Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Dr Pralhad Patki, profile picture
Uploaded byDr Pralhad Patki
PPT, PDF15,489 views

Pp oral hypoglycemic agents

The document provides a comprehensive overview of oral hypoglycemic agents used in diabetes management, classifying them into categories such as secretagogues, sensitizers, and others. It details the mechanisms, pharmacokinetics, and side effects of different drug classes including sulfonylureas, biguanides like metformin, thiazolidinediones, and alpha-glucosidase inhibitors. Additionally, it discusses the roles of incretin mimetics and amylin analogues in enhancing insulin secretion and managing blood glucose levels.

Health & Medicine◦
Downloaded 212 times
ORAL HYPOGLYCEMIC AGENTES DIABETE MANAGEMENT
Classification of oral hypoglycemic agents 1. Secretagogues Sufonylureas a. First generation b. Second generation Meglitinides 2. Sensitizers Bioguanides Thiazolidinediones
Classification of oral hypoglycemic agents (cont) 3. Alpha-glucosidase inhibitors 4. Peptide analogues Incretin mimetic a. Glucagon-like peptide (GLP) analogues and agonists b. Gastric inhibitory peptide (GIP) DPP-4 inhibitors Amylin analogues
Chemical classification  Sulphonylureas  First generation: Tolbutamide, chlorpropamide, acetohexamide, tolazamide  Second generation: Glibenclamide, glipizide, gliclazide, Glemipiride  Biguanides: Phenformin, metformin  Meglitinide Analogues: Repaglinide, Nateglinide  Thiazolidinediones: Rosiglitazone, pioglitazone  α–Glucosidase inhibitors: Acarbose, miglitol
Site of action of Oral Hypoglycemic Drugs
Mechanism of action of Sulfonylureas
Types of Sulfonylureas Generation Agents Duration of action First Tolbutamide 6-12 (hrs) Chlorpropamide 60 Acetohexamide 12-24 Tolazamide 12-24 Second Glipizide 10-16 Glibenclamide 18-24 Glimepiride 18-24
Pharmacokinetic Administered just before or along with meal Moderately protein bound (70-90%) Metabolised in the liver; few are metabolised to active metabolites Low volume distribution Few excreted unchanged in the urine
ADVERSE EFFECTS Hypoglycemia: long acting drugs dangerous (inadequate diet, renal / hepatic diseases, other drug administration) GIT disturbances Weight gain Allergy : Jaundice with chlorpropamide Thyroid dysfunction: tolbutamide reduces iodine uptake.
DRUG INTERACTION Antabuse like effect with alcohol (especially with chlorpramide). Enhancement Highly protein binding drugs (salicylates) increase the concentration. Enzyme inhibitors (cimetidine, chloramphenicol) increase the duration of action.
DRUG INTERACTION Inhibition Enzyme inducers decrease the duration of action. Chronic alcoholism: hyperglycaemia. Acute alcohol intake: hypoglycaemia. Corticosteroids, loop & thiazide diuretics, oral contraceptives decrease insulin and antagonise indirectly. β-adrenergic drugs mask hypoglycemia.
MEGLITINIDE (GLINIDE)  Secretion enhancer (insulin secretagogue)  Mechanism similar to sulfonylureas but binding may be at different site or receptor  Rapid onset (should be taken immediately with food or just before food)  Metabolised in liver (caution: in liver dysfunction)  Suitable to control postprandial hyperglycemia uncontrollable with diet and exercise  Substitute for sulfonylurea in case of allergy  Repaglinide 0.25-0.4 mg, Nateglinide: 60-120 mg
Metformin (biguanides) Mechanism  Increase uptake and utilization of glucose by skeletal muscle, which reduces the insulin resistance  Inhibition of hepatic and renal gluconeogenesis, which decreases hepatic glucose output predominantly  Slow down the intestinal absorption of glucose
Metformin (biguanides) Mechanism  Promote insulin-binding to its receptor  Reduction in plasma glucacon level, does not stimulate insulin, does not reduce blood sugar in normal person  Lowers LDL, VLDL and elevates HDL
Biguides (Metformin) Partially absorbed, Partially metabolised Duration: 8 hr; Taken with food Dose: 500 mg bd (may be increased) Metformin : Only oral anti-diabetic approved in pregnancy Side effects Lactic acidosis (rare) B-12 malabsorption
ACC = acetyl COA carboxylase AMPK = adenosine mono phosphate kinase SREPB = sterol regulatory expression binding Protein
peroxisome proliferators-activated receptor γ
Thiazolidinediones (Glitazones) Two types of PPARs - PPARα and PPARγ. PPARα : ( TG but HDL) PPARγ : insulin sensitizer Thiazolidinediones + PPARγ Transcription of several insulin responsive genes Reverse the insulin resistance Stimulate GLUT4 expression and translocation Entry of glucose into muscle and fat is improved
Pioglitazone  PPAR-α and PPAR-γ activity  Absorbed within 2 hours of ingestion  Food may delay uptake but total bioavailability not affected  Metabolized to active metabolites  estrogen-containing oral contraceptives metabolized by the same microsomal enzymes  Once a day before meals (15 -30 mg)  May be combined with metformin, sulfonylureas, and insulin
ROSIGLITAZONE  Predominantly on PPAR-γ  Rapid absorption & high protein bound  Other properties (kinetic & use) similar Side effects (general)  Fluid retention (weight gain), anemia, headache, myalgia etc  Not advisable in hepatic and CVS complications  Liver function test advisable
α-GLUCOSIDASES  Starch, oligosaccharides and di-saccharides monosaccharides for absorption  Pancreatic α-amylase :sucrose, maltose, glycoamylose, and dextrose  α –glucosidases (intestinal brush ): lactose  Acarbose & Miglitol cometitive inhibitor of α – glucosidases and Pancreatic α-amylase (less)  Miglitol: 6 times more potent against α-amylase  postprandial digestion and absorption of starch and disaccharides
α-GLUCOSIDASES  Dose 25-100 mg (acarbose/miglitol) is taken at the beginning of each meal.  Minimally absorbed  Produces flatulence, abdominal discomfort and loose stool.
PEPTIDE ANALOGUES Incretin Mimetics  Incretins are insulin secretagogues  GLP-1(Glucagon like peptide-1)liraglutide  GIP (Gastric inhibitory peptide)  Bind to GLP (incretin) receptors and increase insulin release  Exenatide: GLP-1 agonist is resistance to degradation by DPP-4 and extends its half-life  weight loss and gastrointestinal side effects
Dipeptidyl peptidase-4  Dipeptidyl peptidase-4 degrades GLP-1  Vildagliptin, sitagliptin, saxagliptin, linagliptin : DPP-4 inhibitors  prevents the action of DPP-4  weight neutral and increased risk for infection and headache
Insulin and Incretin
AMYLIN ANALOGUES • Amylin, produced by pancreatic beta cells, • Slows gastric emptying and suppress glucagon • Pramlintide is the amylin analogue • SC inj. just before meal and it reduces postprandial hyperglycemia • Nausea, vomiting • Your comments- • drpatki@gmail.com