Drugs and Diabetes Flashcards
What are the important cells within the pancreas ?
ISLET OF LANDERHANS
Alpha - produce glucagon
Beta cell - produce insulin
What is a healthy blood glucose leve ?
Healthy fasting blood glucose 4.0 – 5.4 mmol/L
(upto 7.8 - 2h after meal)
When was insulin discovered ?
Where did it orginate
1921
Beef and pork sources.
Nomal HBA1C levels ?
42MMOL BELOW NORMAL
42- 48 at Risk
Diabetic 48mmol/mol (6.5%)
What bacteria was made to make insulin ?
The E. coli expression system was the first expression system used to produce human insulin in 1978, with the use of recombination technology in the two-chain method.
What is the insulin mechanism of action ?
1- Need insulin to activate receptors.
2 - Glut 4 opens and some Glut 1.
You need potassium to promote the uptake of k+.
How to give soluble insulin ?
- Most well-known but less used today.
- Look for lipodystrophy.
Explain how to give short-acting insulin and how it work.
Avoids insulin
dimer/hexamer formation
Faster onset, shorter duration of action
Inject directly before a meal
Multiple daily injection with meals
* Longer acting insulin used at night
Long Acting Insulins
Microcrystals has long duration! Good for elderly with poor compliance.
Intermediate Insulins
Precipitation with protamine or zinc to give finely divided amorphous solid or relatively insoluble crystals. Insulin slowly absorbed from a subcutaneous suspension
Isophane Insulin
suspension with protamine
(twice daily)
Insulin Zinc Suspension
30% amorphous, 70% crystalline
(once daily)
Biphasic Insulin
short acting/soluble plus isophane
(mixed well in the syringe)
Explain the insulin duration of action for
- Short-acting
- Soluble
- Intermediate
- Long-acting (Detemir)
- Long-acting (Glargine)
Explain Insulin Degludecultra-long acting)
The newest ultra long acting insulin is insulin degludec by Novo. It contains a fatty acid substituent on the end of the B-chain which form dihexamers. When injected it firstly forms multihexamers in the interstitial space which degrade into dimers and finally into monomers which diffuse into the circulation. It is described as ultra-long acting.
Explain insulin infusion pump ?
Despite the advances in insulin modifications its difficult for intermittent dosing with fingertip blood sampling to mimic food related insulin release
What two types of drugs induce insulin release ?
How many calories does a T2DM need to eat to reverse diabetes ?
Reversal of type 2 diabetes by diet alone (very low calorie 600/day)
Explain Sulphonylureas.
Name a type
Titration is very very important !!!!!
Explain Meglinides
- Release insulin
- rapidly drops blood glucose.
What two medications are involved in the incretin pathway?
Inhibitors of DDP-4
GIP/GLP-1↑, insulin↑, glucagon↓
slow gastric emptying
ORAL therapy type 2 diabetes
- alone/in combination,
weight neutral.
Gliptins
sitagliptin, linagliptin,
vildagliptin, saxagliptin
GLP-1 agonists
39 amino acid peptide
insulin↑, glucagon ↓
SC injection (long acting forms)
Type 2 diabetes - in combination,
lnduces weight loss.
dulaglutide, liraglutide,
semaglutide, exanetide
Metformin
Drug of choice in overweight patients with type 2 diabetes where dietary control is unsuccessful
(needs residual pancreatic function)
Target Organs
Liver
gluconeogenesis↓ (elevated in type 2 diabetes)
Skeletal muscle
insulin resistance↓ (glucose uptake↑)
Intestine
carbohydrate absorption↓ fatty acid oxidation↑
No hypoglycaemia
Does not stimulate appetite
Adverse Effects
- G/I Tract – diarrhoea/vomiting - Should increase the amount of fibre.
- Lactic Acidosis (renal impairment) Used alone and in combination with sulphonylureas
Lactic Acidosis induced by Metformin
Lactate is a substrate for gluconeogenesis
Lactate uptake by liver reduced
Normally lactate uptake by kidney increased
Impaired renal function – clearance of metformin and lactate reduced
Also beware of conditions with increased lactic acid production (alcoholism, heart failure, respiratory disease)
- Can diabetic women who become pregnant continue to take metformin?
No - Put on insulin
Explain Glitazones
Dont give with heart faulire
What is the cappilarly around pct
peritubular capillaries
around the loop of henle its the vasa recta
Explain Glizlozins
What is the last resort of glucose management you can give for hypoglycemia
Glucagon
What do you do ?
What are the major complications of diabetes
Classifications and types of diabetic neuropathy?
Diabetic Retinopthy prevention ?
Ranibizumab
monoclonal antibody
neutralising VEGF-A (anti-angiogenic
