Vitamin deficiency, oral administration

There are many retinol containing preparations to treat vitamin deficiency states. Retinoids are also used to treat dermatological diseases like acne, psoriasis, Darier s disease, and ichthyosis. Tretinoin, all-trans-retinoic acid, is a topical preparation while isotretinoin or 13-cis-retinoic acid, and etretinate are available for oral administration. 

Vitamins Ki and K2 require bile salts for absorption from the intestinal tract. Vitamin Kl is available clinically in oral and parenteral forms. Onset of effect is delayed for 6 hours but the effect is complete by 24 hours when treating depression of prothrombin activity by excess warfarin or vitamin deficiency. Intravenous administration of vitamin Ki should be slow, because rapid infusion can produce dyspnea, chest and back pain, and even death. Vitamin repletion is best achieved with intravenous or oral administration, because its bioavailability after subcutaneous administration is erratic. Vitamin Ki is... 

The homocystinurias are a group of disorders involving defects in the metabolism of homocysteine. The diseases are inherited as autosomal recessive illnesses, characterized by high plasma and urinary levels of homocysteine and methionine and low levels of cysteine. The most common cause of homocystinuria is a defect in the enzyme cystathionine /3-synthase, which converts homocysteine to cystathionine (Figure 20.21). Individuals who are homozygous for cystathionine [3-synthase deficiency exhibit ectopia lentis (displace ment of the lens of the eye), skeletal abnormalities, premature arte rial disease, osteoporosis, and mental retardation. Patients can be responsive or non-responsive to oral administration of pyridoxine (vitamin B6)—a cofactor of cystathionine [3-synthase. Bg-responsive patients usually have a milder and later onset of clinical symptoms compared with B6-non-responsive patients. Treatment includes restriction of methionine intake and supplementation with vitamins Bg, B, and folate. 

This vitamin is not synthesized in animals, but rather it results from the bacterial or fungal fermentation in the rumen, after which it is absorbed and concentrated during metabolism. Among the known vitamins, this exclusive microbial synthesis is of great interest. One of the major results of vitamin Bn deficiency is pernicious anemia. This disease, however, usually does not result from a dietary deficiency of the vitamin, but rather by an absence of a glycoprotein ( gastric intrinsic factor ) in the gastric juices that facilitates absorption of the vitamin in the intestine. Control of the diseases hence is either by injection of Bn or by oral administration of the intrinsic factor, with or without the vitamin injection. 

Vitamin B12 is available in pure form for oral administration or in combination with other vitamins and minerals for oral or parenteral administration. The choice of a preparation always must be made with recognition of the cause of the deficiency. Although oral preparations may be used to supplement deficient diets, they are of relatively little value in the treatment of patients with deficiency of intrinsic factor or ileal disease. Even though small amounts of vitamin B12 may be absorbed by simple diffusion, the oral route of administration cannot be relied upon for effective therapy in the patient with a marked deficiency of vitamin B12 and abnormal hematopoiesis or neurological deficits. Therefore, the preparation of choice for treatment of a vitamin B12-deficiency state is cyanocobal-amin, and it should be administered by intramuscular or deep subcutaneous injection. 

Q9 Treatment consists of correcting the underlying cause and replacing the deficient iron. Oral administration of ferrous sulphate (containing 120-200 mg of elemental iron daily) is the standard treatment. This should be taken on an empty stomach, if tolerated, with vitamin C (ascorbic acid), which aids absorption. When the normal haemoglobin concentration in blood has been achieved, the treatment should be continued for an extra three to six months to ensure that body iron stores are replenished. 

Tocopherols (vitamin E) occur in many food substances that are consumed as part of the normal diet. The daily nutritional requirement has not been clearly defined but is estimated to be 3.0-20.0 mg. Absorption from the gastrointestinal tract is dependent upon normal pancreatic function and the presence of bile. Tocopherols are widely distributed throughout the body, with some ingested tocopherol metabolized in the liver excretion of metabolites is via the urine or bile. Individuals with vitamin E deficiency are usually treated by oral administration of tocopherols, although intramuscular and intravenous administration may sometimes be used. 

The Schilling test is primarily a test of vitamin B12 absorption and not of status, but it permits differentiation of causes of vitamin B12 deficiency (pernicious anemia or intestinal malabsorption). The proportion absorbed from orally administered Co- or Co-labeled vitamin 6,2 is measured by determining the radioactivity in feces, urine, or serum or by externally scanning the liver. The usual procedure is to measure radioactivity in a 24-hour urine sample, which is collected after oral administration of 0.5 Xg of radioactive Co-labeled vitamin B12 after an overnight fast. In normal individuals, 8% or more of the dose administered is excreted in the urine, whereas in people with pernicious anemia, less than 7% (often 0% to 3%) is excreted. A confirmatory test for lack of IF requires mgestion of vitamin B,2 and IF. ... 

In patients with vitamin D deficiency, oral vitamin D 50,000 units daily for 10 days or once weekly for 8 weeks, or 50,000 to 500,000 units intramuscularly is recommended. Serum calcium and 25(OH) vitamin D should be monitored periodically. Once replete, daily intakes of 600 to 1000 units are usually required. In the community or nursing home, vitamin D 100,000 units once per quarter is reasonable. In patients with vitamin D malabsorption (e.g., gluten-sensitive celiac sprue), 25(OH) vitamin D (calcidiol) administration is needed. In patients with severe hepatic or renal disease, calcitriol therapy may be required. This drug requires careful titration and serum calcium and creatinine monitoring because of its hypercalcemic potential and the limited calciuric ability of the dysfunctional kidney. 

Vitamin deficiency occurs when there is malabsorption because of a lack of intrinsic factor (pernicious anttemia). following gastrectomy (no intrinsic factor), or in various small bowel diseases, where absorption is impaired. Because the disease is nearly always cau.sed by malabsorption. oral vitamin administration is of little value, and replacement Iherapy, usually for life, involves injections of vitamin (left). Hydroxocobulamin is the form of choice for ilierapy because it is retained in Ihe body longer than cyanocobalamin (cyanocobalamin is bound less to plasma proteins and Ls more rapidly excreted in urine). 

Rats made deficient in vitamin B12 are not improved by the oral administration of sorbitol (Okuda et al., 1960). After giving sorbitol to rats for 2 or 3 months, Okuda et al. found that the absorption of radioactive vitamin Bk was less than in normal rats. As we shall see later, similar results in human beings had been reported by Heinrich el al. (1959). 

These earlier effects include the alleviation of nutritional anemia of preg-nancy , and the prevention of dietary deficiency symptoms in monkeys (vitamin M)S2,33 and chicks -ss (Factor U and vitamin Be), and in addition the response of pernicious anemia patients to oral administration of large amounts of liver may have been due to folic acid rather than to vitamin Bi2. 

The only disorder of the y-glutamyl cycle for which treatment principles have been developed is glutathione synthetase deficiency (9.2) [1]. The initial symptoms in the neonatal period may be metabolic acidosis and jaundice. Acidosis usually needs to be corrected with sodium bicarbonate, THAM or sodium citrate. Patients may benefit from oral administration of vitamin E (10 mg/kg/day) and vitamin C (100 mg/kg/day). Trials have also been made with N-acetylcysteine and glutathione esters which increased glutathione in leukocytes and plasma. Both these compounds lead to increased intracellular levels of glutathione. However, no decrease in the excretion of 5-oxoprolinuria has been reported. 

Equal activities for vitamin Ki and menadione were found by Fisher et al. (1956) in the dog, where vitamin K deficiency had been produced by chronic lack of bile. On oral administration the water-soluble menadione was more active than the oily solution of vitamin Ki. 

A test which can be used in the investigation of vitamin Bj2 deficiency. The metabolism of valine contains a step in which methylmalonyl coenzyme A is converted to succinyl coenzyme A, an enzymic reaction which requires vitamin B12 as a cofactor. In vitamin B deficient individuals, administration of an oral load of valine results in a greater than normal excretion of methylmalonate in the urine which can be estimated colorimetrically. 

Although lipoic acid has been found in numerous biological tissues, reports on its concentrations in foods are scarce. Lipoic acid is detectable in wheat germ (0.1 ppm) but not in wheat flour. It has been detected in bovine liver kidney and skeletal muscle. Oral administration of lipoic acid (1.65 g/kg fed) to rats for five weeks resulted in elevated levels of the thiol in liver, kidney, heart, and skin. When lipoic acid was added to diets lacking in vitamin E, symptoms typical of tocopherol deficiency were not observed suggesting that lipoic acid acts as an antioxidant in vivo. However, lipoic acid was not capable of recycling vitamin E in vivo, as determine by the fact that a-tocopherol concentrations are not elevated by dietary lipoic acid in vitamin E deficient rats. 

For acute symptomatic hypocalcemia, 200 to 300 mg of elemental calcium is administered IV and repeated until symptoms are fully controlled. This is achieved by infusing 1 g of calcium chloride or 2 to 3 grams of calcium at a rate no faster than 30 to 60 mg of elemental calcium per minute. More rapid administration is associated with hypotension, bradycardia, or cardiac asystole. Total calcium concentration is commonly monitored in critically ill patients. Under normal circumstances, about half of calcium is loosely bound to serum proteins while the other half is free. Total calcium concentration measures bound and free calcium. Ionized calcium measures free calcium only. Under usual circumstances, a normal calcium level implies a normal free ionized calcium level. Ionized calcium should be obtained in patients with comorbid conditions that would lead to inconsistency between total calcium and free serum calcium (abnormal albumin, protein, or immunoglobulin concentrations). For chronic asymptomatic hypocalcemia, oral calcium supplements are given at doses of 2 to 4 g/day of elemental calcium. Many patients with calcium deficiency have concurrent vitamin D deficiency that must also be corrected in order to restore calcium homeostasis.2,37,38... 

Vitamin B12 (cyanocobalmin) administered both orally and parenterally is equally effective in treating anemia from vitamin B12 deficiency. However, use of parenteral cyanacobalamin is the most common method of vitamin B12 replacement because it may be more reliable and practical. Subcutaneous or intramuscular administration is appropriate. Vitamin B12 is absorbed completely following parenteral administration, whereas oral vitamin B12 is absorbed poorly via the GI tract. Furthermore, use of parenteral vitamin B12 to treat megaloblastic anemia may circumvent the need to perform a Schilling test to diagnose lack of intrinsic factor. 

Deficiencies in vitamin K and the related synthesis of the vitamin K-dependent clotting factors are treated by administering exogenous vitamin K.20 Various commercial forms of this vitamin are available for oral or parenteral (intramuscular or subcutaneous) administration. Specifically, individuals with a poor diet, intestinal disease, or impaired intestinal absorption may require vitamin K to maintain proper hemostasis. 

Deficiencies of vitamin B12 can result from either low dietary levels or, more commonly, from poor absorption of the vitamin due to the failure of gastric parietal cells to produce intrinsic factor (as in pernicious anemia) or to a loss of activity of the receptor needed for intestinal uptake of the vitamin.5 Nonspecific malabsorption syndromes or gastric resection can also cause vitamin B12 deficiency. The vitamin may be administered orally (for dietary deficiencies), or intramuscularly or deep subcutaneously (for pernicious anemia). [Note Folic acid administration alone reverses the hematologic abnormality and thus masks the B12 deficiency, which can then proceed to severe neurologic dysfunction and disease. Therefore, megaloblastic anemia should not be treated with folic acid alone, but rather with a combination of folate and vitamin B12.] Therapy must be continued for the remainder of the life of a patient suffering from pernicious anemia. There are no known adverse effects of this vitamin. 

The polypeptide parathormone is released from the parathyroid glands when the plasma Ca2+ level falls. It stimulates osteoclasts to increase bone resorption in the kidneys it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of Ca2+ to precipitate as bone mineral decreases. By stimulating the formation of vitamin D hormone, parathormone has an indirect effect on the enteral uptake of Ca2+ and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that, unlike parathormone, is effective orally. Teriparatide is a recombinant shortened parathormone derivative containing the portion required for binding to the receptor. It can be used in the therapy of postmenopausal osteoporosis and promotes bone formation. While this effect seems paradoxical in comparison with hyperparathyroidism, it obviously arises from the special mode of administration the once daily s.c. injection generates a quasi-pulsatile stimulation. Additionally, adequate intake of calcium and vitamin D must be ensured. 

Should substitution of haemostatic factors become necessary prior or subsequent to invasive procedures, fresh plasma is the agent of choice, since it contains not only a balanced mixture of procoagulant and anticoagulant factors, but also fibronectin, which serves to reinforce RES clearance. However, relatively large quantities of fresh plasma are required, and it is important that individual volume limits are adhered to for haemodynamic reasons. Preventive administration of vitamin K (10 mg/week), subcutaneously injected if oral application is considered inefficient or an intramuscular injection appears too risky, is recommended in the case of suspected vitamin K deficiency. This measure can also be used prior to treatment with cephalosporins, in particular P-lactam antibiotics, or if the intestinal flora is affected. 

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