Drug Absorption & Distribution

Where does absorption occur?

mainly via intestine and to some extent stomach

What is distribution?

movement of drug from blood to tissues

What is mainly responsible for elimination?

kidney (urine) but can also be via feces

What is biotransformation?

conversion of drug to water soluble form more easily eliminated by the kidney

What are the characteristics of a subcutaneous administration and absorption?

inserted into fatty tissue beneath the skin drug moves through capillaries/lymphatic vessel into systemic circulation

What are the characteristics of an intramuscular administration and absorption?

used when larger volumes of a drug are needed; absorption into the bloodstream depends on blood supply to the muscle

What are the characteristics of an intravenous administration and absorption?

drug action occurs rapidly since injected directly into a vein but duration of action is shorter; monitor patient for undesired effects

What are the characteristics of an transdermal administration and absorption?

drug is delivered slowly and continuously for many hours, days, or longer typically through a patch to keep drug levels in blood relatively constant; useful for drug where only a small amount is required for an effect

What is absorption?

movement of drug into the blood stream

What is bioavailability?

fraction of administered drug that enters the systemic circulation for delivery to target cells or tissue

What does the drug’s bioavailability depend on?

how many cellular barriers exist between administration site and bloodstream

Which of the following has the routes of administration in order form most to least bioavailability?

IV, IM, SQ, PO

What is passive diffusion?

typically associated with hydrophobic (lipophilic) compounds that can easily diffuse across the lipid bilayer; thickness of membrane can impact absorption, smaller molecules move more easily

Passive diffusion occurs for what drug states?

un-ionized (non-polar)

At low pH, the un-ionized form of a weak ______ prevails.

acid

At high pH, the un-ionized form of a weak ______ prevails.

base

In which compartment will the weak acid (like an NSAID) be absorbed? Stomach or intestine?

stomach

In which compartment will the weak base (like propranolol) be absorbed? Stomach or intestine?

intestine

What is absorption through carrier-mediated transport?

drugs are transported via carrier proteins; can be facilitated (require no energy) or active transport (require energy-ATP)

What is efflux through carrier-mediated transport?

P-glycoproteins pump drugs out of the cell; blood brain barrier (BBB), intestinal epithelium in lower GI tract, renal tubular cells

How can P-Glycoprotein transport impart drug resistance?

multi-drug resistance protein (MDR-1) imparts resistance to cancer cells and antibiotics

What is passive paracellular diffusion?

passage between epithelial and endothelial cells; impacts”bulk flow” of drugs

What is an example of drug-food interaction?

sucralfate works to coat the stomach and intestines so should be administered 30 mins-2hours prior to food; can also interfere with absorption of other medications (coating)

What is drug distribution?

movement of drug towards its site of action; process by which drugs leave the bloodstream and enter the extracellular fluid and/or cells of tissues

What can limit the distribution of drugs to the brain?

endothelial tight junctions of blood brain barrier and P-glycoprotein efflux

What can decrease the distribution of drug to tissues?

protein binding since it increase their circulation time but decreases their absorption into tissues

What is an example of a protein binding drug?

weak acids like NSAIDs bind to albumin

What are the implications of protein binding drugs?

decreased amount is available for pharmacologic action and decreases elimination (kidney/liver) but more importantly other drugs can also bing to the protein and displace them from bind site increases likelihood of adverse reactions

What is a drug’s volume of distribution (Vd)?

volume in which the drug is distributed, assuming concentration throughout body are same as the plasma concentration; quantifies the amount of tissue to which drug is distributed; theoretical value

What does a large Vd imply?

drug distributes well to tissues and may be eliminated more slowly

A drug’s Vd can vary with age and species. What are other things that can alter a drug’s Vd?

dehydration and weight loss can decrease while fluid retention and obesity can increase

How do you adjust a dose based on varying bioavailability in administration sites?

original site/new; example oral/recal= 75%/30%=2.5 so if oral dose is 20 so 20×2.5=50 (new dose)

Which of the following is a true statement?

An obese patient may have a higher volume of distribution for a given drug.