Drug elimination(drug sclearance).pptxss

Drug elimination refers to the processes by which drugs are removed from the body. This is a crucial aspect of pharmacokinetics, which studies how drugs are absorbed, distributed, metabolized, and excreted. Drug elimination primarily involves two key processes: metabolism and excretion.

Metabolism
Metabolism is the biochemical alteration of a drug by the body, often making it more water-soluble to facilitate excretion. This process usually occurs in the liver, but other tissues such as the kidneys, lungs, and intestines can also be involved. There are two main phases of drug metabolism:

Phase I Reactions:

These reactions involve the modification of the drug's chemical structure, usually through oxidation, reduction, or hydrolysis.
The cytochrome P450 enzyme system in the liver is a major player in these reactions.
The resulting metabolites can be either active or inactive.
Phase II Reactions:

These involve conjugation, where the drug or its Phase I metabolites are combined with another substance (e.g., glucuronic acid, sulfuric acid, or glycine) to form more water-soluble compounds.
These conjugated metabolites are usually inactive and are readily excreted by the kidneys.
Excretion
Excretion is the process of removing drugs and their metabolites from the body. The main routes of excretion are:

Renal Excretion:

The kidneys play a primary role in excreting water-soluble drugs and metabolites through urine.
This process involves three mechanisms:
Glomerular Filtration: Free, unbound drugs are filtered out of the blood into the urine.
Tubular Secretion: Active transport systems in the renal tubules secrete drugs from the blood into the urine.
Tubular Reabsorption: Drugs may be reabsorbed from the urine back into the blood, depending on their lipid solubility and the pH of the urine.
Biliary and Fecal Excretion:

Some drugs and metabolites are excreted by the liver into the bile, which is then passed into the intestines and eliminated in the feces.
Enterohepatic recycling can occur, where drugs excreted in the bile are reabsorbed from the intestines back into the bloodstream.
Pulmonary Excretion:

Volatile substances, such as anesthetic gases, are excreted through the lungs via exhalation.
Other Routes:

Drugs can also be excreted through sweat, saliva, and breast milk, although these routes are generally less significant.
Factors Influencing Drug Elimination
Several factors can affect how quickly and efficiently a drug is eliminated from the body, including:

Age:

Liver and kidney function decline with age, which can slow down drug metabolism and excretion.
In infants, immature liver and kidney function can also affect drug elimination.
Genetics:

Genetic variations can influence the activity of enzymes involved in drug metabolism, leading to differences in drug elimination rates.
Liver and Kidney Function:

Diseases affecting the liver or kidneys can impair drug metabolism and excretion, leading to accumulation of drugs in the body.

1. Drug elimination By Dr. Sania Hayat

2. Drug elimination Drug elimination  refers to the irreversible removal of drug from the body by all routes of elimination. Drug elimination is usually divided into two major components: excretion and biotransformation.  Drug excretion  is the removal of the intact drug. Biotransformation  or  drug metabolism  is the process by which the drug is chemically converted in the body to a metabolite. Once a drug enters the body, the process of elimination begins. The three major routes of elimination are hepatic metabolism, biliary elimination, and urinary excretion.

3. Drug clearance through metabolism Clearance is an imaginary volume of plasma from which drug is completely removed in unit time. Unit: volume/time, ml/min Clearance is the proportionality factor in determining elimination factor. Clearance is calculated as: CL= 0.693 * Vd / t1/2 Rate of elimination= CL * concentration Unit of rate of elimination is mass/time. CLtotal = Clrenal + Clhepatic + CLlungs

4. Kinetics of metabolism First order kinetics: In first-order kinetics, the rate of drug elimination is directly proportional to the concentration of the drug in the plasma. Characteristics: Rate of elimination of the drug is directly proportional to plasma concentration of the drug. Constant fraction of drug is eliminated at constant interval of time. Plasma half life remains constant. Plot of plasma concentration against time is curvilinear. Single dose of drug is almost completely eliminated after 5 half lives. Most of the drugs follow first order kinetics.

5. Second-order kinetics: In zero-order kinetics, the rate of drug elimination is constant and does not depend on the drug concentration. Characteristics: Elimination process gets saturated. Constant amount of drug is eliminated in unit time i.e rate of elimination is constant irrespective of plasma concentration. Plot of plasma concentration against time is linear. Plasma half life do not remain constant. Very few drugs follow second-order kinetics.

6. Phases of drug metabolism Phase I Phase I reactions convert lipophilic drugs into more polar molecules by introducing or unmasking a polar functional group, such as –OH or –NH2. Phase I reactions usually involve reduction,oxidation , or hydrolysis. Phase I metabolism may increase,decrease , or have no effect on pharmacologic activity. reactions most frequently involved in drug metabolism are catalyzed by the cytochrome P450 system (also called microsomal mixed-function oxidases).

7. Phase II This phase consists of conjugation reactions. If the metabolite from phase I metabolism is sufficiently polar, it can be excreted by the kidneys. However, many phase I metabolites are still too lipophilic to be excreted. A subsequent conjugation reaction with an endogenous substrate, such as glucuronic acid, sulfuric acid, acetic acid, or an amino acid, results in polar, usually more water-soluble compounds that are often therapeutically inactive. A notable exception is morphine-6-glucuronide , which is more potent than morphine. Glucuronidation is the most common and the most important conjugation reaction. [Note: Drugs already possessing an –OH, –NH2, or –COOH group may enter phase II directly and become conjugated without prior phase I metabolism.] The highly polar drug conjugates are then excreted by the kidney or in bile.