Oral Treatment for Type 2 Diabetes Mellitus
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45 terms
Terms | Definitions |
|---|---|
 What are the Sulfonylureas? | Generic - Brand Acetohexamide - Dymelor CHlorproamide - Diabinese Tolazamide - Tolinase Tolbutamide - Orinase Glipizide - Gluctrol Glipizide - Glucotrol XL Glyburide micronized - DiaBeta Micronase Glynase Glimepiride - Amaryl |
| What are the short acting insulin secretagogues? | Generic - Brand Nateglinide - Starlix Repaglinide - Prandin |
| What are the Biguanides? | Generic- Brand Biguanides - Glucophage Metformin Extended- Release -- Glucophage XR |
| What are the Thiazolidinediones? | Generic - Brand Pioglitazone - Actos Rosiglitazone - Avandia |
| WHat are the Alpha- FLucose inhibitors? | Generic - Brand Acarbose - precose Miglitol - Glyset |
| What are the Dipeptidyl peptidase-IV inhibitors (DDPIV inhibitors)? | Generic - Brand Sitagliptin - Januvia |
| What are the combination products? | Glyburide/Metformin Glipidzide/Metformin Rosiglitazone/metformin Rosiglitazone/glimepiride Pioglitazone/Metformin Pioglitazone/Glimepiride Stiagliptin/ Metformin |
| What are the Agents of Sulfonylurea? | Tolbutamide Chlorpropramide GLyburide Glipizide Glimerpiride |
| What is the MOA of Sulfonylurea? | interact with ATP-sensitive K channels in beta cell membrane to increase insulin secretion. Binds to receptor associated with ATP-sensitive K+ channel; dec K+ conductance; membrane depolarization inc Ca influx; inc insulin release extrapancreatic mechanism: inc insulin receptor number; dec hepatic gluconeogenesis stimulate synthesis of glucose transporter proteins |
| What are the characteristics of Sulfonylurea? | need functioning beta cells ---> less effective with time as beta cells decrease in number advantage: less expensive than newer agents 1st and 2nd generation agents: equal efficacy, differ duation and dosage |
| What are the unwanted effects of Sulfonylurea? | hypoglycemia (esp. elderly with impaired renal or hepatic function): glyburide, chlorpropramide >> glipizide, glimepiride >> tolbutamide weight gain GI upste CV complications (tolbutamide) Inc CV death: 1st generation > glyburide > metformin |
| What are the Non-Sulfonylurea secretagogue? (meglitinides) | Repaglinide (Pranidin) Nateglinide (Starlix) |
| What is the PK/PD of Non-Sulfonylurea Secretagogue? | rapidly absorbed peak insulin at 30-60 minutes faster acting than SU duration : 4-6 hours administer before meals only: need to eat soon after |
| What is the MOA of non-sulfonylurea? | same as SU but no sulfur structure - block SU receptor on K ATP channels in pancreatic beta cells (somwewhat selective for beta cells vs. vascular smooth msucle and heart) reduce glucose inc glycogen, fat and protein formation gene regulaton |
| What are the side effects of Non-Sulfonylurea? | less hypoglycemia than SU also have initial weight gain expensive |
| What is the drug of Biguainde? | Metformin (glucophage) |
| What is the PK/PD of Metformin? | excreted unchanged in urine ---> so good renal function is needed half life ~ 3 hours available as extended release from glucophage XR; glumetza 1/3 patients experience treatment failure after average time of 1.5 years |
| What is the MOA of biguanide? | dec hepatic glucose production improves insulin's ability to move glucose into cells dec instetinal glucose absorption - minot inc peripheral glucose utilization - minor reduce blood glucose levels by 20% alone and boost glucose - lowering effects of SU, etc by additional 25% |
| What is unique of Metformin | no increased insulin secretion do not require beta cell function but require insulin for effectiveness ---> no risk for hypoglycemia (sometimes referred to as a euglycemic agent or an antihyperglyemic agent or an antihyperglycemic agent no weight gain (may with weight loss) advantage in obese patients as effective as SUs; inexpensive recommended first line therapy by ADA |
| What are the side effects of Metformin? | mainly GI rare: lactic acidosis CI: renal-impaired patients use with caution in elderly over 80 years; conditions predisposing to tissue anoxia |
| What are the drugs of the Thiazolidinediones (insulin sensitizer)? | Pioglitazone Rosiglitazone |
| What is the PK/PD of Thiazolidinediones? | reduce insulin resistance (often used in obsese patients); no increased insulin release: increase cell sensitivity to insulin; activate nuclear protein in adipose tissue (mainly, but also in muscle and liver) TZDs are ligands of PPAR gamma (peroxisome proliferator-activator receptor gamma) - inc expression of genes for transporter proteins that move glucose into cells inresposne to insulin and also inc fatty acid uptake -PPARgamma: predominantly in adipose tissue, kidney, liver, and small intestine (limited expression in muscle) ---> regulate adipocyte differentiation and insulin sensitization |
| What are the side effects of Thiazolidinediones? | fluid retention may lead to adverse CV events such as HF ---> CI in HF edema seen in 4-6%: more frequent when combined with insulin or insulin secretatgogues Weight gain: 2-10 pounds in 6-12 months; perhaps from fluid retention; due to sodium ion reabsorption in renal collecting ducts low risk for heaptoxicity but FDA requires liver function blood testing for year absorption inhibited by colestipol ---> so do not take at the same time |
| What are alpha-glucosidase inhibitors? | acarbose miglitol |
| What is the PK/pD of Acarbose? | binding affinity for the alpha-glucosidase enzymes is: glycoamylase > sucrase > maltase > dextraase no affinity for the beta-glucosidase enzymes, such as lactase |
| What is PK/PD of Miglitol? | more potent inhibitor of sucrase and maltase than acarbose smaller molecule than acarbose |
| What is the MOA of PK/PD of Miglitol? | comeptitive and reversible inhibitor inhibit alpha glucosidase enzymes, lining border of small intestine interfere with hydrolysis/digestion of complex polysaccharides and sucrose inhibits glucoamulase, sucrase, and maltase delays digestion and absoprtion of sucrose and complex carbohydrates ---> results in dec glucose absorption Main effect: dec postprandial hyperglycemia ---> must be taken with each meal; not effective at other times |
| What is the combination therapy? | TZD and SU - direclty improve in insulin sensitivity (muscle and adipose tissue) and improved estimation of beta-cell function (pancreas beta cells) + inc insulin secretion from functioning pancreatic beta cells to increase plasma insulin levels (pancrease) ---> dec plasma glucose TZD and metformin: direct improve in insulin sensitivity (muscle and adipose tissue) and improved estimation of beta cell function (pancrease beta cells) and dec hepatic glucose and output and dec intestinal absorption of gluocse and increase peripheral glucose uptake and utilization (liver) ---> dec plasma glucose |
| What is the drug for amylin analgoues? | pramlintide (symlin) |
| What is the clincial use of Pramlintide? | ...subQ administration, onlu used with insulin, inject immediately before eating administered in addition to insulin for better glucose control used in type 1 and in insulin-requiring type 2 diabetes |
| What is the mecahsnim of action of Pramlintide | bind to amylin receptors suppresses glucagon release delays gastric emptying suppress appetitive via CNS induces weight loss dec postprandial glucose level |
| What are the side effects of Pramlintide? | hypoglycemia -- significant --> should dec rapi/short- acitng insulin doses by 30 -50 % GI: N/V and anorexia |
| What is the drug of GLIP-1 analog class? | Exenatide (Byetta) |
| What is the PK/PD of Exenatide (Byetta)? | injectable, adjunctive therapy to improve glycemic control in type 2 diabetes taking TZDs, metformin, a SU or met/SU Administer within 60 minutes before am and pm meals absorbedly quickly from injection site, reach peak at 2 hours, duration for 10 hours longer duration of action and same effects as GLP-1; same affinity for GLP-1 receptor sites not metabolized eliminated by renal excretion |
| What is the MOA of Exenatide (Byetta)? | inc glucose dependent insulin secretion, acts only in the presence of hyperglycemia As blood glucose approaches normal, insulin secretion decreases ---> low risk of hypoglycemia inc insulin release: inc cAMP and Ca_@ influx into beta cell ---> trigger insulin granule exocytosis suppress glucagon secretion ---> dec hepatic glucose putput inc glucose tolerance, dec A1c slow gastric emptying _--> dec food intake dec body weight (lose average of 5 pounds in 26 week study) |
| What are the characteristics of Exenatide (Byetta)? | made from saliva of glial monster may prserve some beta cell function and increase beta cell mass |
| What are the SI of Exenatide (Byetta)/ | GI - nauseau hypoglycemia new FDA warning - acute pancreatitis... |
| What are the drugs of the Dipeptidyl peptidase inhibitors (DDP-4)? | sitagliptin (Januvia) Saxagliptin (onglyza) |
| What is the use of PK/PD of DDP-4 inhibitors? | clinical use: monotherapy or in combination with metformin or TZDs in type 2 diabetes; not sued in type 1 diabetes Saxagliptin: same mechanism as sitagliptin: metabolzied by CYP3A4 side effects: URI |
| What is the MOA of DDP-4 inhibitors? | competitive, reversible DPP-4 inhibitor blocks degradation of GLP-1, inc GLP-1 levels DDP-4 : proline peptidase Sitaglipitn binds pocket of active sites inc insulin production/release; dec glucagon in a glucose dependent way ---> No hypoglycemia may improve beta cell function (cell mass) |
| What are the characteristics of DDP-4 inhibitors? | DDP-4 activity inhibited by > 80% for 24 hours with 100 mg dose by oral: DDP-4 inhibits 50% of GLP-1 within 2 minutesl GLP-1 plasma levels increased 2-fold |
| What are the SE of DDP-4 (Sitaglipitn/Saxagliptin)? | mostly well tolerated no hypoglycemia no effect on food intake body weight neutral minimal GI problems expensive New FDA warning: severe allergic and dermatologic /hypersensitivity reactions; ananphylaxis; angioedema; exfoliative skin conditions including SJS; onset within 3 months; some after first dose; Merck indicates no known frequency |
| What are Incretins? | INtestinal seCRETion of INsulin hormones. INcretins : naturally occurring gut hormones secreted rapidly from intestines in response to food in a glucose-dependent manner |
| What is GLP-1? | glucose like peptide 1 secreted from L cells in small intestein/colon GIP -glucose dependent insulinotropic polypeptide secreted from K cells in small intestine. |
| What is the effect of GIP/GLP-1? | stimulate insulin synthesis and release, help modulate pancreatic islet cell secretions glucose dependent insulin release - higher glucose ---> more insulin release elicitis greater insulin release when glucose is administered orally vs intravenously rapidly degraded by DDP-IV (>80% of pool) require continuous subcutaneous infusion ---> limited used. |
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