Insulin And Oral Hypoglycemics Flashcards
What are the insulin responsive cells
Muscle cells and adipose tissue
What is the glucose transporter
GLUT 4
What happens in TYPE 1 diabetes mellitus your
Autoimmune destruction of beta cells in the pancreas by T cells due to eliminated self tolerance
What is type 2 diabetes mellitus
Insulin resistance in peripheral cells hence the pancreas will make even more insulin and over time it will get over worked causing beta cells to atrophy
When is exogenous insulin given in type 2 diabetes
Later in the disease
When is exogenous insulin given in type 1 diabetes
Immediately since the pancreas can’t make insulin anymore
Whats the quickest area of absorption of insulin
1-abdomen 2-arms 3-buttocks 4-thighs Closest to the pancreas the faster!
What are insulin preparations categorised by
Onset of action and duration
What are Rapid acting / short acting insulin
Bolus=prandial
Bolus insulin regimen—>given before meals to counter post meal increase in blood glucose
What are intermediat acting and long acting insluins
They are basal (fasting) insulin regimen—> to maintain steady level given 1 or 2 times a day to regulate fasting blood glucose
What drugs are inhibitors of insulin release
Somatostatin and a2 stimulation
What happens when insulin drops
Lipolysis increases—> leading to increase in production of ketone which could lead to ketoacidosis
Symptoms of ketoacidosis
Acetone breath, abonormal respiration and electrolyte depletion (vomiting, come and death)
What is the only insulin given IV
Regular / human insulin
Why is human insulin given iv
Produced and stored as a hexamer to remain stable within the body
Normal insulin onset and duration
30 mins
5-8 hours
Peak 3-4 hrs
What are the rapid acting insulin
LAG
Lispro
Aspart
Glulisine
Rapid acting insulins duration, onset and peak
5-15 mins
3-4 hrs
1hr is the peak
When is rapid acting insulin used
Injected before a meal
What’s the insulin of choice for diabetic ketoacidosis
Rapid acting insulin
Which insulin’s are used in insulin’s pumps
Rapid acting insulin
Whats an intermediate acting insulin
NPH - isophane
What are NPH and regular insulins
They are human insulins the rest are analogs
NPH onset, duration and peak
1-2 hours
10-16 hours
Peak 4-13 hours
What can NPH be used as
Can be used as basal insulin
What’s the concentration of most commercial insulin preparations
100 U/ml
What are the long acting insulins
Glargine, detemir (has a flat peak) and degludec
Which long acting insulin binds to albumin
Detemir
Long acting insulins onset , duration and peak
1-2 hours
Glargine 24 hrs
Detemir 20 hrs
No peak effect for glargine
Which insulin can’t be mixed with other insulins in one syringe
Glargine
Long acting insulins side effects
Hypoglycaemia
Lipodystrophy
Weight gain
Where are endogenous and injected insulins metabolised
Endogenous insulin - 60% in liver and 40% in kidney
Injected insulin - 60% kidney and 40% liver
Sulfonylurea mode of administration
Oral
Sulfonylurea mechanism of action
- It works like ATP in pancreas work similarly to ATP leading to depolarisation by closing k+ channels
- decreases hepatic gluconeogenesis
- increase peripheral insulin sensitivity
1st generation sulfonylurea
Chlorpropamide
Tolbutamide
Tolazamide
2nd generation sulfonylurea
Glipizide, glyburide and glimeperide (3rd gen)
Difference between first and second generation sulfonylurea
2nd generation is more potent and common
What glucose concentration are Sulfonylureas used for
Any glucose concentration since it secretes insulin regardless
Which oral hypoglycaemic drugs have the highest risk of hypoglycaemia
Sulfonylurea
Side effects of sulfonylurea
Hypoglycaemia Weight gain GI disturbances (nausea) Allergic reactions (SJS) Photosensitivity
1st generation sulfonylurea side effects
Disulfram like reaction (alcohol intolerance giving hangover like symptoms)
Sulfonylurea contraindications
DKA and DM1
Meglitinides mode of administration
Oral
Meglitinides mechanism of action
Prevent K+ channels from opening
List the meglitinides and their onset time
Repaglinide 30 mins
Nateglinide 10 mins
Meglitinides vs sulfonylurea
Meglitinides work faster but for shorter time than sulfonylurea
When are meglitinides taken
Taken before meals
Meglitinides side effects
Weight gain
Hypoglycaemia
What are incertins
Hormones which stimulate insulin release after a meal like GLP1 , which only gets released on an increase in glucose level to release insulin and inhibits glucagon release
What oral hypoglycaemics are glucose dependent
Incertins
List the GLP 1 receptor agonists
Exenatide and liraglutide
GLP1 agonists mode of administration
Subcutaneous
GLP1 agonist suffix
TIDE
GLP 1 agonist Mechanism of action
Increase insulin secretion
Decrease glucagon release
Enhance satiety
GLP 1 agonist adverse effects
GI disturbances
Drop in appetite
Increase in risk for acute pancreatitis
Weight loss
Best drug for weight loss
GLP 1 agonists
List the DPP 4 inhibitors
Sitagliptin
Saxagliptin (orally)
DPP 4 inhibitors mechanism of action
They inhibit DPP-4 which is a protease which breaks down GLP-1
Same effect as incertins
DPP4 side effects
GI disturbances
Headache
NASOPHARYNGITIS
mild respiratory and urinary infections
Which diabetes drugs have beneficial CV effects
GLP1 (LIRAGLUTIDE and SEMAGLUTIDE)
SGLT-2 inhibitor (EMPAGLIFLOZIN)
DPP4 inhibitors are contraindicated in which people
Hepatic and renal impairments
Teratogenic-pregnant women
What’s the mechanism of action biguanides and thiazolidinediones
Increase insulin sensitivity
Decrease production of glucose
List Biguanides
Metformin first line drug for type 2 diabetes
Metformin mechanism of action
- Inhibits hepatic gluconeogenesis
- Increases GLUT4 receptors in the cell membrane
- Decreases intestinal absorption of glucose
Metformin side effects
GI disturbances
Weight gain
Lactic acidosis
Metformin is contraindicated in who
Patients with renal dysfunction
Hepatic dysfunction
COPD
In low vit B12
What does metformin cause to vitamin B12
Decreases it
List the thiazolidinediones
Rosiglitazone
Pioglitazone
Rosiglitazone and Pioglitazone mechanism of action
They are insulin sensitisers increasing sensitivity as they bind to PPAR GAMMA which increases the transcription of insulin responsive genes and decreases hepatic gluconeogenesis
Thiazolidinediones side effects
Increase risk of cardiovascular events MI AND STROKE
Fluids retention causing edema
Pioglitazone side effects
Increases the risk of bladder cancer and increases risk of osteopenia and fractures and liver failure
List alpha glycosides inhibitors
Acarbose and miglitol
alpha glycosides inhibitors mechanism of action
Delay breakdown of starch and carbohydrates to glucose hence it decrease post meal glucose
alpha glycosides inhibitors side effects
GI disturbances
List Synthetic amylin analogs
Pramlintide - injectable
What is amylin
A hormone secreted by B cells alongside insulin
Synthetic amylin analogs mechanism of action
Lowers blood glucose by delaying gastric emptying and inhibiting glucagon secretion and improving satiety
What is the only drug other than insulin used for both DM1 and DM2
Synthetic amylin analogs which is PRAMLINTIDE
list SGLT2 Inhibitors
Canagliflozin
Dapagliflozon
Suffix - gliflozin
SGLT 2 inhibitors
Decrease glucose concentration and decrease HBA1C concentration
What is SGLT 2
It’s a transporter in the kidney which accounts for 90% of absorbed glucose
Blocking it causes glucosuria
SGLT2 inhibitors side effects
It causes glucosurea which leads to UTIs and genital infections
