OUR LADY OF FATIMA UNIVERSITY College of Pharmacy DISPENSING 2 (PDIS 312) POST LABORATORYExercise No. 7 Case on Diabetes Mellitus Type 2 ™~ ue » 1 2 ae(&) LEARNING OUTCOMES At the end of this exercise, the students should be able to: 1.Recognize the signs, symptoms, and risk factors associated with Type 2 diabetes mellitus (DM). 2.Identify the comorbidities in Type 2 DM associated with insulin resistance (metabolic syndrome). 3.Compare the pharmacotherapeutic options in the management of Type 2 DM including mechanisms of action, contraindications, and side effects. 4.Describe the role of self-monitoring of blood glucose (SMBG) and identify factors to enhance patient adherence. 5.Develop a patient-specific pharmacotherapeutic plan for the treatment and monitoring of Type 2 DM.DRUGS FOR DIABETES MELLITUSPancreas > is a mixed gland . Exocrine portion > releases pancrealipase & chymotrypsin . Endocrine portion > 1 million islets of Langerhan > have at least 4 hormone- producing cellsCell Type A (alpha) B (beta) D (delta) F (PP cell) % islet 20 75 3-5 <2 Hormone glucagon proglucagon insulin pro-insulin somatostatin pancreatic polypeptide (PP)is the storage and anabolic ormone of the body produced by the Beta-cells of the pancreas > principal hormone required for proper glucose use in ormal metabolic processes > previously extracted from beef/pork pancreas > now is produced via recombinant technologyInsulin - Effects 1.It facilitates transport of glucose across cell membrane .In the liver, it promotes glycogenesis and INHIBITS gluconeogenesis 3.1n the muscles, it increases amino acid transport, protein synthesis and glycogenesis 4.In adipose tissues, it increases triglyceride storageMuscle Adipose Glucose uptake and storage increased - glycogen synthesis increased - gluconeogenesis decreased Protein synthesis increased - amino acid transport increased - protein synthesis increased Glycogen synthesis increased - glucose transport increased - glycogen synthase activity increased - phosphorylase activity decreased Triglyceride storage increased - lipoprotein lipase activated - triglyceride hydrolysis increased - glucose transport increased - intracellular lipase inhibitedDIABETES MELLITUS typ: | > diabetes = Greek “siphon” el = honey “something sweet is passing hrough or siphoning from the body” a metabolic disorder in which 1 ine because the kidney tubule cells cannot eabsorb it fast enoughTypes of DM DIABETES MELLITUSinsulin-dependent DM (IDDM) juvenile-onset DM ketosis-prone diabetes most common in children insulin secretion is destroyed dependent upon exogenous insulin sustain life ‘oO The insulin-producing cells are destroyed.> adult-onset DM > not insulin dependent > endogenous insulin levels may appear normal or increased but beta-cell dysfunction is manifested by a relative insulin insufficiency- defined as any degree of glucose intolerance that has its onset during pregnancy GESTATIONAL ee| - broad term used to classify patients who have unusual causes of DM due to certain diseases of the pancreas, endocrinopathies or Secondary DM Socondary causes of Diahetes mellitus include + Acromegaly # Cushing syndrome + Thyrotoxicosis3 Cardinal Signs of DM -Polyuria - i to flush out the glucose and ketones 2. Polydipsia - .Polyphagia - due to inability t to use sugars and the loss of fats and proteins from the bodyCARBOHYDRATES , glucose release rom liver , glycogenolysis t glycogen synthesis tT glycolysis ketogenesisLIPIDS , adipose FFArelease + FFA synthesis PROTEINS aa transport to liver and muscle + protein synthesis Facilitate entry of glucose into cellpreviously extracted pancreas — prcinsuin > now is produced via recombinant — DNA technol > ssn technology —_— tee C peptideInsulin - Indications 1.Diabetes Mellitus ype 1 .Diabetes Mellitus ype 2 that cannot be ontrolled by diet, xercise and oral Raspes hypoglycemic agents CU (OHAs) . Ketoacidosis . Diabetic coma1. RAPID ACTING INSULIN 2.2. DERIVED FROM PIG PANCREAS aa. ILETINIL 2.2. INSULIN ANALOG CREATED BY RDNA. TECHNOLOGY INSULIN ASPART (NOVOLOG) INSULIN GLULISINE (APIDRA) INSULIN LISPRO (HUMALOG) am2. SHORT — ACTING INSULIN Regularinsulinc SO/IV;20 min before meals USES: To prevent Postprandial Hyperglycemia TargetPostprandial Glucose = < 18omh/dL. Target Preprandial Glucose= 90-130 mg/dL. Target HbA2C=<7% Regular Insulin3. INTERMEDIATE ACTING INSULIN 2.1. ADDED WITH PROTAMINE AND ZINC 2.2.1 ISOPHANE INSULIN/NPH. an HUMULINN. ae NOVOLIN N 2.2. WITH DIFFERENT SIZES OF 2.2.1. LENTE INSULIN INSULIN CRYSTAL USES: Insulin basal, insulin secretion DOSE: BID: AM 2/3 of the dose PM 1/3 of the dose Lente Insulin prepared by mixing 30% Semilente & 70% Ultralente Insulin Novos4. LONG ACTING INSULIN InsulinGlargine S0,0D (Lantus®, USES: Provide basal insulin requirement Toujeo®) Insulin Detemir (Levemir®) Insulin Glargine has a characterrelease Insulin pattern that Degludec (Tresiba)® LantusPharmakokinetic Type Ultra apkeucieg Insulin Lispro Rapid acting Insulin injection, USP (Regular, Crystalline) Intermediate acting NPH Insulin (Isophane) Lente Insulin (insulin zine susp) Long acting Ultralente Insulin (Insulin zinc susp extended) Ultra long acting Insulin glargine Species Type Human (Modified) Human, Pork Human, Pork Human, Pork Human Human (Modifie d) Peak 0.25-0.50 0.50-3 No peak Activity in hours Duration 3-4 5-7 18-24 18-24 18-28 >24> given SQ consecreted w/ insulin enhances the effect of insulin > MOA: Analog of amylin activates amylin receptors > CLINICAL USE: Type 1 and type 2 diabetes ISE: risk of hypoglycemis, ausea, modest weight oss Flexible Dosage Features9 seene OTE: can cause weight loss insulin secretion; glucagon secretion; GI motility; Gastric Emptying Time GLP-2 analogue (Glucagon-like peptide-a) Exenatide (Byetta®), Liraglutide (Saxenda®, Victoza®) ADMINISTRATION: Parenteral (SQ) Risk: hypoglycemia MOA: Analog of glucagon-like peptide-1 (GLP-1) activates GLP-2 receptors SE: Gi disturbances, headache, increased risk of pancreatitis1. Insulin secretagogues 3. Alpha-glucosidase Sulfonylureas Meglitinides . Insulin Sensitizers Biguanides - Thiazolidinedione derivatives inhibitors 4. Incretin-acting drugs DPP-4 inhibitor (Dipeptidy| peptidase 4) 5.SGLT2 inhibitors (Sodium glucose co-transporter 2 inhibitors)1. Insulin secretagogues MOA: block outward K+ channel lead to to depolarization of cells to release Insulin Cl: Liver disease, Renal Disease Common SE: Hypoglycemia, Weight Gain Reduce both fasting and post-prandial glucose Should be taken shortly before meals1. Insulin secretagogues ast generation Less Potent, More side effects > Chlorpropamide longest t2/2 SE: Disulfiram-like reaction > Tolbutamide most cardiotoxic > Acetahexamide > Tolazamide safest for elderly ee! 2nd generation More potent, Less side effect > Glibenclamide(Euglucon®) > Glipizide (Minidiab®) Euglucone Eris > Gliclazide (Diamicron®) > Glimepiride (Solosa®)- MOA: increase pancreatic insulin secretion inide = | short duration of action: aoe 1 to 3 hours | CLINICALUSE: Control 2hr post prandial Hyperglycemia | SE: Hypoglycemiai MOA: a.Metformin (Glucophage®) > very > Liver: Decrease the amount of glucose low risk of lacticacidosis 2.Phenformin > high risk of lactic Snide ay eretivae acidosi( out in the market) > Muscles and FatTissue: Increase insulin sensitivity of muscles and adipose tissue > 1st line initial treatment of type 2 DM esp. among obese patients SE: Diarrhea, Weight Loss, Inc. risk of lactic acidosis Cl: Chronic Alcoholics, Renal Failure, Hepatitis; MOA: Regulates gene expression by binding to PPAR-/ > Activate PPAR ( Peroxisome Proliferator-acting receptor) amma SE: Hepatotoxicity, May inc. HDL levels, peripheral edema Rosiglitazone (Avandia®)> risk of cardiovascular mortality Pioglitazone (Actos®) > bladder ‘ancer ! i. «3. Alpha-glucosidase inhibitors > may be given to Type 1 DM patients as a combination therapy with Insulin > MOA: Inhibit intestinal -glucosidases . Inhibit a variety of enzymes present in the brush- border of the mucosa of the wall intestine that are responsible for the breakdown of complex polysaccharides & ucrose into asbsorbable monosaccharides SE: Flatulence, Hepatotoxicity (Acarbose) ADMINISTRATION: After 1st bite of food (must be taken w/ food) ‘Acarbose (Glucobay® Gluconase®) Voglibose (Basen®) Miglitol (Glyset®) Alpha-glucosidase Inhibitors4. Incretin-acting drugs >= OTE: can cause weight loss insulin secretion; glucagon secretion; GI motility; Gastric Emptying Time DPP-s inhibitor (Dipeptidy! peptidase 4) Sitagliptin Januvia®) ; Linagliptin (Trajenta®) Saxagliptin (Onglyza®) ; Alogliptin (Nesina®) ADMINISTRATION: Oral MOA: Inhibitor of the dipeptidyl peptidase-4 (DPP-4) that degrades GLP- 2 and other incretins SE: Similar to GLP-2 mimetics. Rhinitis, upper respiratory infections, rare allergic reactions5- SGLT2 inhibitors Sodium qlucose co-transporter 2 inhibitors Dapagliflozin (Farxiga®) Empagliflozin JJardiance®) Canaglifozin (Invokana®) ADMINISTRATION: Oral MOA: Reduced glucose reabsorption in renal tubules ; increased glucose excretion. SE: Thirst, Increased urination, Increased UTI> useful for reversing mete tects ofan overdose of - blocking agents because of its ability to increase cAMP productionin the heart. > MOA: Activates glucagon receptors > CLINICAL USE/S: . mS 1. Severe hypoglycemia(not responding well to glucose). 2. blocker overdose(by increasing cAMP Levels as it binds fo Glucagons Receptors in the Heart) > SE: GI Disturbances, Hypotension, Flatulence (most> parenteral > useful for reversing the cardiac effects of an overdose of - blocking agents because of its ability to increase cAMP productionin the heart. > MOA: Activates glucagon receptors > CLINICAL USE/S: . mS 1. Severe hypoglycemia(not responding well to glucose). 2. blocker overdose(by increasing cAMP Levels as it binds fo Glucagons Receptors in the Heart) > SE: GI Disturbances, Hypotension, Flatulence (most(&) REFERENCE: Katzung, B. G., & Trevor, A. J. (2020). Basic and Clinical Pharmacology 15e. McGraw-Hill Education / Medical. George Dimitriadis, Panayota Mitrou, Vaia Lambadiari, Eirini Maratou, Sotirios A. Raptis, Insulin effects in muscle and adipose tissue, Diabetes Research and Clinical Practice, Volume 93, Supplement 1, 2011, Pages $52-S59, ISSN 0168-8227, https://doi.org/10.1016/S0168-8227(11)70014-6. Website materials: https://www.mims.com/Philippines https://www.drugs.com/ https://www.medscape.com/Thank you.