موضوع كامل عن املاح الكالسيوم Chemistry calciumsalts

CALCIUM SALTS
CALCIUM GLUCONATE
CALCIUM GLUCEPTATE
CALCIUM CHLORIDE
CALCIUM LACTATE
Chemistry - Several different salts of calcium are available in various formulations. Calcium
gluceptate and calcium chloride are freely soluble in water; calcium lactate is soluble in water;
calcium gluconate and calcium glycerophosphate are sparingly soluble in water, and calcium
phosphate and carbonate are insoluble in water. Calcium gluconate for injection has a pH of 6-8.2;
calcium chloride for injection has a pH of 5.5-7.5; and calcium gluceptate for injection has a pH of
5.6-7.
Storage/Stability/Compatibility - Calcium gluconate tablets should be stored in well-closed
containers at room temperature. Calcium lactate tablets should be stored in tight containers at room
temperature. Calcium gluconate injection, calcium gluceptate injection, and calcium chloride
injection should be stored at room temperature and protected from freezing.
Calcium chloride for injection is reportedly compatible with the following intravenous solutions
and drugs: amikacin sulfate, ascorbic acid, bretylium tosylate, cephapirin sodium, chloramphenicol
sodium succinate, dopamine HCl, hydrocortisone sodium succinate, isoproterenol HCl,
lidocaine HCl, methicillin sodium, norepinephrine bitartrate, penicillin G potassium/sodium, pentobarbital
sodium, phenobarbital sodium, sodium bicarbonate, verapamil HCl, and vitamin Bcomplex
with C.
Calcium chloride for injection compatibility information conflicts or is dependent on diluent
or concentration factors with the following drugs or solutions: fat emulsion 10%, dobutamine HCl,
oxytetracycline HCl, and tetracycline HCl. Compatibility is dependent upon factors such as pH,
concentration, temperature and diluents used. It is suggested to consult specialized references (e.g.,
Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.
Calcium chloride for injection is reportedly incompatible with the following solutions or drugs:
amphotericin B, cephalothin sodium, and chlorpheniramine maleate.
Calcium gluceptate for injection is reportedly compatible with the following intravenous solutions
and drugs: sodium chloride for injection 0.45% and 0.9%, RingerÕs injection, lactated
RingerÕs injection, dextrose 2.5%-10%, dextrose-RingerÕs injection, dextrose-lactated RingerÕs
injection, dextrose-saline combinations, ascorbic acid injection, isoproterenol HCl, lidocaine HCl,
norepinephrine bitartrate, phytonadione, and sodium bicarbonate.
Calcium gluceptate for injection is reportedly incompatible with the following solutions or
drugs: cefamandole naftate, cephalothin sodium, magnesium sulfate, prednisolone sodium succinate,
and prochlorperazine edisylate. Compatibility is dependent upon factors such as pH, concentration,
temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on
Injectable Drugs by Trissel; see bibliography) for more specific information.
Calcium gluconate for injection is reportedly compatible with the following intravenous solutions
and drugs: sodium chloride for injection 0.9%, lactated RingerÕs injection, dextrose 5%-20%,
dextrose-lactated RingerÕs injection, dextrose-saline combinations, amikacin sulfate, aminophylline,
ascorbic acid injection, bretylium tosylate, cephapirin sodium, chloramphenicol sodium succinate,
corticotropin, dimenhydrinate, erythromycin gluceptate, heparin sodium, hydrocortisone sodium
succinate, lidocaine HCl, methicillin sodium, norepinephrine bitartrate, penicillin G
potassium/sodium, phenobarbital sodium, potassium chloride, tobramycin sulfate, vancomycin HCl,
verapamil and vitamin B-complex with C.
Calcium gluconate compatibility information conflicts or is dependent on diluent or concentration
factors with the following drugs or solutions: phosphate salts, oxytetracycline HCl,
prochlorperazine edisylate, and tetracycline HCl. Compatibility is dependent upon factors such as
pH, concentration, temperature and diluents used. It is suggested to consult specialized references
(e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.
Calcium gluconate is reportedly incompatible with the following solutions or drugs: intravenous
fat emulsion, amphotericin B, cefamandole naftate, cephalothin sodium, dobutamine HCl,
methylprednisolone sodium succinate, and metoclopramide HCl.
Pharmacology - Calcium is an essential element that is required for many functions within the
body, including proper nervous and musculoskeletal system function, cell-membrane and capillary
permeability, and activation of enzymatic reactions.
Uses/Indications - Calcium salts are used for the prevention or treatment of hypocalcemic conditions.
Pharmacokinetics - Calcium is absorbed in the small intestine in the ionized form only. Presence
of vitamin D (in active form) and an acidic pH is necessary for oral absorption. Parathormone
(parathyroid hormone) increases with resultant increased calcium absorption in calcium deficiency
states and decreases as serum calcium levels rise. Dietary factors (high fiber, phytates, fatty acids),
age, drugs (corticosteroids, tetracyclines), disease states
(steatorrhea, uremia, renal osteodystrophyachlorhydria), or decreased
serum calcitonin levels may all cause reduced amounts of calcium to be
absorbed.
After absorption, ionized calcium enters the extracellular fluid and then is rapidly incorporated into
skeletal tissue. Calcium administration does not necessarily stimulate bone formation.
Approximately 99% of total body calcium is found in bone. Of circulating calcium, approximately
50% is bound to serum proteins or complexed with anions and 50% is in the ionized form. Total
serum calcium is dependent on serum protein concentrations. Total serum calcium changes by
approximately 0.8 mg/dl for every 1.09 g/dl change in serum albumin. Calcium crosses the placenta
and is distributed into milk.
Calcium is eliminated primarily in the feces, contributed by both unabsorbed calcium and calcium
excreted into the bile and pancreatic juice. Only small amounts of the drug are excreted in the urine,
as most of the cation filtered by the glomeruli is reabsorbed by the tubules and ascending loop of
Henle. Vitamin D, parathormone, and thiazide diuretics decrease the amount of calcium excreted by
the kidneys. Loop diuretics (e.g., furosemide), calcitonin, and somatotropin increase calcium renal
excretion.
Contraindications/Precautions/Reproductive Safety - Calcium is contraindicated in patients
with ventricular fibrillation or with hypercalcemia. Parenteral calcium should not be administered to
patients with above normal serum calcium levels. Calcium should be used very cautiously in
patients receiving digitalis glycosides, or with cardiac or renal disease. Calcium chloride, because it
can be acidifying, should be used with caution in patients with respiratory failure, respiratory
acidosis, or renal disease.
Although parenteral calcium products have not been proven to be safe to use during pregnancy,
they are often used before, during, and after parturition in cows, ewes, bitches, and queens to treat
parturient paresis secondary to hypocalcemia.
Adverse Effects/Warnings - Hypercalcemia can be associated with calcium therapy, particularly
in patients with cardiac or renal disease; animals should be adequately monitored. Other effects that
may be seen include GI irritation and/or constipation after oral administration, mild to severe tissue
reactions after IM or SQ administration of calcium salts and venous irritation after IV
administration. Calcium chloride may be more irritating than other parenteral salts and is more
likely to cause hypotension. Too rapid intravenous injection of calcium can cause hypotension,
cardiac arrhythmias and cardiac arrest.
Should calcium salts be infused perivascularly, first stop the infusion. Ttreatment may then include:
infiltrate the affected area with normal saline, corticosteroids administered locally, apply heat
and elevate the area, and infiltrate affected area with 1% procaine and hyaluronidase.
Overdosage/Acute Toxicity - Unless other drugs are given concurrently that enhance the absorption
of calcium, oral overdoses of calcium containing products are unlikely to cause hypercalcemia.
Hypercalcemia can occur with parenteral therapy or oral therapy in combination with
vitamin D or increased parathormone levels. Hypercalcemia should be treated by withholding
calcium therapy and other calcium elevating drugs (e.g., vitamin D analogs). Mild hypercalcemias
generally will resolve without further intervention when renal function is adequate.
More serious hypercalcemias (>12 mg/dl) should generally be treated by hydrating with IV
normal saline and administering a loop diuretic (e.g., furosemide) to increase both sodium and
calcium excretion. Potassium and magnesium must be monitored and replaced as necessary. ECG
should also be monitored during treatment. Corticosteroids, and in humans, calcitonin and
hemodialysis have also been employed in treating hypercalcemia.
Drug Interactions - Patients on digitalis therapy are more apt to develop arrhythmias if receiving
IV calciumÑuse with caution. Calcium may antagonize the effects of verapamil (and other
calcium-channel blocking agents).
Thiazide diuretics used in conjunction with large doses of calcium may cause hypercalcemia.
Oral magnesium products with oral calcium may lead to increased serum magnesium and/or
calcium, particularly in patients with renal failure. Parenteral calcium can neutralize the effects of
hypermagnesemia or magnesium toxicity secondary to parenteral magnesium sulfate.
Parenteral calcium may reverse the effects of nondepolarizing neuromuscular blocking agents
(e.g., metubine, gallamine, pancuronium, atracurium, & vecuronium). Calcium has been reported to
prolong or enhance the effects of tubocurarine.
Oral calcium can reduce the amount of phenytoin or tetracyclines absorbed from the GI tract.
Patients receiving both parenteral calcium and potassium supplementation may have an increased
chance of developing cardiac arrhythmiasÑuse cautiously.
Excessive intake of vitamin A may stimulate calcium loss from bone and cause hypercalcemia.
Concurrent use of large doses of vitamin D or its analogs may cause enhanced calcium absorption
and induce hypercalcemia.
Drug/Laboratory Interactions - Parenteral calcium may cause false-negative results for serum
and urinary magnesium when using the Titan yellow method of determination.Doses -
Dogs:
For hypocalcemia:
a) Calcium gluconate injection: 94 - 140 mg/kg IV slowly to effect (intraperitoneal route
may also be used). Monitor respirations and cardiac rate and rhythm during administration.
(USPC 1990)
b) For acute hypocalcemia: Calcium gluconate 10% injection: Warm to body temperature
and give IV at a rate of 50 - 150 mg/kg (0.5 - 1.5 ml/kg) over 20-30 minutes. If
bradycardia develops, halt infusion. Following acute crisis infuse 10 - 15 ml (of a 10%
solution) per kg over a 24 hour period. Long term therapy may be accomplished by
increasing dietary calcium and using vitamin D. Calcium lactate may be given orally at a
rate of 0.5 - 2 g/day. (Seeler and Thurmon 1985)
c) Calcium gluconate 10% 0.5 - 1.5 ml/kg or calcium chloride 10% 1.5 - 3.5 ml (total) IV
slowly over 15 minutes; monitor heart rate or ECG during infusion. If ST segment
elevation or Q-T interval shortening occur, temporarily discontinue infusion and reinstate
at a slower rate when resolved.
Maintenance therapy is dependent on cause of hypocalcemia. Hypoparathyroidism is
treated with vitamin D analogs (refer to DHT monograph) with or without oral calcium
supplementation. (Russo and Lees 1986)
d) For emergency treatment of tetany and seizures secondary to hypoparathyroidism:
Calcium gluconate 10%: 0.5 - 1.5 ml/kg (up to 20 ml) over 15-30 minutes. May repeat
at 6-8 hour intervals or give as continuous infusion at 10 - 15 mg/kg/hour. Monitor
ECG and stop infusion if S-T segment elevates, Q-T interval shortens, or arrhythmias
occur.
For long-term therapy (with DHTÑrefer to that monograph), calcium supplementation
may occasionally be useful. Calcium gluconate at 500 - 750 mg/kg/day divided tid, or
calcium lactate at 400 - 600 mg/kg/day divided tid, or calcium carbonate 100 - 150
mg/kg/day divided bid. Monitor serum calcium and adjust as necessary. (Kay and
Richter 1988)
For hyperkalemic cardiotoxicity:
a) Secondary to uremic crisis: Correct metabolic acidosis, if present, with sodium bicarbonate
(bicarbonate may also be beneficial even if acidosis not present). Calcium gluconate
(10%) indicated if serum K+ is > 8 mEq/L. Give at an approximate dose of 0.5 -
1 ml/kg over 10-20 minutes; monitor ECG. Rapidly corrects arrhythmias but effects are
very short (10-15 minutes). IV glucose (0.5 - 1 g/kg body weight with or without
insulin) also beneficial in increasing intracellular K+ concentrations. (Polzin and
Osborne 1985)
Cats:
For hypocalcemia:
a) Calcium gluconate injection: 94 - 140 mg/kg IV slowly to effect (intraperitoneal route
may also be used. Monitor respirations and cardiac rate and rhythm during administration.
(USPC 1990)
b) For acute hypocalcemia secondary to hypoparathyroidism: Using 10% calcium gluconate
injection, give 1 - 1.5 ml/kg IV slowly over 10-20 minutes. Monitor ECG if
possible. If bradycardia, or Q-T interval shortening occurs, slow rate or temporarily
discontinue. Once life-threatening signs are controlled, add calcium to IV fluids and
administer as a slow infusion at 60 - 90 mg/kg/day (of elemental calcium). This converts
to 2.5 ml/kg every 6-8 hours of 10% calcium gluconate. Carefully monitor serum
calcium (once to twice daily) during this period and adjust dose as required.
Begin oral calcium initially at 50 - 100 mg/kg/day divided 3-4 times daily of elemental
calcium and dihydrotachysterol once animal can tolerate oral therapy. Give DHT
initially at 0.125 - 0.25 mg PO per day for 2-3 days, then 0.08 - 0.125 mg per day for
2-3 days and finally 0.05 mg PO per day until further dosage adjustments are necessary.
As catÕs serum calcium is stabilized, intravenous calcium may be reduced and
discontinued if tolerated. Stable serum calcium levels (8.5-9.5 mg/dl) are usually
achieved in about a week. Continue to monitor and adjust dosages of DHT and calcium
to lowest levels to maintain normocalcemia. (Peterson and Randolph 1989) (Note: refer
to the DHT monograph for further information.)
c) For hypocalcemia secondary to phosphate enema toxicity or puerperal tetany: follow the
guidelines for use of intravenous calcium in ÒbÓ above. (Peterson and Randolph 1989)
Cattle:
For hypocalcemia:
a) Calcium gluconate injection: 150 - 250 mg/kg IV slowly to effect (intraperitoneal route
may also be used). Monitor respirations and cardiac rate and rhythm during
administration. (USPC 1990)b) Calcium gluconate 23% injection: 250 - 500 ml IV slowly, or IM or SQ (divided and
given in several locations, with massage at sites of injection). (Label directions; Calcium
Gluc. Injection 23%ÑTechAmerica)
c) 8 - 12 grams of calcium IV infused over a 5-10 minute period; use a product containing
magnesium during the last month of pregnancy if subclinical hypomagnesemia is
detected. (Allen and Sansom 1986)
Horses:
For hypocalcemia:
a) Calcium gluconate injection: 150 - 250 mg/kg IV slowly to effect (intraperitoneal route
may also be used). Monitor respirations and cardiac rate and rhythm during
administration. (USPC 1990)
b) Calcium gluconate 23% injection: 250 - 500 ml IV slowly, or IM or SQ (divided and
given in several locations, with massage at sites of injection). (Label directions; Calcium
Gluconate Injection 23%ÑTechAmerica)
c) For lactation tetany: 250 ml per 450 kg body weight of a standard commercially
available solution that also contains magnesium and phosphorous IV slowly while ascultating
heart. If no improvement after 10 minutes, repeat. Intensity in heart sounds
should be noted, with only an infrequent extrasystole. Stop infusion immediately if a
pronounced change in rate or rhythm is detected. (Brewer 1987)
Sheep & Goats:
For hypocalcemia:
a) Sheep: Calcium gluconate injection: 150 - 250 mg/kg IV slowly to effect (intraperitoneal
route may also be used). Monitor respirations and cardiac rate and rhythm during
administration. (USPC 1990)
b) Sheep: Calcium gluconate 23% injection: 25 - 50 ml IV slowly, or IM or SQ (divided
and given in several locations, with massage at sites of injection). (Label directions;
Calcium Gluconate Injection 23%ÑTechAmerica)
Swine:
For hypocalcemia:
a) Calcium gluconate injection: 150 - 250 mg/kg IV slowly to effect (intraperitoneal route
may also be used). Monitor respirations and cardiac rate and rhythm during
administration. (USPC 1990)
b) Calcium gluconate 23% injection: 25 - 50 ml IV slowly, or IM or SQ (divided and given
in several locations, with massage at sites of injection). (Label directions; Calcium
Gluconate Injection 23%ÑTechAmerica)
Birds:
For hypocalcemic tetany:
a) Calcium gluconate: 50 - 100 mg/kg IV slowly to effect; may be diluted and given IM if
a vein cannot be located. (Clubb 1986)
For egg-bound birds:
a) Initially, calcium gluconate 1% solution 0.01 - 0.02 ml/g IM. Provide moist heat (80-
85¡F) and allow 24 hours for bird to pass egg. (Nye 1986)
Reptiles:
a) For egg binding in combination with oxytocin (oxytocin: 1 - 10 IU/kg IM.): Calcium
glubionate: 10 -50 mg/kg IM as needed until calcium levels back to normal or egg
binding is resolved. Use care when giving multiple injections. Calcium/oxytocin is not
as effective in lizards as in other species. (Gauvin 1993)
Monitoring Parameters -
1) Serum calcium
2) Serum magnesium, phosphate, and potassium when indicated
3) Serum PTH (parathormone) if indicated
4) Renal function tests initially and as required
5) ECG during intravenous calcium therapy if possible
6) Urine calcium if hypercalcuria develops
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products (not necessarily a complete list)
Parenteral Products:
Calcium Gluconate (as calcium borogluconate) 23% [230 mg/ml; 20.7 mg (1.06 mEq) calcium
per ml]; in 500 ml bottles; Generic; (Rx) Depending on the product, approved for use in cattle,
horses, swine, sheep, cats, and dogs. No withdrawal times are required.
Products are also available that include calcium, phosphorus, potassium and/or dextrose; refer to the
individual productÕs labeling for specific dosage information. Trade names for these products
include: Norcalciphos¨ÑSKB, and Cal-Dextro¨ Special, #2, C, & KÑFort Dodge. They are
legend (Rx) drugs.Oral Products: No products containing only calcium (as a salt) are available commercially with
veterinary labeling. There are several products (e.g., Pet-Cal¨ and Osteoform¨ Improved) that
contain calcium with phosphorous and vitamin D (plus other ingredients in some preparations).
Parenteral Products::
Calcium Gluconate (9% calcium) Tablets: 500 mg (45 mg of calcium), 650 mg (58.5 mg of
calcium), 975 mg (87.75 mg calcium), 1 gram (90 mg of calcium); Generic; (OTC)
Calcium Lactate (13% calcium) Tablets: 325 mg (42.25 mg calcium), 650 mg (84.5 mg calcium);
Generic; (OTC)
Also available are calcium glubionate syrup, calcium carbonate tablets, suspension & capsules,
calcium citrate tablets, dibasic calcium phosphate dihydrate tablets, and tricalcium phosphate tabl








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