New diabetic drugs Flashcards
Which drugs are used in management of hyperglycaemia
Diet and exercise
Biguanide (Metformin)
Sulphonylureas (eg gliclazide)
Insulin sensitisers : thiozolidinediones such as rosiglitazone or pioglitazone
Insulin itself (there are several new insulin analogues now available)
I
ncretins (GLP-1 analogues)
Gliptins (Dipeptidyl peptidase 4 inhibitors).
T/F Insulin is a useful treatment in T2DM
T
Insulin is an excellent treatment, even for patients who are not dependent on it (NIDDM)
What is the treatment regime for those using insulin in T2DM
Patients need a long acting (depot) insulin
Together with a short acting insulin such as normal soluble insulin with each meal
Give an example of long acting and short acting insulin
Long: insulin Zinc suspension and glargine (lantus)
Short: “Insulatard” and “Actrapid”
What is the problem with insulin use in T2DM
When soluble natural insulin is given subcutaneously, it forms a hexamer under the skin
This delays release
so people must
“Inject 30 mins before meals”.
How can the issue of having to inject insulin 30 minutes before meals be overcome
You can use insulin analogues.
Lispro switch of B28 (Pro)/B29 (Lys)
Aspart switch (Pro 28) to Asp (28)
These analogues are very rapid acting and mean that patients can inject and eat.
How are the benefits and disadvantage of short actin insulin analogues compared with insuln
:D Gives patients a licence to inject immediately before meals (many patients were injecting immediately before the meal when on the old insulins anyway, despite them needing 30 minutes to work)
:D Profile more closely mimics insulin profile following a meal.
:C Twice the cost of soluble insulin
How are long acting insulin analogues used
Different alterations in the molecule to try and attain a plateau like concentration over time.
What is glargine
A long acting insulin that seems to give the least variation in plasma insulin levels for 24 h after injection.
Previous long acting insulins were Zn suspensions of insulin. Efficacy slowly waned over 24 h.
How is the molecular structure of glargine changed compared to insulin
A21 (Asn to Gly)
B31, B32 Arg
Advantage and disadvantage of insulin glargine
Main advance is that this once daily insulin injection improves quality of life as there lower risk of hypoglycaemia.
Gives background concentration of insulin.
Normal pancreas makes continuous secretion of insulin.
What is detemir
14 carbon fatty acid chain attached to B29.
Delayed onset 7h
Can be used as part of basal bolus.
What are the advantages of insulin
Can give best control of HbA1c when combined with diet and exercise.
No side effects compared to metformin, SU, thiazolidinediones
What are the side effects associated with the following diabetic drugs:
metformin,
SU,
thiazolidinediones
metformin (diarrhoea)
SU (occasional reactions)
thiazolidinediones (rare hepatic, ?osteoporosis)
Which thiazolidinedione has been withdrawn and which is still used?
out of: Rosiglitazone and Pioglitazone
Rosiglitazone is withdrawn, Pioglitazone still in use
Why was Rosiglitazone withdrawn
Over heart fears (linked to fluid retention and increased risk of heart failure)
Disadvantage of insulin
Hypos, weight gain, increases hunger, If you drive HGV, cannot work, Increased insulin as a consequence
Huge doses required
Why does one gain weight with insulin
Poor control enables one to lose weight.
If glycosuria stops, many calories saved.
Increased appetite
Improved well being
Set point of body weight (hypothalamic)
What is GLP-1 and what are the physiological actions
GLP-1 is secreted from the gut, and signals the pancreas to make even more insulin.
Also directly affects appetite and gastric emptying
Give an example of a GLP-1 analogue
Exanatide
How do incretins work
Ingestion of food
Release of incretin gut hormones (GLP-1 and GIP)
Increase insulin release from beta cells (glucose dependent)- both GLP1 and GIP
Reduced glucagon release from alpha cells (glucose dependent)- just GLP1
Other effects of GLP-1 other than insulin release
Reduces gastric emptying
Increases hypothalamic satiety.
(directly on hypothalamic GLP-1 receptors).
T/F Exenatide also increases hypothalamic satiety
Yes, like GLP-1 it does do this
What does DPP-4 do physiologically… what are the drug analogues called
DPP-4 enzyme rapidly degrades incretins
DPP4 analogues known as gliptins
What is the downside of incretin
this is an injection
Name of some gliptins
vildagliptin and sitagliptin
Names of GLP-1 analogues
Exanatide
Liraglutide (Victoza or Saxenda)
Semaglutide
Are GLP-1 analogues and gliptins useful for management of diabetes?
Both seem effective strategies in weight reduction in type 2 DM
What is the normal plasma glucose concentration
5-5.5mmol/L
How much plasma is filtered per day
180L/day
How much glucose is filtered and reabsorbed per day
How much is excreted?
160–180 g/day filtered
160–180 g/day reabsorbed
MINIMAL excreted
How is glucose reabsorbed from the tubules
It should be noted that almost all of the glucose filtered by the glomerulus is reabsorbed in the proximal tubule, predominantly by SGLT2
