Sustained-release preparations slow

Nausea and diarrhea are common early side effects. Gastrointestinal symptoms may improve with dose reduction or with ingestion of lithium at meals. Slow-release formulations are more often associated with nausea, whereas sustained-release preparations are more commonly associated with diarrhea. 

Lithium preparations include lithium carbonate, sustained-release preparations, and the liquid form, lithium citrate. The sustained-release preparations allow for a more gradual absorption of the drug, leading to blunted peak plasma levels. Because lithium has a slow onset of action, it can take weeks, and occasionally longer, to obtain an optimal clinical response. Thus, it is important to avoid a premature abandonment in those who are simply slower to respond. 

Sustained release preparations of potassium chloride have been widely used to overcome the gastrointestinal side effects following medication with enteric coated tablets. Such formulation techniques delay the rate of absorption and produce a slow release of potassium chloride during the passage through the gastrointestinal tract [1,2]. 

A suggested course. Start a patient on ferrous sulphate taken on a full stomach once, then twice, then thrice a day. If gut intolerance occurs, stop the iron and reintroduce it with one week for each step. If this seems to cause gastrointestinal upset, try ferrous gluconate, succinate or fumarate. If simple preparations (above) are unsuccessful, and this is unlikely, then the pharmaceutically sophisticated and expensive sustained-release preparations may be tried. They release iron slowly and only after passing the pylorus, from resins, chelates (sodium iron edetate) or plastic matrices, e.g. Slow-Fe, Ferrograd, Feospan, so that iron is released in the lower rather than the upper small intestine. Patients who cannot tolerate standard forms even when taken with food may get as much iron with fewer unpleasant symptoms if they use a sustained-release formulation. 

Use of a slow-infusion pump with a concentrated solution (insulin 1.0 unit/ml) is recommended. Insulin loss is minimised and control of dose is more accurate than when more dilute solutions are used. (For i.v. doses see diabetic ketoacidosis, below.) Insulin is suitable for adimistration by continuous i.v. infusion because its short t/ (5 min) means that the plasma concentration rapidly reaches steady state after initiating the infusion or altering its rate (5 X see p. 101). Long-acting (sustained-release) preparations must not be given i.v. 

Food ordinarily slows the rate of theophylline absorption but does not limit its extent. With sustained-release preparations, food may decrease the bioavailability of theophylline with some products but may increase it with others. Recumbency or sleep also may significantly reduce the rate or extent of absorption. These factors make it difficult to maintain relatively constant concentrations of theophylline in plasma throughout the day. Concentrations required to alleviate asthmatic symptoms do not remain constant, and the emphasis has shifted toward designing dosing regimens that ensure peak concentrations in the early morning hours, when symptoms frequently worsen. 

B. Pharmacokinetics. Absorption may be delayed with sustained-release preparations. The volume of distribution (Vd) is approximately 0.5 Ukg. The normal elimination half-life is 4-6 hours this may be doubled by illnesses or interacting drugs that slow hepatic metabolism, such as liver disease, congestive heart failure, influenza, erythromycin, or cimetidine, and may increase to as much as 20 hours after overdose. (See also Table 11-59, p 381.)... 

A. All patients with potentially serious overdose should be observed for at least 6-8 hours before discharge or transfer to a nonmedical (eg, psychiatric) facility. If signs or symptoms of intoxication develop during this time, admission for further observation and treatment is required. Caution Beware of delayed complications from slow absorption of medications (eg, from a tablet concretion or bezoar, or sustained-release or enteric-coated preparations). In these circumstances, a longer period of observation is warranted. If specific dmg levels are determined, obtain repeated serum levels to be certain that they are decreasing as expected. 

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