SGLT2 Inhibitors

BT_PO 1.90

You will be familiar with the college warning on SGLT2 inhibitors.  Whilst these drugs do appear in the referenced texts, the risk of ketoacidosis is not discussed. These drugs will become more frequently used because they been shown to decrease diabetic nephropathy, cardiac failure and mortality.

Adopting, therefore, the heretical view that the function of the primary is to teach useful pharmacology, I would suggest this review article by Milder et al would be a valuable addition to your reading.

SGLT2 inhibitors

T/F primarily work by reducing glucose uptake from the small intestine

T/F increase the risk of urinary tract infection

T/F have half lives of around 4 hours

T/F are rarely associated with ketoacidosis in type 1 diabetes

T/F rarely cause ketoacidosis at blood glucose levels less than 18mmol/L

BT PO 1.90 Outline the pharmacology of oral hypoglycaemic agents

Previous posts have addressed insulin preparations, glucagon, corticosteroids and DDAVP so we should complete the diabetic pharmacopeia and consider oral hypogylcaemic agents and parenteral agents other than insulin. Although not a core topic for the primary, knowledge about these drugs is vital with regards to managing them appropriately in the perioperative period.

Having just completed revising the perioperative diabetic medication management guidelines in my hospital I am currently at the peak of my powers with regards to knowledge of these medications. (A similar comment could be made about my knowledge of most things physiological and pharmacological in the week prior to my primary exam…) There’s an awful lot of medications on the market and many of them have been relatively recently added- MIMS has over seventy drug preparations listed.  As an aside I predominantly used the 2015 UK Guideline which is very good and you may be surprised re how many of the agents they recommend to continue to take on the day of surgery including our good friend metformin. This guideline precedes the recent alert by our College regarding SGLT-2 transport inhibitors and euglycaemic ketoacidosis. The recommendation is for this particular class of agents to be withheld THREE days prior to surgery.

The answers to the questions below can be found in Stoelting, a book that I quite like in its current incarnation. (Although it has nothing about SGLT-2 inhibitors in it!)

Lactic acidosis is a common problem seen with metformin use in the perioperative period.  T/F

Acarbose (Glucobay) is a alpha-glucosidase inhibitor.   T/F

Glucagon-Like-Peptide 1 agonists are injected subcutaneously like insulin*.  T/F

Dipeptidyl-Peptidase-4 inhibitors increase insulin secretion and decrease glucagon secretion.  T/F

Rosiglitazone can cause a transaminitis.  T/F

*I may have given you a clue about this one already

Rank the following agents in order from most likely to least likely in terms of causing hypoglycaemia if taken while fasting. To ‘help’ you out I will even tell you the drug class each agent is from.

Exenatide (GLP-1 agonist)

Sitagliptin (DPP-4 inhibitor)

Glipizide (sulfonylurea)

Repaglinide (meglitinide)

Some cool trivia: Exenatide is derived from a hormone found in Gila monster lizard saliva!

DDAVP

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The structure of DDAVP (Desmopressin) is shown below. Candidates who can reproduce this structure in the exam should have spent their time studying something more useful.

 

T/F Whilst usually used in Von Willebrand’s Disease, desmopressin is effective at reducing perioperative bleeding in most cases of massive blood loss

T/F After intravenous bolus peak levels of factor VIII and vWF occur between 3 and 6 hours

T/F The effect of demopressin on platelet function lasts for about twenty four hours

T/F Desmopressin reduces the risk of thrombosis in patients with type 2B Von Willibrand’s Disease

T/F Rapid administration of desmopressin intravenously may cause hypotension.