AXCEL EVILINE TABLET

Indication

For use in the management of hypocalcemia and its clinical manifestations in patients with hypoparathyroidism, as well as for the treatment of familial hypophosphatemia (vitamin D resistant rickets). This drug has also been used in the treatment of nutritional rickets or osteomalacia, vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis).

Mechanism of Action

Activated ergocalciferol increases serum calcium and phosphate concentrations, primarily by increasing intestinal absorption of calcium and phosphate through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. 25-hydroxyergocalciferol is the intermediary metabolite of ergocalciferol. Although this metabolite exhibits 2–5 times more activity than unactivated ergocalciferol in curing rickets and inducing calcium absorption and mobilization (from bone) in animals, this increased activity is still insufficient to affect these functions at physiologic concentrations. Activated ergocalciferol stimulate resorption of bone and are required for normal mineralization of bone. Physiological doses of ergocalciferol also promotes calcium reabsorption by the kidneys, but the significance of this effect is not known.

Pharmacokinetics

Absorption

Readily absorbed from small intestine (proximal or distal), requires presence of bile salts.

Distribution

Metabolism

Within the liver, ergocalciferol is hydroxylated to ercalcidiol (25-hydroxyergocalciferol) by the enzyme 25-hydroxylase. Within the kidney, ercalcidiol serves as a substrate for 1-alpha-hydroxylase, yielding ercalcitriol (1,25-dihydroxyergocalciferol), the biologically active form of vitamin D2.

Elimination

Toxicity

LD₅₀ = 23.7 mg/kg (Orally in mice); LD₅₀ = 10 mg/kg (Orally in rats ); Nausea, vomiting and diarrhea, weight loss, irritability, weakness, fatigue, lassitude, and headache.

Active Ingredient/Synonyms

(3β,5Z,7E,22E)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol | (5Z,7E,22E)-(3S)-9,10-seco-5,7,10(19),22-ergostatetraen-3-ol | (5Z,7E,22E)-(3S)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol | Activated ergosterol | Ercalciol | Ergocalciférol | Ergocalciferol | Ergocalciferolum | Oleovitamin D2 | Viosterol | Vitamin D2 | Vitamina D2 | Ergocalciferol |

Indication

Magnesium hydroxide can be used as an antacid or a laxative depending on the administered dose. As an antacid, it is used for the temporary relief of heartburn, upset stomach, sour stomach or acid indigestion. As a laxative, it is used for the relief of occasional constipation by promoting bowel movements for 30 minutes and up to 6 hours.

Mechanism of Action

The suspension of magnesium hydroxide is ingested and enters the stomach. According to the amount ingested, the magnesium hydroxide will either act as an antacid or a laxative. Through the ingestion of 0.5-1.5 grams (in adults) the magnesium hydroxide will act by simple acid neutralization in the stomach. The hydroxide ions from the magnesium hydroxide suspension will combine with the acidic H+ ions of the hydrochloric acid made by the stomachs parietal cells. This neutralization reaction will result in the formation of magnesium chloride and water. Through the ingestion of 2-5 grams (in adults) the magnesium hydroxide acts as a laxative in the colon. The majority of the suspension is not absorbed in the intestinal tract and will create an osmotic effect to draw water into the gut from surrounding tissues. With this increase of water in the intestines, the feces will soften and the intraluminal volume of the feces will increase. These effects still stimulate intestinal motility and induce the urge to defecate. Magnesium hydroxide will also release cholecystokinin (CKK) in the intestines which will accumulate water and electrolytes in the lumen and furthermore increase intestinal motility.

Pharmacokinetics

Absorption

About 15%-50% of magnesium hydroxide is absorbed very slowly through the small intestine.

Distribution

The peak action and distribution of magnesium hydroxide are variable.

Metabolism

Unless a patient is deficient in magnesium, very little is absorbed by the intestine. Overall, about 15%-50% of the magnesium hydroxide suspension is absorbed systemically. However, it does not undergo any metabolism as it is rapidly excreted in the urine.

Elimination

Clearance

Magnesium hydroxide is mainly excreted in the urine by the kidneys. Since the kidneys play a major role in its clearance, individuals with renal failure are at risk of hypermagnesemia with long term consumption as the appropriate amounts of magnesium may not be excreted.

Toxicity

LD50=8500 mg/kg (rat, oral) Common side effects include drowsiness or flushing (warmth, redness or tingly feeling). Daily use of magnesium hydroxide can result in fluid and electrolyte disturbances. Excessive use of the laxative effects of magnesium hydroxide may result in abdominal cramping, nausea and/or diarrhea. In overdose, symptoms of gastrointestinal irritation and/or watery diarrhea may occur. Magnesium hydroxide poisoning can result in hypermagnesemia which includes symptoms of: nausea, vomiting, flushing, thirst, hypotension, drowsiness, confusion, loss of tendon reflexes, muscle weakness, respiratory depression, cardiac arrhythmias, coma and cardiac arrest. Not to be used in individuals with any form of kidney disease or renal failure, a magnesium restricted diet or with any sudden changes in bowel movement lasting over two weeks. Also not to be used in those individuals with abdominal pain, nausea, vomiting, symptoms of appendicitis or myocardial damage, heart block, fecal impaction, rectal fissures, intestinal obstruction or perforation or renal disease. Not to be used in women who are about to deliver as magnesium crosses the placenta and is excreted in small amounts in breast milk. Using magnesium hydroxide with aluminum hydroxide can decrease the absorption rate of these drugs. Magnesium hydroxide can react with digoxin, dicoumerol and cimetidine. Use of ibuprofen with magnesium hydroxide can increase the absorption of the ibuprofen. Use of magnesium hydroxide with penicallamine, bisphosphates, ketoconazole, quinolones or tetracycline can decrease the absorption of these drugs. Enteric-coated tablets can be prematurely released when taken with magnesium hydroxide. It is important to routinely monitor levels of serum magnesium and potassium in patients using magnesium hydroxide. Serum magnesium levels are necessary to determine how much magnesium is being absorbed and how much is being excreted by the kidneys. Excessive diarrhea can occur from use of magnesium hydroxide and thus it is important to also monitor serum potassium levels to ensure hypokalemia does not occur.

Active Ingredient/Synonyms

Magnesium dihydroxide | Milk of magnesia | Magnesium hydroxide |

Indication

1. To relieve pain and discomfort caused by excess gas in the intestine and stomach in cases such as flatulence and post operative gaseous distention. 2. It could be used also prior to an endoscopy to eliminate foam, gas and air from the gastrointestinal tract to reduce gas shadow which will result in better visualization.

Mechanism of Action

Decreases the surface tension of gas bubbles thereby disperses and prevents gas pockets in the GI system.

Pharmacokinetics

Absorption

Not absorbed following oral administration.

Distribution

Simethicone is pharmacologically inert and is not absorbed from the gastrointestinal tract.

Metabolism

The drug is not absorbed and it is excreted in the feces unchanged.

Elimination

Clearance

Excreted unchanged in feces.

Toxicity

LD50 (oral, rat): 4070 mg/Kg.

Active Ingredient/Synonyms

Simeticone | Simethicone |