Ammonium urinary excretion

The rat has been used rather widely to study the relation between dietary protein, or acid salt feeding, and calcium loss. Barzel and Jowsey (19) showed that the rat fed a control diet supplemented with ammonium chloride excreted excessive urinary calcium, and experienced a concomitant loss of fat-free bone tissue. Draper, et al. (20) extending this work, reported an inverse relation between dietary phosphate and loss of bone calcium and dry, fat-free tissue. In subsequent studies (21), they reported that this process was accompanied by reduced serum calcium levels the high phosphorus, low calcium diet increased urinary calcium loss. Whereas, increasing the phosphorus content of the diet stopped the excessive urinary calcium loss. To test possible zinc loss that might result from this sort of acid salt feeding, Jacob and her coworkers (22) fed rats a supplement of ammonium chloride and then measured urinary zinc and calcium. The hypercalciuria occurred exclusive of an effect upon urinary zinc loss. 

After being found to be healthy on a thorough physical examination accompanied by a broad range of laboratory examinations, 22 men were used in studies of the renal clearance of I, after intravenous injection at 5 mg/kg under a variety of conditions.161 Alkaliniza-tion of the urine to a pH above 7.5 by administration of bicarbonate and acidification of the urine to a pH below 5.0 by administration of ammonium chloride both reduced urinary excretion of I. When 200 mg of thiamine was Injected intramuscularly 20-30 min before intravenous injection of I, urinary excretion of I during the 5 h after... 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

There have been many anecdotal reports of metabolic acidosis in glue sniffers, attributed to renal tubular acidosis. However, it has been suggested that it is in fact due to overproduction of hippuric acid resulting from the metabolism of toluene, with or without a reduced rate of urinary ammonium ion excretion (32). 

Disposition in the Body. Rapidly absorbed after oral administration. Excreted in the urine as unchanged drug and also metabolised to ammonium salts in the colon. Endogenous urinary excretion is in the range 10 to 35 g in 24 hours urea is not usually found in the faeces. 

Renal excretion of basic drugs such as amphetamine theoretically can be enhanced by acidification of the urine. Acidification can be accomplished by the administration of ammonium chloride or ascorbic acid. Urinary excretion of an acidic compound is particularly sensitive to changes in urinary pH if its is within the range of 3.0-7.5 for bases, the corresponding pH range is 7.5-10.5. 

A study in 6 healthy subjects found that the cumulative 72-hour urinary excretion of unchanged dextropropoxyphene was increased sixfold by acidification of the urine with oral ammonium chloride and reduced by 95% by alkalinisation with sodium bicarbonate the half-life of dextropropoxyphene was also shortened by ammonium chloride. The excretion of the active metabolite norpropoxyphene was much less dependent on urinary pH. However, the cumulative excretion of dextropropoxyphene and norpropoxyphene, even into acidic urine, accounted for less than 25% of the dose during 72 hours. ... 

The urinary excretion of amfetamines is increased by urinary acidifiers (ammonium chloride) and reduced by urinary alkalinisers (sodium bicarbonate). 

Two studies, one in healthy subjects and the other in patients with onchocerciasis, found that making the urine alkaline with sodium bicarbonate markedly increased the retention of the diethylcarbamazine. The urinary excretion of a 50-mg dose of diethylcarbamazine was 62.3% and its elimination half-life 4 hours when the urine was made aeidie (pH less than 5.5) by giving ammonium chloride, compared with 5.1% and 9.6 hours respectively when the urine was made dkaline (pH more than 7.5) using sodium bicarbonate. ... 

Serum and the 24-hour urinary excretion of urate under nonfasting conditions had been measured in advance. Renal acidification defects were diagnosed through a short ammonium chloride load (6). 

The first enzyme to be crystallized (and hence the first evidence that enzymes are proteins) was urease, which catalyses the hydrolysis of urea to ammonium and carbon dioxide. The original preparation of urease was from plant material, but the enzyme is also known to occur in a number of bacteria. In this study, a group of volunteers were given an intravenous infusion of 20 mmol urea labelled with both and and their urinary excretion of label was measured over 24 hours. Complete recovery of the label in urine would amount to 40 mmol and 20 mmol C. The results are shown in column 2 of Table 9.19. The experiment was repeated a week later, after they had received the antibiotic neomycin for 4 days to sterilize the gut these results are shown in column 3. 

Earlier animal work showed similar results in terms of urinary acid production from dietary precursors that could be converted into acid before excretion. However, most investigators used salts rather than foods containing the anion or its precursor. The addition of acid, in the form of hydrochloric, sulfuric, or ammonium chloride, acid phosphate salts, or ascorbate resulted in enhanced urinary acidity and concomitant calcium excretion. For example, in the detailed study of bone salt metabolism, Barzel and Jowsey (19) showed that the rat fed supplementary ammonium chloride subsequently lost more calcium, and developed markedly demineralized fat-free bone mass. 

This phenomenon also had been reported in human subjects fed acid ash foods. Farquharson, et al. (33) fed a high-protein (200 g) diet to human subjects who promptly excreted more urinary acid and calcium. This occurred whether the protein level was raised to 200 g, or an equivalent amount of ammonium chloride was fed. If, on the other hand, the acid ash in the protein were neutralized with sodium bicarbonate, the hypercalciuria did not occur. 

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. 

Effects of pH on urinary drug elimination may have important applications in medical practice, especially in cases of overdose. For example, one can enhance the elimination of a barbiturate (a weak acid) by administering bicarbonate to the patient. This procedure alka-linizes the urine and thus promotes the excretion of the now more completely ionized drug. The excretion of bases can be increased by making the urine more acidic through the use of an acidifying salt, such as ammonium chloride. 

Ammonium chloride increases urinary volume with acidification of urine. The excretion of amphetamine is decreased in relatively alkaline urine and has proved useful in the treatment of amphetamine intoxication. ... 

The effect of urinary pH on drug ionization also has toxicological implications. For example, in cases of phenobarbital (a weak acid barbiturate) overdose the urine can be alkalinized (the pH elevated) by administering sodium bicarbonate to the patient. The resultant increase in pH shifts the dissociation equilibrium for this weak acid to the right, producing an increase in the proportion of the ionized form, less reabsorption in the kidneys, and more rapid elimination. Conversely, acidifying the urine with ammonium chloride will increase the excretion rate of drugs that are weak bases since they will be more protonated (ionized) and less reabsorbed (more polar, less lipophilic). 

When absorbed into the systemic circulation, ammonia is primarily excreted by the kidney as urea and urinary ammonium compounds (Gay et al. 1969 Pitts 1971). Absorbed ammonia also can be excreted as urea in feces (Richards et al. 1975) and as a perspiration constituent (Guyton 1981 Wands 1981). In a study of male subjects exposed to ammonia at concentrations up to 500 ppm for 30 min, Silverman et al. (1949) found that 70-80% of inhaled ammonia was excreted in expired air. Ammonia in expired air returned to normal concentrations within 3 to 8 min after exposure was stopped. The investigators calculated that if all the retained ammonia were absorbed into the blood, there would be no significant change in blood or urine urea, ammonia, or nonprotein nitrogen. 

FLECAINIDE AMMONIUM CHLORIDE Urinary acidification l flecainide levels Flecainide excretion is T in the presence of an acidic urine flecainide exists in predominantly ionic form, which is less readily reabsorbed from the renal tubules Watch for a poor response to flecainide... 

The kidney plays a major role in the maintenance of acid-base homeostasis, particiilarly with respect to metabolic acidosis. In response to metabolic acidosis, the kidney is able to increase its production of ammonia resulting in enhanced urinary ammonium excretion, a process linked to proton excretion and the generation of... 

When a dmg is in its unionised form it will more readily diffuse from the urine to the blood. In an acidic urine, acidic drugs will diffuse back into the blood from the urine. Acidic compounds such as nitrofurantoin are excreted faster when the urinary pH is alkaline. Amfetamine, imipramine and amitriptyline are excreted more rapidly in acidic urine. The control of urinary pH in studies of pharmacokinetics is thus vital. It is difficult, however, to find compounds to use by the oral route for deliberate adjustment of urinary pH. Sodium bicarbonate and ammonium chloride may be used but are unpalatable. Intravenous administration of acidifying salt solutions presents one approach, especially for the forced diuresis of basic dmgs in cases of poisoning. 

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