DM Drugs

Question 1

What do C peptides indicate?

Answer 1

Endogenous insulin (It is cleaved off to release active insulin)

Question 2

Describe the insulin release pathway in B cells

Answer 2

1. Uptake via GLUT2
2. Glycolysis releases ATP
3. ATP Potassium channel closes, membrane depolarisation
4. Calcium channel opens, Ca2+ influx
5. Insulin exocytosis

Question 3

Describe the insulin signalling pathway

Answer 3

1. Insulin binds to tyrosine kinase receptors, dimerisation and autophosphorylation of tyrosine kinase
2. IRS-1 -> PI 3-kinase -> PIP3 -> Akt -> phosphorylation cascade
3. Glycogen synthase activity increase, GLUT4 recruitment to membrane

Question 4

GLUT2 vs GLUT4

Answer 4

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)

Question 5

Where is the major site for insulin clearance?

Answer 5

Kidneys

Question 6

Approach to treating T1D

Answer 6

Mimic normal pancreatic secretion, including:
Basal insulin- Background insulin to suppress hepatic gluconeogenesis during fasting state
Prandial insulin- Lower glucose spikes after eating

Question 7

Rapid-acting insulin analogues: Names, advantage

Answer 7

Lispro, aspart, glulisine

Fast absorption kinetics, short DOA leads to lower incidence of hypoglycemia

Question 8

Human insulin: indications

Answer 8

Only during emergency, IV

Question 9

Intermediate-acting insulin: Name, advantage, disadvantage

Answer 9

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

Question 10

Long-acting insulin: Name, advantage, disadvantage, indications

Answer 10

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)

Question 11

If NPH is administered just before breakfast, what other drugs do the patient need to take?

Answer 11

Bfast spike needs to be taken care of (since NPH spikes around lunch)- give rapid acting

Question 12

Where is the optimum site of injection?

Answer 12

Abdomen (fastest absorption due to blood flow)

Question 13

How does depth of injection affect absorption?

Answer 13

Absorbed better in muscles due to greater vascularisation

Question 14

Steroids and DM: Precaution

Answer 14

Steroids exacerbate hyperglycemia. Need to monitor blood glucose closely or increase insulin

Question 15

Main ADRs of insulin injections, corresponding risk factors

Answer 15

Hypoglycemia (especially in old age or renal impairment)

Lipodystrophy (either atrophy or hypertrophy if injection site not rotated)