Diabetes drugs

Question 1

Lifestyle change

Answer 1

Action: (+) Insulin sensitivity
Advantages: Low cost, many benefits
Disadvantages: Fails for most in first year

Question 2

Metformin

Answer 2

Action: (- )Gluconeogenesis
Advantages: Weight neutral, inexpensive
Disadvantages: GI side effects, rare lactic acidosis, renal fxn appropriate dosing

Question 3

Sulfonylureas

Answer 3

Action: Insulin secretagogue
Advantages: Inexpensive
Disadvantages: Weight gain, hypoglycemia*

Question 4

Thiazolidinediones

Answer 4

Action: (+)Insulin sensitivity
Advantages: Improved lipid profile, no hypoglycemia,
Disadvantages: Fluid retention, weight gain, expensive

Question 5

α-glucosidase

Answer 5

Action: (-) carb absorption
Advantages: Weight neutral, no hypoglycemia
Disadvantages: Frequent GI side effects, three times/day inhibitors dosing, expensive

Question 6

Exenatide

Answer 6

Action: Multiple
Advantages: Weight loss
Disadvantages: Injections, frequent GI side effects,expensive, little experience

Question 7

Glinides/Meglitinides

Answer 7

Action: Insulin secretagogue
Advantages: Short duration
Disadvantages: Three times/day dosing, expensive

Question 8

Incretin Enhancers

Answer 8

Action: (-) DPP-IV
Advantages: Weight neutral, no hypoglycemia
Disadvantages: Mild GI side effects

Question 9

rapid acting insulins

Answer 9

aspart, lispro, glulisine

Question 10

Aspart & Lispro

Answer 10

• Homologous with regular human insulin
• Single substitution: aspartic acid for proline @ B28 & lysine for proline at B28
• Disrupts monomer-monomer interactions→ decreased hexamer formation
• More rapid absorption after subQ injection → preak time in 1 hour!

Question 11

similarities b/w aspart &lispro vs regular

Answer 11

•	Glucose lowering effects
o	1 units lispro/aspart = 1 unit regular
•	affinity of insulin receptor
•	Induction of receptor mediated cellular signals
•	Similar bioavailability

Question 12

differences b/w aspart &lispro vs regular

Answer 12

•	Pharmacokinetics of Lispro/Aspart
o	2 x faster absorption
o	2 x higher peak concentration
o	Faster onset of action : 10-20 minutes post injection (reg 30 – 60 min)
o	Peak 1 -2 hours (Reg 2 – 4)
o	Shorter duration of action: 3-5 hours

Question 13

options for basal insulin

Answer 13

NPH
glargine
detemir

Question 14

NPH

Answer 14

– suspension of crystalline zinc insulin combined with the positively charged polypeptide protamine → allows for slow release
dosed once or twice daily

Question 15

glargine

Answer 15

modifications to human insulin chain – unique release from injection site → in ph of 7.4 forms micro-precipitate → slow release of insulin

Question 16

insulin prep summary

Answer 16

Insulin preparations	Onset of action	Peak (hr)	Duration of action (hr)
Aspart/Lispro/Glulisine 5–15 min	1–2	4–6
Regular human	30–60 min	2–4	6–10
Human NPH	1–2 hr	4–8	10–20
Glargine	1–2 hr	flat	~24
Detemir	0.8-2 hr	flat	up to 24