Anticoagulant Citrate Phosphate Dextrose/Adsol Red Cell Preservation Solutions

Uses

Adenine is a purine base which forms a component of DNA among other functions and is present in many multivitamins.

For nutritional supplementation, also for treating dietary shortage or imbalance

Citric Acid Monohydrate contains the active ingredient Citric Acid Monohydrate which helps to reduce the dry cough and soothes the throat from any related discomfort and pain. Citric Acid is a demulcent which relieves irritation of the mucous membrane in the throat by forming a protective film. Citric Acid is absorbed after oral administration. It is found naturally in the body and is widely distributed.

Dextrose is administered as a parenteral nutrition solution in the treatment of carbohydrate depletion and hypoglycaemic coma. Because of its high dextrose content it is used in the treatment of cerebral edema, shock, circulatory collapse, unconsciousness and to correct hyperkalaemia with or without insulin.

Mannitol is principally used by IV infusion as an osmotic diuretic to preserve renal function in acute renal failure and to reduce raised intracranial and intraocular pressure. Mannitol is also used as an irrigating solution to prevent hemolysis and hemoglobin buildup during transurethral prostatic resection. It is useful in the management of acute drug poisoning where a route of elimination is through kidney. Besides these, it is also used in symptomatic relief of edema, reperfusion injury, termination of pregnancy, and bowel preparation. So, Mannitol is used for-

Renal insufficiency, Reperfusion injury, Raised intracranial pressure, Bladder irrigation, Raised intraocular presure, Bowel preparation, Edematous status, As a prophylactic in renal failure, Management of poisoning, Termination of Pregnancy

Sodium Chloride Nasal Drops is used for dry nasal membranes including dry nose resulting from cold and allergy medications. It moistens dry nasal passages from dry climates or from airplane travel, may help dissolve mucus from study noses and clears the nose after surgery. This sterile saline solution is also used to cleanse various parts of the body (wounds, body cavities) and medical equipment (e.g., bandages, catheters, drainage tubes). It is also used as a mixing solution (diluent) for other medications used to irrigate the body (e.g., bacitracin, polymyxin).

Sodium citrate is an ingredient used for the anticoagulation of whole blood as part of automated apheresis procedures.

Used as an anticoagulant during plasmophoresis as well as a neutralizing agent in the treatment of upset stomach and acidic urine .

Anticoagulant Citrate Phosphate Dextrose/Adsol Red Cell Preservation Solutions is also used to associated treatment for these conditions: Acidosis, Catheter site calcification caused by appetite, Catheter site calcification caused by struvite, Gouty Arthritis, Headache, Heartburn, Kidney Stones, Metabolic Acidosis, Blood Specimen Collection, Blood sample storage, Bowel preparation therapy, Chemical contraception, Potassium placement, Urine alkalinization therapy, Cleansing of the colon as a preparation for colonoscopy, Oral antisepsisArrhythmia, Caloric Deficit, Edema of the cerebrum, Metabolic Alkalosis, Hypoglycemic reaction, Blood Specimen Collection, Electrolyte replacement, Nutritional supplementation, Parenteral Nutrition, Parenteral rehydration therapy, Plasmapheresis, Positive cardiac inotropic effect, Total parenteral nutrition therapy, Urine alkalinization therapy, Fluid and electrolyte maintenance therapyAcute Renal Failure (ARF), Cystic Fibrosis (CF), Edema of the cerebrum, Increased Intra Ocular Pressure (IOP), Bladder irrigation therapyAllergic Rhinitis (AR), Corneal Edema, Dehydration, Dehydration Hypertonic, Fluid Loss, Hemodilution, Hypertension Intracranial, Hypokalemia, Hyponatremia, Hypotonic Dehydration, Hypovolaemia, Increased Intra Ocular Pressure (IOP), Inflammation of the Nasal Mucosa, Isotonic Dehydration, Metabolic Acidosis, Nasal Congestion, Nasal irritation, Oliguria caused by Acute Renal Failure (ARF), Potassium deficiency, Sinusitis, Skin Irritation, Sodium Depletion, Dryness of the nose, Hypochloremic state, Mild Metabolic acidosis, Mild, moderate Metabolic Acidosis, Electrolyte replacement, Fluid replacement therapy, Heart-Lung-Machine, Oral rehydration therapy, Parenteral Nutrition, Parenteral rehydration therapy, Peritoneal dialysis therapy, Plasma Volume Replacement, Regional Citrate Anticoagulation (RCA), Renal Replacement Therapies, Urine alkalinization therapy, Wound irrigation therapy, Ear wax removal, Fluid and electrolyte maintenance therapy, Increased renal excretion of toxic substances, Maintenance source of fluid and electrolytes, Parenteral drug administration, Reducing brain massAcidosis, Allergic cough, Allergies, Asthma, Asthma Chronic, Cough, Common Cold, Cough, Coughing caused by Bronchitis, Dehydration, Gouty Arthritis, Heartburn, Metabolic Acidosis, Phlegm, Airway secretion clearance therapy, Oral rehydration therapy, Plasmapheresis, Urine alkalinization therapy, Fluid and electrolyte maintenance therapy, Irrigation during surgical procedures, Irrigation of the ocular surface therapy

How Anticoagulant Citrate Phosphate Dextrose/Adsol Red Cell Preservation Solutions works

Adenine forms adenosine, a nucleoside, when attached to ribose, and deoxyadenosine when attached to deoxyribose, and it forms adenosine triphosphate (ATP), which drives many cellular metabolic processes by transferring chemical energy between reactions.

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into 2 main phases where the preparatory phase is initiated by the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. This energy-producing reactions of glucose is limited to D-glucose as L-glucose cannot be phosphorlyated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation in order to preserve cellular and whole body metabolic integrity .

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR).

The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance.

Sodium and chloride — major electrolytes of the fluid compartment outside of cells (i.e., extracellular) — work together to control extracellular volume and blood pressure. Disturbances in sodium concentrations in the extracellular fluid are associated with disorders of water balance.

Citrate chelates free calcium ions preventing them from forming a complex with tissue factor and coagulation factor VIIa to promote the activation of coagulation factor X . This inhibits the extrinsic initiation of the coagulation cascade. Citrate may also exert an anticoagulant effect via a so far unknown mechanism as restoration of calcium concentration does not fully reverse the effect of citrate . Citrate is a weak base and so reacts with hydrochloric acid in the stomach to raise the pH. It it further metabolized to bicarbonate which then acts as a systemic alkalizing agent, raising the pH of the blood and urine . It also acts as a diuretic and increases the urinary excretion of calcium.

Dosage

Anticoagulant Citrate Phosphate Dextrose/Adsol Red Cell Preservation Solutions dosage

Age Dose Dose frequency

1-5 years 5 ml Upto 4 times daily

6-12 years 10 ml Upto 4 times daily

>12 years & Adults 20 ml 3-4 times daily

The volume and rate of infusion of dextrose solution will depend upon the requirements of the individual patient and the judgement of the physician.

The maximum rate at which dextrose can be infused without producing glycosuria is 0.5 gm/kg/hr.

The usual recommended flow rate for adult is 10-35 drops per minute infused intravenously.

Intravenous-

Hyperkalaemia:

• Adult: 25-50 g combined with 10 units of regular insulin, administered over 30-60 minutes; may repeat if necessary. Alternatively, 25 g combined with 5-10 units of regular insulin infused over 5 minutes; may repeat if necessary.
• Child and infants: 0.5-1 g/kg (using 25% or 50% solution) combined with regular insulin (1 unit for every 4-5 g dextrose given); infuse over 2 hr, may repeat if necessary.

Intravenous-

Hypoglycaemia:

• Adult: 10-25 g (40-100 ml of 25% solution or 20-50 ml of 50% solution). Doses may be repeated in severe cases.
• Child: ≤6 mth: 0.25-0.5 g/kg/dose; >6 mth: 0.5-1 g/kg/dose. Doses may be repeated in severe cases. Max: 25 g/dose.

Oral-

Hypoglycaemia:

• Adult: 10-20 g as single dose; may repeat in 10 min if needed.
• Child: >2 yr: 10-20 g as single dose; may repeat in 10 min if needed.

The adult dose of Mannitol ranges from 50 to 100 gm by IV infusion. The rate of administration is usually adjusted to maintain a urine flow of at least 30 to 50 ml/hr. Total dosage, concentration and the rate of administration depends on fluid requirement, urinary output and the severity of the condition being treated

Renal insufficiency-

• Adults: 50 to 100 g of Mannitol administered at a rate adjusted to maintain a urine flow of at least 30 to 50 ml/hr.
• Children: 2 gm/kg or 60 gm/m2of body surface area administered over a period of 2 to 6 hrs.

Cerebral edema, elevated intracranial pressure, elevated intraocular pressure, Glaucoma-

• Adults: 1.5 to 2 gm/kgadministered over a period of 30 to 60 minutes.
• Children: 1 to 2 gm/kg body wt. or 30 to 60 gm/m2 of body surface area administered over a period of 30 to 60 mins.

Adjunctive therapy for removal of toxic substances-

• Adults: 50 to 200 g of Mannitol administered at a rate adjust to maintain a urine flow of at least 100 to 500 ml/hr.
• Children: 2 gm/kg or 60 gm/m2of body surface area

For termination of pregnancy 50 gm of Mannitol (250 ml of Mannitol) is instilled into the amniotic cavity which induces abortion in a high proportion of pregnancies.

Infants, children & adults: 2-6 drops into each nostril as needed daily

Use in Children: Safe for pediatrics

It should not be administered by SC or IM route. Dextrose should be infused through the largest available peripheral vein.

Side Effects

There are no known side effects from using this medicine when used as directed. If taken excessively above the stated dose, glycerol present in the medicine may cause headache, stomach upset and diarrhea.

Venous thrombosis, phlebitis, hypovolemia, hypervolemia, dehydration, oedema, fever, mental confusion, unconsciousness, hyperosmolar syndrome, hyperglycaemia, hypokalaemia, acidosis, hypophosphataemia, hypomagnesemia, polyuria, glycosuria, ketonuria, nausea, diarrhoea, polydipsia, vein irritation, tissue necrosis, pulmonary oedema, tachypnoea.

The most common side effects associated with Mannitol intravenous infusion is fluid and electrolytes imbalance including circulatory overload and acidosis at high doses. Other side effects include nausea, vomiting, thirst, headache, dizziness, fever, tachycardia, chest pain, hyponatraemia, dehydration, blurred vision, urticaria, and hypertension or hypotension.

No side Effects are expected to occur. However stinging, sneezing, increased nasal discharge, or salty taste may occur in some cases.

Toxicity

ORAL (LD50): Acute: 5040 mg/kg [Mouse]. 3000 mg/kg [Rat].

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and/or solute overloading resulting in dilution of the serum electrolyte concentrations, over-hydration, congested states, or pulmonary oedema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.

Mannitol overdose may result in bronchoconstriction and should be counteracted using a short-acting bronchodilator and other symptomatic and supportive care, as necessary.

The rare inadvertent intravascular administration or rapid intravascular absorption of hypertonic sodium chloride can cause a shift of tissue fluids into the vascular bed, resulting in hypervolemia, electrolyte disturbances, circulatory failure, pulmonary embolism, or augmented hypertension.

Overdose toxicity is mainly due to alkalosis as well as tetany or depressed heart function due to lack of free calcium .

Precaution

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Concentrated dextrose solution should not be infused rapidly or for a long period. It may be hazardous in patients with impaired hepatic or renal function and severe sepsis.

Care should be taken to avoid circulatory overload, particularly in patients with cardiac insufficiency. Caution must be exercised in the administration of these injections to patients receiving corticosteroids or corticotropin. These injections should be used with caution in patients with overt or subclinical diabetes mellitus.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear and seal is intact.

Careful monitoring of rate of administration of Mannitol is necessary to avoid fluid and electrolyte imbalance and circulatory overloading. The infusion should be discontinued if the patient develops signs of progressive renal dysfunction, heart failure or pulmonary congestion. Mannitol should not be administered with whole blood.

Interaction

There is no drug drug interaction and none well documented.

Increased nephrotoxicity with ciclosporin.

Volume of Distribution

The mean volume of distribution after intravenous infusion is 10.6L.

Mannitol administered intravenously has a volume of distribution of 34.3 L.

The volume of distribution is 0.64 L/kg.

19-39L .

Elimination Route

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation. SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion . Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.

Approximately 7% of ingested mannitol is absorbed during gastrointestinal perfusion in uremic patients.

Inhalation of 635 mg of mannitol powder yields a plasma C_max of 13.71 μg/mL in 1.5 hours (T_max) and a mean systemic AUC of 73.15 μg*h/mL.

Absorption of sodium in the small intestine plays an important role in the absorption of chloride, amino acids, glucose, and water. Chloride, in the form of hydrochloric acid (HCl), is also an important component of gastric juice, which aids the digestion and absorption of many nutrients.

Tmax of 98-130min .

Half Life

The approximate half-life is 14.3 minutes following intravenous infusion. Gut glucose half-life was markedly higher in females (79 ± 2 min) than in males (65 ± 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001).

Mannitol has an elimination half-life of 4.7 hours following oral administration; the mean terminal elimination half-life is similar regardless of administration route (oral, inhalation, and intravenous.

17 minutes

18-54 min

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglyglycemia.

Intravenous administration of mannitol yields a total clearance of 5.1 L/hr and renal clearance of 4.4 L/hr.

Total clearance of 313-1107mL/min .

Elimination Route

Glucose can be renally excreted.

Mannitol is primarily excreted unchanged in the urine. Following oral inhalation of 635 mg of mannitol in healthy volunteers, 55% of the total dose was recovered unchanged in the urine; following oral or intravenous administration of 500 mg, the corresponding values were 54 and 87%, respectively.

Substantially excreted by the kidneys.

Largely eliminated through hepatic metabolism with very little cleared by the kidneys .

Pregnancy & Breastfeeding use

There are no or limited amount of data from the use of Citric Acid Monohydrate in pregnant women. There is insufficient information on the excretion of Citric Acid Monohydrate & its metabolites in human milk.

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Safety of Mannitol intravenous infusion in pregnancy has not been established yet. No information is available on the excretion of mannitol in breast milk and should be administered after careful consideration of risk-benefit ratio.

It is unknown if this medication passes into breast milk. Consult with your doctor before breast-feeding.

Contraindication

Concentrated dextrose solution is contraindicated in patients with Glucose-Galactose Malabsorption Syndrome and severe hydration. The infusion of hypertonic dextrose injections is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Mannitol intravenous infusion is contraindicated in patients with pulmonary edema or congestive heart failure. It is also contraindicated during inadequate urine flow, dehydration or acidosis, intracranial bleeding and in patients with renal failure unless a test dose has produced a diuretic response

Tell your doctor about your medical history, especially of heart problems (e.g., congestive heart failure), lung problems (pulmonary edema), kidney problems, low levels of potassium (hypokalemia), high levels of sodium (hypernatremia), and any allergies.

Acute Overdose

Reevaluate patient's condition and institute appropriate symptomatic treatment.

Storage Condition

Keep in a cool and dry place, away from light. Keep out of the reach of children.

Store at 25°C.

Mannitol should be stored at a temperature of 20° to 30°. Exposure to lower temperatures may cause deposition of crystals, which should be dissolved by warming the bottle in hot water for about 30 minutes. Cool to body temperature before using. If all crystals can not be dissolved, the solution should not be used. The content of open containers should be used promptly. Unused contents should be discarded.

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