Skip to main content

Diabetes Mellitus: Non Insulin Injectable Agents!

PHARMACOTHERAPY

 NON-INSULIN INJECTABLE AGENTS

1.GLUCAGON-LIKE PEPTIDE 1 AGONSIT:

  • GLP-1 Agonists enhance glucose dependent insulin secretion while suppressing inappropriately high glucagon secretion in the presence of elevated glucose, which results in reduced hepatic glucose production.
  • Exenatide and Liraglutide are both indicated for the treatment of T2 DM to improve glycemic control.

Pharmacokinetics:

  • Plasma concentrations are detected up to 10hrs after injection, although pharmacodynamics action lasts for approximately 6hrs.

Mechanism of Action:

  • GLP-1 agonists lower blood glucose levels by producing glucose dependent insulin secretion, reducing post meal glucose secretion, which decreases post meal glucose output, increasing satiety which decreases food intake and regulating gastric emptying which allows nutrients to be absorbed into the circulation more smoothly.

Clinical uses:

  • In a 26 weeks head-to-tail trial in patients with T2DM with a baseline A1c between 7%-11% who were taking metformin, sulfonylurea, or both; Exenatide lowered A1c levels to 0.8% and Liraglutide lowered A1c levels greater than 1.1%.
  • Both drugs produced similar weights loss, with an average reduction of 3.24kg for liraglutide and 2.87kg for exenatide.

Dose:

  • Exenatide is recommended for twice daily dosing in its intermediate release.
  • As exenatide is excreted renally, it is not recommended for patients with renal impairment.
  • Liraglutides half-life is 13hrs, making it suitable for once daily dosing. No specific dose adjustments are required for liraglutide in renal impairment patients.

Adverse Effects:

  • An increased risk of hypoglycemia occurs when GLP-1 agonists are used in combination with sulfonylurea.
  • Nausea
  • Vomiting
  • Diarrhea
  • GLP-1 Agonists delay absorption of other medications, so it is best to take concomitant medications 1hr. before or 3hr. after a GLP-1 agonist if rapid absorption of concomitant medication is required.
  • Acute pancreatitis

Contraindications:

  • They are contraindicated in pt. with a personal or family history of medullary thyroid cancer and in history of multiple endocrine tumors.


2.AMYLIN

Mechanism of Action:

  • Pramlintide acetate is a synthetic analog of human amylin, which is naturally occurring neuroendocrine peptide that is co-secreted by the Beta cells of the pancreas in response to food.
  • The secretion of Amylin is completely deficient in patients with T1DM and relatively deficient in patients with T2 DM.
  • Pramlintide slower the gastric emptying without altering absorption of nutrients. suppresses glucagon secretion and leads to reduction in food intake by increasing satiety. By slowing the gastric emptying, the normal initial post meal spike in blood glucose is reduced.

Administration and Dose:

  • Pramlintide is given by SC injection before meals to lower the postprandial blood glucose elevations.
  • A disposable pen formulation is now on the market and available as SmylinPen 60 for patients with T1 DM and SmylinPen 120 for people with T2 DM.

  • The no. of days the pen will last will vary depending on the daily dose.

  • The amount of medication is 1.5mL in the SmylinPen and 2.7mL in the SmylinPen 120

When rapid absorption is needed for the efficacy of an agent, pramlintide should be administered 2hrs before or 1hr after this drug.

Clinical Uses:

  • Pramlintide generally results in an average weight loss of 1-2kg.
  • It is injected as a combination therapy with insulin in patients with T1 or T2 DM.
  • It has been shown to decrease A1c levels by 0.4-0.5%

Adverse Effects:

  • Hypoglycemia
  • Nausea
  • Vomiting

Contraindication:

  • It is contraindicated in patients receiving medications that alter GI mobility, such as Acetylcholine agents, or drugs that slower the absorption of nutrients such as a-glucosidase inhibitors.

Labels:

Comments

Post a Comment

Popular posts from this blog

Diabetes Mellitus: Types!

TYPES OF DIABETES MELLITUS 1. TYPE1 DM Type 1 DM is usually diagnosed before age 30 years, but it can develop at any age. T1DM is an autoimmune disease in which insulin producing B-cells are destroyed. The presence of Human Leucocyte Antigens (HLAs ) is associated with the development of T1DM. In addition, these individuals often develop Islet cell antibodies , Insulin Autoantibodies or Glutamic Acid decarboxylase autoantibodies . At the time of development of diagnosis of T1DM, it is usually believed that most of the patients have 80-90%loss of beta cells. The remaining beta cells function at the diagnosis creates a " HONEYMOON PERIOD" during which the blood glucose levels are easier to control, and smaller amounts of insulin are required. after this, the remaining beta cells function is completely lost, and the patients become completely deficient of insulin and hence require exogenous insulin.  2. TYPE1.5 DM:  Also referred as Latent autoimmune diabetes in Adults (LAD)
Post a Comment
Read more

Diabetes Mellitus: Pharmacotherapy- Gliptins and a-Glycoside Inhibitors!

  PHARMACOTHERAPY:  Medications classifications include:  Sulfonyl Urea's Nonsylfonylurea Secretagogues (a-Glinides) Biguanides Thiazolidinediones a-Glucosidase Inhibitors Dipeptidyl Peptidase-4 Inhibitors (Gliptins) Sodium-glucose co-transporter (SGLT) Inhibitors  Central-Acting Dopamine Agonists Bile Acid Sequestrants Insulin therapy 5. a-GLUCOSIDASE INHIBITORS Acarbose and Miglitol are a-glucosidase inhibitors currently approved in the United States. Mechanism of Action: An enzyme that is along the brush border of the intestine cells called a-glucosidase; breaks down the complex carbohydrates into simple sugars, resulting in absorption. The a-glucosidase inhibitors work by delaying the absorption of carbohydrates from the intestinal tract, which reduces the rise in postprandial glucose levels. Therapy: As a monotherapy , a-glucosidase inhibitors primarily reduce post-prandial glucose excursions.  Clinical Use: FPG concentrations have been decreased by 40-50mg/dL and A1c level
Post a Comment
Read more

GASTRO-ESOPHAGEAL REFLUX DISEASE (GERD)!

MANAGEMENT OF GASTRO-ESOPHAGEAL REFLUX DISEASE  "GERD refers to the endoscopically determined esophagitis or endoscopy-negative reflux disease" . "GERD is the term used to describe any symptomatic clinical condition or histopathological alteration resulting from episodes of reflux of acid, pepsin and occasionally, bile into the esophagus from the stomach". Patients with uninvestigated "reflux-like" symptoms should be managed as patients with uninvestigated dyspepsia. There is currently no evidence that H.pylori should be investigated in patients with GERD. Symptoms: Heartburn is the characteristic symptom of GERD. Acid regurgitation Dysphagia Belching Upper abdominal discomfort Bloating and postprandial fullness Chest pain Hoarseness Cough Complications include: Esophageal ulceration Formation of specialized columnar-lined esophagus at the gastro-esophageal junction known as Barretts Esophagus . Mechanism of Acid Reflux: The mechanism of acid reflux is mu
Post a Comment
Read more