1. Diabetes mellitus is a metabolic disorder caused by a combination of genetic and environmental factors. It is classified as type 1 characterized by a lack of insulin production, and type 2 characterized by insulin resistance. Signs and symptoms include increased thirst, fatigue, frequent urination, hunger, and high blood glucose levels.
2. Treatment for diabetes includes lifestyle changes, medications, and insulin injections depending on the type. Insulin is essential for type 1 diabetes treatment, while type 2 may be treated initially through diet, exercise and oral medications to boost insulin secretion, increase insulin sensitivity, decrease glucose absorption, or provide insulin for severe cases.
3. Common oral medications include sulfonylureas to stimulate insulin secretion
1. Diabetes mellitus is a metabolic disorder caused by a combination of genetic and environmental factors. It is classified as type 1 characterized by a lack of insulin production, and type 2 characterized by insulin resistance. Signs and symptoms include increased thirst, fatigue, frequent urination, hunger, and high blood glucose levels.
2. Treatment for diabetes includes lifestyle changes, medications, and insulin injections depending on the type. Insulin is essential for type 1 diabetes treatment, while type 2 may be treated initially through diet, exercise and oral medications to boost insulin secretion, increase insulin sensitivity, decrease glucose absorption, or provide insulin for severe cases.
3. Common oral medications include sulfonylureas to stimulate insulin secretion
1. Diabetes mellitus is a metabolic disorder caused by a combination of genetic and environmental factors. It is classified as type 1 characterized by a lack of insulin production, and type 2 characterized by insulin resistance. Signs and symptoms include increased thirst, fatigue, frequent urination, hunger, and high blood glucose levels.
2. Treatment for diabetes includes lifestyle changes, medications, and insulin injections depending on the type. Insulin is essential for type 1 diabetes treatment, while type 2 may be treated initially through diet, exercise and oral medications to boost insulin secretion, increase insulin sensitivity, decrease glucose absorption, or provide insulin for severe cases.
3. Common oral medications include sulfonylureas to stimulate insulin secretion
1. Diabetes mellitus is a metabolic disorder caused by a combination of genetic and environmental factors. It is classified as type 1 characterized by a lack of insulin production, and type 2 characterized by insulin resistance. Signs and symptoms include increased thirst, fatigue, frequent urination, hunger, and high blood glucose levels.
2. Treatment for diabetes includes lifestyle changes, medications, and insulin injections depending on the type. Insulin is essential for type 1 diabetes treatment, while type 2 may be treated initially through diet, exercise and oral medications to boost insulin secretion, increase insulin sensitivity, decrease glucose absorption, or provide insulin for severe cases.
3. Common oral medications include sulfonylureas to stimulate insulin secretion
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Insulin & Oral Antidiabetic Drugs
Diabetes mellitus Definition: a syndrome of disordered metabolism due to a combination of hereditary and environmental causes. Classification: Type 1: Lack of insulin. Type 2: Cells resistance to insulin Signs & symptoms: Very thirsty Feeling tired Using the toilet often to urinate Constant hunger High level of glucose in urine & in fasting blood 2 Harms (complications) Acute Diabetic ketoacidosis (DKA) Nonketotic hyperosmolar coma Chronic Microvascular disease: impotence & poor wound healing Atherosclerosis : Strokes, coronary heart disease Renal failure, retinal damage, nerve damage Infective disease: Tuberculosis 3 Treatment Type 1: Insulin must be injected or inhaled Type 2: Food control, exercise, medicines (1) agents which increase insulin secretion; (2) agents which increase the sensitivity of target organs to insulin; (3) agents which decrease glucose absorption (4) Insulin needed for patients with serious complications or an emergency. 4 Section 1 Insulin Chemistry: 51 aa arranged in two chains (A & B) linked by disulfide bridges. Secretion: By cells in pancreatic islet. Degradation: Liver & kidney Endogenous: Liver (60 %) & kidney (35 %-40 %) Exogenous: Liver (35 %-40 %) & kidney (60 %) T1/2 in plasma: 3-5 min 5 6 Physiological & pharmacological actions 1. Sugar metabolism: Stimulates glucose uptake & use by cells; inhibits gluconeogenesis blood sugar 2. Fatty metabolism: Improves fatty acid transportation & fat anabolism; inhibits fat catabolism & fatty acid and acetone body generation 3. Protein metabolism: Improves aa transportation & protein anabolism; inhibits protein catabolism & aa utilization in liver 7 8 Physiological & pharmacological actions 4. Potassium : Stimulates K + entering cellsblood K +
5. Long-term action: Improves or inhibits the synthesis of some enzymes. Mechanism of its action Insulin receptor in cell membrane mediates the effect; Insulin receptor is consisted by 2subunits, which constitutes the recognition site, and 2 subunits, which contains a tyrosine kinase 9 Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6). 10 Sources of exogenous insulin Bovine & porcine insulin Human insulin by replacement of porcine insulin 30- alanine in B chain by threonine Recombinant human insulin by Escherichia coli Clinical use 1. Diabetes mellitus The only effective drug for type 1 diabetes The following situations of type 2 diabetes (1) Not effectively controlled by food limitation & oral antidiabetic drugs; 11 (2) Accompanies DKA & nonketotic hyperosmolar hyperglycemia coma; (3) Accompanies serious infection, hyperpyrexia, injury, gestation and consumptive diseases. 2. Others Hyperkalemia A component of GIK solution which is for limiting myocardial infarction & arrhythmias 12 Adverse reactions 1. Insulin allergy: itching, redness, swelling, anaphylaxis shock 2. Insulin resistance 3. Hypoglycemia: nausea, hungry, tachycardia, sweating, and tremulousness. First aids needed while convulsions & coma happens 4. Lipodystrophy at injection sites: atrophy 13 Duration Insulin Path Times on action (h) Given time start peak duration Short Regular i.v St! 0.5 2 Cito! (DKA and etc.). i.h 0.5~1 2~3 6~8 0.5 h, a.c., t.i.d. or q.i.d. Medium Isophane i.h 2~4 8~12 18~24 1 h, a.c., q.d. or b.i.d. Globin zinc i.h 2~4 6~10 12~18 Long Protamine zinc i.h 3~6 16~1 8 24~36 1 h, a.c., q.d. Insulin preparations and administration 14 Section 2 Oral Antidiabetic Drugs Classification Sulfonylureas Thiazolidinediones Biguanides -glucosidase inhibitors Meglitinides 15 . Sulfonylureas Representative Drugs 1st generation: tolbutamide chlorpropamide tolazamide 2nd generation: glybenclamide glyburide glipizide glymepride 3rd generation: glyclazipe 16 Pharmacological effects 1. Hypoglycemic effect 2. Antidiuretic effect chlorpropamide & glybenclamide 3. Antiplatelete-aggregation effect glyclazipe 17 Hypoglycemic mechanism 1. Rapid mechanism: stimulation of insulin secretion Sulfonylurea receptor in -cell membrane activated ATP-sensitive K + -channel inhibited Cellular membrane depolarized Ca 2+ entry via voltage-dependent Ca 2+ channel Insulin release 2. Long term profit involved mechanism Inhibition of glucagon secretion by pancreas cells; Ameliorating insulin resistance Increase insulin receptor number & the affinity to insulin 18 Clinical use 1. Type 2 diabetes mellitus 2. Diabetes insipidus: chlorpropamide Adverse reactions 1. Gastrointestinal disorders 2. Allergy 3. Hypoglycemia Chlorpropamide forbidden for ageds & patients with functional disorder in liver or kidney. 4. Granulocytopenia, cholestasis & hepatic injury 19 . Thiazolidinediones (Tzds) Representative Drugs rosiglitazone troglitazone pioglitazone ciglitazone Pharmacological effects Improving function of pancreas cells Ameliorating insulin resistance Ameliorating fat metabolic disorder Preventing and treating type 2 diabetes mellitus and their cardiovascular complications 20 Mechanism (possible) Peroxisome proliferator-activated receptor-(PPAR-) activated Nuclear genes involved in glucose & lipid metabolism and adipocyte differentiation activated Clinical use Insulin resistance & type 2 diabetes mellitus Adverse reactions Troglitazone occasionally induces hepatic injury 21 . Biguanides Representative Drugs phenformin metformin Key points insulin secretion unchanged, and appetite unchanged Hypoglycemic mechanism remains unclear Use for obese diabetes and type 2 diabetes Alone or co-administered with insulin or Sulfonylureas Metformin also used to treat atherosclerosis for down- regulation of LDL& VLDL Ketonemia & lactic acidosis are major adverse reactions 22 . -glucosidase inhibitors Representative Drugs acarbose voglibose miglitol Key points To inhibit digestion of starch & disaccharides via competitively inhibiting intestinal -glucosidase (sucrase, maltase, glycoamylase, dextranase) Used alone or together with sulfonylureas to treat type 2 diabetes Main adverse reaction: flatulence, diarrhea, bellyache. Patients with inflammatory bowel disease & kidney impaired forbidden. 23 . Meglitinides Representative Drugs Repaglinide Key point To increase insulin release by inhibiting ATP- sensitive K + -channel Unlike sulfonylureas, they have no direct effect on insulin release Used alone or together with biguanides to treat type 2 diabetes Carefully used for patients with kidney or liver impaired. 24 Michigan lake 2007.5 Thank you!