Oral Antidiabetic Agents Flashcards

Question

Cardiovascular effects of GLP-1

Answer 1

HEART - lower inflammation - higher glucose uptake - lower ischemic injury - higher LV function - higher heart rate VASCULATURE - lower inflammation - higher endothelial function - higher vasodilation - higher plaque stability - higher blood flow - lower smooth muscle proliferation - lower platelet aggregation

Answer 2

EXENATIDE - homology: 53 % - T1/2: 2.5 h LIXISENATID - homology: 53 % - T1/2: 3 h - withdrawal LIRAGLUTID - homology: 97 % - T1/2: 24 h DULAGLUTID - homology: recombinant GLP-1 fusionprotein - T1/2: 4.7 d ALBIGLUTID - homology: DPP-IV resistant GLP-1 dimer fused to human albumin - T1/2: 5 d - withdrawal

Answer 3

COMPETITIVE Sitagliptine (Januvia®) Vildagliptine (Galvus®, withdrawn 2014) Linagliptine (Trajenta®, not available) NON COMPETITIVE Saxagliptine (Onglyza®)

Answer 4

* cold,diarrhoea,pharyngitis,headache,arthralgia * insomecasesaftermarketrelease:anaphylaxis,angioedemaandskinirritation. * Lessselectivity? – Beside GLP-1 and GIP other substrates (e.g. PACAP, trypsinogen, procolipase, somatoliberin, GLP-2, NPY) also contain a proline residue at the correct position enabling these peptides for DPP-4 degradation. The consequences of a reduced metabolism of these peptides is not known. – DPP-4 inhibitors also block DPP-8 and DPP-9. The clinical relevance of blocking DPP-8/-9 is not known. – DPP-4 is also involved in regulation of other biological functions (e.g. immune reactions, cell adhesion). Considering the presence of DPP-4 in various cell types and also in blood cells, GLP-1 independent effects are assumed to be of clinical relevance.

Answer 5

When SGLT1 is blocked, more glucose remains in the lumen of the intestine being eliminated. Plasma glucose is indeed reduced, but higher GUT levels induced GUT related adverse effects (diarrhea). When SGLT 2 is blocked, more glucose will be renally eliminated. This indeed decreases blood glucose but also induce caloric loss and reduction of blood pressure (by osmotic diuresis). Both effects are beneficial. In Germany, Canagliflozin is withdrawn (2014).

Answer 6

- but SGLT 2 is mainly (90%) responsible for renal glucose reabsorption - However, using SGLT-2 knock out mice, glucose reabsorption was 40 %, thus indicating that the impact of SGLT-1 for glucose reabsorption is more than 10%. These results suggest that the contribution of SGLT1 to renal glucose reabsorption is greater under lower glycemic conditions than under hyperglycemic conditions. - These results suggest that SGLT2-selective inhibitors pose a lower risk of hypoglycemia than SGLT1/2 inhibitors.

Answer 7

The U.S. Food and Drug Administration (FDA) has strengthened the existing warning about the risk of acute kidney injury for the type 2 diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). Based on recent reports, we have revised the warnings in the drug labels to include information about acute kidney injury and added recommendations to minimize this risk. From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases* of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use (see Data Summary). This number includes only reports submitted to FDA, so there are likely additional cases about which we are unaware. In approximately half of the cases, the events of acute kidney injury occurred within 1 month of starting the drug, and most patients improved after stopping it. Some cases occurred in patients who were younger than 65 years. Some patients were dehydrated, had low blood pressure, or were taking other medicines that can affect the kidneys. We urge health care professionals and patients to report side effects involving canagliflozin, dapagliflozin, or other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

Answer 8

- SGLT-2 inhibition reduces hyperfiltration via TGF

Answer 9

Case reports have suggested that SGLT2 inhibitors may be associated with an increased risk of diabetic ketoacidosis, which led to a warning from the FDA in May 2015. The objective of our study was to assess the risk of diabetic ketoacidosis after the initiation of an SGLT2 inhibitor. In conclusion, shortly after initiation, SGLT2 inhibitors were associated with approximately twice the risk of diabetic ketoacidosis as were DPP4 inhibitors, although cases of diabetic ketoacidosis leading to hospitalization were infrequent. The increased risk of diabetic ketoacidosis with SGLT2 inhibitors is among the factors to be considered at the time of prescribing and throughout therapy if patients present with symptoms suggestive of diabetic ketoacidosis. Leber: higher Ketogenesis Niere: higher Glucosuria

Oral Antidiabetic Agents Flashcards

(33 cards)