Sodium clinical importance

Indicine IV-oxide (169) (Scheme 36) is a clinically important pyrrolizidine alkaloid being used in the treatment of neoplasms. The compound is an attractive drug candidate because it does not have the acute toxicity observed in other pyrrolizidine alkaloids. Indicine IV-oxide apparently demonstrates increased biological activity and toxicity after reduction to the tertiary amine. Duffel and Gillespie (90) demonstrated that horseradish peroxidase catalyzes the reduction of indicine IV-oxide to indicine in an anaerobic reaction requiring a reduced pyridine nucleotide (either NADH or NADPH) and a flavin coenzyme (FMN or FAD). Rat liver microsomes and the 100,000 x g supernatant fraction also catalyze the reduction of the IV-oxide, and cofactor requirements and inhibition characteristics with these enzyme systems are similar to those exhibited by horseradish peroxidase. Sodium azide inhibited the TV-oxide reduction reaction, while aminotriazole did not. With rat liver microsomes, IV-octylamine decreased... 

Dextrans of low molecular weight have also been fractionated by gel chromatography. Bremner and coworkers,67 in preparing (by alkaline degradation) dextrans of low molecular weight suitable for incorporation in the clinically important iron-dextran complex, fractionated their product on Sephadex G-50, with (O M sodium chloride as the eluant. Separate fractions, ranging in Mn (as determined by osmometry) from 1510 to 4860, were obtained in this way. 

For a displacement interaction to become clinically important, a second mechanism usually operates sodium valproate can cause phenytoin toxicity because it both displaces phenytoin from its binding site on plasma albumin and inhibits its metabolism. Similarly aspirin and probenecid (and possibly other nonsteroidal anti-inflammatory drugs) displace the folic acid antagonist methotrexate from its protein-binding site and reduce its rate of active secretion by the renal tubules the result is serious methotrexate toxicity. 

Salem M, Munoz R, Chernow B 1991 Hypomagnesemia in critical illness. A common and clinically important problem. Critical Care Clinics 7 225-252 Schaer M 1999 Disorders of serum potassium, sodium, magnesium and chloride. Journal of Veterinary Emergency and Critical Care 9 209-217... 

Clinically important, potentially hazardous interactions with carbamazepine, clonazepam, phenobarbital, phenytoin, sodium valproate... 

Excessive urinary losses of magnesium from the kidneys are important causes of magnesium deficiency. Clinically important causes include alcohol, diabetes meUitus (osmotic diuresis), loop diuretics (furosemide), and aminoglycoside antibiotics. Increased sodium excretion (parenteral fluid therapy) and increased calcium excretion (hypercalcemic states) also result in renal magnesium wasting. 

Potential adverse effects associated with hypertonic fluid administration for circulatory insufficiency include cellular crenation and damage caused by the dramatic fluid shifts, as well as peripheral vein destruction from their high osmolality. Also, in the case of hypertonic sodium chloride solutions, there are the possibilities of neurologic damage from hypernatremia and hyperchloremic metabolic acidosis from hyperchloremia. In the limited number of studies conducted in humans to date, such adverse effects have been uncommon and apparently of little clinical importance. ... 

Once inside the neuron dissociation is necessary, because it is the ionized form binds to the sodium ion channel. Local anaesthetic activity is dependent on pH, because pH determines the degree of dissociation into ions. This becomes of clinical importance in inflamed and infected tissue, which often has a more acid pH. Acid conditions result in increased degree of ionization and reduced diffusion of local anaesthetic into neurons. This makes them less effective anaesthetics. 

The most clinically important adverse effects of sodium nitroprusside are profound hypotension and the accumulation of cyanide and thiocyanate. Thiocyanate may accumulate in the blood of patients receiving sodium nitroprusside therapy, especially in those with impaired renal function. Thiocyanate is mildly neurotoxic at serum concentrations of 60 pg/mL and may be life-threatening at concentrations of 200 pg/mL. Other adverse effects of thiocyanate includes inhibition of both the uptake and binding of iodine producing symptoms of hypothyroidism. 

Serious systemic reactions occurred when three patients taking enaiaprii were given infusions of ferric sodium gluconate however, there was no increase in the incidence of such adverse reactions in patients taking ACE inhibitors in a very large clinical study. Oral ferrous sulfate may decrease the absorption of capto-pril, but this is probably of little clinical importance. 

The interaetions involving polymyxin B, colistin, colistimethate sodium, lineomyein, and elindamyein are established and clinically important. The ineidenee is uneertain. Coneurrent use need not be avoided, but be alert for inereased and prolonged neuromuscular blockade. The recovery period should be well monitored beeause of the risk of recurarisation. Check the outeome of using amphoteriein. No interaction would be expeeted with... 

A well established and clinically important interaction for those receiving long-term treatment with large doses of salicylates because the serum salicylate level may become subtherapeutic. This interaction can occur with both systemic antacids (e.g. sodium bicarbonate) as well as some non-systemic antacids (e.g. aluminium/magnesium hydroxide), but only appears to occur if there is an increase in the urinary pH. Care should be taken to monitor serum salicylate levels if any antacid is started or stopped in patients where the control of salicylate levels is critical. 

The excretion of fleeainide is increased if the urine is made acidic (e.g. with ammonium chloride) and reduced if the urine is made alkaline (e.g. with sodium bicarbonate). The clinical importance of these changes is not known. 

Established interactions, but their clinical importance is still uncertain. The effects of these changes on the subsequent control of arrhythmias by fleeainide in patients seem not to have been studied, but the outcome should be well monitored if patients are given drugs that alter urinary pH to a significant extent (such as ammonium chloride, sodium bicarbonate). Large doses of some antacids may possibly do the same, but nobody seems to have studied this. 

Valproate toxicity developed in three patients given large and repeated doses of aspirin. Increased levels of free valproate were found in S children within hours of them taking aspirin. Con-versefy, a slightly reduced valproate level was reported in one patient who took ibuprofen. Modestly altered protein binding has been shown when sodium valproate was given with diflunisal or naproxen, but this appears unlikely to be clinically important... 

The clearance of a single oral dose of sodium valproate was reduced in 6 patients by 2 to 17% after a 4-week course of cimetidine, but was not affected by ranitidine. It seems doubtful if the interaction between valproate and cimetidine is of clinical importance. However, a case of fatal hyperammonaemia in a patient with systemic lupus erythematosus was speculated to have been induced by valproate, and the authors also considered that the concurrent use of cimetidine and aspirin (see Valproate + Aspirin or NSAIDs , p.575) may have contributed. The general importance of this case is unknown. 

The interactions of ergot derivatives with erythromycin and troleandomycin are well documented, well establish, and clinically important, whereas information about clarithromycin appears to be eonfined to three possible cases and that relating to oleandomycin to one case. There are no adverse reports about midecamycin, but it is expected to interact similarly. The concurrent use of all of these macrolides and ergot derivatives should be avoided. Some of the cases cited were effectively treated with sodium nitroprusside or naftidrofuryl oxalate, with or without heparin. "" " Spiramycin, and josamycin would not be expected to interact because they do not inhibit CYP3A4. However, there is one unexplained and unconfirmed report of an interaction with josamycin. "... 

A comparative study the pharmacological mechanisms underlying the way drugs interfere with the actions of loop diuretics found that indometacin 50 mg three times daily for 2 days reduced the peak fractional excretion of sodium in response to a single 6-mg dose of piretanide. The clinical importance of this change was not studied. 

The concurrent use of furosemide and probenecid has been closely studied to determine the renal pharmacological mechanisms of loop diuretics. One study in patients given furosemide 40 mg daily found that the addition of probenecid 500 mg twice daily for 3 days reduced their urinary excretion of sodium by about 36% (from 56.3 to 35.9 mmol daily). Other studies have also found some changes in overall diuresis (a fall, a rise, and no change in some studies), and a reduction of 35 to 80% in the renal clearance of furosemide. One study found that probenecid 1 g increased the half-life of furosemide by 70% and decreased its oral clearance by 65%. Similar results were found in another study. The clinical importance of these changes is uncertain, but probably small. 

None of these interactions is extensively documented but all appear to be established and of clinical importance. Serum ciclosporin levels should be well monitored if carbamazepine, phenobarbital or phenytoin are added and the ciclosporin dosage increased appropriately. Primidone is metabolised to phenobarbital by the liver, and therefore would be expected to reduce ciclosporin levels. Information about oxcarbazepine is very limited but small reductions in its dose, together with an increase in ciclosporin dose, may be adequate to control any interaction. However, more study is required before oxcarbazepine can be recommended as a suitable alternative. The effects of the interaction may persist for a week or more after the anticonvulsant is withdrawn. Sodium valproate seems not to alter ciclosporin levels, but the case reports of nephritis and hepatotoxicity suggest some caution is warranted. 

In contrast, one patient had no clinically significant changes in her serum-lithium levels when treated with cisplatin, but 2 months later her deteriorating renal function resulted in a rise in her serum-lithium levels. None of these interactions was of great clinical importance, but the authors of the first report pointed out that some regimens of cisplatin involve the use of higher doses (40 mg/m daily) with a sodium chloride 0.9% fluid load over 5 days, and under fhese circumstances it would be prudent to monitor the serum-lithium levels carefully. Concurrent use should be monitored in all patients. 

Aluminium hydroxide may possibly cause a more rapid onset of pseudoephedrine activity (but this needs confirmation). Any interaction seems unlikely to be clinically significant. Similarly, the effects of kaolin on absorption are small and unlikely to be clinically important. For the effect of sodium bicarbonate on pseudoephedrine and ephedrine, see urinary alka-Iinisers%(p.l277). 

The oral dose of voriconazole does not have to be adjusted in patients who have renal impairment. However, intravenous administration of voriconazole should be avoided in these patients as the carrier vehicle sulfobu-tyl ether P-cyclodextrin sodium can accumulate in these patients. Dosage adjustment is required in patients who have chronic hepatic impairment. As voriconazole is a substrate for a number of cytochrome P450 enzymes, a number of clinically important dmg interactions occur with dmgs including ciclospotin, tacrolimus, phenytoin, warfarin, HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors. 

High Osmolality Contrast Media. An important advance in radiopaques came with the synthesis of aminotriiodoben2oic acid and its acetylated derivative, acetrizoic acid [85-36-9] (5) (8,9). Aqueous solutions of sodium acetrizoate possessed the thermal stabiUty so that they could be autoclaved (10) with minimal decomposition. The higher iodine content, ie, 3 atoms/molecule, increased the contrast efficiency, and the clinical safety of acetrizoate was improved over that of the earlier urographic agents. 

Eluoride added to a compatible dentifrice base at a level of 1000 ppm has been clinically proven to reduce the incidence of dental caries by about 25% on average, even in areas where the water supply is fluoridated (4). Elevation to 1500 ppm increases the protection. Sources of fluoride approved for use in dentifrices are sodium fluoride [7681-49-4] (0.22%), sodium monofluorophosphate (0.76%), and stannous fluoride [7783-47-3] (0.41%). The Eood and Dmg Administration regulates fluoridated dentifrices as dmgs and has estabUshed parameters for safe and effective products. CompatibiUty of the fluoride with the abrasive is an important requirement. 

In addition, the physician with the aid of the clinical chemist, needs to calculate salt and water requirements for the newborn infant. Of prime importance is the determination of how much sodium bicarbonate is required to correct an acidosis, or in rare cases, how much ammonium chloride might be required to correct an alkalosis ( ). 

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