Anti-Diabetic Drugs PDF

Anti-Diabetic Drugs Prepared by: Samah M. Elaidy, PhD, MD Professor of Clinical Pharmacology FOM-SCU Presented by: · Dr.Fatema Saad, MD, PhD Lecturer of Clinical Pharmacology · Vo Faculty of Medicine, Suez Canal Universi...

Anti-Diabetic Drugs Prepared by: Samah M. Elaidy, PhD, MD Professor of Clinical Pharmacology FOM-SCU Presented by: · Dr.Fatema Saad, MD, PhD Lecturer of Clinical Pharmacology · Vo Faculty of Medicine, Suez Canal University Diabetes Mellitus Insulin Therapy Oral Antidiabetic Agents Diabetic comas: Hypoglycemic coma, & Diabetic ketoacidosis. Diabetes Mellitus: Definition Absent or Elevated - inadequate blood pancreatic insulin - glucose* secretion, with or - levels without - impairment of insulin actions. insumense rest Diabetes Mellitus: CLASSIFICATION IDDNebra -n) Type 1 diabetes Type 2 diabetes IDDM. Cain oral) most ;longueentroids common Gestational & Diabetes with other causes: = diabetes as drug-induced mellitus & diabetes eg : glucocorticoid  Diabetes Mellitus Management: Type2 careSeeg 1. Diet regulation, with loa caloric restriction in type II obese patients. 2. Physical exercise. ! 3. Medications: S ▫ Insulin therapy. ▫ Oral antidiabetic agents. Diabetes Mellitus Insulin Therapy Oral Antidiabetic Agents Diabetic comas: Hypoglycemic coma, & Diabetic ketoacidosis. how Insulin Release vimp - C in co ↑ is release from the moto-a insulin y roll exocy 8 t M as vo inge ① ① ⑭ - ③ coltage gated as yo ca-chans a - receptin Insulin release from the pancreatic beta cell by glucose and by sulfonylurea drugs. Tyrosine ninase Insulin Therapy Mechanism of action: Insulin acts with its receptors (tyrosine kinase receptors) → affecting different metabolic enzymes that regulate carbohydrates, fat, and protein metabolism. Insulin Therapy Pharmacological actions : role a insulin 1- On carbohydrate metabolism: = ↓blood glucose by :- ~▫ ↓ hepatic glucose production. ▫ ↑ glucose uptake in skeletal muscles and fat cells. insuli 2- On fat metabolism: human n I. ↑ fat storage. te"smin dity pirra ~ iS mey mone 3- On protein metabolism: 15o to ma pe ↑~protein storage.  natur energ Insulin Preparations is... nsom Ultrashort-acting · Short (Rapid)- Insulin acting Insulin ber ↓ Lispro, Aspart & Regular insulin, name Glulisine preparations -3 soluble, crystalline zinc insulin / when ereit slee e ① on Intermediate- Long-acting -to be iney acting Insulin insulin varin Isophane NPH Insulin glargine, insulin Detemir insulin ↑ the iat onlyn betauenc sy one Insulin Preparations e warn congact ng robe time peacies - Insulin Delivery Systems j51 d.. Insulinen wal ra 1. Standard Delivery (SC). - 2. Portable Pen Injectors. 3. Continuous Subcutaneous Insulin Infusion Devices (CSII, 8 in Insulin Pumps). now 4. Inhaled Insulin. ~ Qmost insulin-given in emergency 2 solubles crystallin  ⑭ when to use ! Indications of insulin therapy - Q diabetes in types 1. IDDM -used - 2. NIDDM:- after failure of diet regulation - and SU. 3. DM with stress :- DKA , surgery, infection (stress increases insulin requirements). 4. DM with pregnancy and lactation. 5. DM with severe renal or liver disease. 6. ttt of hyperkalemia. a del ↳ insulin grerol  indications - endocrinal/ non-diabetic diabetic indications indications * IDDM (typel) @ tet in (type2)@ hyperkalemia * NIDDM = Latter fail of changes diet in elifestyle > - to treat , I * diabetes wires insulin helps u Leysurgery - to d from blood so need astress ↓ insulin) & enter tissue Qash if come pt diabetic +2 I need surgery so it need to shift /cells to take insulin Instead a the oral antidiabetic unLL finish Surgery ⑪ Adiabete, in preg / lactation I can't take or al as = ⑤ If * has renal a liver disease - Adverse effects of insulin > give - 1. Hypoglycemia, ttt I.V glucose. - Ph-ex 2. Insulin= resistance, ttt:- reduce wt. - abnormal far distribution C 3. Lipodystrophy, ttt change site of ⑪ injection. hype hophy/atrophy - 4. Allergy (rare with human insulin). - 5. Increased cancer risk. - Diabetes Mellitus Insulin Therapy Oral Antidiabetic Agents ( Diabetic comas: Hypoglycemic coma, & Diabetic ketoacidosis. given toTypethinhisbode rece bur has ros) ORAL ANTIDIABETIC AGENTS⑮ > - - canuse fa only d Yeale 10 upro The D - - ↓ Begn Sulphonylureas (SU) - ↑ enhance secreta & Mechanism of action : insu Closure of ATP sensitive K channels→depolarization →calcium influx →release of insulin. & Q & · & - Pancreas Sulphonylureas (SU) Indications: ▫ NIDDM (more effective in non-obese patients & - patients with 5-10 years of diabetes). Preparations: ▫ 1st generation: chlorpropamide, tolbutamide. - ▫ 2nd generation: e.g glyburide, glipizide, - - gliclazide and glibenclamide (150 more potent - - than 1st generation). - ▫ 3rd generation: glimepiride (rapid association & = - and dissociation and ↓risk of hypoglycemia). - - adv  Sulphonylureas (SU) Adverse Effects : Y 4H sensitiv g. Hypoglycemia. = 1+ y G Hypersensitivity. sulpha - Heavy weight. nor with obese - GHeart (v.c). estgen Chloropropamide causes: - likepp who sound 1. Cholestatic-- jaundice. 2. Disulfuram like effect (vomiting and flushing). - 3. Dilutional hyponatremia (potentiate ADH). - Fanat -- Non SU secretagogues: Meglitinide analogs (Glinides: repaglinide , nateglinide) Similar in mechanism of action to SU but very rapid onset with shorter duration of action. & better pas G Less post prandial hyperglycemia. They are called prandial and post- as it don't cause prandial glucose regulators. hypo /hyper gluemia  - ORAL ANTIDIABETIC AGENTS Pancreas - &  ② is & Biguanides (Metformin) ( antidiabetic/ - * = euglycemic not hypoglycemic ) If There's hypog = norma -- Mechanism of action: · it make is - ↓ hepatic glucose production.Xy : - Improves glucose utilization in skeletal and adipose tissue. ↓intestinal glucose absorption. Direct stimulation of glycolysis with slight increased blood lactate. - ⑨ = - as tis a datemen Indications: dit 1. - Obese NIDDM/ Non-obese NIDDM. - 2.-Combined with SU in uncontrolled DM. * = 3. PCO as ovulation inducing agent. - Biguanides (Metformin) imp Side effects: 1. GIT: ⑤ metallic taste ,anorexia, dyspepsia , and diarrhea (fermented - sugar). - 2. Lactic acidosis. & muchalsc ze - E - 3. Interfere with vitamin B12 :- with long = term therapy. - Thiazolidinediones (TZDs): enhance + issue respons Rosiglitazone, pioglitazone insulin Par game a to Mechanism of action: receptors e ⑳ ▫ Selective agonist for PPAR gamma (peroxisome- proliferator activated receptor gamma) - in liver, skeletal muscles and adipose tissues-↑ insulin -- sensitivity of these target tissues. - ② - ▫ ↓ Insulin resistance. - Adverse effects & precautions: ▫ Weight gain, edema, heart failure. - - ▫ Anemia. e - ▫ Avoided in liver dysfunction. ORAL ANTIDIABETIC AGENTS Incretin Therapy glucose hormone ama Incretins - - - are natural hormones in the gut. ↑ Levels of active incretins when food ingested. -- - insulin secretio Endogenous incretins: ⑪ ▫ GLP-1 (glucagon-like peptide-1). -- ▫ GIP (glucose-dependent insulinotropic peptide) & release. - · 6 The enzyme dipeptidyl peptidase-4 (DPP-4), · rapidly degrades the active incretins after their -so = give its inhibitors - - The Incretin Effect Is Diminished in so given rub Type 2 Diabetes Mellitus. & &Incretin Therapy & GLUCAGON-LIKE POLYPEPTIDE-1 (GLP-1) ↓ ② ⑧ RECEPTOR AGONISTS: as Exenatide. s DIPEPTIDYL PEPTIDASE-4 (DPP-4) & 5 j - - T & INHIBITORS (Gliptins): as Sitagliptin, ↓ - Saxagliptin, - and Linagliptin. - Diabetes Mellitus Insulin Therapy Oral Antidiabetic Agents Diabetic comas: Hypoglycemic coma, & Diabetic ketoacidosis. Comas in DM: Hypoglycemic coma Warning signs: 1. Increasing adrenergic discharge: ↑ HR, sweating, tremors, hunger pain, pallor. TN - 2. Neurological signs (neuroglycopenia): weakness, irritability, dizziness, confusion, convulsions & coma. a Treatment: be ↓ 1. Glucose: rapid administration of 50% glucose (IV – 50ml), OR, 2. Glucagon (SC -1 mg). & response to giu se is no  Comas in DM: Diabetic Ketoacidosis hypoglycemia more dang ThanYhype (DKA) - comeconcio to Sasse than Causes: severe insulin deficiency due to: hypo 1. Stopping insulin therapy. 2. Exposure to stress (surgery, infection, trauma). Warning signs: polyurea, vomiting, - & dehydration, ↑ respiration & coma. - - Investigations: ▫ Blood: hyperglycemia, ketoacidosis (due to fat breakdown for energy production). ▫ Urine: glucosuria, acetone in urine.  Comas in DM: Diabetic Ketoacidosis vin ins (DKA) give Snor at 1st - ↓ Management: separatet 1. Fluid replacement. 2 nerguidfast + ) 7 wangiven - 2. Insulin therapy : regular insulin => IV need to ↓ > insulin infusion. - be powe given udedso a3. Potassium replacement. - sugive togethe bath W 4. Bicarbonate. - - to balance acidity e S ↑ Diabetes Mellitus Insulin Therapy Oral Antidiabetic Agents Diabetic comas: Hypoglycemic coma, & Diabetic ketoacidosis.  Home Message THANKS