Excretion Course Materials

Excretion Elimination of substances from the body. (unchanged or as a metabolite) Renal channel Excretion through the kidneys via urine Non-renal channels • Liver - Bile • Skin (Sweat) • Lungs • Intestine • Milk • Hair • Nail • Saliva passage of drugs into breast milk occurs through passive diffusion breast milk is more acidic than plasma, why can drugs concentrate in breast milk especially basic drugs tend to concentrate in breast milk Pulmonary Excretion Excretion of substances through lungs how can Gaseous or the volatile subby passing across the endothelium and stances pass from the blood circulation epithelium of the alveolar membrane (via into the alveoli passive diffusion) deposited from the capillaries, which how are drugs excreted through Hair and supply blood to the follicles, or excreted Nails in the sebum, oil, or sweats that coat the hair shafts. nails tests can show how drug use up to how many months prior 12 where does arsenic accumulate keratin fibres can use hair to detect arsenic poisoning hair Sweat, saliva, and tears Excretion of drugs through sweat, saliva, and tears Biliary excretion substances are secreted into the biliary ducts from the hepatocytes by active transport and finally they are drained into the intestines. 1/5 most suitable molecular weight for the drugs to be secreted into the bile 500 daltons characteristics of compounds that can be secreted into the bile in remarkable amounts highly ionized polar compounds (conjugation products) where do bile duct empty into the duodenum • >500 mainly excreted in the bile • 300-500, excreted both in urine and how does Molecular weight affect excrebile. tion • <300, almost exclusively excreted via kidney bile consists of water, bile salts, bile pigments, electrolytes, and to a lesser extent, cholesterol and fatty acids Glucuronide conjugates Metabolites excreted into bile Enterohepatic circulation Cycle of drug metabolism between liver and small intestine process of Enterohepatic circulation After biotransformation, metabolites are drained into the small intestine by biliary duct. • Drug metabolites are broken down again in the small intestine and reabsorbed back reaching the liver by portal vein again why is the enterohepatic cycle important increase in the duration of the drugs effect Activated charcoal Charcoal thats been treated with oxygen at high temps preventing drug absorption Can hinder enterohepatic circulation by Antibiotics affect the enterohepatic circusuppressing intestinal flora and reducing lation how the levels of deconjugating enzymes. Soluble fiber affects the enterohepatic circulation how Found in nuts, seeds, beans, fruits; inhibits bile salt reabsorption Renal excretion 2/5 Mainly eliminates metabolite waste, maintains fluid balance normal fluid and composition about 180 L fluid/day is filtered through kidneys Nephrons Basic functional units in the kidneys for filtration Psychoactive drugs are often reabsorbed where out of the kidneys, so the liver has to enzymatically transform the drugs so with minimal reabsorption they can exit in urine. Inulin Impacts Glomerular Filtration Rate (GFR) in renal excretion Glomerular filtration rate 110-130 ml/min filtration rate, except for bound drug fraction filtered from the glomerulus into proximal tubules Hydrostatic pressure Force aiding glomerular filtration in renal excretion Ampicillin Antibiotic excreted mainly via glomerular filtration Furosemide Used for hypertension, excreted via glomerular filtration Tubular secretion occurs Mainly in proximal tubules, tubular secretion uses what transport mechanism active transport efficiency of tubular secretion compared tubular secretion has a higher maximum to glomerular filtration cleareance - more efficient active renal secretion uses (system) a carrier-mediated system Carrier system Capacity-limited, may get saturated; competes for similar drugs. requires energy Tubular reabsorption Occurs mainly in distal tubules, reduces drug excretion 3/5 Tubular reabsorption uses what transport mechanism passive diffusion Urinary pH basic causes an increase in the excretion of weak acid drugs Urinary pH acidic causes the reabsorption of the weak acid drug from the renal tubules into the blood will increase, thus the excretion will decrease. Artificial excretion Hemodialysis eliminates drugs, uses semipermeable membranes treament for acute drug intoxication Semipermeable membranes Allow passage of low-molecular-weight molecules in dialysis Uremic toxins Accumulate in kidney disease, not efficiently removed by dialysis Clearance Volume of plasma cleared from drug per unit time (ml/min) Total Body Clearance Plasma volume cleared from drug per unit time via the elimination of the drug from all biotransformation and excretion mechanisms in the body. Renal Clearance Plasma Protein Binding Factor affecting renal drug clearance (should be low) Physiological Clearance normal range Normal clearance range (120-130 ml/min) Elimination Half-life Time for drug concentration to reduce by 50% elimination half life equation t1/2 = 0.693x Vd / clearance 4/5 Apparent Volume of Distribution How high the apparent volume of distribution of a drug, that high is the duration of stay of that drug in the body Half-life Correlation relationship with clearance Inversely proportional the effect of the drug is considered to Considered negligible after 4 half-lives have a negligible therapeutic effect after Heroin Half-life Short, 2-6 minutes due to rapid metabolism Patient-specific Half-life Factors Variables like age, kidney function, and diet Drug-specific Half-life Factors Influences like formulation and administration Accumulation Ratio of drug added to body vs. eliminated shorter half lives tend to act very quickly, but their effects wear off rapidly longer half life take longer to start working, but their effects persist for longer Steady-State Equilibrium when elimination equals intake Zero-order Elimination Constant drug elimination regardless of concentration First-order Elimination Elimination proportional to drug concentration. constant fraction of drug is eliminated per unit time Michaelis-Menten Elimination Accumulation Misconception Saturable enzyme kinetics affecting drug elimination .non-linear elimination kinetics. At high concentrations, the rate of reaction remains the same because all the enzyme molecules are "busy", i.e. the system is saturated. Often linked with toxicity but relates to dosing 5/5