HEALTH AND MEDICAL PRODUCTS:DIUR ETICS.

DIUR ETICS

The term “diuresis” (dia = through, ouresis = urination) refers to urine excretion. Drugs called diuretics (from the Greek word diouretikos, meaning promoting urine) cause an overall removal of fluid from the body by targeting the kidneys and increasing the rate of urine flow and sodium excretion from the body. The physiological goal of diuretic administration is to promote the loss of water in the urine and thereby cause a reduction in blood volume, blood pressure, or both within the individual. Diuretics are often used to treat a variety of clinical situations, including hypertension (high blood pressure), congestive heart failure, kidney failure, and edema (abnormal localized accumulation of tissue fluids). Many diuretics available in over-the-counter formulations are considered relatively mild acting and are marketed to alleviate the feelings of bloating, swelling, puffiness, and fullness often associated with monthly premenstrual and menstrual periods in reproductively capable females and temporary water weight gain in both males and females. Common side effects of these agents may include potassium depletion, hypotension (low blood pressure), dehydration, and hyponatremia (sodium depletion).

The basic blood-processing and urine-forming unit of the kidney is the nephron. Each of the two human kidneys contains more than 1 mil- lion nephrons, each of which carries out the processes that form urine. In addition, each kidney contains thousands of collecting ducts, each of which collects urine from several nephrons and conveys it to a medial area of the kidney called the renal pelvis. Each nephron consists of a renal corpuscle (containing a tuft of capillaries called the glomerulus and the associated glomerular [Bowman’s] capsule) and a renal tubule. Filtration occurs at the renal corpuscle as blood pressure forces fluid and dissolved solutes out of the blood contained in the glomerular capillaries and into the capsular space and then the renal tubule. This filtration process produces an essentially protein-free, plasma-derived fluid solution, known as filtrate, which is the raw material processed by the renal tubules to form urine. The glomerular filtration rate is the total amount of filtrate formed per minute by the kidneys. The renal tubule is approximately three centimeters long and has three named parts. The renal tubule leaves the glomerular capsule as the coiled proximal convoluted tubule, then makes a hairpin loop turn called the loop of Henle, and then finally twists and winds again as the distal convoluted tubule before it empties the fluid product into a collecting duct. Along the renal tubule, water, urea, and various solutes (e.g., ions including sodium, potassium, chloride, bicarbon- ate, calcium, ammonium, and hydrogen, and molecules such as creatinine, glucose, amino acids, vitamins, and organic acids) may be reabsorbed back into the bloodstream of the body or secreted from the blood of the surrounding peritubular capillaries through the tubule cells, or from the tubule cells themselves, into the filtrate. Thus, urine that is eventually excreted from the body is composed of both filtered and secreted substances.

Diuretics have many different mechanisms of action, but all of them affect transport activity or water reabsorption along the nephron and collecting duct system. Over-the-counter orally administered diuretics can contain chemically active ingredients such as pamabrom or caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione; C8H10N4O2). In 1955, the diuretic activity of pamabrom, chemically prepared from 2-amino-2- methyl-1-propanol and 8-bromotheophylline, was characterized. Pam- abrom (8-bromo-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione com- pound with 2-amino-2-methyl-1-propanol [1:1]; C11H18BrN5O3) is therapeutically considered a drug combination, meaning a single preparation containing two active ingredients for the purpose of a concurrent administration as a fixed-dose mixture. Chemically, it contains both a propanolamine (amino alcohol) group and a theophylline group. Al- though caffeine was first synthesized in 1895, the stimulatory actions of caffeine have been known since ancient times. Structurally, caffeine is a methyl xanthine, in the same class of compounds as theophylline. Xanthine itself is a nitrogenous compound (dioxypurine) and is structurally related to uric acid. Theophylline and caffeine are closely related alkaloids that occur in plants widely distributed geographically. For example, tea prepared from the leaves of Thea sinensis, a bush native to southern China and now extensively cultivated in other countries, contains caffeine and theophylline. Caffeine is also found as a natural component of cocoa and chocolate, coffee (often extracted from the fruit of Coffea arabica and related species), and cola-flavored drinks (contents extracted from the nuts of Cola acuminata). Methylated xanthines, theophylline, and caffeine inhibit the 3151-cyclic nucleotide phosphodiesterase enzyme that normally degrades cyclic adenosine monophosphate (cAMP). cAMP is important in a wide variety of metabolic responses to cell stimuli, including signal transduction. Thus, the pharmacological actions of these compounds are mediated through a generalized increase in cAMP levels within specific cells of the body to cause various effects, most frequently within organs of the cardiovascular, respiratory, and nervous systems.

Caffeine, and the theophylline chemical group of pamabrom, in- creases renal (kidney) blood flow and glomerular filtration rate and may also decrease proximal tubular reabsorption of sodium and water, causing a mild diuretic effect. The amino alcohol group of pamabrom may also function as a diuretic, as alcohols act indirectly as diuretics by sup- pressing the release of antidiuretic hormone from the posterior pituitary gland. After release from the posterior pituitary gland, antidiuretic hormone normally travels through the bloodstream and targets the distal convoluted tubules and collecting ducts of the kidney nephrons to pro- mote water retention, thus decreasing urine output. The diuretic effect of both caffeine and pamabrom is directly dependent on the amount of drug consumed and the duration of intake.