Drug absorption

Drugs need to … Be effectively absorbed Be properly distributed Remain to produce an effect

Developments towards efficacy… Capsules – against degradation by gastric acid Modified –release tablets- extend action duration Prodrugs- precursor (forerunner) of a drug. It must undergo chemical conversion by metabolic processes before becoming an active pharmacological agent using body processes to convert agents into active compounds patches for trans-dermal delivery Dermal implants Inhalers Intrauterines – long term drug delivery in women Dosage- adjustable self- injection devices

Examples - prodrugs E.g. Sulfasalazine is a prodrug. It is not active in its ingested form. It has to be broken down by bacteria in the colon into two products aminosalicylic acid (5ASA) and sulfapyridine -- before becoming active as a drug.

MR Tablets Gliclazide 30mg used in diabetes mellitus increases the amount of insulin released by the pancreas and helps the body use insulin more efficiently.

Dosage- adjustable self- injection Nutropin AQ Pen ® delivers liquid GH (growth hormone) from a prefilled cartridge For children/ teenagers with growth failure

How drugs are absorbed… Passive diffusion down a concentration gradient Cell membrane and fat-solubility of drugs Active transport Disintegration and dissolution of tablets Presystemic metabolism

Passive diffusion Drugs are absorbed from intestine, skin, mucous membranes by diffusion across cell membranes through the concentration gradient ( the movement of a substance from a higher to lower place concentration)

Cell membrane and fat-solubility of drugs Oral drugs must cross the cell membranes of the intestinal villi Fat soluble molecules can pass directly through the cell membrane. E.g. instantaneous absorption of anti-anginal drug GTN ( glyceryl trinitrate )across the buccal mucosa - lining of the cheeks and the back of the lips, inside the mouth where they touch the teeth. The spray is absorbed almost as fast as an i.v. injection

Active transport Cells have active transport mechanisms- carriers transporting ions, sugars, amino acids in and out of cells that can move drugs from low to high concentration E.g. levodopa (to treat Parksinson’s disease) Fluorouracil ( anti-cancer drug) are actively transported across the intestinal mucosa. N.B – important to know that some cardiac drugs act by increasing or decreasing cellular transport mechanisms

Disintegration and dissolution of tablets Plain tablets disintegrate then dissolve in stomach For maximal concentration in small intestine, a drug should be taken before food

Presystemic metabolism Break down of drugs by enzymes- mainly in liver and some in intestinal mucosa, lungs and skeletal muscle Extensive metabolism results in decreased plasma concentration of drug. Drug dosage already accounts for the calculation