufacturing processes
For absorption to occur, drug molecules need to be in ____ at the absorption site
Solution
Rank the rate of drug absorption from the oral dosage forms
Solutions
Emulsions
Suspensions
Capsules
Tablets
Coated Tablets
Enteric coated tablets
Sustained release tablets
Drugs administered in ____ usually produce the most available drug product
Solution
What is the most important physicochemical parameter for absorption of the drug
Solubility
Low aqueous solubility results in ____ oral absorption
poor
Solubility of weak acids and bases in aqueous medium is dependent on __
pH
What happens when you decrease the particle size of a hydrophobic particle?
Surface area decreases
Need a surface active agent to increase effective surface area
What is the rate of absorption of an ionizable drug predicted by?
The pKa of the drug and the pH of the absorption environment
What must high lipid soluble drugs be accompanied by?
adequate water solubility
Equation for permeability
Permeability = ((๐ท๐๐๐๐ข๐ ๐๐๐ ๐๐๐๐๐๐๐๐๐๐๐ก) (๐๐๐๐ก๐๐ก๐๐๐ ๐๐๐๐๐๐๐๐๐๐๐ก))/(๐๐๐๐๐๐๐๐ ๐กโ๐๐๐๐๐๐ ๐ ))
What is stomach emptying?
It is the normal physiological process of the progression of the gastric contents toward the duodenum
What can the rate of drug absorption be influenced by when talking about gastric emptying?
The rate at which the drug arrives at the small intestine
What can gastric emptying rate be modified by?
Light physical activity - faster
Vigorous exercise delays it
Type, volume, viscosity, temperature of the ingested food (liquids eave the stomach faster than semisolids)
Concurrent drug therapy with cholinergic drugs increase the rate of gastric emptying
What can limit the availability of drug molecules for absorption in the gut wall?
Enterocytes in the upper segment of the small intestine that express cytochrome P450 (CYP3A4)
How can oxidation reactions mediated by CYP affect absorption?
Reactions involving the removal of various groups that make it less soluble
Biliary salts example
They can interact with drugs such as neomycin and kanamycin to form insoluble and non-absorbable complexes
What happens during drug secretion by efflux transporters in the GI?
after a drug penetrates the intestinal membrane and is in the cytoplasm of the enterocyte it may be subjected to secretion process mediated by a transporter which moves the drug back to the intestinal lumen
What are the active carrier mediated efflux transporter proteins?
P-glycoprotein or multi drug resistance 1
What does p-glycoprotein do?
limits drug absorption
Where is p-glycoprotein expressed?
in the luminal membrane of the small intestine enterocytes
How does drug degradation occur in the GI?
Gastric acid or several enzymes through enzyme mediated metabolism
Examples of enzymes that degrade drugs?
lyases
hydrolases
proteases
glycosidases
sulfatases
What is found more which decreases pH?
more bacteria
Where in the GI tract are bacteria low in numbers?
The proximal part of the small intestine
What pathologic conditions can change stomach emptying and GI permeability?
Celiac disease
constipation
diarrhea
vomiting
What alterations of the GI causes changes in drug absorption?
Population of intestinal drug metabolizing enzymes
pH of the intestine
Normal GI flora (antibiotics)
Secretion of digestive enzymes
Intestinal blood flow (CV diseases)
Hepatic diseases ( liver cirrhosis)
