ABSORPTION

ABSORPTION
transfer of a drug from its site of administration to the bloodstream

TRANSPORT OF A DRUG FROM THE GI TRACT

MECHANISM PASSIVE DIFFUSION ENERGY NO CARRIER NO NOTES Rapid Lipohilic Nonionic Small molecules Slow Hydrophilic Ionic Large molecules Bind to carrier Chemically similar drugs compete for carrier Small (<200 MW) hydrophilic drugs diffuse along concentration gradient by passing though aqueous channels (pores)

FACILITATED DIFFUSION AQUEOUS CHANNELS

NO

YES

NO

NO

ACTIVE TRANSPORT

YES

YES

ATP powers transport against concentration gradient

A. PHYSIOCHEMICAL/BIOLOGIC FACTORS THAT AFFECT ABSORPTION

PHYSICAL STATE
SOLIDS (pills, tablets) FIRST PASS EFFECT
disintegration degradation dissolution

LIQUIDS
must be aqueous to facilitate absorption absorbed faster Intravenous 100% enters circulation

GAS Inhalation Rapid absoprtion

A. FACTORS THAT INFLUENCE ABSORPTION

DEGREE OF IONIZATION AND LIPID SOLUBILITY ONLY NON-IONIZED FORMS WILL BE ABSORBED!!!!!!
Lipoidal/ Lipid Soluble Form easily absorbed

HA Nonionized Acidic drug BOH Nonionized Basic Drug

H+ Hydronium Ion B+ cation

AAnion OHHydroxyl group

WEAK ACIDS - most un-ioninzed form (lipoidal) WEAK BASE - ionized only to a limited extent (cation + hydroxyl ion) EASILY ABSORBED EASILY EXCRETED Protonated (HA) Deprotonated (A-) Deprotonated (B-) Protonated (HB)

A. FACTORS THAT AFFECT ABSORPTION

CONCENTRATION OF DRUG IN A SOLUTION
HIGH CONCENTRATION IN SOLUTION = HIGH CONCENTRATION IN PLASMA

CIRCULATION TO THE SITE OF ABSORPTION

INSTESTINAL ABSORPTION IS FAVORED

AREA OF ABSORBING SURFACE

ABSORPTION AREA * MICROVILLI RATE OF ABSORPTION

A. FACTORS THAT AFFECT ABSORPTION

GASTRIC EMPTYING TIME
SHORTER EMPYING TIME = FASTER ABSORPTION Prolonged gastric emptying time > prolonged exposure of drug to acid environment> DRUG DEGREDATION

FACTORS THAT AFFECT GASTRIC EMPTYING TIME (GET)

INCREASED GET
Hot heavy meals Vigorous exercise Emotion/pain L side lying position

DECREASED GET
Fasting Hunger Cold meals R side lying position Prokinetic drugs Bilroth Surgery (Gastric Resection) > DUMPING SYNDROME!!!

B. ROUTE OF ADMINISTRATION
ORAL most compatible with drugs that are self administered must: withstand acidic environment of stomach
permeate gut lining before entering bloodstream absorption affected by: gastric emptying intestinal motility

SUBLINGUAL capillary bed under the tongue (GOOOOOOD ABSORPTION!!!) RECTAL

unconscious or vomiting patients or small children valuable means of localized drug delivery into the large bowel (rectal steroids in the form of enemas or suppositories, antiemetics can be administered rectally for nausea and vomiting)
INHALATION fast absorption due to excellent perfusion of the lungs (highly vascularized) (Halothane) TOPICAL for local delivery of agents (dermatologic, opthalmologic, nasal, vaginal, otic preparations)

B. ROUTE OF ADMINISTRATION
TRANSDERMAL patch containing the drug is applied to the skin (skin>capillary bed) INTRAVENOUS rapid onset injected directly into the blood stream (INSOLUBLE DRUGS CANNOT BE ADMINISTERED INTRAVENOUSLY) INTRAMUSCULAR passes through capillary walls to enter blood stream absorption rate depends on formulation: OIL BASED slower absorption rate AQEOUS faster absorption rate SUBCUTANEOUS SQ layer > capillary wall>blood stream

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