ORAL HYPOGLYCAEMIC AGENT. PRESENTER:UDIGWE CHIOMA. OUTLINE. INTRODUCTION CLASSIFICATION MECHANISMS OF ACTION,INDICATIONS, BENEFITS AND RISKS OF EACH CLASS. CONTRAINDICATIONS TO USE OF OHA. TARGETS OF TREATMENT WITH OHA. CONCLUSION. INTRODUCTION.
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singly or in combination to lower the blood glucose in type 2 diabetes.
or to reduced secretion of insulin.
Oral hypoglycaemic agent are not usually used in type 1 diabetics but metformin may be of use in combination with insulin for overweight type 1 diabetics.
Conserve islet cell function
- delay the subsequent use of insulin.
Improve patient compliance- single daily dosing.
Reduce the incidence of hypoglycaemic events
. An extended-release form is available and may have fewer gastrointestinal side effects (diarrhea, anorexia, nausea, metallic taste).
Metformin is effective as monotherapy and can be used in combination with other oral agents or with insulin.
The major toxicity of metformin, lactic acidosis is very rare and can be prevented by careful patient selection.
Vitamin B12 levels are 30% lower during metformin treatment.
Metformin should not be used in patients with renal insufficiency [GFR < 60 mL/min], any form of acidosis, CHF, liver disease, or severe hypoxemia.
Metformin should be discontinued in patients who are seriously ill, in patients who can take nothing orally, and in those receiving radiographic contrast material.
Benefits and indications: Metformin is the only oral hypoglycaemic shown to reduce macrovascular complications and death.
Sulphonylureas stimulate insulin secretion by interacting with the ATP-sensitive potassium channel on the beta cell .
. Sulfonylureas reduce both fasting and postprandial glucose and should be initiated at low doses and increased at 1- to 2-week interval.
Alpha-Glucosidase inhibitors (acarbose and miglitol) reduce postprandial hyperglycemia by delaying glucose absorption; they do not affect glucose utilization or insulin secretion .
Postprandial hyperglycemia, secondary to impaired hepatic and peripheral glucose disposal, contributes significantly to the hyperglycemic state in type 2 DM.
These drugs, taken just before each meal, reduce glucose absorption by inhibiting the enzyme that cleaves oligosaccharides into simple sugars in the intestinal lumen.
Therapy should be initiated at a low dose (25 mg of acarbose or miglitol) with the evening meal and may be increased to a maximal dose over weeks to months (50–100 mg for acarbose or 50 mg for miglitol with each meal)
. The major side effects (diarrhea, flatulence, abdominal distention) are related to increased delivery of oligosaccharides to the large bowel and can be reduced somewhat by gradual upward dose titration.
alpha-Glucosidase inhibitors may increase levels of sulfonylureas and increase the incidence of hypoglycemia.
. These agents should not be used in individuals with inflammatory bowel disease, gastroparesis, or a serum creatinine >177 mol/L (2 mg/dL).
This class of agents is not as potent as other oral agents in lowering the A1C but is unique because it reduces the postprandial glucose rise even in individuals with type 1 DM. If hypoglycemia from other diabetes treatments occurs while taking these agents, the patient should consume glucose since the degradation and absorption of complex carbohydrates will be retarded by the drug.
The prototype of this class of drugs, troglitazone, was withdrawn from the U.S. market after reports of hepatotoxicity and an association with an idiosyncratic liver reaction that sometimes led to hepatic failure. Although rosiglitazone and pioglitazone do not appear to induce the liver abnormalities seen with troglitazone,
Risks:Do not commence or continue a TDZ in patients who have heart failure, or who are at higher risk of fracture:
GLP-1 actions include stimulating insulin secretion in a glucose-dependent manner’
1)Body Mass Index : Metformin, Gliptins
2)Presence of GI symptoms: Sulpha, Gliptins, Glitazones
3)Renal Dysfunction: Gliptins, Glitazones(+/-),Sulpha (variable)
4) Aging Meglitinides, Gliptins(?)
5) Hepatic Dysfunction Nateglinide, Saxagliptin(?)
6) Compliance Gliptins, Glitazones,
7) Cost Metformin, Sulphas, Glitazones
In conclusion,OHA are agents that helpin lowering blood glucose in DM, more useful in type 2 DM.the different classes target the various pathophysiological mechanisms involve in type2 dm.the main limitation to the usage of available OHA is their inability to alter the progressive nature of the dx. Efforts should be geared towards developing drugs that will address this problem.