Endo_Test 2: Maloney_Diabetes Pharm

Front 1

Name the rapid acting insulin preparation

Back 1

Insulin lispro

Front 2

Name the short acting insulin preparation

Back 2

Regular Humulin R

Front 3

Name the intermediate acting insulin preparations (2)

Back 3

NPH Humulin N

NPH Novolin N

Front 4

Name the long acting insulin preparation

Back 4

Insulin glargine

Front 5

Name the Insulin Preparation:

Onset of action: 15 min

Peak effect: 0.6-0.8hr

Duration of action: 3-5 hr

Back 5

Insulin Lispro

**Given IV for Emergencies**

Front 6

Name the Insulin Preparation

Onset of action: 1.1 hr

Peak effect: 5-24 hr

Duration of action: 24 hr

Back 6

Insulin Glargine

**Basal level throughout the day**

Front 7

Name the Insulin Preparation:

Onset of action: 30-60 min

Peak effect: 1.5-4hr

Duration of action: 5-8hr

Back 7

Regular Insulin

**Covers you before meals**

Front 8

Name the Insulin Preparation:

Onset of action: 1-1.5 hr

Peak effect: 6-12 hr

Duration of action: 18-24 hr

Back 8

NPH Insulin

**sets a basal level**

Front 9

Back 9

Front 10

A typical type I diabetic's regimen is? (2)

Back 10

- Take a long acting insulin (eg glargine) to cover your basal rate

- Take rapid acting insulin (eg aspart) before meals to cover the carbohydrates (aka glucose) in the meal

Front 11

What types of insulin preparations would you use for basal insulin levels?

Back 11

Insulin NPH

Insulin Glargine

Front 12

How does Hypoglycemia cause the following effects:

-Sweating
-Hunger
-Paresthesias
-Palpitations
-Tremor
-Anxiety

Back 12

Activates the SNS

Front 13

How does Hypoglycemia cause the following effects:

-Difficulty concentrating
-Confusion
-Weakness
-Drowsiness
-Blurred vision
-Loss of consciousness

Back 13

Insufficient Glucose for Brain

Front 14

_____ is the only resource of energy for the Brain...

Back 14

Glucose

Front 15

How do you treat hypoglycemia from an insulin overdose?

Back 15

Sugar --> cookies, candy, OJ

Administer Glucose

Administer Glucagon

Front 16

What hormone increases gluconeogenesis and glycololysis in the liver --> raises blood glucose ?

Back 16

Glucagon

Front 17

____ cells release glucagon

Back 17

alpha cells

Front 18

What is the clinical use for glucagon?

*****

Back 18

Hypoglycemia

(SubQ injection)

Front 19

Do the following drugs treat type I or type II diabetes?

-Biguanides (Metformin)
-Meglitinides
-Sulfonylureas
-Thiazolidinediones
-Incretin mimetics
-Amylin analog
- a-glucosidase inhibitors

Back 19

Type II Diabetes

Front 20

A 52-year-old male is newly diagnosed with type 2 diabetes mellitus. He begins lifestyle modifications. What will be the initial drug therapy for this patient?

Back 20

Metformin

**1st line drug for type II DM**

Front 21

What is the 1st line drug for type II diabetes?

Back 21

Metformin

It combats insulin resistance!!

Front 22

T/F:

Metformin is ineffective in the absence of insulin

Back 22

True

Front 23

MOA:

**Liver**
-Decrease hepatic glucose output

-Probably reduces gluconeogenesis


**Skeletal muscle and adipose tissue**
-Enhances insulin stimulated glucose uptake

-Enhances utilization of glucose

-Decreases insulin resistance

Back 23

Metformin

Front 24

What will happen to serum insulin concentrations with metformin?

Back 24

Serum insulin will decrease since metformin works on peripheral tissues

Front 25

What will happen to post-prandial glucose concentrations with metformin?

Back 25

After eating, metformin decreases glucose concentration

Front 26

What will happen to fasting blood glucose (FBG) levels with metformin?

Back 26

FBG levels decrease when taking metformin

Metformin decreases insulin release while fasting, this decreases glucose released from the liver --> ↓FBG levels

Front 27

With type II diabetes there is an increase/decrease in both postprandial and glucagon levels

Back 27

INCREASE

Front 28

What is the biggest side effect we worry about with Metformin use?

Back 28

Lactic Acidosis

Front 29

How does Metformin result in Lactic Acidosis?

Back 29

Metformin increases lactate production caused by tissue hypoxia

(favors ANAEROBIC metabolism)

Front 30

***Contraindications***

- Renal disease

- Hepatic disease or alcohol abuse

- History of lactic acidosis

- Decreased tissue perfusion or hemodynamic instability:
-Acute MI-
-Acute left ventricular failure-
-Chronic hypoxic lung disease-
-Septicemia-

Back 30

METFORMIN

**Increased risk of lactic acidosis**

Front 31

Why is metformin therapy halted prior to:

-Administration of IV contrast media

-Surgery

Back 31

IV contrast media → acute renal failure

Surgery → compromised circulation

**These procedures predispose to lactic acidosis**

Front 32

While lactic acidosis is very rare or essentially zero without a predisposing condition, why is this such a big deal?

Back 32

**Potentially Fatal**

Lots of people with type II diabetes have contraindications for metformin use

Front 33

Two of the biggest concerns in treating type 2 diabetes mellitus is whether or not the drug causes hypoglycemia or weight gain. What effect will metformin most likely have on these parameters?

Back 33

**Hypoglycemia**
NO.. metformin doesn't increase insulin levels

**Weight Gain**
NO.. Nausea causes you to eat less.. Decreased insulin activity will actually promote weight loss

Front 34

Will metformin cause weight gain or hypoglycemia?

Back 34

Nope

Front 35

How does metformin protect a type II diabetes patient from Coronary artery disease and Peripheral Vascular Disease?

Back 35

**Decrease TG, total and LDL-C**
- Decrease VLDL synthesis

Front 36

If your patient developed significant renal impairment should you continue metformin use?

Back 36

NO...

metformin is contraindicated in patients with renal failure → LACTIC ACIDOSIS

Front 37

MOA:

Stimulate peroxisome proliferator-activated receptor-γ (PPAR-γ)

Back 37

Pioglitazone

Rosiglitazone --> never used

**Thiazolidinediones**

Front 38

Name the Thiazolidinedione used for the treatment of type II diabetes to decrease insulin resistance

Back 38

Pioglitazone

Front 39

What 2 drugs decrease insulin resistance in type II diabetics?

Back 39

Metformin

Pioglitazone

Front 40

What is PPAR-γ?

A.G protein-coupled plasma membrane receptor

B.Tyrosine kinase plasma membrane receptor

C.Intracellular receptor that increases transcription

Back 40

C.Intracellular receptor that increases transcription

Front 41

Where is PPAR-γ located?

A.Lots in adipose tissue and some in skeletal muscle and liver

B.Only in pancreatic beta cells

Back 41

A.Lots in adipose tissue and some in skeletal muscle and liver

Front 42

PPAR-γ activation ____ GLUT 4 expression allowing you to get more glucose into the cell

Back 42

increases

Front 43

MOA:

- Activates the nuclear peroxisome proliferator-activated receptor-γ (PPAR-γ)

- This increases transcription of genes such as the glucose transporter, GLUT4.

- In adipose tissue and skeletal muscle, it increases uptake and utilization of glucose.

- In liver, it inhibits gluconeogenesis.

Back 43

Pioglitazone

Front 44

Is insulin required for the glucose lowering effect of pioglitazone?

Back 44

YES

Insulin stimulates glucose uptake!

Front 45

Will pioglitazone tend to cause hypoglycemia?

Back 45

No...

Insulin activity of the pancreas is not effected so you will not get hypoglycemia (i.e. insulin activity is normal)

Front 46

Does Pioglitazone cause weight gain? If so, how?

Back 46

Pioglitazone causes weight gain

**Kidneys**
↑ Na+ reabsorption→EDEMA



**PPAR-γ activation**
↓
differentiation of pre-adipocytes to mature fat cells
↓
Weight Gain

Front 47

Would you use pioglitazone in a patient with bad heart failure?

Back 47

You would AVOID using a glitazone becuase they cause EDEMA which would make CHF worse...

Use Metformin instead = no weight gain/edema

Front 48

How could pioglitazone cause decreased bone density and increased fracture risk?

***

Back 48

PPAR-γ activation
↓
Bone marrow stromal cells diverted to form adipocytes
↓
Decrease bone density Increase fracture risk

Front 49

Adverse Effects:

-Fluid retention
Contraindicated in NYHA Class III and IV heart failure

-Weight gain

-Increased risk fracture
Women only

Back 49

pioglitazone

Front 50

Why is Rosiglitazone almost never used?

Back 50

Data suggesting increased risk of carddiovascular events --> MI, stroke

Front 51

Name the class of drugs:

-Glimepiride
-Glipizide
-Glyburide

Back 51

Sulfonylurea Drugs

Front 52

Name the sulfonylurea drugs

Back 52

-Glimepiride
-Glipizide
-Glyburide

** "GL-" **

Front 53

MOA:

- Binding of a ___ causes the K channel to close, thereby preventing K efflux.

- This depolarizes the cell, opening a voltage gated Ca channel.

- This increases the pulsatile secretion of insulin

Back 53

**Sulfonylurea Drugs**

-Glimepiride
-Glipizide
-Glyburide

Front 54

A person with type 2 diabetes took glipizide which increased insulin release from pancreatic b cells. What effect will that have on glucagon secretion from pancreatic a cells?

Back 54

Insulin inhibits glucagon release

(Decreased glucagon)

Front 55

Why may sulfonylurea drugs fail?

Back 55

They may cause permanent membrane depolarization!!

Front 56

Will a sulfonylurea cause hypoglycemia and weight gain?

***

Back 56

Yes

You are increasing insulin secretion which promtote hypoglycemia and weight gain

Front 57

Adverse Effects:

-Allergic Skin Reactions

-Hyponatremia and SIADH

Back 57

Sulfonylureas

Front 58

Name the Meglitinide Drugs

Back 58

Repaglinide

Nateglinide

Front 59

Repaglinide

Nateglinide

Back 59

Meglitinide Drugs

Front 60

Which 2 drug classes treat reduced insulin secretion caused by type II diabetes?

Back 60

Sulfonylureas

Meglitinides

Front 61

These drugs:

Have a similar MOA to Sulfonylureas
↓
Inhibit the ATP-sensitive K channels

Back 61

Meglitinides

Front 62

Clinical use of Meglitinides?

Back 62

-Type 2 diabetes

-Take before meals to control post preandial glycemia

Front 63

What class of drugs treat reduced GLP-1 secretion in tpye 2 diabetics?

Back 63

Incretins

Front 64

Name the actions of GLP-1 on:

-The stomach

-The brain

-The pancreas

Back 64

**Stomach**
Slows Gastric Emptying

**Brain**
Promote a sense of satiety

**Pancreas**
-↑ glucose-dependent Insulin secretion
-↓ Glucagon secretion

Front 65

What enzyme metabolizes GLP-1?

Back 65

DDP-IV

Front 66

How can you increase GLP-1 effects in the body?

Back 66

Give GLP-1 analog

Block DPP-IV activity

Front 67

Will meglitinides cause allergic reactions, cholestatic jaundice and SIADH like sulfonylureas?

Back 67

No..

Sulonylureas will cause these adverse effects

Front 68

name the GLP-1 agonists

Back 68

Exenatide ***

Liraglutide

** "-tide" **

Front 69

name the DPP-IV inhibitors

Back 69

Sitagliptin

Saxagliptin

** "-gliptin" **

Front 70

Which can cause a higher concentration of ‘GLP-1’ (greater GLP-1 effect)?

A. Exenatide

B. Sitagliptin

Back 70

Exenatide!!
You can give the patient as much exenatide (exogenous GLP-1 promoter) as you want for a larger effect.

Sitagliptin will only give you as much GLP-1 as your body can produce

Front 71

Which agent will most likely reduce appetite and food intake?

A. Exenatide

B. Sitagliptin

Back 71

Exenatide!

Exenatide will give you higher concentration of GLP-1 which will affect the brain!

Front 72

Sitagliptin vs. Exenatide:

-Increases glucose stimulated β-cell secretory activity

- Reduces α-cell secretory activity

Back 72

Both Exenatide and Sitagliptin will produce these low concentration GLP-1 effects on the pancreas

Front 73

Sitagliptin vs. Exenatide:

- Delays gastric emptying

- Increases satiety

Back 73

Exenatide

Will produce a high concentration of GLP-1 which will affect the brain

Front 74

What is the advantage of increasing glucose stimulated insulin release?

Back 74

Hypoglycemia WILL NOT be an issue..

The body won't secrete enough insulin to cause hypoglycemia if FBG levels are normal/low

Front 75

What is the advantage of decreasing glucagon release?

Back 75

You help normalize high glucagon levels which would (normally) increase hepatic glucose production

Front 76

Which incretin drug delays gastric emptying?

Back 76

Exenatide

Front 77

What is the advantage of delayed gastric emptying?

Back 77

Decrease the rate that carbs or absorbed and eliminate post prandial glucose spike

This allows the pancreas to "catch-up" and gain control of blood glucose levels after eating

Front 78

Why do the GLP-1 agonists cause nausea and vomiting?

Back 78

Delayed Gastric Emptying

Front 79

Adverse Effects:

Hypoglycemia – low risk

**Allergic reactions**
- Rash, hives, angioedema, anaphylaxis, Stevens Johnson syndrome

Back 79

DPP-IV inhibitors

Front 80

Adverse Effects:

Nausea, vomiting

Hypoglycemia – low risk

Pruritus, urticaria, rash

Acute pancreatitis

Back 80

Exenatide

Liraglutide

(GLP-1 Agonists)

Front 81

What effect will exenatide have on body weight?

Back 81

Delayed gastric emptying/nausea--> weight loss

Satiety factor = weightloss

(GLP-1 effects on brain)

Front 82

What effect will sitagliptin have on body weight?

Back 82

NO EFFECT

GLP-1 levels won't be high enough to affect the brain

Front 83

What drug will treat reduced amylin secretion caused by type 2 diabetes?

Back 83

Pramlintide

Front 84

This hormone is secreted and works with insulin to control glucose levels

Back 84

Amylin

Front 85

Name the amylin mimetic drug

Back 85

Pramlintide

Front 86

Clinical Use:

-Type 1 and Type 2 diabetics who inject insulin at meal times

-SubQ injection

Back 86

Pramlintide

(Amylin mimetic)

Front 87

MOA:

____ is co-secreted with insulin from pancreatic beta cells.
**Inhibit glucagon secretion
**Delay gastric emptying
**Increase satiety

- These actions slow and reduce the entry of glucose into circulation – works with insulin to regulate glucose levels.

Back 87

Pramlintide

(Amylin mimetic)

Front 88

Adverse effects:

Nausea, vomiting, anorexia

Headache

Hypoglycemia when combined with insulin

Back 88

Pramlintide

(Amylin mimetic)

Front 89

Why does pramlintide cause hypoglycemia when combined with insulin?

Back 89

You take pramlitide and insulin before eating...

The satiety caused by pramlintide (amylin) causes you to eat less so you overshoot the amount of insulin you needed for that particular meal

The excess insulin causes hypoglycemia

Front 90

What type 2 diabetes drugs reduce gastric emptying and reduce post-prandial spike in blood glucose levels? (3)

****

Back 90

Exenatide

Pramlitide (amylin)

Acarbose

Front 91

Name the α-glucosidase inhibitor

Back 91

Acarbose

Front 92

Acarbose is a ______ inhibitor

Back 92

α-glucosidase inhibitor

Front 93

MOA:

-Inhibits α-glucosidase metabolism of disaccharides to glucose
↓
-Slower absorption of glucose
↓
-Reduced post-prandial peak in blood glucose

Back 93

Acarbose

Front 94

Will acarbose reduce fasting blood glucose levels ?

Back 94

No...

It acts in the small intestine to reduce post-prandial glucose spikes

Front 95

Adverse Effects:

Flatulence
Bloating
Abdominal discomfort
Diarrhea
Elevation of liver enzymes

Back 95

Acarbose

(α-glucosidase inhibitor)

Front 96

Explain these adverse effects with acarbose:

Flatulence
Bloating
Abdominal discomfort

Back 96

Decreased breakdown of carbs in the small intestine causes colonic bacteria to breakdown the carbs and produce gas, bloating, etc...

Front 97

Know this...

Back 97

Also, Meglinitides increase weight and cause hypoglycemia by increasing insulin secretion...

Front 98

What type of effect to meglitinides have on overnight glucose levels?

Back 98

Little effect...

They have a quick onset of action and a short duration!!