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Similar to Antidiabetics.ppt ANTIDIABETIC DRUGS. Nursing
Antidiabetics.ppt ANTIDIABETIC DRUGS. Nursing
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- 2. NORMOGLYCEMIA (WHO) NORMOGLYCEMIA (WHO) Fastingglucose: Fasting glucose: 3.8 3.8 6.1 mmol/l 6.1 mmol/l HbA HbA1C 1C: 4.7– : 4.7–6 6.0% .0% Glucose Glucose occupies a central position in metabolism as the predominant substrate for energy production energy production.
- 3. Random Random blood glucose blood glucose <7.8mmol/l <7.8 mmol/l 7.8–11.1 mmol/l 7.8–11.1 mmol/l ≥ ≥11.1 mmol/l 11.1 mmol/l Normal Normal Impaired Glucose Impaired Glucose Tolerance (IGT) Tolerance (IGT) Diabetes mellitus Diabetes mellitus Suspected diabetes mellitus Suspected diabetes mellitus 75 g glucose p.o.: 75 g glucose p.o.: 2 h later 2 h later
- 4. IGT IGT (7.8–11.1 mmol/l) (7.8–11.1 mmol/l) 1/3become 1/3 become normal normal 1/3 remain 1/3 remain IGT IGT 1/3 become 1/3 become DM DM
- 5. HbA HbA1 1C C is alab test that shows is a lab test that shows the average amount of sugar the average amount of sugar in blood over in blood over 2– 2–3 months. It shows 3 months. It shows how well you are controlling how well you are controlling DM DM. . A An HbA n HbA1 1C C of 6% or less is normal. of 6% or less is normal. The following are the results The following are the results when the HbA when the HbA1 1C C is being used is being used to diagnose diabetes: to diagnose diabetes: •Normal Normal: Less than 5.7% : Less than 5.7% •Pre-diabetes Pre-diabetes: 5.7% to 6.4% : 5.7% to 6.4% •D DM M: 6.5% or higher : 6.5% or higher Values of HbA1C 1C ≥ 7% are a signal for emergency change in treatment.
- 7. Worldwide prevalence ofdiabetes mellitus
- 8. Type 1 DM(beta-celldestruction) – about 10% of all patients. a) Autoimmune DM (the so called insulin-dependent DM – IDDM or juvenile-onset diabetes). It results from autoimmune mediated destruction of the beta cells of the pancreas. The rate of destruction is quite variable (and may reach 80% of the beta- cells of the Langerhans islets), being rapid in some individuals and slow in others. The rapidly progressive form is commonly observed in children, but also may occur in adults. The slowly progressive form generally occurs in adults and is sometimes referred to as latent autoimmune DM in adults (LADA). b) Idiopathic type 1 DM, which has no known etiology (has no evidence of autoimmunity). This form is more common among individuals of African and Asian origin. Patients periodically develop ketoacidosis. Diabetes mellitus (DM)
- 9. Type 2 DM(predominantly insulin resistance with relative insulin deficiency or predominantly an insulin secretory defect with/without insulin resistance). DM of this type previously encompassed non- insulin-dependent diabetes (NIDDM), or adult-onset diabetes. It is a term used for individuals who have relative (rather than absolute) insulin deficiency. People with this type of diabetes (> 80% of patients with DM) frequently are resistant to the action of insulin. Other specific types of DM •Genetic defects of beta-cell function (mutations on chromo- some 12 in a hepatic nuclear transcription factor referred to as HNF13. A second form is associated with mutations in the glucokinase gene on chromosome 7p.
- 10. •Genetic defects ininsulin action (It is connected with some pediatric syndromes that have mutations in the insulin receptor gene with subsequent alterations in the insulin receptor function and extreme insulin resistance). •Diseases of the exocrine pancreas (pancreatitis, trauma, cancer) •Endocrinopathies (acromegaly, Cushing’s syndrome, glucagonoma, and pheochromocytoma). •Drug- or chemical-induced (pentamidine, glucocorticoids, etc.). •Viral infections may cause beta-cell destruction (e.g. mumps, adenovirus, cytomegalovirus, Coxsackie B, congenital rubella). •Other genetic syndromes sometimes associated with DM (Down’s, Klinefelter’s and Turner’s syndromes, etc.). •Gestational diabetes includes the former categories of gestational impaired glucose tolerance.
- 11. large blood vesselatherosclerosis •coronary heart disease (CHD) •limb ischaemia (diabetic foot! diabetic foot!) •stroke small blood vessel atherosclerosis •retinopathy •neuropathy •nephropathy •skin ulceration infection (mycoses, etc.) DM – complications:
- 12. Diabetic retinopathy results inscattered haemorrhages, yellow exudates, and neovascularization Diabetic nephropathy
- 13. •Normoglycemia - avoiding hypoglycemia orketosis - HbA HbA1C 1C < 6.5% < 6.5% ( (glycosylated hemoglobin glycosylated hemoglobin) •Reduce - nephropathy - neuropathy - retinopathy - infections (mycoses, etc) Management goals
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- 15. •Diet – weight control –low fat intake – normal protein intake – carbohydrates ~ 50% of total energy •Control blood pressure (120/80 mm) BMI 18.5–24.9 •Motor activity and compliance! !
- 16. Insulin is aprotein, secreted from the β-cells of the islets of Langerhans in the pancreas in response to a rise in blood glucose, and inhibited by a fall. t1/2: 5–6 min molecule mass: 5734 Da I. Insulin I. Insulin
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- 18. Amylin (Islet AmyloidPolypeptide – IAPP) reperesents a 37-residue peptide hormone. It is cosecreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1. Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.
- 19. Mechanism of action •Insulinacts via receptors that are transmembrane glycoproteins. •Each receptors has two binding sites. Receptor occupancy results in:
- 20. 1. Activation ofinsulin-dependent glucose transport processes in adipose tissue and muscle. 2. Inhibition of adenylyl cyclase- dependent processes (lipolysis, proteolysis, glycogenolysis).
- 21. ATP cAMP 3’,5’-AMP Lipolysisin adipose tissue (hypercholesterolemia) AC PD (+) (-) (-) Insulin Insulin
- 22. 4. Intracellular accumulationof potassium and phosphate (which are linked to glucose transport in some tissue). 5. Increased cellular amino acid uptake, DNA and RNA synthesis. 6. Increased oxidative phosphorylation.
- 24. Insulin is extractedeither from cattle or pig pancreas. Bovine (B) insulin differs from human insulin in three amino acid residues, and porcine (S) insulin in one, but their action is very similar to human. Nobel prize (1923)
- 25. More recently, recombinant DNAtechnology has allowed in vitro manufacturing of insulin with the same structure as human (H) insulin. All current insulin preparations have a low content of impurities.
- 26. Insulin is initiallypurified by protein extraction to form a crystalline product. It may then undergo either gel filtration to produce a single peak (SP) insulin or gel filtration and ion exchange chromatography which generates:
- 27. •monocomponent (MC), •single component(SC) and •rarely immunogenic (RI) insulin. Other abbreviations which are used for insulins are: •Hum- and -man (for human ), •PP (purified preparation)
- 28. MAIN TYPES OF INSULINPREPARATIONS •Short-acting •Intermediate-acting (they contain protamin or Zn) •Long-acting (they contain both protamin & Zn) Injectors (with cartridge): OptiPen, OptiSet, Penfill, etc.
- 29. Comparisons among insulins TypeOnset of Peak Duration action activity Short- acting 10–20 min 1–2 h 5–7 h Interme- diate-act. 1–2 h 5–7 h 13–18 h Long-act. 2–4 h 8–14 h 18–36 h
- 30. Insulins are usedmainly in type 1 DM. Patients with type 2 DM use insulins in the following cases too: •acute infections •pregnancy •surgical operations •burn •myocardial infarction •ketoacidosis
- 31. Therapy of DM Therapyof DM with insulin is with insulin is a replacement a replacement therapy. therapy. s.c.: 6 sec High compliance!
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- 33. Insulin pumps: Insulin pumps: Theyinfuse They infuse subcutaneously subcutaneously fast-acting fast-acting insulin through insulin through small catheter small catheter (very handy (very handy and very and very expensive). expensive).
- 34. a) Insulins: Actrapid ,Humulin R b) Analogues: Insulin aspart, Insulin lispro 1. Short-acting insulins and analogues s.c. 15 min before meal 4 times daily chronobiologically
- 36. Ketoacidosis Short-acting insulin (i.v. or i.v.infusion) with physiological saline and potassium chloride
- 37. •Humulin M •Humulin N •Insulatard •Mixtard 2.Intermediate-acting insulins and analogues s.c. 20 min before meal 2 times daily Chronobiologically
- 38. 3. Long-acting insulins s.c.20 min before meal once daily •Insulin detemir (Levemir ) •Insulin glargine (Lantus )
- 39. Adverse effects ofinsulins •hypoglycemia/coma •allergic reactions •insulin resistance •lipodystrophia of subcutane- ous fat at or near injection •local fibrosis
- 40. II. Oral hypoglycemicand II. Oral hypoglycemic and other drugs, used other drugs, used in DM type 2 in DM type 2
- 41. 1. Biguanides: Metformin •usually firstline drug for type 2 DM •reduces intestinal glucose absorption •stimulates anaerobic glycolysis •stimulates glucose uptake •enhances insulin receptor binding
- 42. •excreted exclusively by thekidney •does not increase weight and preferable in the obese preferable in the obese •GI side effects GI side effects •rarely lactic acidosis lactic acidosis Metformin Metformin
- 43. 2. Sulfonylureas I generation: •Chlorpropamideand Tolbutamide (Out) II generation: •Glibenclamide (Daonil: tab. 5 mg) •Gliclazide (Diaprel MR ) •Glipizide •Gliquidone
- 44. Unwanted effects •Hypoglycemia, weightgain •facial flushing following alcohol ingestion Mechanism of action •promote enhanced insulin release from the pancreas •leads to a reduction in hepatic glucose production
- 45. •displacement from proteinbinding sites – salicylates and sulphonamides •interference with hepatic metabolism – inducers: rifampicin, phenytoin – inhibitors: cimetidine •reduction of renal elimination – allopurinol, salicylates Sulfonylureas – important drug interactions:
- 46. •Inhibits intestinal alpha-glucosidase •Decreasesintestinal absorption of the mono- and polysaccharides. •Produces flatulence and diarrhoea flatulence and diarrhoea. - Acarbose (Gluco Bay ): p.o. 4. Glucosidase inhibitors 3. Meglitinides: stimulate the release of insulin from pancreas by closing ATP-dependent potassium channels. - Nateglinide - Repaglinide
- 47. 5. Thiazolidinediones (TZDs) Theyincrease tissue insulin sensitivity but have serious ADRs and the EMA but have serious ADRs and the EMA recommended in Sept (2010) that they recommended in Sept (2010) that they be be suspended from the EU market suspended from the EU market: - Rosiglitazone (Avandia ) has high high cardiovascular risks cardiovascular risks. - Pioglitazone causes bladder tumors bladder tumors. - Troglitazone causes hepatitis hepatitis.
- 48. 6 6. . Glucagon-like peptide Glucagon-likepeptide-1 -1 (GLP (GLP-1 -1) ) agonists (in type 2 DM): agonists (in type 2 DM): increase pancreatic secretion of insulin: Exenatide Bydureon (s Bydureon (s. .c./ c./7 7 days days) ): : $323/4 doses, resp. $323/4 doses, resp. $4200 per year $4200 per year
- 49. Liraglutid Liraglutid Liraglutid Liraglutid agonist, which reduces, HbA1C, andsystolic blood pressure, and improves beta cell function of the pancreas (s.c. once a day) (s.c. once a day)
- 50. 7 7. Inhibitors ofDipeptidil . Inhibitors of Dipeptidil peptidase peptidase-4 ( -4 (DPP DPP-4) -4): : prevent degradation of incretin Sitagliptin (p.o.) Vildagliptin (p.o.)
- 51. 8. Inhibitors ofreabsorption of glucose (SGLT2 inhibitors): p.o. •Canagliflozin blocks in renal proximal tubule sodium / glucose co-transporter protein 2 (SGLT2), which re-absorbed 90% of the filtrated glucose. The result is increased glucosuria and plasma glucose levels are lowered. ADRs: Hypoglycaemia, vulvovaginal candidiasis urinary tract infections, polyuria, frequent urination.