Pharm2 - #05 - Drugs To Treat Diabetes

Front 1

Hyperglycemia in DM may be caused by what 3 defects?

Back 1

defect in:
1. insulin production
2. insulin action
3. combo of the two

Front 2

Treatment goal of diabetes?

Back 2

To achieve and maintain glycemic levels as close to the non-diabetic range as possible in order to prevent the development of complications of chronic diabetes.

Front 3

Rapid-acting insulins?

Duration?

Back 3

Insulin aspart, lispro, and glulisine

2-4 hours

Front 4

Regular insulin duration?

Back 4

6-8 hours

Front 5

Intermediate insulin?

Duration?

Back 5

NPH insulin (Lente if OTM)

16-24 hrs

Front 6

Long-acting insulin?

Back 6

insulin glargine, insulin detmir

Front 7

Glargine duration?

Detmir duration?

Back 7

glargine: 20-24 hrs

detmir: 6-24 hrs

Front 8

How does insulin correct hyperglycemia?

Back 8

1. promotes glucose uptake in muscle, liver, and adipose
2. inhibits hepatic glucose production (gluconeogenesis/glycogenolysis)
3. inhibits flow of gluconeogenic precursors from muscle/adipose to liver
4. inhibits secretion of counter-regulatory hormone glucagon

Front 9

Why should sites of insulin injection be varied?

Back 9

to avoid injection site lipodystrophy

Front 10

Initial insulin dose?

Back 10

0.2-0.6 units/kg/day in divided doses

Front 11

How are insulin types usually divided up for a person in general?

Back 11

50-75% of dose given as intermediate/long-acting insulin and remainder given as rapid-acting or short-acting insulin at meals.

Front 12

Adverse reactions with insulin therapy?

Back 12

1. headache
2. tachycardia
3. fatigue
4. mental confusion
5. injection site lipodystrophy
6. diaphoresis
7. hypersenstivity (less common w./ human insulin)

Front 13

What drugs DECREASE hypoglycemic effects of insulin?

Back 13

1. oral contraceptives
2. corticosteroids
3. diltiazem
4. niacin
5. epinephrine
6. thiazide diuretics

Front 14

What drugs INCREASE hypoglycemic effects of insulin?

Back 14

1. alcohol
2. alpha-blockers
3. beta-blockers
4. salicylates
5. sulfinpyrazone
6. tetracyclines

Front 15

What does intensive/standard insulin therapy consist of?

Back 15

1. a basal level of insulin to lower fasting glucose (daily or twice daily injections of long-acting insulin)

2. pre-meal boluses of a rapid or very rapid-acting insulin to control postprandial glucose elevations

Front 16

Why give a type 1 diabetic intensive insulin therapy?

Back 16

Significantly reduces risk of diabetes complications.

Front 17

What two classes of drugs are insulin secretagogues?

Back 17

1. Sulfonylureas
2. Meglitinides

Front 18

What specific drugs are sulfonylureas?

Back 18

1st generation:
-Chlorpropamide
-Tolbutamide

2nd generation:
-Glimepiride (Amaryl)
-Glyburide (DiaBeta, Micronase)
-Glipizide (Glucotrol)

Front 19

What specific drugs are meglitinides?

Back 19

-Repaglinide (Prandin)
-Nateglinide (Starlix)

Front 20

MOA of the sulfonyureas?

Back 20

-sulfonylureas interact w/ SUR1 subunit of ATP-sensitive K+ channels (Kir6.2) on pancreatic beta cells --> inhibits channel activity --> cell deploarization triggers voltage-gated Ca++-channels to open --> influx of Ca++ and secretion of insulin

Front 21

Sulfonylurea action on fasting and postprabdial sugars?

Back 21

-primarily reduce fasting
-little effect on postprandial glucose

Front 22

Who are sulfonylureas most effective in?

Back 22

T2DM pts who have had diabetes for <10 years.

Front 23

How do 2nd generation drugs differ from 1st generation drugs?

Back 23

2nd gen are:
1. more potent
2. lower freq of hypoglycemia
3. fewer drug interactions

Front 24

Adverse effects of sulfonylureas?

Back 24

1. modest weight gain (~2 kg)
2. hypoglycemia - pts w/ impaired renal and/or hepatic function

Front 25

What is the DOC for elderly pts or pts w/ chronic renal failure?

Back 25

Glipizide - b/c it is metabolized in the liver and inactive metabolites are excreted in the urine

Front 26

Why do sulfonylureas have many drug interactions? What are some specific ones?

Back 26

They are highly protein bound: interact w/ salicylates, beta-blockers, warfarin, and phenylbutazone.

Front 27

MOA of Meglitinides?

Back 27

Meglitinides trigger insulin secretion by similar mechanism to sulfonylureas, but interact w/ different region of the SUR1 subunit of beta cell ATP-sensitive K+ channel.

Front 28

Peak action and duration of Meglitinides?

How often should they be given?

Back 28

peak: 1 hr
duration: 4 hrs

need to give 3 times daily

Front 29

How do they alter fasting and postprandial glucose levels?

Back 29

-primarily affect postprandial glucose

-likely beneficial in pts w/ barely elevated FPG but prominent postprandial hyperglycemia

Front 30

By how much do Meglitinides decrease HbA1C?

Back 30

by 1.0-1.5% points

Front 31

What's the difference in effectiveness b/w nateglinide and repaglinide?

Back 31

Nateglinide is less effective than repaglinide.

Repaglinide is as effective as sulfonylureas or metformin at lowering HbA1c.

Front 32

Adverse effects of Meglitinides?

Back 32

1. weight gain
2. hypoglycemia (less than w/ sulfonylureas)

Front 33

C/Is of Meglitinides?

Back 33

1. liver disease
2. pregnancy

Front 34

What anti-diabetic drug is a biguanide?

Back 34

Metformin

Front 35

**What is the 1st line therapy for type 2 diabetes?**

Back 35

Metformin! (along w/ diet and exercise)

Front 36

Primary action of Metformin?

Back 36

Reduces hepatic glucose production (does not promote insulin production).

Front 37

Likely MOA of Metformin?

Back 37

activates AMP-dependent protein kinase (AMPK)

Front 38

How does activation of AMPK by Metformin improve hyperglycemia?

Back 38

1. promotes glucose uptake into muscle and adipose
2. inhibits hepatic glucose production, and hepatic cholesterol and TG biosynthesis
3. promotes FFA ocidation --> reduces FFA stores that contribute to insulin resistance
4. inhibits activity of inhibitors of insulin signaling pathway thereby enhancing insulin signaling and prevents insulin resistance

Front 39

Metformin: time to peak plasma concentration and duration of action?

Back 39

peak: 2 hrs
duration: 6 hrs

Front 40

How dwell does Metformin improve FBG and HbA1c?

Back 40

FBG: 20% decrease
HbA1c: ~1.5% decrease

Front 41

Advantages of Metformin with regards to weight and hypoglycemia?

Back 41

1. does NOT cause weight gain (promotes weight loss)
2. does NOT cause hypoglycemia

Front 42

Advantages if Metformin over other oral hypoglycemic agents?

Back 42

1. decreases frequency of MI
2. decreases diabetes-related death
3. decreases all-cause mortality in type-2 obese pts

Front 43

Why does Metformin have beneficial effects on CD outcomes?

Back 43

improves lipid profiles: dec TG and FFA, small dec in LDL, modest increase in HDL

Front 44

Most common adverse effect w/ Metformin? How is it avoided?

Back 44

GI tract problems - take w/ food

Front 45

What can Metformin decrease the absorption of?

Back 45

Decrease vitamin B12 absorption (folic acid) - rarely causes megaloblastic anemia.

Front 46

Rare potentially fatal S/E of Metformin?

What drug showed increased frequency of this problem ans whas removed from the market?

Back 46

Lactic acidosis (<1:100,000)- due to glucose metabolism in absence of adequate oxygen.

Phenformin was removed.

Front 47

Contraindications of Metformin therapy?

Back 47

1. pregnancy
2. impaired renal function (more susceptible to lactic acidosis)
3. elderly (>80 y/o)
4. Dicontinue in pts injected with iodinated contrast agents for radiographic studies. Restart 48 hrs later to avoid contrast-induced renal failure (use insulin during this time).
5. Conditions predisposing to lactic acidosis: CHF, impaired liver fxn/excessive EtOH consumption, shock/septicemia, serious acute illness or hypoxic condition

Front 48

Metformin drug interactions?

Back 48

Cimetidine - can increase Metformin by 60% --> hypoglycemia

Front 49

What 2 drugs are Thiazolidinediones?

Back 49

Pioglitazone
Rosiglitazone

Front 50

MOA: TZDs?

Back 50

agonists of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) transcription factor --> involved in regulation of many genes involved in insulin sensitivity

Front 51

What does activation of PPAR-gamma result in? (2)

Back 51

overall: promotes insulin sensitivity

adipose remodeling

Front 52

TZD effects in FPG and PPG?

Back 52

decreases FPG

Front 53

Adverse effects of TZDs?

Back 53

1. weight gain
2. fluid retention (peripheral edema) - occurs more w/ concurrent insulin use; due to increased Na+ reabsorption

Front 54

C/Is for TZDs? (2)

Back 54

1. liver dz
2. heart failure

Front 55

What drugs are alpha-glucosidase inhibitors?

Back 55

Acarbose
Miglitol

Front 56

MOA of alpha-glucosidase inhibitors?

Back 56

Reduce PPG by inhibiting rate of digestion of polysaccharides in small intestine (i.e. delays absorption of glucose).

Front 57

Do alpha-glucosidase inhibitors cause hypoglycemia?

Back 57

No

Front 58

Why are alpha-glucosidase inhibitors not 1st line drugs?

Back 58

less potent; poor tolerance due to S/Es

Front 59

Why do patients stop taking alpha-glucosidase inhibitors?

Back 59

GI problems (25-45%)

Front 60

When should insulin be considered 1st line for T2DM?

Back 60

HbA1c > 10%
FBG > 250
random BG > 300

Front 61

When is insulin the preferred 2nd line for T2DM?

Back 61

HbA1c > 8.5%

Front 62

Who needs more insulin T1 or T2 diabetics?

Back 62

T2 due to insulin resistance

Front 63

What drug is an amylin homolog?

Back 63

Pramlintide

Front 64

MOA: Pramlintide?

Back 64

synthetic analog of amylin - helps control postprandial glucose

Front 65

MOA of amylin/Pramlintide?

Back 65

1. decreases postprandial glucagon levels
2. slows gastric emptying (T1 and T2)
3. increases satiety

Front 66

How is Pramlintide used?

Back 66

adjunct to insulin therapy in T1 and T2 diabetics

additive to insulin: decreases insulin dose by 50%

postprandial control

Front 67

Positive S/E of Pramlintide?

Back 67

weight loss

Front 68

Adverse effects of Pramlintide? (one major one)

Back 68

increases risk of severe hypoglycemia (need to reduce insulin dose by 50%!)

nausea, vomiting, anorexia, headache

Front 69

Drug interactions w/ Pramlintide?

Back 69

affect absorption of other orally admin drugs, thus need to take them 1 hr before or 2 hrs after

Front 70

MOA of Exenatide?

Back 70

GLP-1 analog

Front 71

What is action of GLP-1?

Back 71

produced by L-cells in small intestine

binds to GLP-1 receptor on pancreatic beta cells and causes insulin secretion

Front 72

What is the Incretin Effect?

Back 72

plasma insulin levels are higher in response to oral glucose compared to IV glucose --> indicates that factors produced in the GI tract influence insulin secretion

Front 73

What is an alternative to starting insulin therapy in type 2 diabetic patients?

Back 73

Exenatide

Front 74

Action of Exanatide on BG levels?

Back 74

reduces both PPG and FBG levels

Front 75

What drugs for diabetes cause weight loss?

Back 75

Metformin
Exenatide
Pramlintide

Front 76

MOA: Sitagliptin?

Back 76

inhibitor of DPP-IV, the peptidase that cleaves and inactivates GLP-1

Front 77

Effect of Sitagliptin on BG?

Back 77

decrease both FPG and PPG

Front 78

What does the ADA recommend as DOC for new-onset T2DM?

Back 78

Metformin

Front 79

Advantages of Metformin?

Back 79

efficacy
safety
weight loss
no risk of hypoglycemia
beneficial effects on CV mortality

Front 80

If T2DM is not controlled after 2-3 months of therapy w/ Metformin what do you do?

Back 80

add:

1. sulfonylurea
2. TZD
or
3. insulin (>8.5%)

Front 81

When should a T2DM be switched to insulin?

Back 81

if failure on combo of 2 oral agents, switch to 2X daily insulin plus metformin

Front 82

What classes of anti-diabetic drugs lowers FPG only?

Back 82

Metformin
Sulfonylureas
TZDs

Front 83

What classes of anti-diabetic drugs lowers PPG only?

Back 83

Meglitinides
alpha-glucosinase inhibitors
Pramlintide

Front 84

What class of anti-diabetic drugs lowers both FPG and PPG?

Back 84

Exenatide

Front 85

Which class of anti-diabetics has NO hypoglycemia risk?

Back 85

alpha-glucosidase inhibitors