The study of how the body interacts with drugs is called pharmacokinetics, encompassing absorption, distribution, metabolism, and excretion (ADME). The latter two stages, metabolism and excretion, constitute drug elimination, a vital process preventing drug accumulation and toxicity. Understanding drug elimination is key for appropriate dosing and comprehending medication schedules.
The Mechanisms of Drug Elimination
Drug elimination involves metabolism and excretion.
Metabolism: Transforming Drugs into Excretable Forms
To be excreted, primarily through urine, lipophilic drugs are metabolized into more water-soluble compounds. The liver is the main site for this, occurring in two phases. Phase I reactions add or expose polar groups via enzymes like CYP450. Phase II reactions involve conjugation with highly polar molecules, making the compound water-soluble and typically inactive for excretion.
Excretion: The Final Removal
After metabolism, drugs are excreted, mainly by the kidneys.
- Renal Excretion: Kidneys filter, secrete, and reabsorb drugs. Small, unbound molecules are filtered, some drugs are actively secreted, and others reabsorbed. Urine pH can influence reabsorption.
- Hepatic and Biliary Excretion: The liver transports some drugs into bile, which goes to the intestines for elimination in feces. Some drugs can be reabsorbed from the intestine in the enterohepatic cycle.
- Minor Excretion Routes: Lungs, sweat, saliva, and breast milk are minor routes, important for volatile substances, drug monitoring, or effects on infants.
Factors Influencing Drug Clearance
Individual variations in drug elimination are due to several factors.
- Organ Function: Impaired liver or kidney function reduces drug clearance, risking accumulation and toxicity.
- Genetics: Genetic differences affect drug-metabolizing enzymes and transporters.
- Age: Infants have immature elimination systems, while the elderly may have reduced organ function.
- Drug-Drug Interactions: Some drugs can alter the activity of metabolic enzymes, affecting the elimination of other medications.
First-Order vs. Zero-Order Kinetics
Drug elimination follows either first-order or zero-order kinetics.
- First-Order Kinetics: Elimination rate is proportional to drug concentration; a constant fraction is eliminated per unit time. Half-life is constant.
- Zero-Order Kinetics: Elimination rate is constant, regardless of concentration, due to saturated mechanisms. A constant amount is eliminated, and half-life is not constant, increasing toxicity risk. Examples include high doses of ethanol or phenytoin.
Comparison of Elimination Kinetics
| Feature | First-Order Elimination | Zero-Order Elimination |
|---|---|---|
| Rate of Elimination | Proportional to drug concentration | Constant, regardless of drug concentration |
| Mechanism | Elimination enzymes and transporters are not saturated | Elimination pathways are saturated |
| Half-Life | Constant | Not constant; decreases as plasma concentration decreases |
| Risk of Toxicity | Lower risk at therapeutic doses | Higher risk of toxicity due to accumulation |
| Examples | Most drugs at normal doses | Ethanol, high-dose phenytoin, aspirin |
Conclusion
Drug elimination, involving metabolism and excretion, is the body's key process for clearing medications. Understanding "what is the removal of all drugs from the body" involves recognizing the complex interplay of pathways, primarily in the liver and kidneys, influenced by individual factors like age and genetics. Knowledge of drug clearance and elimination kinetics is vital for patient safety, achieving therapeutic goals, and avoiding toxicity. More information on pharmacokinetics can be found at the National Center for Biotechnology Information.
