Calcium tetracycline interactions

Gastrointestinal distress (nausea, vomiting, diarrhea) may be a problem with tetracycline use. Hypersensitivity reactions (such as rashes) may also occur, as well as an increase in skin sensitivity to ultraviolet light (photosensitivity).16 Tetracyclines form chemical complexes with calcium that may impair the growth and development of calcified tissues such as bone and teeth, especially in children.69 Tetracyclines also cause discoloration of teeth in children and pregnant women, apparently because of the tetracycline-calcium interaction.69 As mentioned previously, development of tetracycline-resistant strains and resulting superinfections may be a serious problem during tetracycline therapy. 

There are problems as well in the absorption of certain drugs in the presence of specific food components. L-Dopa absorption may be inhibited in the presence of certain amino acids formed from the digestion of proteins [43], The absorption of tetracycline is reduced by calcium salts present in dairy foods and by several other cations, including magnesium and aluminum [115-117], which are often present in antacid preparations. In addition, iron and zinc have been shown to reduce tetracycline absorption [118], Figure 17 illustrates several of these interactions. These cations react with tetracycline to form a water-in-soluble and nonabsorbable complex. Obviously, these offending materials should not be co-administered with tetracycline antibiotics. 

Reduced absorption due to complex formation or other interactions between drugs and intestinal components leading to poor absorption has been described in a few cases. One example is the precipitation of cationic drugs as very poorly-soluble salts with bile acids, which has been reported for several compounds [62], Another well-known example is the complex formation between tetracycline together with calcium due to chelation after administration of the drug together... 

Calcium Acetate (PhosLo) [Calcium Supplement/ Anti arrhythmic/Mmeral/ Electrolyte] Uses ESRD-associated hyper-phos-phatemia Action Ca " supl w/o aluminum to X P04 absorption Dose 2-4 tabs PO w/ meals Caution [C, ] Contra t Ca Disp Gelcap SE Can t Ca, hypophosphatemia, constipation Interactions t Effects OF quinidine X effects W/ large intake of dietary fiber, spinach, rhubarb X effects OF atenolol, CCB, etidronate, tetracyclines, fluoroquinolones, phenytoin, Fe salts, thyroid hormones EMS Pts have reduced renal Fxn, monitor ECG for signs of electrolyte disturbances OD S/Sxs of hypercalcemia (confusion, weakness, GI upset, constipation, N, V, and cardiac arrhythmias) give IV fluid for diuresis symptomatic and supportive Calcium Carbonate (TumS/ Alka Mints) [Antacid/ Calcium Supplement/Mineral/ Electrolyte] [OTC] Uses Hyperacidity associated w/ peptic ulcer Dz, hiatal hernia, etc Action Neutralizes gastric acid Dose 500 mg—2 g PO PRN -1- in renal impair Caution [C, ] Disp Chew tabs, susp SE t -1- PO constipation Interactions X Effect OF tetracyclines, fluo-... 

We have already met several of the important concepts in this topic, so now it is time to round them up and bring out the major principles. In the first place drug molecules clearly might interact with food molecules in the lumen of the gut. Perhaps the best-known example of this is the interaction between the tetracyclines and dietary calcium and iron. The binding, which occurs between them, produces a chelate, which is not particularly lipid-soluble, and therefore the overall absorption of tetracycline may be reduced to the point where plasma levels do not achieve effective antibiotic concentrations. The commonest dietary constituent to produce this binding is milk with its high calcium content. Tetracycline ingestion should be separated from food as far as possible. 

Drugs may bind to other drugs in the gut. We have already met the iron/calcium interaction with tetracyclines, which reduces the absorption of the antibiotic. 

Excipients may interact directly with the drug to form a water-soluble or water-insoluble complex. If tetracycline is formulated with calcium carbonate, an insoluble complex of calcium tetracycline is formed that has a slow rate of dissolution and poor absorption. 

Tetracyclines and Metals. Tetracyclines can combine with metal ions, such as calcium, magnesium, aluminum, and iron, in the GI tract to form complexes that are poorly absorbed. Thus, the simultaneous administration of certain drugs (e.g., antacids, iron preparations, products containing calcium salts) by patients on tetracycline therapy could result in a significant decrease in the amount of antibiotic absorbed. When two drugs are recognized as having a potential to interact, there is sometimes a tendency to believe that one of them should be discontinued. In the case of the tetracycline antacid interactions, problems can be... 

Since calcium salts can bind tetracyclines, leading to reduced absorption (SED-14, 910), an interaction of this kind might be expected with calcium polystyrene sulfonate, but it does not seem to have been reported. 

Drug interactions The bioavailability of tetracyclines is significantly deaeased when administered with antacids containing aluminum, calcium, or magnesium, with iron-containing products, or with food. Food or dairy products do not affect the bioavailability of doxycycline or minocycyline. 

Chemical interactions in the gastrointestinal tract between nutrients and drugs may considerably reduce the absorption of some drugs calcium ions from dairy products form insoluble and therefore nonabsorbable complexes with the antibiotic tetracycline. On the other hand, certain drugs are irritants to the gastrointestinal tract (nonsteroidal antiinflammatory drugs and potassium chloride tablets) and must be ingested with food. 

Clinically important, potentially hazardous interactions with acetazolamide, aminoglycosides, anticholinesterases, bambuterol, calcium channel blockers, chloroquine, chlorpromazine, clindamycin, d-pencillamine, ecothiophate iodine, enflurane, furosemide, halothane, hexomethonium, isoflurane, ketamine, lidocaine, lincomycin, lithium salts, magnesium salts, mannitol, MAO inhibitors, organophosphates, pancuronium, phenytoin, polymyxins, procainamide, quinidine, sevoflurane, spectinomycin, tetracyclines... 

Clinically important, potentially hazardous interactions with antacids, calcium products, quinolone antibiotics, tetracycline... 

Despite the fact that a plethora of dietary factors could, and will, affect the absorption characteristics of phytochemicals, this area has not been systematically explored. One reason might be the complexity of dietary factors and their interactions that could affect absorption. A nonexhaustive list would include the volume and composition of the food consumed, pH, caloric density, viscosity, nutrients (carbohydrates, protein, fat, fibers), alcohol, caffeine, and the presence of other phytochemicals. Such dietary factors affect the functional status, motility, and acidity of the gastrointestinal tract in a complex manner and modify the physicochemical properties, formulation, and dissolution characteristics of the compound of interest. Calcium in dairy products, for example, has the potential to chelate tetracyclines and fluoroquinolones and, thereby, reduce their bioavailability and biological activity [31]. 

There seem to be no direct clinical studies with calcium-containing antacids, but a clinically important interaction seems almost a certainty, based on in vitro studies with calcium carbonate, calcium in milk, (see Tetracyclines + Food or Drinks , p.347), dicalcium phosphate, and calcium as an excipient in tetracycline capsules. 

The calcium in food can complex with tetracycline to reduce its absorption. This is particularly notable with dairy products, which can reduce the absorption of the tetracyclines by up to 80%, thereby reducing or even abolishing their therapeutic effects. Doxyeyeline and minocycline are less affected by daily products (25 to 30% reduction). Orange juice and coffee do not interact with tetracycline. 

Orange juice appears not to interact, despite its calcium content, because at the relevant pH values in the gut, the calcium is bound to components within the orange juice (citric, tartaric and ascorbic acids) and is not free to combine with the tetracycline. ... 

Well documented and very well established interactions of clinical importance. Reductions in serum tetracycline levels of 50 to 80% caused by calcium-rich foods are sufficiently large to reduce or even abolish their... 

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