Sodium depletion

Figure 1.25. Map of probabilities of centres of Kuroko deposits based on sodium depletion, sericite, and gypsum plus anhydrite (Singer and Kouda, 1988).

Comparison of SQ 20,881 with fifty-seven related synthetic peptides indicated that the last five amino acids of the sequence are required for significant enzyme inhibiting activity (100). This nonapeptide, intravenously, lowered blood pressure even in patients with normal renin levels (101. 102). This effect is strongly augmented by sodium depletion. 

Most of the lithium is eliminated in the urine, the first phase of the elimination being 6-8 hours after administration, followed by a slower phase which may last for 2 weeks. Sodium-depleting diuretics such as frusemide, ethacrynic acid and the thiazides increase lithium retention and therefore toxicity, while osmotic diuretics as exemplified by mannitol and urea enhance lithium excretion. The principal side effects of lithium are summarized in Table 8.1. 

Sodium chloride (normal saline)- 0.9% Sodium chloride (normal saline), which is isotonic, restores both water and sodium chloride losses. Other indications for parenteral 0.9% saline include Diluting or dissolving drugs for IV, IM, or subcutaneous injection flushing of IV catheters extracellular fluid replacement treatment of metabolic alkalosis in the presence of fluid loss and mild sodium depletion as a priming solution in hemodialysis procedures and to initiate and terminate blood transfusions without hemolyzing red blood cells. 

Orai Prevention or treatment of extracellular volume depletion, dehydration, or sodium depletion aid in the prevention of heat prostration. 

High-risk patients The risk of lithium toxicity is very high in patients with significant renal or cardiovascular disease, severe debilitation, dehydration, or sodium depletion, or in patients receiving diuretics. Undertake treatment with extreme caution. 

Sodium depletion Lithium decreases renal sodium reabsorption, which could lead to sodium depletion. Therefore, the patient must maintain a normal diet (including salt) and an adequate fluid intake (2,500 to 3,000 mL). 

Patients who present with heat exhaustion require fluid resuscitation. An attempt should be made to assess the amount of salt depletion and dehydration. This may be difficult clinically although the presence of symptoms such as muscle cramps in sodium depletion, and signs such as loss of tissue turgor may help. Laboratory measurement of sodium, urea, creatinine and haematocrit are the best guide. Pre-renal renal impairment is common. Treatment usually requires 5-10 1 of oral or intravenous isotonic fluids in the first 24 hours. In severe hyponatraemia the rapid correction of sodium should be carefully monitored with frequent sodium measurements and a reduction in fluid infusion rate if necessary to reduce the risk of osmotic demyelination (central pontine myelinol-ysis). 

Contraindications Debilitated patients, severe cardiovascular disease, severe dehydration, severe renal disease, severe sodium depletion... 

Diuretics lower blood pressure by reducing blood volume and promoting sodium depletion (e.g., diuretics such as hydrochlorothiazide (5.153))... 

Renal lithium excretion sensitive to changes in sodium balance. (Sodium depletion tends to cause lithium retention.) Susceptible to drugs enhancing central nervous system lithium toxicity. 

The most serious side effects of diuretics are fluid depletion and electrolyte imbalance.13,88 By the very nature of their action, diuretics decrease extracellular fluid volume as well as produce sodium depletion (hyponatremia) and potassium depletion (hypokalemia). Hypokalemia is a particular problem with the thiazide and loop diuretics, but occurs less frequently when the potassium-sparing agents are used. Hypokalemia and other disturbances in fluid and electrolyte balance can produce serious metabolic and cardiac problems and may even prove fatal in some individuals. Consequently, patients must be monitored closely, and the drug dosage should be maintained at the lowest effective dose. Also, potassium supplements are used in some patients to prevent hypokalemia. 

The main mineralocorticoid is aldosterone, with a daily secretion of 100 pg. Aldosterone is synthesized from 18-hydroxy corticosterone by a dehydrogenase. The consequence of 18-hydroxy-cortisterone dehydrogenease deficiency is diminished secretion of aldosterone, and the clinical manifestations consist of sodium depletion, dehydration, hypotension, potassium retention, and enhanced plasma renin levels (Figure 61.3). 

Kowarski (K3) has shown that the serum calcium level in idiopathic hypercalcemia can be reduced by the administration of sodium sulfate. Kendall (Kl) has pointed out that prolonged low-calcium feeding may involve a low sodium intake and lead ultimately to severe sodium depletion. 

Kl. Kendall, A. C., Infantile hypercalcaemia with keratopathy and sodium depletion. Brit. Med. J. ii, 682-683 (1957). 

The randomized controlled clinical trials performed by Freis and his colleagues at the Veterans Administration Hospitals have provided some of the first solid evidence that moderate permanent hypertension has an improved prognosis when actively treated by sodium depletion (hydrochlorothiazide), by interruption of the sympathetic nervous system (reserpine) and with a vasodilator (hydralazine) (262). In parallel, the beneficial effects of this triple therapy were demonstrated in spontaneously hypertensive rats by the spectacular prevention and cure of their cardiac, vascular, and renal lesions (263). 

Further optimization of the P3 substituent revealed that 3,4-bis-alkoxy substitution of the phenyl ring improved potency, with the optimal combination 3-(3-methoxypropoxy) and 4-methoxy (7, Table 2). Compound 7 exhibits exceptional renin inhibitory activity in both buffer and plasma and showed moderate in vivo activity in telemetered, sodium-depleted marmosets, with peak reduction of mean arterial pressure of 9 mm Hg and an 8-h duration of action.20 An X-ray co-crystal structure of compound 7 with recombinant human renin established that the methoxypropoxy sidechain occupies a narrow nonsubstrate pocket, termed S3sp. The importance of terminal methoxy group is... 

Because of the serious risks involved in long-term lithium treatment, patients plasma levels are reassessed regularly, usually every three months. If plasma lithium concentration becomes too high, administration of the drug is suspended and large amounts of sodium salts and fluids are given. Since lithium toxicity is enhanced by sodium depletion, the increased plasma sodium and fluids can reduce its toxic effects. 

It appears that, like SSRIs, reboxetine can cause sodium depletion in elderly people. However, in this case the contributions of concomitant general medical illness and its treatment were uncertain. 

The authors suggested that topiramate reduced renal lithium excretion through several mechanisms, possibly as a carbonic anhydrase inhibitor coupled with sodium depletion. They suggested that patients taking lithium and topiramate be carefully monitored for lithium concentrations and hydration. 

The effects of lithium can be enhanced by sodium depletion caused by any diuretic. 

The loop diuretics increase the renal excretion of lithium after single-dose intravenous administration in both animals (711) and man (712). Furosemide has been used to treat lithium intoxication (713). The effect of etacrynic acid is larger than those of furosemide and bumetanide (712). However, long-term treatment with furosemide and bumetanide can cause lithium intoxication in some patients (714,715), perhaps by causing sodium depletion and a secondary increase in lithium reabsorption. An adverse interaction of lithium during long-term therapy with etacrynic acid is therefore theoretically likely. 

Development of alteration layers on minerals dissolved under neutral and alkaline conditions has not been thoroughly investigated, but some work has been completed, especially on feldspar compositions (Chou and Wollast, 1984 Hellmann et al, 1989, 1990a Muir et al, 1990 Nesbitt et al, 1991 Hellmann, 1995, Hamilton et al, 2000). Under neutral conditions, the leached layer thickness (tens of angstroms to a few hundred angstroms) is generally less than that observed for more acid dissolution, with variability reported in the composition and thickness of the layer i.e., sodium depletion is generally observed, but both aluminum depletion and enrichment (with respect to silicon) have been reported. Variations in solution chemistry (see Section 5.03.7) and feldspar composition may explain some of these differences for... 

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