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Galanthamine is natural extracted from Lycoris radiate, is a tertiary
alkaloid derived from snowdrop and closely related species.galantamine powder
Galanthamine acts as a reversible competitive acetylcholinesterase
(AChE) inhibitor, while acts weaker on butyrylcholinesterase (BuChE).
Galanthamine is used in the treatment of disorders of the central
nervous system and may be used as an antidote to nonpolarizing muscle
relaxants.Galantamine hydrobromide is a white to almost white powder;
sparingly soluble in water; insoluble chloroform, ether and alcohol..
Application of Galantamine
Galantamine is the anti-cholinesterase, weak effect. Galantamine has
strong effect to the central nervous system through the blood brain
barrier. Galantamine mainly cures the infantile paralysis sequelae,
sweeny and myasthenia gravis pseudoparalytica, etc. Galantamine also can
be applied to puerilism, posttraumatic apoplexy, polyneuritis and
radiculitis.
Function of Galantamine
Galanthamine is the anti-cholinesterase, weak effect.
Galantamine has strong effect to the central nervous system through the blood brain barrier.
Galantamine mainly cures the infantile paralysis sequelae, sweeny and myasthenia gravis
pseudoparalytica, etc.
Galantamine also can be applied to puerilism, posttraumatic apoplexy, polyneuritis and radiculitis.
Clinic function: mainly used in myasthenia gravis, poliovirus quiescent stage and sequela, also in polyneuritis, funiculitis and sensorimotor barrier caused by nervous system disease or traumatism. Galantamine major used in Alzheimer’s disease, has the principal function for dement and dysmnesia caused by organic brain damage.
Calculate the quantity of each ingredient for the amount to be prepared.
Accurately weigh or measure each ingredient. Mix the furosemide powder
with a small quantity of SyrSpend SF Alka or simple syrup to form a
smooth paste. Geometrically, add the SyrSpend SF Alka or simple syrup to
final volume, mixing well after each addition. Package and label.Furosemide powder
Use: Furosemide is used to treat edema associated with a number of disorders, including congestive heart failure, nephrotic syndrome, and hepatic cirrhosis; it also has been used as an adjunct in the treatment of acute pulmonary edema.
Packaging: Package in tight, light-resistant containers.1
Labeling: Keep out of reach of children. Shake well. Store in a refrigerator. Discard after ____ [time period].Stability: A beyond-use date of 14 days when stored in a refrigerator may be used for this preparation made with SyrSpend SF Alka or syrup NF.1,2
Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).3
Discussion: Furosemide (Lasix, Frusemide, C12H11ClN2O5S, MW 330.74) is a sulfonamide-derivative loop diuretic that inhibits the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle. Furosemide is a fine, white to slightly yellow, odorless, practically tasteless, crystalline powder with a pKa of 3.9, and it melts at about 203°C-205°C with decomposition. Chemically, furosemide is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Furosemide is practically insoluble in water or dilute acids. It is freely soluble in solutions of alkali hydroxides and sparingly soluble in alcohol. Furosemide is subject to photodegradation by several mechanisms; consequently, it should be preserved in light-resistant containers. This photodegradation is minimized at pH 7, and the degradation rate increases as the pH becomes more acidic or basic. Furosemide should be packaged in well-closed containers and stored at room temperature, with excursions permitted between 15°C and 30°C, and it should be protected from light. The injection has a pH in the range of 8.0 to 9.3 and contains not more than 3.6 USP EU per mg of furosemide.1
If the source of the active drug is tablets, Lasix tablets for oral administration also contain lactose monohydrate NF, magnesium stearate NF, starch NF, talc USP, and colloidal silicon dioxide NF. The white Lasix tablets for oral administration are available in dosage strengths of 20, 40, and 80 mg. Tablets, if used, must be thoroughly pulverized before incorporation into the vehicle. To obtain 1 gram of the drug from tablets, from 12.5 to 50 tablets may be required depending on which strength is used. The 80-mg strength is preferred; obviously, the use of fifty 20-mg tablets would yield a large quantity of powder, resulting in some thickening of the preparation.
SyrSpend SF Alka is a dry powder for reconstitution. SyrSpend SF Alka provides a reasonable solution for preparing oral liquid dosage forms with acid-labile active pharmaceutical ingredients, including furosemide. It is preservative-free and alcohol-free and is suitable for problematic patients, such as neonates. SyrSpend SF Alka also allows for direct compounding in the dispensing container for maximum efficiency if the prescription or order requires 100 mL. Smaller or larger volumes may be feasible with some manipulation. SyrSpend SF Alka is buffered to pH levels 7 for acid-labile active pharmaceutical ingredients. It is preservative-free and unflavored, and it is available in a dispensing container with preweighed powder to make 100 mL (contains 6.3 g powder) or 200 mL (contains 12.6 g powder).4
Syrup (simple syrup) is a clear, sweet vehicle used as a sweetening agent and as the base for many flavored and medicated syrups. It contains 85% w/v sucrose in water and has a specific gravity of not less than 1.30. Syrup is generally self-preserving as long as the sucrose concentration is maintained sufficiently high. However, syrup NF contains a preservative unless it is used when freshly prepared. It is preferable to prepare syrup NF without the use of heat, but it may be prepared with boiling water. It should be stored in tight containers, preferably in a cool place. The pH is in the range of 6.5 to 7.5
Use: Furosemide is used to treat edema associated with a number of disorders, including congestive heart failure, nephrotic syndrome, and hepatic cirrhosis; it also has been used as an adjunct in the treatment of acute pulmonary edema.
Packaging: Package in tight, light-resistant containers.1
Labeling: Keep out of reach of children. Shake well. Store in a refrigerator. Discard after ____ [time period].Stability: A beyond-use date of 14 days when stored in a refrigerator may be used for this preparation made with SyrSpend SF Alka or syrup NF.1,2
Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).3
Discussion: Furosemide (Lasix, Frusemide, C12H11ClN2O5S, MW 330.74) is a sulfonamide-derivative loop diuretic that inhibits the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle. Furosemide is a fine, white to slightly yellow, odorless, practically tasteless, crystalline powder with a pKa of 3.9, and it melts at about 203°C-205°C with decomposition. Chemically, furosemide is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Furosemide is practically insoluble in water or dilute acids. It is freely soluble in solutions of alkali hydroxides and sparingly soluble in alcohol. Furosemide is subject to photodegradation by several mechanisms; consequently, it should be preserved in light-resistant containers. This photodegradation is minimized at pH 7, and the degradation rate increases as the pH becomes more acidic or basic. Furosemide should be packaged in well-closed containers and stored at room temperature, with excursions permitted between 15°C and 30°C, and it should be protected from light. The injection has a pH in the range of 8.0 to 9.3 and contains not more than 3.6 USP EU per mg of furosemide.1
If the source of the active drug is tablets, Lasix tablets for oral administration also contain lactose monohydrate NF, magnesium stearate NF, starch NF, talc USP, and colloidal silicon dioxide NF. The white Lasix tablets for oral administration are available in dosage strengths of 20, 40, and 80 mg. Tablets, if used, must be thoroughly pulverized before incorporation into the vehicle. To obtain 1 gram of the drug from tablets, from 12.5 to 50 tablets may be required depending on which strength is used. The 80-mg strength is preferred; obviously, the use of fifty 20-mg tablets would yield a large quantity of powder, resulting in some thickening of the preparation.
SyrSpend SF Alka is a dry powder for reconstitution. SyrSpend SF Alka provides a reasonable solution for preparing oral liquid dosage forms with acid-labile active pharmaceutical ingredients, including furosemide. It is preservative-free and alcohol-free and is suitable for problematic patients, such as neonates. SyrSpend SF Alka also allows for direct compounding in the dispensing container for maximum efficiency if the prescription or order requires 100 mL. Smaller or larger volumes may be feasible with some manipulation. SyrSpend SF Alka is buffered to pH levels 7 for acid-labile active pharmaceutical ingredients. It is preservative-free and unflavored, and it is available in a dispensing container with preweighed powder to make 100 mL (contains 6.3 g powder) or 200 mL (contains 12.6 g powder).4
Syrup (simple syrup) is a clear, sweet vehicle used as a sweetening agent and as the base for many flavored and medicated syrups. It contains 85% w/v sucrose in water and has a specific gravity of not less than 1.30. Syrup is generally self-preserving as long as the sucrose concentration is maintained sufficiently high. However, syrup NF contains a preservative unless it is used when freshly prepared. It is preferable to prepare syrup NF without the use of heat, but it may be prepared with boiling water. It should be stored in tight containers, preferably in a cool place. The pH is in the range of 6.5 to 7.5
How does formoterol for COPD work?
Formoterol is a long-acting beta2-adrenergic receptor agonist (beta2-agonist) that works in the lungs as a bronchodilator. Its action has a rapid onset and its effects are maintained for at least 12 hours.
It becomes effective after binding to correspondent receptors, called beta-adrenoceptors, and activating them by stimulating the adenyl cyclase, an enzyme found inside the cells of the lung muscles and is involved in the synthesis of cyclic adenosine monophosphate (cAMP). When cAMP levels are elevated, the muscle cells of the airways become relaxed, leading to bronchodilation.
There are three types of beta-adrenoceptors in three different types of cells: the muscle cells of the airways, the heart, and the adipose (fat) tissue cells. This means that formoterol may have functions in other cells, but its precise function is not known.
Studies of formoterol
The effectiveness of formoterol in the treatment of COPD has been shown in various clinical studies, whether as a pressurized metered dose inhaler or a dry powder inhaleMost studies show that formoterol has proven efficacy, safety, and tolerability profiles in people with COPD.
The National Heart, Lung and Blood Institute and the World Health Organization collaborated on the Global Initiative for COPD – GOLD, and according to this initiative, long-acting bronchodilators are of primary importance to manage COPD symptoms, are used on an as-need or regular basis to reduce or prevent symptoms, and are convenient and effective.Most studies evaluating formoterol for the treatment of COPD attribute its success to its rapid action and selective activity toward the beta2-adrenergic receptors. Formoterol can work as rapidly as five minutes, and its effects are maintained for up to 12 hours.
Studies have also shown that formoterol controls symptoms better than ipratropium and is more effective than theophylline in reducing exacerbations and increasing the number of days without rescue medication, and with a better tolerance.
Indications and side effects
Formoterol is not intended to be used to treat asthma. People with asthma who take LABA medicines such as formoterol have an increased risk of death due to severe asthma problems.Formoterol won’t cure COPD but it will help relieve symptoms of the condition. It also doesn’t relieve sudden breathing difficulties. For an attack that has already started, short-acting bronchodilators such as albuterol, levalbuterol, ipratroprium or the combination albuterol/ipratropium can be used if prescribed by your doctor.
Formoterol side effects can include flu-like symptoms, headache, sore throat, dry throat, cough, runny nose, chills, fever, loss of voice, muscle cramps, or swollen glands in the neck. See your doctor if these occur.
Formoterol is a long-acting beta2-adrenergic receptor agonist (beta2-agonist) that works in the lungs as a bronchodilator. Its action has a rapid onset and its effects are maintained for at least 12 hours.
It becomes effective after binding to correspondent receptors, called beta-adrenoceptors, and activating them by stimulating the adenyl cyclase, an enzyme found inside the cells of the lung muscles and is involved in the synthesis of cyclic adenosine monophosphate (cAMP). When cAMP levels are elevated, the muscle cells of the airways become relaxed, leading to bronchodilation.
There are three types of beta-adrenoceptors in three different types of cells: the muscle cells of the airways, the heart, and the adipose (fat) tissue cells. This means that formoterol may have functions in other cells, but its precise function is not known.
Studies of formoterol
The effectiveness of formoterol in the treatment of COPD has been shown in various clinical studies, whether as a pressurized metered dose inhaler or a dry powder inhaleMost studies show that formoterol has proven efficacy, safety, and tolerability profiles in people with COPD.
The National Heart, Lung and Blood Institute and the World Health Organization collaborated on the Global Initiative for COPD – GOLD, and according to this initiative, long-acting bronchodilators are of primary importance to manage COPD symptoms, are used on an as-need or regular basis to reduce or prevent symptoms, and are convenient and effective.Most studies evaluating formoterol for the treatment of COPD attribute its success to its rapid action and selective activity toward the beta2-adrenergic receptors. Formoterol can work as rapidly as five minutes, and its effects are maintained for up to 12 hours.
Studies have also shown that formoterol controls symptoms better than ipratropium and is more effective than theophylline in reducing exacerbations and increasing the number of days without rescue medication, and with a better tolerance.
Indications and side effects
Formoterol is not intended to be used to treat asthma. People with asthma who take LABA medicines such as formoterol have an increased risk of death due to severe asthma problems.Formoterol won’t cure COPD but it will help relieve symptoms of the condition. It also doesn’t relieve sudden breathing difficulties. For an attack that has already started, short-acting bronchodilators such as albuterol, levalbuterol, ipratroprium or the combination albuterol/ipratropium can be used if prescribed by your doctor.
Formoterol side effects can include flu-like symptoms, headache, sore throat, dry throat, cough, runny nose, chills, fever, loss of voice, muscle cramps, or swollen glands in the neck. See your doctor if these occur.
Foradil is a bronchodilator that belongs to the long-acting
beta2-adrenergic receptor agonist class of compounds. Novartis' Foradil
Aerolizer was approved in February 2001 for the maintenance treatment of
asthma and the prevention of bronchospasm in reversible obstructive
airways disease. Foradil is also indicated for the acute prevention of
exercise-induced bronchospasm (EIB), when administered on an occasional,
as needed basis.Formoterol powder
In September 2001, a second FDA approval was obtained - the Foradil Aerolizer can now be used for long term administration in the maintenance treatment of bronchoconstriction in patients with COPD, including chronic bronchitis and emphysema.
Foradil is administered via a dry powder inhaler called the Aerolizer, which unlike traditional metered-dose inhalers, provides patients with the reassurance that they are in control of dosing. The Aerolizer offers patients little resistance to inhalation, and produces a whirring noise which signals that the drug is being inhaled. Patients can taste the powder and then open the device to check that they have inhaled all of the dose.
Asthma is a chronic inflammatory lung disease that affects 15 million Americans. According to the World Health Organization, each year 180,000 people die from asthma worldwide. The disease is characterized by shortness of breath, wheezing, tightness in the chest, and a cough that lasts more than a week.
COPD is a common chronic lung disease and a leading cause of mortality worldwide, with 2.25 million deaths a year. By 2025, the World Health Organization estimates that COPD will be the third leading cause of death globally. Since both asthma and COPD are chronic conditions, the goal of treatment is management and improvement of quality of life, rather than cure.
Clinical Results
The effectiveness of Foradil as a treatment for asthma was evaluated in five key trials involving more than 7,000 subjects, including over 1,600 mild to moderate asthmatics. In these placebo-controlled trials, Foradil was administered in 12 and 24 mcg twice daily doses.
Overall, these studies demonstrated both dosages of Foradil to be significantly better than placebo at improving lung function and quality of life in asthmatic subjects. Foradil provided subjects with clinically significant bronchodilation for a 12 hour period.
Clinical trials were also conducted to compare Foradil to the compound ipratropium bromide in subjects with COPD. Results showed that Foradil was significantly superior at reducing clinical symptoms and improving quality of life scores.
Formoterol fumarate is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator.
The pharmacologic effects of beta2 adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. (from Foradil Prescribing Information)
In September 2001, a second FDA approval was obtained - the Foradil Aerolizer can now be used for long term administration in the maintenance treatment of bronchoconstriction in patients with COPD, including chronic bronchitis and emphysema.
Foradil is administered via a dry powder inhaler called the Aerolizer, which unlike traditional metered-dose inhalers, provides patients with the reassurance that they are in control of dosing. The Aerolizer offers patients little resistance to inhalation, and produces a whirring noise which signals that the drug is being inhaled. Patients can taste the powder and then open the device to check that they have inhaled all of the dose.
Asthma is a chronic inflammatory lung disease that affects 15 million Americans. According to the World Health Organization, each year 180,000 people die from asthma worldwide. The disease is characterized by shortness of breath, wheezing, tightness in the chest, and a cough that lasts more than a week.
COPD is a common chronic lung disease and a leading cause of mortality worldwide, with 2.25 million deaths a year. By 2025, the World Health Organization estimates that COPD will be the third leading cause of death globally. Since both asthma and COPD are chronic conditions, the goal of treatment is management and improvement of quality of life, rather than cure.
Clinical Results
The effectiveness of Foradil as a treatment for asthma was evaluated in five key trials involving more than 7,000 subjects, including over 1,600 mild to moderate asthmatics. In these placebo-controlled trials, Foradil was administered in 12 and 24 mcg twice daily doses.
Overall, these studies demonstrated both dosages of Foradil to be significantly better than placebo at improving lung function and quality of life in asthmatic subjects. Foradil provided subjects with clinically significant bronchodilation for a 12 hour period.
Clinical trials were also conducted to compare Foradil to the compound ipratropium bromide in subjects with COPD. Results showed that Foradil was significantly superior at reducing clinical symptoms and improving quality of life scores.
Formoterol fumarate is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator.
The pharmacologic effects of beta2 adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. (from Foradil Prescribing Information)
What is ethacrynic acid?
Ethacrynic acid is a loop diuretic (water pill) that prevents your body from absorbing too much salt, allowing the salt to instead be passed in your urine.
Ethacrynic acid is used to treat fluid retention (edema) in people with congestive heart failure, liver disease, or a kidney disorder such as nephrotic syndrome.Ethacrynic acid may also be used for purposes not listed in this medication guide.
Important Information
You should not use ethacrynic acid if you are unable to urinate, or if you have recently had severe watery diarrhea.
Before taking this medicine
You should not use ethacrynic acid if you are allergic to it, or if:you are unable to urinate; oryou have recently had severe watery diarrhea.To make sure ethacrynic acid is safe for you, tell your doctor if you have:
cirrhosis or other liver disease;
heart disease;an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);kidney disease;gout; orif you are on a low-salt diet.
Ethacrynic acid is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using ethacrynic acid.It is not known whether ethacrynic acid passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.Ethacrynic acid is not approved for use by anyone younger than 18 years old.
How should I take ethacrynic acid?
Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.
Take this medicine after a meal, unless your doctor tells you otherwise.Ethacrynic acid will make you urinate more often and you may get dehydrated easily. Follow your doctor's instructions about using potassium supplements or getting enough salt and potassium in your diet.While using ethacrynic acid, you may need frequent blood tests and weight checks.Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.
Ethacrynic acid is a loop diuretic (water pill) that prevents your body from absorbing too much salt, allowing the salt to instead be passed in your urine.
Ethacrynic acid is used to treat fluid retention (edema) in people with congestive heart failure, liver disease, or a kidney disorder such as nephrotic syndrome.Ethacrynic acid may also be used for purposes not listed in this medication guide.
Important Information
You should not use ethacrynic acid if you are unable to urinate, or if you have recently had severe watery diarrhea.
Before taking this medicine
You should not use ethacrynic acid if you are allergic to it, or if:you are unable to urinate; oryou have recently had severe watery diarrhea.To make sure ethacrynic acid is safe for you, tell your doctor if you have:
cirrhosis or other liver disease;
heart disease;an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);kidney disease;gout; orif you are on a low-salt diet.
Ethacrynic acid is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using ethacrynic acid.It is not known whether ethacrynic acid passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.Ethacrynic acid is not approved for use by anyone younger than 18 years old.
How should I take ethacrynic acid?
Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.
Take this medicine after a meal, unless your doctor tells you otherwise.Ethacrynic acid will make you urinate more often and you may get dehydrated easily. Follow your doctor's instructions about using potassium supplements or getting enough salt and potassium in your diet.While using ethacrynic acid, you may need frequent blood tests and weight checks.Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.
Esmolol hydrochloride is a beta1-selective (cardioselective) adrenergic
receptor blocking agent with a very short duration of action
(elimination half-life is approximately 9 minutes). The chemical name
for esmolol hydrochloride is (±)-Methyl
p-[2-hydroxy-3-(isopropylamino)propoxy]hydrocinnamate hydrochloride and
it has the following structure:
structure
Esmolol hydrochloride has the molecular formula C16H26NO4CI and a molecular weight of 331.8. It has one asymmetric center and exists as an enantiomeric pair.Esmolol Hydrochloride is a white to off-white crystalline powder. It is a relatively hydrophilic compound which is very soluble in water and freely soluble in alcohol. Its partition coefficient (octanol/water) at pH 7.0 is 0.42 compared to 17.0 for propranolol.Esmolol HCl Injection is a clear, colorless to light yellow, sterile, nonpyrogenic solution.Esmolol powder
100 mg, 10 mL Single Dose Vial - Each mL contains 10 mg Esmolol Hydrochloride and Water for Injection; buffered with 2.8 mg Sodium Acetate Trihydrate and 0.546 mg Glacial Acetic Acid. Sodium Hydroxide and/or Hydrochloric Acid added, as necessary, to adjust pH to 4.5 to 5.5.
3CLINICAL PHARMACOLOGY
Esmolol hydrochloride is a beta1-selective (cardioselective) adrenergic receptor blocking agent with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilizing activity at therapeutic dosages. Its elimination half-life after intravenous infusion is approximately 9 minutes. Esmolol inhibits the beta1 receptors located chiefly in cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit beta2 receptors located chiefly in the bronchial and vascular musculature.
3.1Pharmacokinetics and Metabolism
Esmolol hydrochloride is rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylchoIinesterase. Total body clearance in man was found to be about 20 L/kg/hr, which is greater than cardiac output; thus the metabolism of esmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flow. Esmolol has a rapid distribution half-life of about 2 minutes and an elimination half-life of about 9 minutes.
Using an appropriate loading dose, steady-state blood levels of esmolol for dosages from 50 to 300 mcg/kg/min (0.05 to 0.3 mg/kg/min) are obtained within five minutes. (Steady-state is reached in about 30 minutes without the loading dose.) Steady-state blood levels of esmolol increase linearly over this dosage range and elimination kinetics are dose-independent over this range. Steady-state blood levels are maintained during infusion but decrease rapidly after termination of the infusion. Because of its short half-life, blood levels of esmolol can be rapidly altered by increasing or decreasing the infusion rate and rapidly eliminated by discontinuing the infusion.
Consistent with the high rate of blood-based metabolism of esmolol, less than 2% of the drug is excreted unchanged in the urine. Within 24 hours of the end of infusion, approximately 73% to 88% of the dosage has been accounted for in the urine as the acid metabolite of esmolol.
Metabolism of esmolol results in the formation of the corresponding free acid and methanol. The acid metabolite has been shown in animals to have about 1/1500th the activity of esmolol and in normal volunteers its blood levels do not correspond to the level of beta blockade. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. Excretion of the acid metabolite is significantly decreased in patients with renal disease, with the elimination half-life increased to about ten-fold that of normals, and plasma levels considerably elevated.
Methanol blood levels, monitored in subjects receiving esmolol for up to 6 hours at 300 mcg/kg/min (0.3 mg/kg/min) and 24 hours at 150 mcg/kg/min (0.15 mg/kg/min), approximated endogenous levels and were less than 2% of levels usually associated with methanol toxicity.Esmolol has been shown to be 55% bound to human plasma protein, while the acid metabolite is only 10% bound.
structure
Esmolol hydrochloride has the molecular formula C16H26NO4CI and a molecular weight of 331.8. It has one asymmetric center and exists as an enantiomeric pair.Esmolol Hydrochloride is a white to off-white crystalline powder. It is a relatively hydrophilic compound which is very soluble in water and freely soluble in alcohol. Its partition coefficient (octanol/water) at pH 7.0 is 0.42 compared to 17.0 for propranolol.Esmolol HCl Injection is a clear, colorless to light yellow, sterile, nonpyrogenic solution.Esmolol powder
100 mg, 10 mL Single Dose Vial - Each mL contains 10 mg Esmolol Hydrochloride and Water for Injection; buffered with 2.8 mg Sodium Acetate Trihydrate and 0.546 mg Glacial Acetic Acid. Sodium Hydroxide and/or Hydrochloric Acid added, as necessary, to adjust pH to 4.5 to 5.5.
3CLINICAL PHARMACOLOGY
Esmolol hydrochloride is a beta1-selective (cardioselective) adrenergic receptor blocking agent with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilizing activity at therapeutic dosages. Its elimination half-life after intravenous infusion is approximately 9 minutes. Esmolol inhibits the beta1 receptors located chiefly in cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit beta2 receptors located chiefly in the bronchial and vascular musculature.
3.1Pharmacokinetics and Metabolism
Esmolol hydrochloride is rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylchoIinesterase. Total body clearance in man was found to be about 20 L/kg/hr, which is greater than cardiac output; thus the metabolism of esmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flow. Esmolol has a rapid distribution half-life of about 2 minutes and an elimination half-life of about 9 minutes.
Using an appropriate loading dose, steady-state blood levels of esmolol for dosages from 50 to 300 mcg/kg/min (0.05 to 0.3 mg/kg/min) are obtained within five minutes. (Steady-state is reached in about 30 minutes without the loading dose.) Steady-state blood levels of esmolol increase linearly over this dosage range and elimination kinetics are dose-independent over this range. Steady-state blood levels are maintained during infusion but decrease rapidly after termination of the infusion. Because of its short half-life, blood levels of esmolol can be rapidly altered by increasing or decreasing the infusion rate and rapidly eliminated by discontinuing the infusion.
Consistent with the high rate of blood-based metabolism of esmolol, less than 2% of the drug is excreted unchanged in the urine. Within 24 hours of the end of infusion, approximately 73% to 88% of the dosage has been accounted for in the urine as the acid metabolite of esmolol.
Metabolism of esmolol results in the formation of the corresponding free acid and methanol. The acid metabolite has been shown in animals to have about 1/1500th the activity of esmolol and in normal volunteers its blood levels do not correspond to the level of beta blockade. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. Excretion of the acid metabolite is significantly decreased in patients with renal disease, with the elimination half-life increased to about ten-fold that of normals, and plasma levels considerably elevated.
Methanol blood levels, monitored in subjects receiving esmolol for up to 6 hours at 300 mcg/kg/min (0.3 mg/kg/min) and 24 hours at 150 mcg/kg/min (0.15 mg/kg/min), approximated endogenous levels and were less than 2% of levels usually associated with methanol toxicity.Esmolol has been shown to be 55% bound to human plasma protein, while the acid metabolite is only 10% bound.
Purpose: The objective of this study was to evaluate the thermal behavior of crystalline and amorphous bisoprolol fumarate and its compatibility with amorphous valsartan. This pharmacologically relevant drug combination is a potential candidate for fixed-dose combination formulation. Methods: DSC and TMDSC were used to examine thermal behavior of bisoprolol fumarate. SSNMR and XRPD were applied to probe the solid state forms. The thermal behavior of physical mixtures with different concentrations of bisoprolol and valsartan were examined by DSC and TMDSC, and the observed interactions were investigated by XRPD, solution- and solid-state NMR. Results: The phase transitions from thermal methods and solid-state NMR spectra of crystalline and amorphous bisoprolol fumarate are reported.Bisoprolol
Strong interactions between bisoprolol fumarate and valsartan were observed above 60 C, resulting in the formation of a new amorphous material. Solution- and solid-state NMR provided insight into the molecular nature of the incompatibility. Conclusions: A combined analysis of thermal methods, solution- and solid-state NMR and XRPD experiments allowed the investigation of the conformational and dynamic properties of bisoprolol fumarate. Since bisoprolol fumarate and valsartan react to form a new amorphous product, formulation of a fixed-dose combination would require separate reservoirs for bisoprolol and valsartan to prevent interactions. Similar problems might be expected with other excipients or APIs containing carboxylic groups.
Bisoprolol fumarate is a synthetic, beta1-selective (cardioselective)
adrenoceptor blocking agent. The chemical name for Bisoprolol fumarate
is (±)-1-[4-[[2-(1-Methylethoxy) ethoxy]methyl]
phenoxy]-3-[(1-methylethyl)amino]-2-propanol(E)-2-butenedioate (2:1)
(salt). It possesses an asymmetric carbon atom in its structure and is
provided as a racemic mixture. The S(-) enantiomer is responsible for
most of the beta-blocking activity. Its empirical formula is
(C18H31NO4)2•C4H4O4 and its structure is:β-agonist Powder
Bisoprolol fumarate has a molecular weight of 766.97. It is a white crystalline powder which is approximately equally hydrophilic and lipophilic, and is readily soluble in water, methanol, ethanol, and chloroform.
Bisoprolol Fumarate Tablets, USP is available as 5 and 10 mg tablets for oral administration.
Inactive ingredients include colloidal silicon dioxide, partially pregelatinized starch, crospovidone, anhydrous dibasic calcium phosphate, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide and talc.
Bisoprolol fumarate is a beta1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing activity or intrinsic sympathomimetic activity in its therapeutic dosage range. Cardioselectivity is not absolute, however, and at higher doses ( 20 mg) Bisoprolol fumarate also inhibits beta2-adrenoceptors, chiefly located in the bronchial and vascular musculature; to retain selectivity it is therefore important to use the lowest effective dose.
Pharmacokinetics and Metabolism
The absolute bioavailability after a 10 mg oral dose of Bisoprolol fumarate is about 80%. Absorption is not affected by the presence of food. The first pass metabolism of Bisoprolol fumarate is about 20%.
Binding to serum proteins is approximately 30%. Peak plasma concentrations occur within 2 to 4 hours of dosing with 5 to 20 mg, and mean peak values range from 16 ng/mL at 5 mg to 70 ng/mL at 20 mg. Once daily dosing with Bisoprolol fumarate results in less than twofold intersubject variation in peak plasma levels. The plasma elimination half-life is 9 to 12 hours and is slightly longer in elderly patients, in part because of decreased renal function in that population. Steady state is attained within 5 days of once daily dosing. In both young and elderly populations, plasma accumulation is low; the accumulation factor ranges from 1.1 to 1.3, and is what would be expected from the first order kinetics and once daily dosing. Plasma concentrations are proportional to the administered dose in the range of 5 to 20 mg. Pharmacokinetic characteristics of the two enantiomers are similar.
Bisoprolol fumarate is eliminated equally by renal and non-renal pathways with about 50% of the dose appearing unchanged in the urine and the remainder appearing in the form of inactive metabolites. In humans, the known metabolites are labile or have no known pharmacologic activity. Less than 2% of the dose is excreted in the feces. Bisoprolol fumarate is not metabolized by cytochrome P450 II D6 (debrisoquin hydroxylase).
In subjects with creatinine clearance less than 40 mL/min, the plasma half-life is increased approximately threefold compared to healthy subjects. In patients with cirrhosis of the liver, the elimination of Bisoprolol fumarate is more variable in rate and significantly slower than that in healthy subjects, with plasma half-life ranging from 8.3 to 21.7 hours.
Bisoprolol fumarate has a molecular weight of 766.97. It is a white crystalline powder which is approximately equally hydrophilic and lipophilic, and is readily soluble in water, methanol, ethanol, and chloroform.
Bisoprolol Fumarate Tablets, USP is available as 5 and 10 mg tablets for oral administration.
Inactive ingredients include colloidal silicon dioxide, partially pregelatinized starch, crospovidone, anhydrous dibasic calcium phosphate, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide and talc.
Bisoprolol fumarate is a beta1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing activity or intrinsic sympathomimetic activity in its therapeutic dosage range. Cardioselectivity is not absolute, however, and at higher doses ( 20 mg) Bisoprolol fumarate also inhibits beta2-adrenoceptors, chiefly located in the bronchial and vascular musculature; to retain selectivity it is therefore important to use the lowest effective dose.
Pharmacokinetics and Metabolism
The absolute bioavailability after a 10 mg oral dose of Bisoprolol fumarate is about 80%. Absorption is not affected by the presence of food. The first pass metabolism of Bisoprolol fumarate is about 20%.
Binding to serum proteins is approximately 30%. Peak plasma concentrations occur within 2 to 4 hours of dosing with 5 to 20 mg, and mean peak values range from 16 ng/mL at 5 mg to 70 ng/mL at 20 mg. Once daily dosing with Bisoprolol fumarate results in less than twofold intersubject variation in peak plasma levels. The plasma elimination half-life is 9 to 12 hours and is slightly longer in elderly patients, in part because of decreased renal function in that population. Steady state is attained within 5 days of once daily dosing. In both young and elderly populations, plasma accumulation is low; the accumulation factor ranges from 1.1 to 1.3, and is what would be expected from the first order kinetics and once daily dosing. Plasma concentrations are proportional to the administered dose in the range of 5 to 20 mg. Pharmacokinetic characteristics of the two enantiomers are similar.
Bisoprolol fumarate is eliminated equally by renal and non-renal pathways with about 50% of the dose appearing unchanged in the urine and the remainder appearing in the form of inactive metabolites. In humans, the known metabolites are labile or have no known pharmacologic activity. Less than 2% of the dose is excreted in the feces. Bisoprolol fumarate is not metabolized by cytochrome P450 II D6 (debrisoquin hydroxylase).
In subjects with creatinine clearance less than 40 mL/min, the plasma half-life is increased approximately threefold compared to healthy subjects. In patients with cirrhosis of the liver, the elimination of Bisoprolol fumarate is more variable in rate and significantly slower than that in healthy subjects, with plasma half-life ranging from 8.3 to 21.7 hours.
These medicines help decrease extra water in the body by increasing the
amount of urine the body makes. They also treat high blood pressure and
can be used to help a weak heart.
How should I give it?
Furosemide and bumetanide come in liquid and tablet form. It is usually given 1 to 3 times a day. Your child should be awake and alert when taking any medicine. Follow the checked instructions below:β-agonist Powder
___ If using the liquid form, draw up the correct amount of medicine in the medicine dropper or a syringe. Give a small squirt of the medicine inside the cheek. To avoid choking, let your child swallow each squirt before giving more.
___ For babies, you may want to mix the medicine with a small amount of formula or breast milk and give it with a bottle nipple before a feeding. Do not add medicine to a whole bottle because if your baby does not finish it, you will not know how much of the medicine was taken.
___ For children who cannot swallow pills:
Crush it between 2 spoons, inside a plastic bag, or in folded paper.
Mix the powder with a very small amount (about 1 teaspoon) of soft food, such as applesauce, chocolate syrup, ice cream, jelly, or yogurt.Furosemide and bumetanide can be given with or without food or milk. These medicines can decrease the potassium level in the blood, so your child may need to have potassium blood tests.
How should I give it?
Furosemide and bumetanide come in liquid and tablet form. It is usually given 1 to 3 times a day. Your child should be awake and alert when taking any medicine. Follow the checked instructions below:β-agonist Powder
___ If using the liquid form, draw up the correct amount of medicine in the medicine dropper or a syringe. Give a small squirt of the medicine inside the cheek. To avoid choking, let your child swallow each squirt before giving more.
___ For babies, you may want to mix the medicine with a small amount of formula or breast milk and give it with a bottle nipple before a feeding. Do not add medicine to a whole bottle because if your baby does not finish it, you will not know how much of the medicine was taken.
___ For children who cannot swallow pills:
Crush it between 2 spoons, inside a plastic bag, or in folded paper.
Mix the powder with a very small amount (about 1 teaspoon) of soft food, such as applesauce, chocolate syrup, ice cream, jelly, or yogurt.Furosemide and bumetanide can be given with or without food or milk. These medicines can decrease the potassium level in the blood, so your child may need to have potassium blood tests.
Chemical Name: 1-(9H-Carbozol-4-yloxy)-3-[[2-(2-methoxy phenoxy)ethyl] amino]-2-propanol
Cas No.: 72956-09-3
Molecular Formula: C24H26N2O4
Molecular Weight: 406.48
Melting point: 113-117ºC
Density:1.25 g/cm3
Boiling Point: 655.2 °C at 760 mmHg
Flash Point: 350.1 °C
Appearance: white or almost white crystalline powder
Assay:98%min
Usage: Carvedilol powder is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure (CHF).
Carvedilol is a AR (α1 and β-adrenergic receptor) antagonist with antioxidant properties. Studies show that the receptors α1D-AR and α1B-AR have a greater affinity for Carvedilol in comparison to the receptor β1-AR subtype. Carvedilol has been observed to block the oscillatory intracellular calcium changes induced by α1D-AR and α1B-AR, and shown to have a higher oxidative effect than Atenolol (sc-204895). The S(-) enantiomer of Carvedilol acts as a β-blocker, and the R(+) and S (-) enantionmers both block the α1. Carvedilol is an inhibitor of α1B-AR, β1-AR, β2-AR and α1D-AR.
Cas No.: 72956-09-3
Molecular Formula: C24H26N2O4
Molecular Weight: 406.48
Melting point: 113-117ºC
Density:1.25 g/cm3
Boiling Point: 655.2 °C at 760 mmHg
Flash Point: 350.1 °C
Appearance: white or almost white crystalline powder
Assay:98%min
Usage: Carvedilol powder is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure (CHF).
Carvedilol is a AR (α1 and β-adrenergic receptor) antagonist with antioxidant properties. Studies show that the receptors α1D-AR and α1B-AR have a greater affinity for Carvedilol in comparison to the receptor β1-AR subtype. Carvedilol has been observed to block the oscillatory intracellular calcium changes induced by α1D-AR and α1B-AR, and shown to have a higher oxidative effect than Atenolol (sc-204895). The S(-) enantiomer of Carvedilol acts as a β-blocker, and the R(+) and S (-) enantionmers both block the α1. Carvedilol is an inhibitor of α1B-AR, β1-AR, β2-AR and α1D-AR.