Drug Excretion: Miscellaneous Routes

Nonionized lipophilic drugs passively diffuse through epithelial cells into ducts, leading to excretion via sweat on the skin and tears in the eyes. This passive diffusion process allows fat-soluble drugs to move across cell membranes without requiring energy. Though quantitatively minor, detection of drugs in sweat and tears has significant forensic implications.

Drugs and metabolites excreted through sweat may cause skin allergies including urticaria, dermatitis, or hypersensitivity reactions. These adverse reactions occur when excreted substances irritate or sensitize the skin. Individual susceptibility varies based on drug properties and skin sensitivity to the excreted compounds.

When renal function is compromised, drugs normally excreted in urine, such as digoxin, can be eliminated through feces instead. This alternative excretion route becomes clinically significant in renal impairment, preventing toxic drug accumulation. Understanding this compensatory mechanism is essential for dose adjustments in patients with factors affecting renal clearance renal impairment.

Enterohepatic recycling occurs when drugs or metabolites excreted in bile enter the duodenum and are reabsorbed from the intestine back into the body. This process significantly prolongs drug presence and effects. Administering oral substances that bind biliary metabolites can interrupt this cycle and promote fecal elimination.

Basic compounds concentrate slightly in acidic fluids like milk, while acidic compounds have lower concentrations. Non-electrolytes like ethanol and urea readily enter breast milk, reaching plasma-equivalent levels. Understanding drug physicochemical properties and plasma levels helps predict infant exposure when mothers are breastfeeding.

Although drug excretion into skin and hair is quantitatively minor, detection from these sources is significant in forensic investigations. Drugs and metabolites deposited in hair and skin can persist longer than in other matrices, providing valuable evidence. This makes these tissues valuable targets for forensic analysis despite their limited role in overall drug elimination.

After oral ingestion, some drugs remain unabsorbed and reach the intestines, subsequently getting expelled through fecal excretion. Additionally, drugs or metabolites actively secreted into bile by hepatocyte transporters enter the gastrointestinal tract and are eliminated in feces. This dual pathway ensures elimination of both unabsorbed and biliary-excreted substances.