Pharmacokinetics - Drug Excretion: Download PDF, Notes, and PPT
Explore the final phase of Pharmacokinetics: Drug Excretion. This downloadable PDF resource details the processes by which drugs and their metabolites are eliminated from the body. Access comprehensive notes and related PowerPoint presentations (PPTs) covering major routes of excretion such as renal (kidney) and biliary (liver/bile) pathways, as well as minor routes like pulmonary, salivary, and sweat. This material is crucial for students of pharmacology, medicine, and pharmacy to understand drug clearance and duration of action.
Our PDF explains concepts like glomerular filtration, tubular secretion, tubular reabsorption, enterohepatic circulation, and factors affecting drug excretion. Download now to master this essential component of ADME, critical for determining dosing intervals and managing drug therapy in patients with impaired organ function.
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Pharmacokinetics: The Final Step - Drug Excretion
Excretion is the terminal phase of the pharmacokinetic journey (Absorption, Distribution, Metabolism, Excretion - ADME). It refers to the irreversible removal of drugs and their metabolites from the body. Effective excretion is vital to prevent drug accumulation and potential toxicity, and it plays a key role in determining the duration of a drug's action and the dosing interval. This PDF on "Pharmacokinetics excretion" delves into the mechanisms and pathways involved in this critical process.
Major Routes of Drug Excretion
Drugs are eliminated from the body through various routes, with the kidneys and liver being the most important organs of excretion.
- Renal Excretion (Kidneys):
The kidneys are the primary organs for excreting most water-soluble drugs and their metabolites. The overall renal excretion of a drug is a net result of three processes occurring in the nephron (the functional unit of the kidney):
- Glomerular Filtration: Blood flows through the glomeruli, and a portion of plasma water, along with dissolved small molecules (including most drugs), is filtered into Bowman's capsule. This is a passive process. Only free (unbound) drugs are filtered; protein-bound drugs are too large to pass through the glomerular pores. The glomerular filtration rate (GFR) is a key determinant of the filtration of many drugs.
- Active Tubular Secretion: Some drugs, particularly weak acids (e.g., penicillin, probenecid) and weak bases (e.g., morphine, histamine), are actively transported from the blood in peritubular capillaries into the tubular fluid of the proximal convoluted tubule. This process requires energy, involves carrier proteins (e.g., Organic Anion Transporters - OATs, Organic Cation Transporters - OCTs), can move drugs against a concentration gradient, and is saturable. It can lead to more rapid elimination than by filtration alone and can even remove protein-bound drugs as the free drug is removed, causing dissociation from proteins.
- Passive Tubular Reabsorption: As the filtrate moves along the renal tubules, water is reabsorbed, concentrating the drug in the tubular fluid. If the drug is lipid-soluble and un-ionized, it can diffuse back from the tubular lumen into the bloodstream (passive reabsorption), primarily in the distal convoluted tubule and collecting ducts. The pH of the urine can significantly influence this process for weak acids and bases:
- Alkalinization of urine (e.g., with sodium bicarbonate) increases the ionization of acidic drugs (like aspirin, phenobarbital), making them less lipid-soluble and reducing their reabsorption, thereby enhancing their excretion. This principle is used in treating acidic drug overdose.
- Acidification of urine (e.g., with ammonium chloride) increases the ionization of basic drugs (like amphetamine), reducing their reabsorption and enhancing their excretion.
- Biliary and Fecal Excretion (Liver/Bile):
The liver can excrete drugs and their metabolites into the bile, which is then emptied into the duodenum (small intestine). This is a significant route for:
- Large molecular weight drugs (typically >300-500 Da).
- Drugs with polar groups or those conjugated with glucuronic acid or sulfate (making them more water-soluble).
- Active transport systems in hepatocytes (liver cells) secrete these substances into bile.
Once in the intestine, drugs excreted in bile can either be eliminated in the feces or undergo enterohepatic circulation (recycling). This occurs if the drug (or its metabolite, which may be deconjugated by intestinal bacteria) is reabsorbed from the intestine back into the portal circulation and returns to the liver. Enterohepatic circulation can prolong the presence and action of a drug in the body (e.g., digoxin, oral contraceptives, morphine).
Minor Routes of Drug Excretion
While kidneys and liver are dominant, other routes contribute to drug elimination to a lesser extent:
- Pulmonary Excretion (Lungs): Volatile substances, such as general anesthetics (e.g., halothane) and alcohol, are excreted via the lungs through exhalation. This is a simple diffusion process.
- Salivary Excretion: Some drugs can be excreted in saliva (e.g., lithium, phenytoin). This can sometimes lead to a metallic taste or adverse effects in the mouth. Salivary drug concentrations may sometimes be used for therapeutic drug monitoring.
- Sweat and Tears: Trace amounts of some drugs can be excreted in sweat and tears. This is generally a minor pathway but can cause skin reactions or discoloration in some cases.
- Mammary Excretion (Breast Milk): Many drugs can pass into breast milk, which is a concern for nursing infants. The amount depends on the drug's lipid solubility, pKa, and degree of plasma protein binding. Basic drugs tend to concentrate in the slightly more acidic breast milk.
- Gastrointestinal Excretion: Some drugs, even if not administered orally, can be secreted directly into the GI tract lumen from the bloodstream, although this is usually a minor route unless it's part of biliary excretion.
Key Pharmacokinetic Parameters Related to Excretion
- Clearance (CL): This is the most important concept in drug elimination. Clearance is a measure of the body's efficiency in eliminating a drug. It is defined as the theoretical volume of plasma (or blood) from which the drug is completely removed per unit of time (e.g., mL/min or L/hr). Total body clearance is the sum of clearances by all routes (e.g., CL_total = CL_renal + CL_hepatic + CL_other).
- Elimination Half-Life (t½): This is the time taken for the plasma concentration of a drug (or the amount of drug in the body) to decrease by 50%. It is dependent on both clearance (CL) and volume of distribution (Vd): t½ = (0.693 * Vd) / CL. The half-life determines the dosing interval and the time taken to reach steady-state concentrations with multiple dosing.
Factors Affecting Drug Excretion
- Renal Function: Impaired kidney function (e.g., in renal disease, elderly patients) significantly reduces the excretion of renally cleared drugs, necessitating dose adjustments. GFR is often estimated using creatinine clearance.
- Liver Function: Liver disease can impair both the metabolism and biliary excretion of drugs.
- Age: Both newborns (immature renal and hepatic function) and the elderly (declining organ function) often have altered drug excretion.
- Urine pH: As discussed, can affect renal reabsorption of weak acids and bases.
- Drug Interactions: Some drugs can compete for active tubular secretion transporters or alter urine pH.
- Blood Flow to Excretory Organs: Reduced blood flow can decrease the rate of drug delivery to the kidneys or liver.
Understanding drug excretion is fundamental for designing safe and effective dosing regimens. It allows for adjustments in patients with compromised excretory functions and helps predict the duration of drug effects. This PDF provides a solid foundation for these principles.
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