[PHT] P.09.02 PANCREATIC HORMONES & ANTI-DIABETIC DRUGS (PART 2).docx copy_compressed.pdf

PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.09.02 PANCREATIC HORMONES & ANTI-DIABETIC DRUGS 1. Insulin secretagogues S/mulates release of endogenous insulin by promo/ng closure of Potassium channels in pancrea/c B-cell Most are in class known as Sulfonylureas (2nd gen: Glipizide, Glimepiride) SE: H...

PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.09.02 PANCREATIC HORMONES & ANTI-DIABETIC DRUGS 1. Insulin secretagogues S/mulates release of endogenous insulin by promo/ng closure of Potassium channels in pancrea/c B-cell Most are in class known as Sulfonylureas (2nd gen: Glipizide, Glimepiride) SE: Hypoglycemia, weight gain, allergic reac/on PHARMACOLOGY LECTURE LECTURER: Dr. Marcelino Salango DATE: February 5, 2024 OUTLINE I. Oral An*diabe*c Agents II. Insulin and Insulin Analogues III. Other An*diabe*c Parenteral Agents IV. Pathophysiology of Diabetes Mellitus NOTE: Weight gain is undesirable in large frac/on of pa/ents with type 2 diabetes who are already overweight I. ORAL ANTIDIABETIC AGENTS à Depending on the dura/on of ac/on and speed of ac/on, the increase of sugar can be controlled. Short ac)ng (eq. sulfonylureas) Fast ac/ng Targets postprandial (a;er meal) Kaya lang pag mul+ple dose mahirap ang compliance ng pa+ent. That lead to crea+on of extended-release para mas mahaba ang dura+on of ac+on. Long ac)ng (eg. Glimepiride, Gliclizide) Targets Fas)ng and postprandial SE: Decrease β-cell func)on → If you have pancreas that is already subjected to a lot of stress kasi mataas ung sugar kay double time trabaho ng pancreas then you give medicine that orders the pancreas to release insulin which is what secretagogues do kaya napapagod. In the end bumababa ung Beta cell function. NON-INSULIN ANTIDIABETIC DRUGS (7) 1. Insulin secretagogues 2. Biguanides (MeHormin) 3. Alpha-glucosidase (Acarbose, Miglitol) 4. Thiazolidinediones (Rosiglitazone, Ploglitazone) 5. Amylin analogs (Pramlintide) 6. Incre/n modulators 7. Sodium-Glucose Transporter 2 / SGLT-2 Control of insulin release from the pancrea2c beta cell by glucose and by sulfonylurea drugs. When the extracellular glucose concentra2on increases, more glucose enters the cell via the GLUT2 glucose transporter and leads, through metabolism, to increased intracellular ATP produc2on with subsequent closure of ATP-dependent K+ channels, membrane depolariza2on, opening of voltage-gated Ca2+channels, increased intracellular Ca2+, and insulin secre2on. Sulfonylurea and other insulin secretagogues enhance insulin release by blocking ATP-dependent K+ channels and thereby triggering the events subsequent to reduced K+ influx. 2. Biguanides (MeHormin) MOA: Ac/vates AMP kinase and reduces hepa/c and renal gluconeogenesis Improve insulin sensi)vity at peripheral level therefore it does not increase weight → Example, in Skeletal muscle increased GLUT 4 (Glucose transporter) Target fas)ng (since no gluconeogenesis) and postprandial(Delayed absorp/on) Mabagal magpababa ng sugar level Considered as Drug of choice specially in overweight pa/ents (T2DM) SE: Lac/c acidosis (Specially in pa/ents with renal or liver disease) (Canaglifozin, Dapaglifozin) N OT E TA K E R : TONY. L.JANELLE.XYRA. JOAN. JUDAH. AFRIL. P a g e 1 | 25 PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.09.02 PANCREATIC HORMONES & ANTI-DIABETIC DRUGS 3. Alpha-glucosidase (Acarbose, Miglitol) Alpha-glucosidases digest carbohydrates therefore inhibi/ng the enzyme will slow down the absorb/on of sugar. So it causes leveling of prandial glucose. Kaya target postprandial Taken just before meal SE: Flatulence STUDY: Blood sugar vs Insulin lvl INCRETIN EFFECT: It describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glucose, in healthy individuals. So pagkatapos kumain mataas sugar ibigay mo ito (or any na good for postprandial) pagka umaga mataas ang sugar magbigay ka ng iba (Drugs lowering Fasting sugar) depende sa gusto mo 4. Thiazolidinediones (Rosiglitazone, Ploglitazone) Increase target /ssue sensi/vity to insulin by ac)va)ng PPAR-γ (Proliferator-ac/vated receptor-gamma nuclear receptor) Also inhibit gluconeogenesis and have effect on lipid metabolism and distribu/on. It has something to do with adipocytes differentiation also, so ang ginagawa nito ginagawa nyang mature agad yung adipocytes kaya di na makadivide kaya di ka na tataba The main effect is not to lower blood sugar but target more on insulin resistant. Efficient using of carbohydrates kaya mas long term Reduce both Fas)ng and postprandial hyperglycemia SE: Edema 5. Amylin analogs (Pramlin/de) Pramlin/de suppresses glucagon release, slows gastric emptying, and works in the CNS to reduce appe/te. Amylin, is a hormone produced by pancrea/c cells, contributes to glycemic control and osteogenesis. Actually, works by inhibiting more insulin release so parang may negative feedback Have a short dura/on of ac/on and is used in combina/on with insulin to control postprandial glucose levels. SE: Hypoglycemia, Amyloid deposits accumula/on (which can lead to autophagy and self-destruct) 6.A. Glucagon-Like Pep)de-1 Analog (Exena/de, liraglu/de, Semaglu/de) GLP-1 receptor is a G-protein-coupled receptor (GPCR) that increases cAMP and also increases the free intracellular concentra/on of calcium. Produced by intestine, and the purpose is to produce satiety and increases B cell sensitivity Magnified yung lakas ng insulin tapos kailangan mas kokonti kailangang insulin STUDY: Everyone produce GLP-1 but the duration of action is only 10min.Pag nagsimula ka kumain maglalabas ka ng GLP-1 and it will last for 10min. For Those with diabetes naglalabas silang GLP-1 pero very short yung duration(