Metformin + Glimepiride + Pioglitazone Pharmacology

Metformin + Glimepiride + Pioglitazone

About Metformin + Glimepiride + Pioglitazone
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Mechanism of Action of Metformin + Glimepiride + Pioglitazone
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Pharmacokinets of Metformin + Glimepiride + Pioglitazone
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Onset of Action for Metformin + Glimepiride + Pioglitazone
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Duration of Action for Metformin + Glimepiride + Pioglitazone
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Half Life of Metformin + Glimepiride + Pioglitazone
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Side Effects of Metformin + Glimepiride + Pioglitazone
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Contra-indications of Metformin + Glimepiride + Pioglitazone
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Special Precautions while taking Metformin + Glimepiride + Pioglitazone
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Pregnancy Related Information
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Old Age Related Information
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Breast Feeding Related Information
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Children Related Information
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Indications for Metformin + Glimepiride + Pioglitazone
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Interactions for Metformin + Glimepiride + Pioglitazone
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Typical Dosage for Metformin + Glimepiride + Pioglitazone
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Schedule of Metformin + Glimepiride + Pioglitazone
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Storage Requirements for Metformin + Glimepiride + Pioglitazone
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Effects of Missed Dosage of Metformin + Glimepiride + Pioglitazone
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Effects of Overdose of Metformin + Glimepiride + Pioglitazone
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Metformin

About Metformin
Biguanide derivative, Oral anti-diabetic.
Mechanism of Action of Metformin
It is a biguanide which exerts antidiabetic action. The drug suppresses gluconeogenesis in liver and thus suppresses hepatic glucose output. It enhance insulin mediated glucose disposal in muscle and adipose tissue. It enhance GLUT1 (glucose transporter-1) transport from intracellular site to plasma membrane. It also interferes with respiratory chain in mitochondria and promotes peripheral glucose utilization by increasing anaerobic glycolysis. It inhibits intestinal absorption of glucose, other hexose sugars, amino acids and vitamin B12. It also improves lipid profile in type-2 diabetics.
Pharmacokinets of Metformin
Absorption: Absorbed orally and bioavailability is about 50% to60%. Distribution: It is distributed in to erythrocytes, Metabolism: Not metabolized in the body, Excretion: Excreted mainly through urine.
Onset of Action for Metformin
N/A
Duration of Action for Metformin
6 to 8 hours
Half Life of Metformin
1.5 to 3hours
Side Effects of Metformin
1. Abdominal pain
2. Nausea
3. Vomiting
4. Anorexia
5. Metalic taste
6. Mild diarrhea
7. Tiredness
8. Small increase in blood lactate
9. Lactic acidosis (rare)
10. Vitamin B12 deficiency
11. Megaloblastic anaemia
12. Diarrhoea
13. Flatulence
14. Dermatitis
15. Rashes.
Contra-indications of Metformin
1. Hypersensitivity to the drug
2. Renal impairment
3. Hepatic impairment
4. Diabetic ketoacidosis
5. Cardiovascular collapse
6. Hypotensive states
7. Respiratory disease
8. Alcoholics.
Special Precautions while taking Metformin
1. Alcohol intake can precipitate severe lactic acidosis
2. Vitamin B12deficiency
3. In malnourished and deliberate individuals
4. Adrenal insufficiency
5. Pituitary insufficiency.
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Contraindicated
Indications for Metformin
Non-insulin dependent diabetes mellitus (as adjunct to diet and exercise).
Interactions for Metformin
N/A
Typical Dosage for Metformin
Adults: Initial dose: 250mg twice or thrice daily with meals. Increase gradually at 2 week intervals, if required to a maximum of 3g daily.
Children: Not applicable.
Schedule of Metformin
G
Storage Requirements for Metformin
Store at room temperature at a range of 15 to 30 degree C. in a well closed container.Keep out of reach of children.
Effects of Missed Dosage of Metformin
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose
Effects of Overdose of Metformin
Provide supportive measures and symptomatic treatment. Remove accumulated drug from the body by haemodialysis.

Glimepiride

About Glimepiride
Third-generation sulfonylurea, Oral Antidiabetic Agent.
Mechanism of Action of Glimepiride
It is a potent antidiabetic drug which exerts its action by increasing insulin release from the pancreas and by improving glucose tolerance. It acts on the "sulfonylurea receptors" on pancreatic ?-cell membrane and reduces conductance of ATP sensitive K+ channels and thus causes depolarization. This enhances Ca2+ influx and degranultion and thus increases insulin secretion rate at any glucose concentration. It primarily increases 2nd phase insulin secretion and has little effect on 1st phase. It also slows hepatic degradation of insulin and minor action of reducing glucagon release and increasing Somatostatin release. It also exerts stronger extrapancreatic action; by sensitizing the target tissues such as liver to insulin action. It increases the number of insulin receptors and through a post receptor action improving translation of receptor activation.
Pharmacokinets of Glimepiride
Absorption: Well absorbed orally
Distribution: Distributed in a highly protein bound form
Metabolism: Completely metabolized in to inactive metabolites in liver
Excretion: Excreted mainly through urine and also through faeces as metabolites.
Onset of Action for Glimepiride
N/A
Duration of Action for Glimepiride
>24 hours
Half Life of Glimepiride
5 to 7 hours
Side Effects of Glimepiride
1. Hypoglycemia
2. Nausea
3. Vomiting
4. Diarrhoea
5. Constipation
6. Headache
7. Paresthesia
8. Hypersensitivity reactions
9. Rashes
10. Photosensitivity
11. Purpura
12. Transient leucopenia
13. Agranulocytosis
14.Temporary visual impairment
Contra-indications of Glimepiride
1. Hypersensitivity to the drug
2. Diabetic ketoacidosis
3. Diabetic coma
4. Juvenile diabetes mellitus
Special Precautions while taking Glimepiride
1. Malnourished and deliberate individuals
2. Strenous exercise and irregular meals may leads to hypoglycemia
3. Hepatic impairment
4. Renal impairment
5. Monitor glucose levels during therapy
6. Adrenal insufficiency
7. Pituitary insufficiency
8. Any work requiring mental alertness such as operating a vehicle or machine
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Contraindicated
Indications for Glimepiride
1. Non insulin dependent diabetes mellitus.
Interactions for Glimepiride
Hypoglycaemic effect of glimepiride is enhanced by : Anticoagulants, Androgens, Chloramphenicol, Clofibrate, Fenfluramine, Fluconazole, Gemfibrozil, Histamine H2 anta-gonists, Magnesium Salts, Methyldopa, MAOIs, Phenylbutazone, Probenecid, Salicylates, Sulfinpyrazone, Sulfonamides, TCAs, & Urinary acidifiers.
Hypoglycemic effect of glimepiride inhibited by the following drugs : Beta-blockers, Cholestyramine, Diazoxide, Hydantoins, Rifampicin, Thiazide diuretics & Urinary alkalisers.
Charcoal : Reduces the absorption of glimepiride thus reducing its efficacy or toxicity.
Digitalis glycosides : Coadministration results in increased digitalis serum levels.

Typical Dosage for Glimepiride
Oral: Starts with 1mg daily; immediately before 1st main meals. Adjust the dosage by increments of 1to 2mg at 1 to 2week intervals based on patients response up to 6mg/day as required.
Maintenance dosage: 1 to 4mg once daily
Maximum dose: 8mg once daily
Schedule of Glimepiride
N/A
Storage Requirements for Glimepiride
Store at room temperature at a range of 15 to 30 degree C. in a well closed container away from light. Protect from excess heat and moisture. Keep out of reach of children.
Effects of Missed Dosage of Glimepiride
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Glimepiride
Mild hypoglycemia can be treated with oral glucose and dosage adjustment. It there is loss of consciousness or neurological findings the patient should receive rapid injection of dextrose 50%; followed by continuous infusion of dextrose 10% at a rate to maintain blood glucose levels greater than 100mg/dl. Monitor patient for 24 to 48 hours.

Pioglitazone

About Pioglitazone
Thiazolidinedione (TZD) derivative, Insulin Sensitizer, Oral anti diabetic.
Mechanism of Action of Pioglitazone
The drug exerts antidiabetic action by acting as a selective agonist for the nuclear "peroxisome proliferator-activated receptor Gama (PPAR Gama); which enhances the transcription of several insulin responsive genes. It reverses insulin resistance by stimulating GLUT4 (glucose transporter 4) expression and translocation and improves entry of glucose in to muscle and adipose tissue. It also suppresses hepatic gluconeogenesis. Activation of genes regulating fatty acid metabolism and lipogenesis in adipose tissue also contributes to the insulin sensitizing action of drug. It reduces blood glucose and HbA1c; improves glycaemic control and lowers circulating levels of Insulin.
It also raises HDL level and lowers serum triglyceride level without significant change in LDL level.
Pharmacokinets of Pioglitazone
Absorption: Well absorbed orally, Distribution: Widely distributed in a highly protein bound form, Metabolism: Extensively metabolized in the liver in to metabolites; of which 3 metabolites are active. Excretion: Excreted mainly through faeces and rest is excreted through urine.
Onset of Action for Pioglitazone
N/A
Duration of Action for Pioglitazone
24 hours
Half Life of Pioglitazone
3 to 5 hours
Side Effects of Pioglitazone
1. Oedema
2. Plasma volume expansion
3. Weight gain
4. Headache
5. Myalgia
6. Mild anaemia
7. Back pain
8. Sinusitis
9. Pharyngitis
10. Upper respiratory tract infections
Contra-indications of Pioglitazone
1. Hypersensitivity to the drug
2. Hepatic impairment
3. Cogestive heart failure
4. Patients with moderately severe to severe cardiac disease(New York Heart Association class III and class IV cardiac diseases)
5. Incresed liver enzyme levels(ALT level greater than 2. 5 times than normal)
6. Type 1 diabetes mellitus
7. Diabetic ketoacidosis
Special Precautions while taking Pioglitazone
1.Cardiac diseases
2.Alcoholics
Pregnancy Related Information
Contraindicated
Old Age Related Information
May be used
Breast Feeding Related Information
Contraindicated

Children Related Information
Contraindicated
Indications for Pioglitazone
1. Non-insulin dependent diabetes mellitus (as adjunct to diet and exercise)
Interactions for Pioglitazone
N/A
Typical Dosage for Pioglitazone
Oral: Starts with 15 to 30mg once daily; Increase if required based on patient`s response in increments up to 45mg once daily.
Schedule of Pioglitazone
N/A
Storage Requirements for Pioglitazone
Store at controlled room temperature at a range of 15 to 30 degree C.; in a well closed container. Protect from moisture. Keep out of reach of children.
Effects of Missed Dosage of Pioglitazone
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Pioglitazone
Provide symptomatic treatment and supportive measures.

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