Management of Diabetes Flashcards
What the mechanism of action of Sulphonylureas
Binds to sulfonylurea receptors (SUR-1) on functioning pancreatic beta-cells.
Binding closes the linked ATP-sensitive potassium channels
Decreased potassium influx depolarization of the beta-cell membrane.
Voltage-dependent calcium channels open and result in an influx of calcium
Translocation and exocytosis of secretory granules of insulin to the cell surface
How often do you take glimepiride
once daily
What is metformins action
Metformin works by improving insulin action which then lowers blood glucose because the insulin works more effectively
What drug is first line treatment for diabetes
Metformin
What two GLP analogues have cardiovascular benefit
Liraglutide and semaglutide
What are the Dis-advantages of Pioglitazone
Increase risk of bladder cancer - Caution in those of increased risk bladder cancer (Age, industry etc) Fluid retention - CCF Weight gain Fractures in females
What is a THIAZOLIDINEDIONE
Pioglitazone
What is the dose of glimepiride
1-6mg
What is the mechanism of action of Pioglitazone
Selectively stimulates thenuclear receptorperoxisome proliferator-activated receptor gamma (PPAR-gamma) and to a lesser extentPPAR - alpha
Modulates the transcription of theinsulin-sensitive genes involved in the control of glucose andlipid metabolismin themuscle,adipose tissue, and theliver.
Reduces insulin resistancein the liver and peripheral tissues;
increases the expense of insulin-dependent glucose;
Decreases withdrawal of glucose from the liver;
Reduces quantity of glucose, insulin andglycated haemoglobinin the bloodstream.
Are Sulphonylurea’s used as first line treatment?
No - Metformin is
How long does it take for the effect of metformin to start
Effect is quick but usually optimal after 2-3 weeks
What are Dis-advantages of gliflozins
Expensive SE: - UTI, fungal infections, osmotic symptoms Risk of digital amputation Glucoseuria – Gluocse in urine Risk of DKA CI in pregnancy and breastfeeding. Cannot use in renal impairment
Whats the mechanism of action for DPP IV inhibitors
They delay the breakdown of incretins by DPP-4 and thereby increase active incretin levels
What are advantages of Sulphonylureas
Used with metformin Rapid improvement in control Rapid improvement if symptomatic Rapid titration Cheap - Gliclazide 160mg bd £3.30 X1.4 - Glimepiride 6mg od £1.72 x0.7 Generally well tolerated
What are Dis-advantages of GLP analogues
Injection
Expensive
Contra Indicated in pregnancy and breastfeeding.
Nausea, vomiting
Where are Sulphonylureas metabolised
liver
Whats the mechanism of action of GLP-1 Analogues
work similar to bodies normal GLP BUT:
resistant to enzymatic degradation
greatly prolonged biological half-life
How are GLP-1 analogues taken
Most are subcutaneous
What are incretins and what do they do
Incretinsare a group of metabolic hormones that stimulate a decrease in blood glucose levels and are released after eating.
They augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism.
What are the DPP IV-inhibitors
Saxagliptin,
Sitagliptin,
Vildagliptin
Alogliptin
What are the Sulphonylurea
Gliclazide
Glimepiride
Glipizide
What are side effects of GLP-1 analogues
People can get nausea but others can get early satiety (helpful with people who eat lots of shite)
What are dis-advantages of Sulphonylureas
Risk of hypoglycaemia Weight gain Caution in renal and hepatic disease CI in pregnancy and breastfeeding. SE include - Hypersensitivity and photosensitivity reactions - Blood disorders
What does Pioglitazone do
It increases insulin sensitivity and decreases liver production of glucose
What kind of insulins are there
Rapid acting insulins Short acting insulins Intermediatte acting insulins Long acting insulins Combination insulins
What is the dose of gliclazide
40-320mg
What is the SGLT-2 protein
The SGLT-2 protein is responsible for reabsorbing glucose from the urine into the blood in the proximal tubukes of the kindeys
What is the dose of glipizide
2.5-20mg
What are the GLP1 and DPP IV known as
The incretin mimetics
What are advantages of metoformin
Improves cardiovascular outcomes and mortality in obese T2 DM
Efficaceous
Used alone can decrease fasting blood glucose by 22- 26%
Normally well tolerated
Not associated with weight gain
HbA1c by 12 – 17% reduction
Also used in pregnancy now
Cheap
What are advantages of gliflozins
Weight loss No risk of hypoglycaemia Good effects on glycemic control May have beneficial effect on cardiovascular morbidity & mortality 2nd or 3rd line agent Can add to insulin regimens in T2DM
What drug categories are available for diabetes
Metformin Sulphonylureas Thazolidinedione GLP1 DPP IV Gliflozins
What are dis-advantages of metoformin
GI side effects 20 – 30 %
(diarrhoea and abdo pain)
Risk of lactic acidosis by inhibiting lactic acid uptake by liver
Hypoxia
Renal failure (CI if creat<150)
Hepatic failure
Alcohol abuse
Risk vitamin B12 malabsorption
What is the mechanism of action of the gliflozins
SGLT-2 inhibitors. They block the action of SGLT-2 protein and cause glucose to be excreted in the urine – reducing the blood glucose levels
What is GLP
Glucagon-like peptide 1 (GLP-1) is a potent incretin hormone produced in the L-cells of the distal ileum and colon
What are the Gliflozins
Canagliflozin,
Dapagliflozin,
Empagliflozin
What do the Sulphonylurea’s do?
Stimulate insulin release from the pancreas
What are the GLP-1 Analogues
Exenatide,
Liraglutide,
Lixisenatide
What are the advantages of Pioglitazone
Good for people if insulin resistance significant HbA1c by 0.6-1.3% Cheap - Pioglitazone 45mg od £1.50 x 0.6 Cardiovascular safety established (Contrast with rosiglitazone
Whats the advantage of DPP IV-inhibitors
Usually well tolerated Can be used as 2nd or 3rd line agent Can be used in renal impairment No risk of hypoglycaemia Weight neutral
Whats a Biguanide
Biguanideis a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea
What are advantages of GLP analogues
Weight loss No risk of hypoglycaemia 3rd line agent Can be used with basal insulin Some have benefit for CV disease
When do you use insulin injections
Usually used as a last resort when all other non-insulin drugs don’t work.
What is the DPP-4 enzyme
An enzyme that rapidly degrades incretins
What is the dose of glipizide
Twice daily
How often do you take gliclazide
Twice daily
Whats the Dis-advantages of DPP IV-inhibitors
Trial data shows relatively small effects on glycemic control
CI in pregnancy and breastfeeding.
SE:x
- nausea
