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Drugs used for Diabetes Mellitus

Drugs used for Diabetes Mellitus. Introduction. There are 2 types of diabetes mellitus: Type 1: Insulin-dependent diabetes mellitus (IDDM) Destruction of pancreatic beta cells Is the result of an autoimmune process Type 2: Non-insulin dependent diabetes mellitus (NIDDM)

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Drugs used for Diabetes Mellitus

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  1. Drugs used for Diabetes Mellitus

  2. Introduction • There are 2 types of diabetes mellitus: • Type 1: Insulin-dependent diabetes mellitus (IDDM) • Destruction of pancreatic beta cells • Is the result of an autoimmune process • Type 2: Non-insulin dependent diabetes mellitus (NIDDM) • Results from a combination of insulin resistance and altered insulin secretion

  3. Characteristics of Type 1 & Type 2 Diabetes Mellitus

  4. Oral Antidiabetic Drugs • For the treatment of type 2 (non-insulin-dependent) diabetes mellitus • Use only after diet modification & exercise fail to produce glycemic control • Should be used to augment the effect of diet & exercise, not to replace them

  5. Summary of treatment targets for cardiovascular risk factor intervention in diabetic patients

  6. Sulphonylureas • Act mainly by augmenting insulin secretion • May also increase tissue response to insulin • Effective only when some residual pancreatic beta-cell activity is present • Considered for patients who are not overweight, or in whom Metformin (Glucophage®) is contraindicated or not tolerated

  7. Sulphonylureas (Cont‘d) • Short-acting: • Tolbutamide: 0.5-1.5 g daily in divided doses, with or immediately after breakfast; Max: 2 g daily • Gliclazide (Diamicron®): 40-160 mg daily in divided doses, with breakfast; Max: 320 mg daily • Intermediate-acting: • Glipizide (Minidiab®): 2.5-15 mg daily in divided doses, before breakfast; Max: 20 mg daily

  8. Sulphonylureas (Cont‘d) • Long-acting: • Chlorpropamide (Diabinese®): 250 mg daily with breakfast; Max: 500 mg • Glibenclamide (Daonil®): 5 mg daily with or immediately after breakfast; Max: 15 mg daily • Glimepiride (Amaryl®): 1-4 mg daily shortly before or with first main meal; Max: 4 mg daily

  9. Sulphonylureas (Cont‘d) • Contraindications: • Severe hepatic and renal impairment • Breast-feeding and pregnancy • Elderly (Chlorpropamide, glibenclamide) • Adverse effects: • Nausea, vomiting, diarrhoea and constipation • Increased appetite and weight gain • Hypoglycaemia • Hypersensitivity

  10. Biguanides • Decreasing gluconeogenesis in the liver • Increase peripheral utilisation of glucose by muscle • Acts only in the presence of endogenous insulin • Metformin (Glucophage®) is the only available biguanide • Is antihyperglycemic, not hypoglycemic • Recommended for obese or insulin resistant diabetic patients

  11. Biguanides (Cont’d) • Metformin: • 500 mg bd-tid; Max: 3 g, usually limit to 2 g daily • Contraindications: • Hepatic or renal impairment (must withdraw) • Ketoacidosis • Predisposition to lactic acidosis: severe dehydration, which is most likely to occur in patients with renal impairment

  12. Biguanides (Cont’d) • Contraindications (Cont’d): • Infection, shock, trauma, heart failure, respiratory failure, recent myocardial infarction, severe peripheral vascular disease • Hepatic impairment, alcohol dependency • Use of iodine-containing x-ray contrast media (do not restart melformin until renal function returns to normal) • Pregnancy and breast-feeding

  13. Biguanides (Cont’d) • Adverse effects: • Decreased appetite • Nausea, vomiting and diarrhoea • Lactic acidosis (rarely) • Decreased absorption of vitamin B12 and folic acid • Allergic skin reactions

  14. Biguanides (Cont’d) • Nursing alerts: • Take metformin with meals and increase dosage slowly to minimise GI adverse effects • Lactic acidosis, characterised by drowsiness, malaise, bradycardia and hypotension is a rare but serious adverse effect. Since this is a medical emergency, report to the physician immediately if suspected

  15. Alpha glucosidase inhibitor • Delay the digestion & absorption of starch & sucrose by inhibition of intestinal alpha glucosidase in the intestine • Acarbose (Glucobay®) • 50-100 mg tid; Max: 200 mg tid

  16. Alpha glucosidase inhibitor (Cont’d) • Contraindications: • Pregnancy and breast-feeding • Inflammatory or malabsorptive intestinal disorders • Hepatic impairment • Severe renal impairment

  17. Alpha glucosidase inhibitor (Cont’d) • Adverse effects: • Flatulence, soft stools, diarrhoea, abdominal distention and pain • Liver dysfunction

  18. Alpha glucosidase inhibitor (Cont’d) • Nursing alerts • Tablets should be taken with first mouthful of food • Absorption of sugar (sucrose) is blocked by acarbose. When hypogylcaemia occurs, only glucose should be given

  19. Metglitinides • Stimulate insulin release • Rapid onset of action & short duration • Taken shortly before meals

  20. Metglitinides (Cont’d) • Repaglinide (NovoNorm®): • 500 mcg – 4 mg daily within 30 min before main meals; Max: 16 mg daily • Nateglinide: • 60 mg tid within 30 min before main meals; Max: 180 mg tid

  21. Metglitinides (Cont’d) • Contraindications: • Ketoacidosis • Pregnancy and breast-feeding • Severe hepatic impairment (for repaglinide)

  22. Metglitinides (Cont’d) • Adverse effects: • Hypoglycaemia • Hypersensitivity reactions including pruritus, rashes and urticaria • Abdominal pain, diarrhoea, constipation, nausea and vomiting (repaglinide) • Nursing alert: • Administration must always be associated with meals

  23. Thiazolidinediones • Also known as Glitazones • Reduce peripheral insulin resistance by enhancing uptake of glucose by skeletal muscle cells • Rosiglitazone (Avandia®): • 4 mg daily in combination with metformin or a sulphonylurea; Max: 8 mg daily when with metformin • Pioglitazone (Actos®): • 15-30 mg daily

  24. Thiazolidinediones (Cont’d) • Contraindications: • Hepatic impairment • History of heart failure, combination of insulin • Pregnancy and breast-feeding

  25. Thiazolidinediones (Cont’d) • Adverse effects: • GI disturbances, headache, anaemia • Weight gain • Oedema • Hypoglycaemia (less common for Pioglitazone) • Liver dysfunctions (rare)

  26. Thiazolidinediones (Cont’d) • Nursing Alerts: • Monitor liver function before treatment, then every 2 months for 1 year and periodically thereafter • Seek immediate medical attention if symptoms such as nausea, vomiting, abdominal pain, fatigue & dark urine develop • Discontinue if jaundice occurs • Monitor closely for oedema & other signs of congestive heart failure

  27. Non-oral antidiabetic drugs • Insulin: • Supplement the insulin secreted by pancreas • Promote uptake of glucose in muscle • Facilitate conversion of glucose to glycogen in liver, inhibit gluconeogenesis & glycogenolysis in liver

  28. Actions of Insulin • Glucose transport into muscle & fat cells. • Increased glycogen synthesis. • Inhibition of gluconeogenesis. • Inhibition of lipolysis & increased formation of triglycerides. • Stimulation of membrane-bound energy-dependent ion transporters (e.g. Na/K ATPase). • Stimulation of cell growth

  29. Insulin (Cont’d) • They are divided into short, intermediate & long-acting preparations: • Short-acting: • Neutral/soluble insulin • E.g. Actrapid®HM, Humulin R® • Insulin Lispro • E.g. Humalog® • Insulin Aspart • E.g. NovoRapid®

  30. Insulin (Cont’d) • Intermediate-acting: • Isophane insulin • E.g. Protaphane®HM, Humulin N® • Insulin zinc suspension • E.g. Monotard®, Humulin L®

  31. Insulin (Cont’d) • Long-acting: • Crystalline insulin zinc • E.g. Ultratard®HM • Insulin glargine • E.g. Lantus®

  32. Insulin (Cont’d) • Mixed Insulins: • Biphasic isophane insulin • 30% soluble insulin/70% isophane insulin • E.g. Mixtard ®30, Humulin ®70/30 • 20% soluble insulin/80% isophane insulin • E.g. Mixtard ®20

  33. Insulin (Cont’d) • Dose: • Given through subcutaneous injection • According to the requirements • Short-acting: • Usually inject 15-30 min before meals • Intermediate- & long-acting: • Once or twice daily • Can be given in conjunction with short-acting insulin

  34. Insulin Formulations

  35. Insulin (Cont’d) • Precautions: • may decrease requirements in renal or hepatic impairment, some endocrine disorders, coeliac disease

  36. Insulin (Cont’d) • Nursing Alerts: • Teach patients how to prepare & use the subcutaneous (SC) injection, and the usual areas used for SC injection including abdomen, thigh & upper arm • Rotate the injection site within the general area employed. Allow about 1 inch between sites

  37. Insulin (Cont’d) • Nursing Alerts (Cont’d): • Storage • Penfill • Cartridges not in use should be stored between 2-8 ℃ • Cartridges used in the pen or carried as spare can be used for up to one month • Vial • Vials not in use should be stored between 2-8 ℃ • Vial in use can be kept at room temp for 6 weeks (Novo Nordisk) • Vials in use can be kept at room temp for 28 days (Lilly)

  38. Hypoglycaemia • Nursing Alerts: • Observe for and teach the patient about signs and symptoms of hypoglycaemia • Tachycardia, palpitations • Sweating • Nervousness, headache, confusion, drowsiness • Fatigue • Rapid treatment is required • Patient is conscious: oral glucose should be given • Patient is unconscious: IV glucose should be used

  39. BREAK

  40. Drugs that affect the gastrointestinal system

  41. Introduction • Drugs used in gastrointestinal system or digestive disorder primarily exert their action by altering GI • Secretion • Absorption • Motility • They may act systemically or locally in the GI tract

  42. Physiologic and pathologic (i.e. inflammatory) prostaglandins Cell activated by physical, chemical, or hormone stimuli Arachidonic acid Traditional NSAIDs Block COX-1 and COX-2 enzymes COX-2inhibitor NSAIDs Block COX-2 enzyme Cyclooxygenase-1 (COX-1) Cyclooxygenase-2 (COX-2) Physiologic prostaglandins Pathologic prostaglandins • Inflammation • Vasodilation, • ↑Capillary permeability • Edema • Pain • Leukocytosis • Activatye white blood cells to • release inflammatory cytokines • GI protection (↓gastric acid,↑mucus • production, maintain blood flow to mucosa) • Renal protection (help maintain blood flow • and function) • Regulate smooth muscle tone in blood • vessels (e.g., vasodilation) and lungs • (e.g., bronchodilation) • Regulate blood clotting

  43. Antacids & Simethicone • Antacids • Drugs that neutralize or reduce the acidity of stomach & duodenal contents by combining with HCl & producing salt & water • Relieve symptoms in dyspepsia, gastro-oesophageal reflux disease (GERD), peptic ulcers • Simethicone • Added to antacids as an antifoaming agent to relieve flatulence

  44. Antacids & Simethicone (Cont’d) • Antacids • Aluminium Hydroxide (500mg tablet /6% suspension) • 1-2 tablets chewed qid • Magnesium trisilicate (Mixture) • 5% BP Mixture: 10ml tid po

  45. Antacids & Simethicone (Cont’d) • Antacids combination products: • Triact tablet • Al(OH)3 Dried Gel 200 mg & Mg(OH)2 150 mg & Simethicone 25 mg • Chew 1-2 tab q4-6h • Gastrocaine suspension • Oxethazaine 10mg, Al(OH)3 Dried Gel 300mg, Mg(OH)2 100mg in 5 ml • Alumag suspension • Al(OH)3 & Mg Trisilicate

  46. Antacids & Simethicone (Cont’d) • Antacids combination products (Cont’d): • Gelusil tablet • Mg Trisilicate+ Dried Aluminium Hydroxide gel • Mylanta tablet / suspension • CaCO3 & Mg(OH)2 • Simethicone • Dimethylpolysiloxane (Gasteel® 40 mg tablet)

  47. Antispasmodics • Relax smooth muscle • Relieve GI smooth muscle spasm • Include antimuscarinics & others

  48. Antispasmodics (Cont’d) • Antimuscarinics: • Hyoscine Butylbromide (Buscopan®) • Adult: 20 mg qid po; • Child: 10 mg tid po • Propantheline bromide • 15 mg tid at least 1 hr before meals & 30 mg at night; Max: 120 mg daily • Not recommended for children

  49. Antispasmodics (Cont’d) • Side effects: • Constipation • Urinary urgency and retention • Dry mouth • Transient bradycardia

  50. Antispasmodics (Cont’d) • Others: • Mebeverine HCl (Duspatalin®) • Adult & child over 10 years: 135-150 mg tid preferably 20 min before meals • Peppermint oil (0.2 ml capsule) • 1-2 capsules tid • Not recommended for children under 15 years

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