Drug Disposition - Absorption, Distribution, and Excretion of Drugs Flashcards
Drug Elimination
Metabolism (Biotransformation; Liver) or Excretion
Modes of drug transportation across membranes
Passive Diffusion, Passive Transport, and Active Transport
2 Major classes of drug transporters
Uptake - Solute Carriers (SLC) co-transport solutes like sodium
Efflux - ABC transporters use ATP
Prostaglandins
Physiologically active lipid compounds that act like hormones in the body.
Effect of drug ionization on disposition
Drugs are weak electrolytes, Ionized forms of chemicals do not penetrate lipid membranes, and the degree of drug ionization is dependent on pKa and pH of surrounding medium.
Ionization of acids and bases
weak acids are ionized when pH > pKa
weak bases are ionized when pH < pKa
Ion Trapping
Drugs tend to stay localized in areas where they are highly ionized, highly affected by the surrounding pH
Properties of GI epithelium
Tight junctions
Lipid diffusion only
Modes of molecule transport across capillary epithelium tissue
Transcellular diffusion Aqueous diffusion (convection, ultrafiltration) Receptor mediated endocytocis/pinocytosis
Factors affecting oral absorption
Solubility
Stomach Acid
pH range
Tight Junctions, Lipid Solubility
Surface Area
Transport to Liver Portal Vein (first pass metabolism)
Intestinal Mobility, Gastric Emptying, Blood Flow
Enteral Drug administration
Oral
Rectal
Buccal (sublingual, ie. fentanyl and nitroglycerin)
Parenteral Drug administration
IV IM Sub Q Inhalational Nasal Transdermal Topical
Bioavailability
The fraction or percent of administered dose that reaches systemic circulation.
Affected by the dissolution of substrate in GI fluids, absorption and first pass metabolism in liver.
Volume distribution of drugs
amount of drug (mg) / plasma concentration (mg/ml)
Consequence of drug binding to plasma proteins
Only free drugs are active and can cross membranes
Onset of drug action is slowed; reduction in rate of equilibration
Decrease in Vd (app)
