VISIONOL EYE DROPS

Indications

• Type 2 diabetes mellitus
• Gestational diabetes

Dosage

Children: Acarbose is not recommended for use in children under the age of 18. For specific pediatric dosing, please refer to the BNF for Children.

Adults: The usual starting dose of acarbose for adults is 50 mg taken orally with the first mouthful of food, three times daily. The dose may be increased to a maximum of 100 mg three times daily based on glycemic control and tolerability.

Mechanism of action

Acarbose inhibits the enzymes alpha-glucosidase in the intestinal brush border, which are responsible for breaking down carbohydrates such as starch and sucrose into glucose. This inhibition slows down the digestion and absorption of carbohydrates, leading to a reduction in postprandial blood glucose levels. By delaying carbohydrate digestion, acarbose effectively lowers the peak blood glucose levels after meals.

Pharmacodynamics

The pharmacodynamic effects of acarbose are characterized by its ability to lower postprandial blood glucose levels by modulating carbohydrate metabolism. This results in a modest reduction in overall glycemic levels, contributing to better glycemic control in patients with type 2 diabetes. Acarbose has been shown to result in a decrease in insulin secretion and a potential reduction in the risk of hypoglycemia when used alone.

Pharmacokinetics

Acarbose is minimally absorbed from the gastrointestinal tract, which limits systemic exposure and potential side effects. The drug reaches peak plasma concentrations within 1 to 2 hours after administration. Its effects are primarily local in the intestines, where it acts on the digestive enzymes. Acarbose is metabolized by intestinal bacteria and has an elimination half-life of 2 hours. Renal impairment can affect the drug's pharmacokinetics, and dosage adjustments may be necessary for patients with reduced kidney function.

Contra-indications

• Severe hepatic impairment
• Renal impairment with creatinine clearance less than 25 mL/minute
• Hypersensitivity to acarbose or any of its components

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Flatulence
• Hepatic disorders
• Edema
• Thrombocytopenia
• Acute generalised exanthematous pustulosis (AGEP)

Interactions

• Digoxin (may decrease concentration)
• Pancreatin (may decrease effects)
• Antacids containing magnesium and aluminium salts (may not be beneficial for treating side effects)

Precautions

• Monitor liver function during treatment
• Patients should be advised on how to administer acarbose tablets
• Patients receiving insulin or sulfonylureas should be informed about the risk of hypoglycemia

Pregnancy

Avoid during pregnancy. Consult relevant guidelines for management.

Breast-feeding

Avoid during breastfeeding.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Acarbose 50 mg tablets
• Acarbose 100 mg tablets

Mechanism of action

Alpha-glucosidase enzymes are located in the brush-border of the intestinal mucosa and serve to metabolize oligo-, tri-, and disaccharides (e.g. sucrose) into smaller monosaccharides (e.g. glucose, fructose) which are more readily absorbed. These work in conjunction with pancreatic alpha-amylase, an enzyme found in the intestinal lumen that hydrolyzes complex starches to oligosaccharides. Acarbose is a complex oligosaccharide that competitively and reversibly inhibits both pancreatic alpha-amylase and membrane-bound alpha-glucosidases - of the alpha-glucosidases, inhibitory potency appears to follow a rank order of glucoamylase > sucrase > maltase > isomaltase. By preventing the metabolism and subsequent absorption of dietary carbohydrates, acarbose reduces postprandial blood glucose and insulin levels. In contrast to sulfonylureas, acarbose does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia. Because its mechanism of action is different, the effect of acarbose to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, acarbose diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance. Acarbose represents a pharmacological approach to achieving the metabolic benefits of a slower carbohydrate absorption in diabetes, by acting as a potent, competitive inhibitor of intestinal alpha-glucosidases. Acarbose molecules attach to the carbohydrate binding sites of alpha-glucosidases, with an affinity constant that is much higher than that of the normal substrate. Because of the reversible nature of the inhibitor-enzyme interaction, the conversion of oligosaccharides to monosaccharides is only delayed rather than completely blocked. Acarbose has the structural features of a tetrasaccharide and does not cross the enterocytes after ingestion. Thus, its pharmacokinetic properties are well suited to the pharmacological action directed exclusively towards the intestinal glucosidases. ... The aim of the present study was to reveal the possible involvement of thyroid hormones in the antihyperglycaemic and antiperoxidative effects of acarbose. The effects of acarbose on changes in serum concentration of thyroid hormones, insulin and glucose in dexamethasone-induced type 2 diabetic mice were investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) content and the activity of associated endogenous anti-oxidant enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were investigated in renal and cardiac tissues, which are commonly affected in diabetes mellitus. Although administration of dexamethasone (1.0 mg/kg, i.m., for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD and CAT. When dexamethasone-induced hyperglycemic mice were treated with acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were increased and most of the abnormalities, including serum insulin and glucose levels, tissue LPO, SOD and CAT activity and GSH content, were reversed. These findings suggest the involvement of thyroid hormones in the mode of action of acarbose in amelioration of type 2 diabetes mell

Pharmacodynamics

Acarbose is a complex oligosaccharide that competitively inhibits the ability of brush-border alpha-glucosidase enzymes to break down ingested carbohydrates into absorbable monosaccharides, reducing carbohydrate absorption and subsequent postprandial insulin levels. Acarbose requires the co-administration of carbohydrates in order to exert its therapeutic effect, and as such should be taken with the first bite of a meal three times daily. Given its mechanism of action, acarbose in isolation poses little risk of contributing to hypoglycemia - this risk is more pronounced, however, when acarbose is used in conjunction with other antidiabetic therapies (e.g. sulfonylureas, insulin). Patients maintained on acarbose in addition to other antidiabetic agents should be aware of the symptoms and risks of hypoglycemia and how to treat hypoglycemic episodes. There have been rare post-marketing reports of the development of pneumatosis cystoides intestinalis following treatment with alpha-glucosidase inhibitors - patients experiencing significant diarrhea/constipation, mucus discharge, and/or rectal bleeding should be investigated and, if pneumatosis cystoides intestinalis is suspected, should discontinue therapy.