EXCRETION OF DRUGS

INTRODUCTION:  Drugs are removed from the body by the process of excretion. The rate at which medications are excreted determines the concentration of the drugs in the bloodstream and tissues. This is important because the concentration of drugs in the bloodstream determines their duration of action. Pathologic states, such as liver disease or renal failure, often increase the duration of drug action in the body because they interfere with natural excretion mechanisms. Dosing regimens must be carefully adjusted in these patients. Although drugs are eliminated from the body by numerous organs and tissues, the primary site of excretion is the kidney. 

ROLE OF THE KIDNEY IN DRUG EXCRETION:  In an average-size person, approximately 180 L of blood is filtered by the kidneys each day. Free drugs, water soluble agents, electrolytes, and small molecules are easily filtered at the glomerulus. Proteins, blood cells, conjugates, and drug–protein complexes are not filtered because of their large size. After filtration at the renal corpuscle, chemicals and drugs are subjected to the process of reabsorption in the renal tubule.  Mechanisms of reabsorption are the same as absorption elsewhere in the body. Nonionized and lipid soluble drugs cross renal tubular membranes easily and return to the circulation; ionized and water-soluble drugs generally remain in the filtrate for excretion. 

FACTORS AFFECTING DRUG EXCRETION:  There are many factors that can affect drug excretion. These include the following:  Liver or kidney impairment, Blood flow, Degree of ionization, Lipid solubility, Drug–protein complexes, Metabolic activity, Acidity or alkalinity (pH), Respiratory, glandular or biliary activity. 

Drug–protein complexes and substances too large to be filtered at the glomerulus are sometimes secreted into the distal tubule of the nephron. For example, only 10% of a dose of penicillin G is filtered at the glomerulus; 90% is secreted into the renal tubule. As with metabolic enzyme activity, secretion mechanisms are less active in infants and older adults. 

THE ROLE OF pH IN DRUG EXCRETION:  Certain drugs may be excreted more quickly if the pH of the filtrate changes. Weak acids such as aspirin are excreted faster when the filtrate is slightly alkaline, because aspirin is ionized in an alkaline environment, and the drug will remain in the filtrate and be excreted in the urine. Weakly basic drugs such as diazepam (Valium) are excreted faster with a slightly acidic filtrate, because they are ionized in this environment. This relationship between pH and drug excretion can be used to advantage in critical care situations. To speed the renal excretion of acidic drugs such as aspirin in an overdosed patient, an order may be written to administer sodium bicarbonate. Sodium bicarbonate will make the urine more basic, which ionizes more aspirin, causing it to be excreted more readily. The excretion of diazepam, on the other hand, can be enhanced by giving ammonium chloride. This will acidify the filtrate and increase the excretion of diazepam. 

KIDNEY STATUS AND DRUG EXCRETION:  Impairment of kidney function can dramatically affect pharmacokinetics. Patients with renal failure will have diminished ability to excrete medications and may retain drugs for an extended time. Doses for these patients must be reduced to avoid drug toxicity. Because small to moderate changes in renal status can cause rapid increases in serum drug levels, the medical workers must constantly monitor kidney function in patients receiving drugs that may be nephrotoxic (low margin of safety). 

LEVELS OF EXCRETION OF DIFFERENT DRUGS:  Drugs that can easily be changed into a gaseous form are especially suited for excretion by the respiratory system. The rate of respiratory excretion is dependent on factors that affect gas exchange, including diffusion, gas solubility, and pulmonary blood flow.  The elimination of volatile anesthetics following surgery is primarily dependent on respiratory activity; the faster the respiratory rate, the greater the excretion. Conversely, the respiratory removal of water-soluble agents such as alcohol is more dependent on blood flow to the lungs; the greater the blood flow into lung capillaries, the greater the excretion. In contrast with other methods of excretion, the lungs excrete most drugs in their original nonmetabolized form. 

Glandular activity is another elimination mechanism. Water-soluble drugs may be secreted into the saliva, sweat, or breast milk. The odd taste that patients sometimes experience when given IV drugs is an example of the secretion of agents into the saliva. Another example of glandular excretion is the garlic smell that can be detected when standing next to a perspiring person who has recently eaten garlic. Excretion into breast milk is of considerable importance for basic drugs such as morphine or codeine, because these can achieve high concentrations and potentially affect the nursing infant.  Nursing mothers should always check with their health care provider before taking any prescription medication, OTC drug, or herbal supplement.

RELATED;

1.  PHARMACOKINETICS

2.  PHARMACODYNAMICS

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES