New Diabetic Drugs for diabetes Flashcards
How do you manage hyperglycaemia conservatively. (2)
Diet.
Exercise.
How do you manage hyperglycaemia medically. (6)
Biguanide. Sulphonylureas. Insulin sensitisers (thiozolidinediones) Insulin. Incretins. Gliptins.
Give an example of a biguanide.
Metformin.
Give and example of a sulphonylurea.
Gliclazide.
Give an example of a thiozolidinediones.
Rosiglitazone.
Pioglitazone.
Give an example of an incretin.
GLP-1
Give an example of a gliptin.
Dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors)
How do you use insulin in diabetes. (2)
Long acting (depot) insulin. (eg insulin zinc suspension). Short acting (eg normal soluble insulin) with each meal.
Give two examples of short acting insulins.
Insulatard.
Actrapid.
What problem is there with administering soluble natural insulin to diabetics.
When soluble natural insulin is given subcutaneously, it forms a hexamer under the skin, delaying release.
What must you do if you are using soluble natural insulin as a short acting insulin.
Inject it 30mins before a meal.
What are two examples of insulin analogues.
Lispro.
Aspart.
How does lispro differ from natural insulin.
It replaces a proline with a lysine at position 28
How does aspart differ from natural insulin.
It replaces the proline to aspartate at position 28
What benefit is there to using lispro or aspart instead of natural insulin before means.
They are very fast acting, so the patient can eat immediately after injecting.
What is the purpose of long acting insulin analogues.
Different alterations in the insulin molecule to try and attain a plateau like concentration over time.
What is insulin glargine.
A long acting insulin that seems to give the least variation in plasma insulin levels for 24h after injection.
How many insulin gargine injections do you need/day.
One per 24h period.
What is the structure of insulin detemir.
14C fatty acid chain attached to B29.
How long does it take for the effects of insulin detemir to come on.
It has a delayed onset of 7h.
What are the main advantages of using insulin to control DM.
Can give the best control of HbA1c when combined with diet and exercise.
No side effects compared to the others.
What is a side effect of metformin.
Diarrhoea.
What are the side effects of thiozolidinediones. (2)
Rarely hepatic.
Osteoporosis.
Which thiozolidinediones has been withdrawn from the market. Why.
Rosiglitazone has been withdrawn from the market over a link to fluid retention and increased risk of heart failure.
What are the disadvantages of insulin. (5)
If you drive HGM, you cannot work.
Hypoglycaemia common even with good control.
Weight gain common.
Huge doses required.
Which insulin is exempt from not allowing you to work with HGM.
Exenatide.
Why do you gain weight with insulin treatment.
Glycosuria is stopped, saving many calories.
Increasing your appetite, and improving your well being.
Where is GLP-1 and GIP released from.
GI tract.
What two hormones does the pancreas release.
Insulin.
Glucagon.
What cells release insulin.
Beta cells in the pancreas.
What cells release glucagon.
Alpha cells in the pancreas.
What effect does GLP-1 and GIP have on the pancreas (2)
Decrease glucagon.
Increases insulin.
Insulin ______ peripheral glucose uptake.
Increases.
Increased insulin and ______glucagon ______hepatic glucose output.
Decreased.
Reduce.
What is the incretin effefct.
You get a much more intense insulin response if you administer glucose orally, than if you administer it intravenously.
What effects (besides insulin control) does GLP-1 have. (2)
Reduces gastric emptying.
Increases hypothalamic satiety.
What is interesting about the venom produced by the gila monster.
It produces a venom called exendin 4, which is very similar to GLP-1 (an incretin!)
What venom is produced by the gila monster.
Exendin 4.
What is the difference between endogenous GLP-1 and exendin 4 from gila monsters.
Exendin 4 is similar in structure to GLP-1, but has a longer half life.
What is exenatide a synthetic version of.
Exendin 4.
What is the main function of exenatide. (4)
To increase hypothalamic satiety.
Stimulates insulin secretion.
Slows gastric emptying.
Inhibits insulin production by the liver.
What is the action of the DPP-4 enzyme.
To rapidly degrade incretins.
Give two examples of gliptins.
Vildagliptin.
Sitagliptin.
Where is the SGLT2 and SGLT1 cotransporter located.
In the proximal tubule of the kidney nephron.
What is the function of SGLT1/2.
To reabsorb glucose in the proximal tubule of the kidney.
What volume of plasma is filtered by the kidney in a day.
180L
What volume of glucose is filtered by the kidney in a day.
180g
How much glucose is reabsorbed by the kidney every day.
160-180g
How much glucose is excreted by the kidney every day.
Minimal.
What is the renal threshold.
It is the ‘tipping point’ at which the reabsorptive capacity of SGLT2 is exceeded, and urinary glucose excretion in increased.
What happens to SGLT2 in T2DM.
Increased expression, causing more absorption of glucose.
What happens to the adaptive increase in renal threshold in response to hyperglycaemia in T2DM.
It becomes maladaptive, reinforcing raised glucose levels.
What is the renal threshold increased to in people with T2DM.
14mmol/L
What is the purpose of an SGLT2 inhibitor in treating T2DM.
It lowers the inappropriately elevated renal threshold for glucose in T2DM, increasing glucose excretion.
Give an example of an SGLT2 inhibitor.
Canagliflozin.
What are some common side effects of canagliflozin (>1% (8)
Constipation. Thirst. Nausea. Polyuria (increased volume) or pollakiuria (increased frequency). UTIs. Balanitis or balanoposthitis. Increased haematocrit.
What are some very common side effects of canagliflozin. (>10%) (2)
Hypoglycaemia when used in combination with insulin or sulphonylurea. Vulvovaginal candidiasis (thrush).
