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
Uploaded byAnthonyMoro2
PDF, PPTX853 views

342702880 antidiabetics-ppt

This document discusses various classes of antidiabetic drugs used to treat diabetes mellitus. It describes metformin, sulfonylureas, meglitinides, thiazolidinediones, and alpha-glucosidase inhibitors. Metformin works by reducing hepatic glucose production and increasing glucose uptake in muscle. Sulfonylureas stimulate insulin secretion from pancreatic beta cells. Meglitinides also stimulate rapid insulin secretion. Thiazolidinediones enhance insulin sensitivity. Alpha-glucosidase inhibitors delay carbohydrate absorption in the gut. The document outlines the mechanisms of action, adverse effects, clinical uses, and considerations for each drug class.

Education◦
Download as PDF, PPTX
ANTIDIABETIC DRUGS
ANTIDIABETIC DRUGS Classification and the nomenclature of diabetes mellitus (DM): DM is a chronic metabolic disorder characterised by a high blood glucose concentration-hyperglycemia (fasting plasma glucose > 7.0 mmol//L, or plasma glucose > 11.1 mmol/L 2hr after a meal) - caused by insulin deficiency, often combined with insulin resistance.
ANTIDIABETIC DRUGS Hyperglycemia occurs because of uncontrolled hepatic glucose output and reduced uptake of glucose by skeletal muscle with reduced glycogen synthesis. When the renal threshold for glucose reabsorption is exceeded, glucose spills over into the urine -glycosuria and causes an osmotic diuresis - polyuria, which in turn, results in dehydration, thirst and increased drinking – polydipsia. Diabetic ketoacidosis is an acute emergency- it develops because of accelerated fat breakdown to acetyl-CoA, which, in the absence of aerobic carbohydrate metabolism, is converted to acetoacetate and beta- hydroxybutyrate (which cause acidosis) and acetone (a ketone)
Various complications develop as a consequence of the metabolic derangements in DM, often over many years Many of these are the results of disease of blood vessels, either large (macrovascular disease) of small (microangiopathy). Macrovascular disease consists of acclerated atheroma, which is much more common and severe in diabetic patients. Microangiopathy particularly affects the retina (blindness), kidney (chronic renal failure) and peripheral nerves (diabetic neuropathy,which is associated with accumulation of osmotically active metabolites of glucose. Coexisting hypertension promotes progressive renal damage.
ANTIDIABETIC DRUGS Classification and the nomenclature of diabetes mellitus (DM): Type 1 diabetes encompasses cases resulting from pancreatic B cell destruction (immune-mediated in most cases). Type 2 diabetes consists of combined defects of insulin secretion and action ranging from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance.
• Type 1 diabetes (DM1) - is a severe form associated with ketosis in the untreated state. It occurs most commonly in juveniles but occasionaly in adults, the nonobese. It is a catabolic disorder form in which circulating insulin is virtually absent, plasma glucagon elevated, and the pancreatic B cells fail to respond to insulinogenic stimuli.
• Type 2 diabetes (DM2) - represents a heterogenous group comprising milder forms of DM that occur predominantly in adults. Circulating endogenous insulin is often subnormal or relatively inadequate because of tissue insensitivity. Obesity, which generally results in impaired insulin action, is a common risk factor, and most patients with DM2 are obese. In addition to tissue insensitivity to insulin, there is an accompanying deficiency of the pancreatic B cells´s response to glucose
Oral hypoglycemic agents Biguanides Sulfonylureas Meglitidines Thiazolidinediones Alpha-glucosidase inhibitors
Oral hypoglycemic agents Biguanides -Metformin Lowers blood glucose- increases glucose uptake and utilisation in muscle + reduces hepatic glucose production (gluconeogenesis) Adverse effects: - GIT disturbancies (anorexia + weight loss, diarrhea) = transient - lactic acidosis rare but potencially fatal Metformin should be avoided in patients who predispose to lactic acidosis (renal and hepatic disease, heart failure…) Use: DM2, patients obese and who fail treatment with diet alone. It does not cause hypoglycemia
BIGUANIDES (metformin) • MECHANISM OF ACTION • exerts its effect by activating adenosine monophosphate (AMP) kinase in the hepatocytes, an important enzyme in metabolic control: hepatic glucose production (gluconeogenesis) ↓ - ↑ glucose uptake and utilization in skeletal muscles (reduce insulin resistance) - ↓ carbohydrate absorption - ↑ fatty acid oxidation - ↓ circulating LDL and VLDL
Cont. • UNWANTED EFFECTS AND CONTRAINDICATIONS - Gastrointestinal disturbaces most common = 30% ( anorexia, diarrhoea, nausea, Flactulence, bloating) - Lactic acidosis is rare but fatal : should be avoided in patients with renal / hepatic disease/ hypoxic pulmonary disease or shock - Long term use may interfere with absorption of vit B12
Oral hypoglycemic agents Sulfonylureas stimulate insulin secretion by B-cells (the equivalent of phase 1- secretagogues) and thus reducing plasma glucose. Pharmacokinetics: . well absorbed orally, . all bind strongly to plasma albumin and compete for these binding sites with salicylates and sulfonamides, . most are excreted in the urine  their action is increased in the elderly and in patients with renal disease . cross the placenta  severe hypoglycemia at birth s. are generally contraindicated in pregnancy
Mechanism of Action
Cont. ADVERSE EFFECTS • Weight gain • Hypoglycemia (chlorpropamide, glibenclamide) • GI symptoms • Skin eruptions • Bone marrow suppression CLINICAL USE • Type 2 diabetes
Cont. CONTRAINDICATIONS • Renal impairment • Severe liver dysfunction • Caution in elderly • Allergies DRUG INTERACTIONS • NSAIDs • Monoamine oxidase inhibitors • Antibacterial (trimethoprim, sulfonamides, chlorampenicol)
Doses Glibenclamide: Starting dose 2.5 mg once daily; maximal dose 15 mg daily. Doses exceeding 10 mg per day to be given in two divided doses. Gliclazide: Starting dose 40 mg once daily; maximal dose 320 mg daily. Doses exceeding 80 mg per day to be given in two divided doses. Gliclazide modified-release: Starting dose 30 mg once daily; maximal dose 120 mg once daily. Glimepiride: Starting dose 1 mg daily; maximal dose 6 mg once daily. Glipizide: Starting dose 2.5 mg once daily; maximal dose 40 mg daily. Doses exceeding 15 mg per day to be given in two divided doses.
Oral hypoglycemic agents First generation: Tolbutamide Second generation: glibenclamide, glipizide
Oral hypoglycemic agents Meglitidines • A new class of insulin secretagogues modulates B cell insulin release by regulating potassium efflux through the potassium channels • Repaglinid has a very fast onset of action, with a peak concentration and peak effect within approximately 1 hour after digestion.
Oral hypoglycemic agents Thiazolidinediones a recently introduced class of drugs that enhance target tissue insulin sensitivity- rosiglitazone, pioglitazone Their main action is to diminish insulin resistance by increasing glucose uptake and metabolism in muscle and adipose tissues. Alpha-glucosidase inhibitors Acarbose and miglitol are competitive inhibitors of the intestinal enzymes and modulate the postprandial digestion and absorption of starch and disacharides.
ADVERSE EFFECTS AND CONTRAINDICATIONS • Weight gain • Fluid retention • Increased risk of fracture with chronic use • Headache, fatigue, GI symptoms • Cardiovascular complications • Contraindicated in pregnancy/ breastfeeding women,
ALPHA-GLUCOSIDASE INHIBITORS • Acarbose • MECHANISIM OF ACTION - Competitively inhibits alpha glucosidase on the brush border of the small intestine. This inhibits the conversion of complex carbohydrates into monosaccharides, and results in a reduction and delay in the absorption of glucose
ADVERSE EFFECTS AND DOSING • GI symptoms : Flactulence, diarrhoea, bloating, abd pain • may aggravate hypoglycaemia caused by sulphonylureas and insulin. • Start with 50 mg once daily with meals, and increase by 50 mg every two weeks if tolerated. The maximum dose is 100 mg three times daily,
Oral hypoglycemic agents Clinical uses of oral hypoglycemic drugs: • DM2 as a supplement to diet and excercise to reduce symptoms from hyperglycemia • Metformin is preferred for obese patients unless contraindicated by factors that predispose to lactic acidosis • Drugs that act on the sulfonylurea receptors are well tolerated but often promote weight gain.