DM Drugs Flashcards
What do C peptides indicate?
Endogenous insulin (It is cleaved off to release active insulin)
Describe the insulin release pathway in B cells
- Uptake via GLUT2
- Glycolysis releases ATP
- ATP Potassium channel closes, membrane depolarisation
- Calcium channel opens, Ca2+ influx
- Insulin exocytosis
Describe the insulin signalling pathway
- Insulin binds to tyrosine kinase receptors, dimerisation and autophosphorylation of tyrosine kinase
- IRS-1 -> PI 3-kinase -> PIP3 -> Akt -> phosphorylation cascade
- Glycogen synthase activity increase, GLUT4 recruitment to membrane
GLUT2 vs GLUT4
GLUT2 is insulin-independent, constitutively expressed in B cells. Low affinity (high Km)
GLUT4 is insulin-dependent, expressed in muscle and fat cells. High affinity (low Km)
Where is the major site for insulin clearance?
Kidneys
Approach to treating T1D
Mimic normal pancreatic secretion, including:
Basal insulin- Background insulin to suppress hepatic gluconeogenesis during fasting state
Prandial insulin- Lower glucose spikes after eating
Rapid-acting insulin analogues: Names, advantage
Lispro, aspart, glulisine
Fast absorption kinetics, short DOA leads to lower incidence of hypoglycemia
Human insulin: indications
Only during emergency, IV
Intermediate-acting insulin: Name, advantage, disadvantage
Neutral protamine hagedorn (NPH)
Can be mixed with rapid-acting insulin
Highest risk of hypoglycemia (long peak effect as it acts as both basal and prandial insulin), patients need to eat meal at peak timing
Long-acting insulin: Name, advantage, disadvantage, indications
Glargine, detemir
No plasma peak, reduced risk of hypoglycemia, used as background insulin
Cannot mix with other insulins (glargine is formulated at an acidic pH)
If NPH is administered just before breakfast, what other drugs do the patient need to take?
Bfast spike needs to be taken care of (since NPH spikes around lunch)- give rapid acting
Where is the optimum site of injection?
Abdomen (fastest absorption due to blood flow)
How does depth of injection affect absorption?
Absorbed better in muscles due to greater vascularisation
Steroids and DM: Precaution
Steroids exacerbate hyperglycemia. Need to monitor blood glucose closely or increase insulin
Main ADRs of insulin injections, corresponding risk factors
Hypoglycemia (especially in old age or renal impairment)
Lipodystrophy (either atrophy or hypertrophy if injection site not rotated)