Diabetes drugs/strategy

Question 1

Treatment strategy for DM1

Answer 1

insulin dependent
goal is maintain insulin levels compared to physiological levels by combining long and short acting insulin
solely dependent on insulin

Question 2

Treatment strategy for DM2

Answer 2

early in disease course promote weight loss exercise, add metformin to decrease glucose release from liver, then prevent resistance at peripheral tissue and delay absorption, finally add insulin when pancreas fails

Question 3

Pathophys of DM2

Answer 3

Slow progression (years) from obesity to IFG to diabetes to hyperglycemia
initially, pancreas secretes more insulin to overcome resistance, but eventually pancreas fails and they need insulin too

Question 4

Most important diagnostic measure in DM1

Answer 4

blood glucose levels

Question 5

Most important diagnostic measure in DM2

Answer 5

hbA1C

Question 6

Sulfonylureas MOA

Answer 6

bind K+ receptors on pancreatic beta cells, Ca2+ rushes in, depolarization and increased insulin release
Promote release of endogenous insulin- worthless in type 1

Question 7

First-gen sulfonylureas?

Answer 7

Tolbutamide

Chlorpropamide

Question 8

First-gen sulfonylurea tox?

Answer 8

Disulfiram-like effect

Question 9

Second gen sulfonylureas?

Answer 9

Glyburide
Glimerpiride
Glipizide
Repaglinide (short-give with meals)
Nateglinide (short)

Question 10

Second gen sulfonylureas tox?

Answer 10

HYPOGLYCEMIA when insulin is greater than food intake
weight gain
increased TGs and LDLs

Question 11

Metformin MOA

Answer 11

Biguanide family
1. enhances suppression of gluconeogenesis with insulin decreasing hepatic glucose output
2. enhances glucose uptake and utilization at skeletal muscle
initial monotherapy for DM2

Question 12

Metformin tox

Answer 12

nausea, diarrhea
LACTIC ACIDOSIS- rare but high mortality
don’t give to pt’s with renal, hepatic or heart issues
NO RISK HYPOGLY OR WEIGHT GAIN

Question 13

Thiozolidenedines (TZD) MOA

Answer 13

increase insulin sensitivity in peripheral tissue
internalized, binds PPAR nuclear transcription regulator increasing genes for glucose and lipid metabolism
TAKES WEEKS TO HAVE EFFECT

Question 14

Thiozolidenedines (TZD) Tox

Answer 14

Weight gain from fluid retention
CONTRAINDICATED in CHF pts
rosiglitazone pulled for MI risk

Question 15

Thiozolidenedines (TZD) Drugs?

Answer 15

Pioglitazone- only one in use

Rosglitazone

Question 16

Alpha-glucosidase inhibitors?

Answer 16

acarbose

miglitol

Question 17

Alpha-glucosidase inhibitors MOA

Answer 17

Inhibit intestinal brush border alpha glucosidases
Delay (not prevent) sugar hydrolysis and glucose absorption
Which prevents blood glucose spike postprandial

Question 18

Alpha-glucosidase tox

Answer 18

abd discomfort, flatulence, diarrhea

Question 19

Management of hyperglycemia in DM2?

Answer 19

1. weight loss/exercise
2. metformin
3. consider combo therapy, add sulfonylurea or glitazone
4. continue to modulate and monitor
5. if combo therapies no longer effective, need to start insulin

Question 20

DPP4 inhibitors?

Answer 20

sitagliptin,

saxagliptin

Question 21

DPP4 inhibitors MOA

Answer 21

bind and inhibit DPP4, preventing the breakdown of GLP1/GIP- which are released from duodenum following oral glucose load and promote insulin release and glucagon suppression

Question 22

Exenatide/liraglutide MOA

Answer 22

GLP1 analog that is injected every 12 hours and is resistant to DPP4
liraglutide is longer acting

Question 23

Insulin therapy principles

Answer 23

REPLACES complete lack of insulin in type 1
SUPPLEMENTS progressive def. in Type 2
basal to start
full replacement needs basal-bolus
hypoglycemia and weight gain are risks

Question 24

Insulin native form/physio

Answer 24

natural insulin secreted as hexamer and needs 1-2 hours to be broken down to monomeric form
drugs developed by modifying AA chain for longer/shorter onset analogs

Question 25

Rapid acting insulin

Answer 25

monomeric
LISPRO
ASPART
onset= 5-15 min, 4-6 hr duration

Question 26

Intermediate insulin

Answer 26

NPH- protamine bound

onset=2-4 hours. 12-18 hr. duration

Question 27

Long acting insulin

Answer 27

Glargine
Detemir
once daily dosing- basal level

Question 28

Insulin analogs MOA in dift tissues

Answer 28

BIND INSULIN RECEPTOR (TK activity)

liver: increased glucose stored as glycogen
muscle: increase glycogen and protein syn
fat: aids TG storage

Question 29

insulin analogs tox

Answer 29

HYPOGLYCEMIA

Question 30

Insulin therapy to mimic physio

Answer 30

Long acting (glargine/detemir) + short-acting (lispro, aspart, glulisine)