Urinary alkalinization

Probenecid is rapidly absorbed after oral administration, with peak plasma levels usually reached in 2 to 4 hours. Its half-life is somewhat variable (6-12 hours) because of both its extensive plasma protein binding and its active proximal tubular secretion. Since tubular back-diffusion is decreased at alkaline urinary pH ranges, probenecid excretion increases with increasing urinary pH. Probenecid is rapidly metabolized, with less than 5% of an administered dose being eliminated in 24 hours. The major metabolite is an acyl monoglucuronide. 

BUN, Cr, urine pH (alkaline urinary pH decreases renal damage)... 

Half-life. Plasma half-life, about 10 hours under alkaline urinary pH conditions or 3 hours if an acidic urinary pH is maintained. 

Loop diuretic therapy has been implicated in the development of renal calcifications in both preterm and fuU-term infants [109-115]. According to a study by Jacinto et al., nephrocalcinosis occurred in 20 out of 31 (64%) premature infants with birth weights less than 1500 g [112]. Of those infants, 65% were receiving fu-rosemide. Nephrocalcinosis also was found in 14% of full-term infants with congestive heart failure receiving long-term furosemide therapy [113]. Furosemide may induce high minary calcium excretion rates, low urinary citrate to creatinine ratios, and an alkaline urinary pH, aU of which are considerable risk factors for renal calcifications [116]. 

Urinary pH. The solubility of phosphate salts increases at lower pH values, while pH scarcely affects the solubility of Ca(C204) over a pH range of 5.7 to 7.5. Bacteria that metabolize urea contribute to an alkaline medium, thus decreasing the solubility of phosphates. 

This electrolyte plays a vital role in the acid-base balance of the body. Bicarbonate may be given IV as sodium bicarbonate (NaHC03) in the treatment of metabolic acidosis, a state of imbalance that may be seen in diseases or situations such as severe shock, diabetic acidosis, severe diarrhea, extracorporeal circulation of blood, severe renal disease, and cardiac arrest. Oral sodium bicarbonate is used as a gastric and urinary alkalinizer. It may be used as a single drug or may be found as one of the ingredients in some antacid preparations. It is also useful in treating severe diarrhea accompanied by bicarbonate loss. 

Inhibitors should be removed from sample. An example is urinary phosphate, which can be removed by dialysis prior to measuring the urinary alkaline phosphatase activity (18). 

Urinary alkaline phosphatase activity. II. An analytical validation of the assay method. JAMA (1963), 185, 953-957. 

Prolonged residence in the intestine or urinary bladder lumen could allow time for significant reaction with tissue components however, N-glucuronyloxy-AAF was only weakly carcinogenic at local subcutaneous sites of application (89). Enzymatic deacetylation to N-glucuronyloxy-AF has been detected in hepatic tissue but this activity in different species does not correlate with their relative susceptibility to AAF hepatocarcinogenesis (94). On the other hand, the alkaline pH-induced conversion to a reactive derivative may play an important role in urinary bladder carcinogenesis (87) by AAF and other arylamides in those species or individuals where normal urine pH is alkaline (e.g. normal rabbit urine pH is 8.5-9.0). 

The answer is c. (Hardman, pp 6917 693 J Acetazolamide is a carbonic anhydrase inhibitor with its primary site of action at the proximal tubule of the nephron. Acetazolamide promotes a urinary excretion of Na, K, and bicarbonate There is a decrease in loss of Cl ions The increased excretion of bicarbonate makes the urine alkaline and may produce metabolic acidosis as a consequence of the loss of bicarbonate from the blood. None of the other diuretic drugs promote a reduction in the excretion of the Cl ion... 

The answer is a. (Hardman, pp 16-20.) Sodium bicarbonate is excreted principally in the urine and alkalinizes it. Increasing urinary pH interferes with the passive renal tubular reabsorption of organic acids (such as aspirin and phenobarbital) by increasing the ionic form of the drug in the tubular filtrate. This would increase their excretion. Excretion of organic bases (such as amphetamine, cocaine, phencyclidine, and morphine) would be enhanced by acidifying the urine. 

Hall et at. 300) described an indirect method for the determination of urinary a-amino nitrogen. Copper is solubilized from insoluble copper phosphate by complexing with a-amino groups at slightly alkaline pH. The remaining copper phosphate is removed by filtration and the filtrate is diluted 1 10 or 1 20 with 0. IN hydrochloric acid to measure the dissolved copper by atomic absorption. Standards are prepared using alanine. 

Once a food was consumed and oxidized in the human body, the urinary acidity would reflect the nature of the ash of the food as observed in the rehydrated ash care had to be taken to avoid losing sulfur and chlorine during ashing. They pointed out that meats showed a predominance of acid forming elements, milk tended toward milk alkalinity, and the ash of fruit and vegetables was largely alkaline. 

In a feeding study with one male subject, a calciuretic effect prevailed when an acidic, rice-enriched diet was fed compared with a potatoe diet, in studies with women, Bogert and Kilpatrick (24) showed that feeding subjects an acidic diet resulted in elevated urinary calcium, whereas an alkaline diet induced a decline in urinary calcium. 

Acidosis induced by salt feeding to humans influenced urinary calcium loss as effectively as feeding whole foods. Martin and Jones (25), for example, fed adult subjects a diet supplemented with ammonium chloride which resulted in marked hypercalciuria and an acidified urine. In a follow-up trial, feeding alkali as sodium bicarbonate, they also demonstrated that human hypercalciuria could be prevented by adding an alkaline supplement to the diet. 

Alkaline supplement to the diet, urinary Ca loss, 76 Aluminum, effect on Ca metabolism, 162 Amino acids... 

A number of animal studies have revealed extrapulmonaiy effects. Again, there is some question as to which of these may represent an effect of ozone, or a direct ozone-induced intermediate, rather than a more indirect response to pulmonary toxicity, perhaps mediated by neurohumoral factors. Thus, for instance, the observations of altered hepatic nucleic acid concentrations, shifts in the content of metals in the liver, alterations in urinary pH, increases in liver weight and alkaline phosphatase... 

Excretion of drugs will be affected by the pH of the urine. If the urine is acidic, weak bases are ionized and there will be poor re-absorption. With basic urine, weak bases are non-ionized and there is more re-absorption. The pH of the urine can be artificially changed in the range 5-8.5 oral administration of sodium bicarbonate (NaHCOs) increases pH values, whereas ammonium chloride (NH4CI) lowers them. Thus, urinary acidification will accelerate the excretion of weak bases and retard the excretion of weak acids. Making the urine alkaline will facilitate the excretion of weak acids and retard that of weak bases. 

The same considerations hold for acidic molecules, with the important difference that alkalinization of the urine (increased pH) will promote the deprotonization of -COOH groups and thus impede reabsorption. Intentional alteration in urinary pH can be used in intoxications with proton-acceptor substances in order to hasten elimination of the toxin (alkalinization phenobarbi-tal acidification amphetamine). 

Metabolism/Excretion - From 60% to 80% of a dose is metabolized via the liver into several metabolites. Quinidine is excreted unchanged (10% to 50%) in the urine within 24 hours. The elimination half-life ranges from 4 to 10 hours in healthy patients, with a mean of 6 to 7 hours. Urinary acidification facilitates quinidine elimination, and alkalinization retards it. In patients with cirrhosis, the elimination half-life may be prolonged and the volume of distribution increased. 

Drugs that may affect mexiletine include aluminum-magnesium hydroxide, atropine, narcotics, cimetidine, fluvoxamine, hydantoins, metoclopramide, propafenone, rifampin, urinary acidifiers, and urinary alkalinizers. 

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