Antidiabetic Drugs

Question 1

Insulin’s MOA

Answer 1

Insulin binds to receptor on cell and GLUT 4 transported moves to cell surface and brings glucose into the cell
* without insulin, glucose cannot enter the cell

Question 2

Insulin actions

Answer 2

⬆️ glucose, aa, fatty acid and K uptake 
⬆️ glycogenolysis
⬆️ protein synthesis 
⬆️ TG synthesis 
Gluconeogenolysis

Question 3

How much do insulins lower HBa1c levels?

Answer 3

2% decrease

Question 4

Adverse effects of all insulins

Answer 4

Hypoglycemia
Lipodystrophies
Hypokalemia

Question 5

Hypoglycemia and hyperglycemia cause problems for diabetics?

Answer 5

Hypoglycemia: can kill you
Hyperglycemia: DKA, increase fluid loss, dehydration

Question 6

Rapid acting and long acting insulins have a Lower risk of hypoglycemia versus what?

Answer 6

Regular human insulin and NPH

Question 7

Slow acting/long duration insulin

Answer 7

Modified chain of amino acids of human insulin

• huddle after SQ for a long time and are released slowly over time into blood
• onset slow
• duration: up to 24hrs

Question 8

Lispro (humalog)
Aspart (novalog)
Glusine (apidra)

Answer 8

Rapid acting short duration insulin

Question 9

Detemir (levimir)

Glargine (lantus)

Answer 9

Slow acting long duration insulin

Question 10

NPH

Answer 10

Suspension in injected liquid- NO IV only SQ

• available for aspart and lispro
• 2% ⬇️ in Hba1c levels with insulin
• ⬆️ risk of hypoglycemia
• must be gently mixed

Question 11

What kind of insulin can be given IV or mixed with other insulin?

Answer 11

Short duration/rapid acting

• when mixing draw short duration first
• lispro, aspart, glusine

Question 12

Insulin: rapid acting/short duration

Answer 12

Modified chain of amino acids of human insulin

• rapid onset shirt duration (3-5 HR)
• no huddle after SQ-straight to blood stream
• preferred over regular/human insulin bc of fast onset and lower risk of hypoglycemia

Question 13

Non insulin drug therapy

Answer 13

-1% Hba1c levels
All similiar in effectiveness
Duration varies by drug
*none of these are shown to have positive effects on macrovascular outcomes

Question 14

Metformin (glucophage) 
Sulfonylures
Meitinides
Thiazolineadiones TZDs 
Alpha-glucoside inhibitors 
SGLT2 inhibitors 
GLP analogs
DPP-IV inhibitors 
Pramlintide (symlin)

Answer 14

Non-insulin diabetic therapy

Question 15

Metformin (glucophage)

MOA

Answer 15

⬇️ hepatic glucose production, ⬇️ intestinal glucose absorption: sensitizes target cells to insulin
*stops gluconeogenesis and glycogenolysis

Question 16

Metformin (glucophage)

MOA

Answer 16

⬇️ hepatic glucose production, ⬇️ intestinal glucose absorption: sensitizes target cells to insulin

• stops gluconeogenesis and glycogenolysis
• superior to sulfonylureas: low risk of heart attack, no weight gain, improved lipids

Question 17

Metformin (glucophage)

Adverse effects

Answer 17

Stinky 
Lactic acidosis- lower risk: high with phenformin-low with metformin 
* renal dysfunction- do not give!!
Diarrhea 
Anorexia 
Dyspepsia 
*B12 folate deficiency
-GI low absorption

Question 18

Metformin (glucophage)

Inx

Answer 18

*Cimetidine: H2 receptor antagonist

Question 19

Sulfonylureas -“ide”

MOA

Answer 19

Indirectly ⬆️ insulin release/levels
Long duration
-two generations (1 old, 2 new)

Question 20

Sulfonylureas

Adverse effects

Answer 20

* hypoglycemia 
Impaired B-cell fxn 
* cardiovascular toxicity- ⬆️ heart attack risk 
Weight gain 
Increase BP
* risk of disulfiram rxn

Question 21

Sulfonylureas

Disulfiram rxn

Answer 21

Disulfiram (anabuse): anti alcoholic drug
Makes body intolerant to alcohol
*mimic disulfiram with OLD sulfonylureas
-N/V
-sweating
-severely sick

Question 22

Tolbutamide (orinase) 
Acetohexamide (dymelor)
Tolazamide (tolinase) 
Chlorpropamide (diabinese) 
* old- 1st generation 
Glipizide (glucotrol, glucotrol XL) 
Glyburide 
-nonmicronized (diabeta, micronase)
-micronized (glynase prestab) 
Glimepride (amaryl) 
* second generation-new

Answer 22

Sulfonylureas

Question 23

Meglitinides (new)

MOA

Answer 23

Promote insulin release- control postprandial hyperglycemia

• short duration (1-4 HR)
• dosed 30 min prior to meal (few times a day)
• cannot skip meals!!!!

Question 24

Meglitinides

Adverse effects

Answer 24

• hypoglycemia

- many drug inx risks

Question 25

Repaglinide (prandin) | Nateglinide ( starlix)

Answer 25

Meglitinides

Question 26

Thiazolidinediones-2

Answer 26

MOA- decrease insulin sensitivity -almost never used AE: fluid retention, edema, weight gain

Question 27

1) Pioglitazone (actos) | 2) Rosiglitazone (arandia)

Answer 27

Thiazolidinediones 1) worsens HF, 2012 bladder cancer 2) MI, cardiovascular related deaths, DC in 2010

Question 28

Alpha Glucosidase inhibitors-2 | MOA

Answer 28

Reduce post prandial rise in glucose Delays carb absorbtion * prevent gut from breaking down big sugars into small Sugars Absorb sugar slowly-delayed -given at start of a meal * do not use oral sucrose for treatment of hypoglycemia-use glucose

Question 29

Alpha Glucoside inhibitors | AE

Answer 29

``` Flatulence Cramps Bloating Constipation * hepatic dysfunction with long term use ```

Question 30

Acarbose (precose) | Miglitol (glyset)

Answer 30

Alpha Glucoside inhibitors

Question 31

Sodium glucose cotransporter 2 inhibitors (SGLT2) -"flozin" MOA

Answer 31

Increase urinary excretion of glucose; blocks kidneys ability to reabsorb filtered glucose * blocks SGLT2 pump= pee out glucose = lower blood sugar - newest class - favorable on wt and BP - BS of 150-180= kidney cannot filter anymore sugar conc too high

Question 32

SGLT2 inhibitors | AE

Answer 32

``` High risk of UTI High risk of vaginal yeast infections Hypotension Orthostatic hypotension Low BP Dehydration * will not work if renal fxn is impaired -not reccomeneded for PTs with renal dysfunction ```

Question 33

Drugs working via incretins 1) GLP-1 analogs 2) DPP-IV inhibitors

Answer 33

Hormones that are released from the GI tract for gastric emptying, glucose absorbtion, tells pancreas how quickly to make insulin

Question 34

GLP-1 analogs Incretins MOA

Answer 34

Stimulate insulin release in a glucose dependent manner Act like GLP * injectable -⬆️ satiety and ⬇️ food intake: weight loss or neutral effect on WT Preserve B cell fxn * control post prandial glucose concentration: ⬇️ glucagon ⬆️ insulin

Question 35

DPP-IV inhibitors -"gliptin" Incretins MOA

Answer 35

Stimulate insulin release in a glucose dependent manner * slows down the breakdown of GLP1 and GIP * effectiveness is half of GLP analogs (less potent) * PO 1x a day -well tolerated -⬆️ satiety and ⬇️ food intake: weight loss or neutral effect on WT Preserve B cell fxn * control post prandial glucose concentration: ⬇️ glucagon ⬆️ insulin

Question 36

GLP-1 analogs | AE

Answer 36

``` N/V Diarrhea Caution with some orally admin drugs * acute pancreatitis Low risk of hypoglycemia when used with a sulfonylureas ```

Question 37

DPP-IV inhibitors | AE

Answer 37

Low risk of hypoglycemia Low risk of GI effects Low risk regarding pancreatitis -theoretical concerns regarding cancer

Question 38

Exenatide (byetta): avoid in severe renal dysfunction Liraglutide (victoza) Albiglutide (tanzem) Dulaglutide (triulicity)

Answer 38

GLP-1 analogs | Incretins

Question 39

Sitagliptin (januvia) Saxagliptin (anglyza): high drug inx risk Linagliptin (trajenta): not sensitive to renal fxn Alogliptin (nesina) * all available in combo with metformin

Answer 39

DPP-IV inhibitors | Incretins

Question 40

GLP1 analogs and DPP-IV inhibitors

Answer 40

``` Low risk of hypoglycemia Slows the rate of gastric emptying Increase satiety N/V Impairs body ability to absorb other drugs ```

Question 41

Pramlintide (symlin)

Answer 41

An amylin mimetic- pancreas - lowers postprandial glucagon - slows gastric emptying- increase satiety - can be used for type 1 and type 2 DM - dosed prior to meals * SQ injection - acts like a GLP-1: decreases GI absorbtion of glucose * may increase insulin related hypoglycemia * caution with drugs that slows down gastric emptying

Question 42

Canagliglozin (invokana) Dapagliflozin (farxiga) Empagliflozin (jardiance)

Answer 42

SLGT2 inhibitors