Anti-diabetic drugs.Oral hypoglycemics

Jehan Zeb khanPharm.D

Oral Hypoglycemic Agents

BiguanidesSulfonylureasMeglitidinesThiazolidinedionesAlpha-glucosidase inhibitorsDipeptidyl Peptidase-4 (DPP-4) Inhibitors

Classification Biguanides: Metformin (Glucophage)Phenformin Sulfonylureas: 1ST Generation: Tolbutamide, Chlorpropamide,

Tolazolide2nd Generation: glyburide, glibenclamide, glipizide,

glimipride, ThiazolidinedionesPioglitazone, rosiglitazone, troglitazone MeglitinidesRepaglinide Alpha-glucosidase inhibitorsAcarbose, Meglitol. Dipeptidyl Peptidase-4 (DPP-4) InhibitorsValdegliptin, sitagliptin

Biguanides

Pharmacological Effects:>increase insulin sensitivity>Increases glucose uptake and utilisation >reduces hepatic glucose production>decreases glucose absorption from GIT>decrease plasma glucagon level

Decrease blood glucose >Metformin has no direct effect on the β cells, although insulin

levels are reduced, reflecting increases in insulin sensitivity.

Biguanides…

Clinical uses:Hyperglycemia due to ineffective insulin

action.>Type II diabetes +- Tzd or insulin

secretagogues>Prevention of type II DM Dosage: 500mg to maximum 2.55gm daily

with the lowest effective dose being recommended. Dosage always be divided since dose greater than 1000mg provoke GI-upsets.

Biguanides…

Adverse Effects:>GI-Upsets: anorexia, nausea, vomiting,

abdominal discomfort, diarrhea. >Decrease VitaminB12 absorption.>lactic acidosis: more common with

phenformin than with metformin.Contraindications:Renal diseaseHepatic diseaseConditions predisposing to tissue anoxia

Thiazolidinediones (Tzds)

Pharmacological actions:>Decrease insulin resistance>Enhance insulin sensitivity>Increase uptake and utilization of

glucose in muscles and adipose tissues

Thiazolidinediones (Tzds)Indications: As monotherapy or in combination with

biguanides or Sulfonylureas in type II DMAdverse effects: Fluid retention Weight gain Increased fracture rate Anovulatory women may starts ovulation and

risk of pregnancy HepatotoxicityContraindications: Liver disease Heart failure pregnancy

Alpha glucosidase inhibitors

Pharmacological action:Inhibit alpha glucosidases (sucrase,

maltase,dextranase,glycoamylase) that converts complex starches, oligosaccharides and disaccharides to their respective monosacharides.

Their inhibition causes decrease absorption of glucose.

How to treat hypoglycemia here?!

Alpha glucosidase inhibitors

Adverse effects:Flatulence, diarrhea, abdominal pain.

Sulfonylureas

Pharmacological actions: Insulin release from beta cells of

pancreasThrough inhibition of ATP-sensitive

potassium channels that results in depolarization and opens calcium channels with results in influx of calcium ions and the release of insulin.

Reduces glucagon secretion

Sulfonylureas

Uses: Sulfonylureas are used primarily for the treatment

of diabetes mellitus type 2. Sulfonylureas are ineffective where there is absolute deficiency of insulin production such as in type 1 diabetes

Adverse effects:Hypoglycemia as a result of excesses in insulin

release.Abdominal upsets, headache and hypersensitivity

reactions.Impairment of liver or kidney function increase the

risk of hypoglycemia, and are contraindications.

Diabetic complications

Retinopathy: Patients with established retinopathy should be examined by an ophthalmologist at least every 6 to 12 months.

Neuropathy: Paresthesias, numbness, or pain can be the predominant symptom. If neuropathy is painful, symptomatic therapy is empiric, including low-dose tricyclic antidepressants, anticonvulsants (gabapentin, pregabalin, carbamazepine, and maybe phenytoin), duloxetine, venlafaxine, topical capsaicin, and various pain medications, including tramadol and nonsteroidal antiinflammatory drugs.

Diabetic complications Gastroparesis can be severe and debilitating.

Improved glycemic control, discontinuation of medications that slow gastric motility, and use of metoclopramide.

Patients with orthostatic hypotension may require mineralocorticoids or adrenergic agonists.

Diabetic diarrhea is commonly nocturnal and frequently responds to a 10- to 14-day course of an antibiotic such as doxycycline or metronidazole. Octreotide may be useful in unresponsive cases.

Erectile dysfunction is common, and initial treatment should include one of the oral medications currently available (e.g., sildenafil, vardenafil, tadalafil).

Diabetic complications

Nephropathy: Glucose and blood pressure control are most

important for prevention of nephropathy, and blood pressure control is most important for retarding the progression of established nephropathy.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have shown efficacy in preventing the clinical progression of renal disease in patients with type 2 DM. Diuretics are frequently necessary due to volume-expanded states and are recommended second-line therapy.

Diabetic complications

Peripheral Vascular Disease and Foot Ulcers

Coronary Heart Disease