1. Diabetes Mellitus Pharmacology
Presented by: Wanda Lovitz, APRN

2. Diabetes Pharmacology: Objectives
Discuss the nursing implications of oral anti-diabetes agents and and injectable anti-diabetes agents including Byetta and insulins.
Describe teaching guidelines for clients receiving oral anti-diabetes agents, insulins, or glucose-elevating drugs.
Discuss the mechanisms of action, therapeutic uses, adverse effects, and interactions of the various type of agents for type 1 diabetes mellitus.
Discuss the mechanisms of action, therapeutic uses, adverse effects, and interactions of the various types of insulins.

3. Drugs to Know glyburide (Micronase)…sulfonylurea
glipizide (Glucotrol)…sulfonylurea
metformin (Glucophage)… biguanide
pioglitazone (Actos)… glitazone (TZD)
sitagliptin (Januvia)…incretin enhancer/DPP-4 inhibitor
exanatide (Byetta)…incretin mimetic/enhancer/GLP-1 agonist (INJECTABLE FOR TYPE II)
Insulins: Novolog, Regular, NPH, Lantus & Levemir
Glucagon…glucose elevating drug used as tx for HYPOGLYCEMIA

4. High blood sugar can cause many problems
Type 2 Diabetes
can lead to:
Heart Disease
Eye Damage
Nerve damage/neuropathy
Foot Problems
Kidney Disease
Depression
Managing type 2 diabetes properly can help stop or slow down these problems

5. Agents used to treat Diabetes
Oral Agents
Sulfonylureas
Biguanides
Thiazolidinediones (TZDs)
DPP-4 inhibitors
Combinations
Injectable
…but NOT insulin
Incretin mimetic
exenatide/Byetta
Insulins
Novolog (rapid)
Regular (short)
NPH (intermediate)
Lantus/Levemir (long)
Agents to RAISE blood sugar
1. Glucagon
2. Dextrose 50%

6. Normal blood sugar ranges

7. American Diabetes Association (ADA) Blood Sugar Goals (FOR THE DIABETIC):
mg/dL before meals
Less than 180 mg/dL two hours after starting a meal (2H PP = 2 hours post prandial)
Less than 7% hemoglobin (A1C) level

8. What is a Hemoglobin A1C?
A serum blood test which measures the average glucose level over the preceding 2-3 months
Is a better indicator of glycemic control over time than the FBS
Note that a HbA1C of 6%
corresponds to an AVERAGE
blood sugar of 135

9. A better estimate of glycemic control over time: the Ha1C
Excess glucose attaches to RBC.
The life of a RBC is about 3 months

10. Target sites of the oral agents
Pancreas
Liver
Intestine
Adipose tissue
Muscle
Kidneys

11. Limitations of oral agents for TYPE II diabetics only!
Usually started after diet and exercise fail to adequately control blood sugars
Can typically reduce HbA1c by 0.5 – 2.0%
Mechanism of action addresses THE SYMPTOMS of diabetes rather than the underlying pathophysiology
Many UNDESIRABLE SIDE EFFECTS which often affects adherence (hypoglycemia, n/v, peripheral edema, weight gain)
BETA CELL FUNCTION TENDS TO WORSEN OVER TIME
Clinicians often fail to intensify therapy/start insulin to obtain good control

12. Oral agents: nursing implications
Wanda as a “Baby Nurse”
Oral agents: nursing implications
Nursing implications –
monitoring of glucose levels and glycosylated hemoglobin (HA1C)
assessing for sulfa hypersensitivity (sulfonylureas)
administering most agents with meals
understanding the onset of action, peak, and duration associated with oral agents
assessing patient teaching needs
assessing for hypoglycemia

13. Patient Voices: Larry with Type II
Copy and paste the address above into your browser to hear several different patients talk about living with diabetes.

14. Hyperglycemia vs Hypoglycemia
High blood sugar
FBG levels of greater than 126 on 2 or more occasions=DM
Insulin Resistance when FBG is greater than 100 but less than 126
BG normally rises after food consumption
Should return to near normal in 2H = 2hPP
Hypoglycemia
Low blood sugar
Most people are symptomatic with when levels are below 60
Diabetics may have ‘hypoglycemic’ reactions when BS drops after they receive anti-diabetic meds
Especially if oral intake is insufficient

16. SULFONYLUREAS MOA: (1) act in pancreas to  insulin production
INSULIN SECRETOGOGUES
Think of sulfonylureas as “oral insulin”
Sulfonylureas increase insulin output from the pancreas
Any agent that increases insulin output from the pancreas has the potential to cause hypoglycemia

17. Sulfonylureas
First-generation agents – chlorpropamide (Diabinese), older, less potent drugs
Second-generation agents –
*glyburide (Micronase)
glipizide (Glucotrol)
glimepiride (Amaryl); newer, more potent drugs

18. SULFONYLUREAS
Adverse effects - nausea, vomiting, epigastric discomfort, heartburn, skin rash, HYPOGLYCEMIA, photosensitivity, hematologic problems (e.g., hemolytic anemia), thrombocytopenia), WEIGHT GAIN
Contraindication: allergy to sulfa

19. Sulfonylurea: glyburide/Micronase
glyburide/Micronase is the most frequently
prescribed 2nd generation sulfonylurea
Micronase has a slower onset and longer duration of action than another frequently rx sulfonylurea -*glipizide (Glucotrol)
These agents are beneficial in controlling glucose levels throughout the day and night
glyburide/Micronase is sometimes used with glipizide/Glucotrol to better control glucose levels at meals = SYNERGISTIC EFFECT
Onset 1 – 1.5 hours; peak 4 hours; duration hours

20. BIGUANIDE: metformin *THE most popular oral anti-diabetic agent in the U.S.
metformin (Glucophage) often used as monotherapy with type 2 diabetes
may also be used with a sulfonylurea
MOA:
(1) DECREASES HEPATIC GLUCOSE PRODUCTION and production of triglycerides and cholesterol from the liver
(2) enhances glucose transport into cells
IMPROVES INSULIN SENSITIVITY by increasing peripheral glucose uptake and use
(3) decreases glucose uptake in the intestine
SOME WEIGHT LOSS EXPECTED 

21. MOA: metformin/Glucophage
1. intestinal absorption of glucose
2.  hepatic glucose production
3. insulin sensitivity by
 glucose uptake in tissue
Advantage over sulfonylureas: Since it has little to no effect
on pancreatic output, NOT AS MUCH CONCERN
WITH HYPOGLYCEMIA!

22. BIGUANIDE: (metformin/Glucophage)
Onset several DAYS
peak 2-4 weeks
Adverse effects:
abdominal bloating
nausea, vomiting, DIARRHEA
diarrhea can be uncontrollable; fecal incontinence issues for some
“Metformin moment”
risk for LACTIC ACIDOSIS in pts with  creatinine
can be life threatening!
Nursing implications –
recognize that it will not immediately lower BG
monitor serum glucose level
give 30 minutes before a meal
Hold before any test which requires IV contrast dye d/t risk of lactic acidosis!!

23. THIAZOLIDINEDIONES /GLITAZONES or TZDS
MOA:
1. Decreases INSULIN RESISTANCE
does this by:
increasing sensitivity of insulin receptors
increaseing glucose uptake and use in skeletal muscle
2. Decreases fatty acid
output in adipose tissue
3. Decreases glucose output in the liver

24. Insulin Resistance

25. TZD: pioglitazone/Actos
Available agents
pioglitzaone/Actos
rosiglitazone (Avandia)
Adverse effects
EDEMA
weight gain
mild anemia
MAY CAUSE LIVER DAMAGE
Onset unknown; peak unknown, duration hours

26. TZDs pioglitazone/Actos rosiglitazone/Avandia
ADVANTAGE of glitazones:
DOES NOT CAUSE HYPOGLYCEMIA since they do not have an affect on pancreatic production of insulin
May PRESERVE SOME BETA CELL FUNCTION
MAY HAVE PROTECTIVE VASCULAR effects (lowering chlolesterol)
DISADVANTAGE: may be toxic to the LIVER
Must have LFTs (ALT and AST) monitored

27. Newest Class: Incretin MIMETICS: exenatide INJECTION (Byetta)
Incretins are INTESTINAL HORMONES released in response to ingestion of food
Incretins increase the insulin response and depress the gluconeogenesis in the liver ↑insulin and ↓ glucose = lower BG
Incretins naturally decrease appetite
NOTE: The incretin response is DIMINISHED in type II diabetics!
Incretin mimetics, mimic the response of endogenous incretin
So….. Mimicking/enhancing the incretin response would result in lower glucose levels

28. exenatide/Byetta

29. exenatide/Byetta “Incretin Enhancer”
Given as a SQ INJECTION within 1H of morning and evening meal (BID)
Major SE is NAUSEA AND HYPOGLYCEMIA
Not a substitute for insulin!!
Serious SE: pancreatitis
Should NOT be used in Type I DM!!
Is NOT to be used to treat DKA
Average weight loss is 5-10 pounds

30. DPP-4 INHIBITOR/incretin enhancer: sitagliptin/Januvia
A once a day oral agent
Is a DPP-4 inhibitor – Blocks DPP-4
DPP-4 breaks down the hormone incretin
Low levels of incretin result in a DECREASE in the response from the pancreas and less insulin is secreted
Low levels of incretin also result in an increase in glucose output from the liver
Leading to Hyperglycemia

31. MOA: sitagliptin/Junuvia
So…DPP-4 inhibitors slow the degradation of incretins thus prolonging the action of the incretins increasing/enhancing incretin levels
The result in an  in output of insulin from the pancreas and a in glucose output from the liver
End result is lower glucose levels

32. DPP-4 inhibitors: MOA

33. Summary Slide: Effects of oral agents on diabetes

34. Combination Drugs: Many out there
glyburide/metformin (Glucovance)
1.25/250; 2.5/500; 5/500
rosiglitzone/metformin (Avandamet)

35. Summary Slide/ Side Effects of Antidiabetic Agents

36. Anti-diabetic Agents: the Insulins

37. INSULINS Various types of insulins:
Effects similar to the endogenous insulin produced from the pancreas
Primary treatment for type 1 diabetes
may also be used in the management of type 2 diabetes and gestational diabetes
Various types of insulins:
rapid acting
short acting
intermediate acting
long acting
mixed
Pork, beef in the past
Now human source insulins
Human more effective, causes fewer SE
and has a lower incidence of resistance

38. Which type of diabetic patients receive insulin?
TYPE I DM
and
TYPE II DM

39. Insulin as the “key” Insulin allows the glucose to get inside the cell
Without insulin, the glucose stays in the bloodstream causing hyperglycemia

40. RAPID ACTING INSULINS Nursing implication
Types of rapid acting insulins:
lispro (Humalog)
aspart *(Novolog)
Onset 0-15 minutes!!!
Peak 1H
Duration 3H
Used with sliding scale regimens (SSC)
“CORRECTION INSULIN”
“BOLUS INSULIN”
Nursing implication
risk for hypoglycemia by making sure that the meal is available before administering
Subcutaneous use: Humalog and Novolog
Intravenous use (Novolog only)

41. SHORT ACTING INSULINS Regular Onset 30-60 minutes (sub-cu)
Intravenous or subcutaneous use
Onset minutes (sub-cu)
Peak 2-3H
Duration 4-6H
Also used with SLIDING SCALE/CORRECTION REGIMENS

42. INTERMEDIATE ACTING INSULINS
Neutral Protamine Hagedorn (NPH) forms
Types include:
*Humulin N and Novolin N
Onset hours
Peak 6-14 hours
Duration hours
CLOUDY insulin
NPH is given BID
NPH is normally given 30 min before
1st meal of the day (2/3 dose) and
(1/3 dose) before the evening meal or
at bedtime. BID dosing

43. LONG ACTING “BASAL” INSULINS
Two types:
*glargine/Lantus
detemir/Levemir
Onset 2-4 hours;
Duration 24 hours
Closest insulin to the body’s own basal insulin
Constant duration with NO DEFINED PEAKS
A basal or slow acting insulin
Important note:
Lantus and Levemir
MUST NOT BE MIXED with any
other insulin

44. MIXED/Combination Insulins
Developed to more closely stimulate varying levels of normal endogenous insulin production
Varying types – Humulin 70/30, 50/50, Novolin 70/30
Contain varying amounts of intermediate and short acting insulin

45. INSULIN REGIMENS BASAL/BOLUS INSULIN
Basal insulin: example: Lantus or Levemir
provides “basal” coverage
usually once a day dose
Bolus insulin: example: Regular or Novolog
given before meals to “cover” elevated BS
FSBS or CHO count done to determine dose
CORRECTION INSULIN/Sliding scale regimens (SSI/SSC)-
regular insulin dosages are adjusted based on finger stick blood sugar(FSBS)
TYPICALLY AC AND HS
May or may not be used with a basal insulin

46. Comparison of action of NPH and Lantus
Note that the Regular insulin
peaks in about 3H and is just
about gone within 10H.
Note that the Lantus has no
peaks and is present for about
24H.
Also, the action of Lantus
most resembles the body’s
own (endogenous) insulin.

47. The Ideal Insulin Regimen
Simulates the body’s own normal insulin output
Combines “Basal” insulin with “mealtime” insulin
Is called a “basal-bolus” regimen
Bolus also known as “correction” insulin- it corrects high BS before a meal- “sliding scale insulin”
Uses rapid- and short-acting (bolus) insulin before meals PLUS
Uses a background insulin once a day
Commonly prescribed as 4 injections a day:
Lantus or Levemir at bedtime
Novolog or Regular before each meal

48. Adverse Effects of Insulin
Insulin Reaction
AKA: HYPOGLYCEMIA – occurs when there is more insulin in the blood than is needed for the amount of circulating glucose
Causes:
Med error
Patient exercised and insulin peaked
Patient doesn’t eat after taking insulin
SX usually seen when BG 60 or less
R/t hypoglycemia, hyperglycemia, or hyper-insulinemia
Localized allergic reactions at the injection site
Generalized urticaria and swollen lymph glands

49. Insulin delivery methods
Wireless pumps
Insulin pens

50. GLUCOSE – ELEVATING DRUGS GLUCAGON & 50% DEXTROSE
MOA: STIMULATES hepatic production of glucose from glycogen stores. Used to treat hypoglycemia.
RAISES THE BLOOD SUGAR
Administered IM, IV, or SC
Indication: To treat hypoglycemic reactions
Adverse effects – nausea and vomiting, tachycardia, and anaphyaxis
**50% Dextrose (D50W) IVP is also given to raise low blood sugar for severe hypoglycemia**

51. Summary Slide: Hypoglycemia vs Hyperglycemia

52. Case study: Bill
Bill is a 68 year old male hospitalized at UKMC for treatment of a left leg wound INFECTION. Because he has had a flare of his asthma, Bill was also placed on po PREDNISONE.
PMH of type 2 DM and is currently taking metformin (Glucophage) and glyburide (Micronase). He is ordered FSBS with SSI. His BS at 7:00 am is 352 and the nurse gives him 12 units of Regular insulin per the SSI protocol. He c/o nausea and only drinks 30cc of juice for breakfast. At 10:30 he is c/o being “shaky”, is diaphoretic and his HR is 110. A FSBS shows his glucose is now 44.
Discussion Questions
Bill’s BG is very high. What are the factors that may be contributingto this spike? His wound infection and the prednisone would both cause elevated BG levels.
What has happened to Bill? Hypoglycemic reaction
What are the contributing factors? Did not eat breakfast, so not enough CHO and the SSI given caused his BG to drop too much
What action/actions should the nurse take? Use the Rule of 15 and give Bill food/drink that contains 15 GM of CHO to quickly raise his BS. Can then follow with a comples CHO such as peanut butter and crackers to help stabilize his BG.

53. Case Study: Bryan
Bryan is a 9 year old boy who has had type 1 since the age of 6. He has an insulin pump and does that delivers a basal dose of Lantus insulin. He also gives himself correction Novolog insulin as needed before meals (AC). Bryann has been in good control and his last Ha1c was 6.5%.
Bryan is being treated with antibiotics for a sinus infection.Today he is brought to the ED after collapsing on the soccer field.
He is responsive but confused, has a RR of 32 with deep rapid respirations and you note a “fruity” smell to his breath. A FSBS is 448.
Discussion Questions:
What is going on? Acute complication of type I DM...DKA
Why? High BS causing formation of ketones as fat is being used for energy
What further information would you want to collect? Any s/s of infection? Infection can cause elevated BG as well
What do you anticipate the MD will order? Either IV insulin (regular or humalog) to quickly bring down his blood sugar. IV fluids to treat the dehydation that occurs with DKA
If blood gases were drawn, what would you anticipate his PH to be?
Metabolic acidosis

54. Case Study: Mary
Assessment data:
FSBS was 623
Mucous membranes dry
Only responsive to painful stimuli
There is a Stage III decubitus ulcer on her sacrum that is draining purulent material
Discussions Questions:
What is going on with Mary? Acute complication of type II DM...HHNKS
Why factors might have contributed to this condition? Dehydration
What treatment will likely be ordered? IV insulin to quickly lower the BG and IVF to treat the dehydration
How could this be prevented?
By improved care in ensuring Mary ate and drank adequately.
Mary, an 82 year old resident of a nursing home, is brought to the ED for evaluation because this morning the staff could not awaken her for breakfast.
Mary has a h/o left sided weakness d/t a CVA and mild dementia.
The nurse tech accompanying her to the ED tells you she has been having a hard time getting Mary to eat and drink for the last couple of weeks.

55. TIME IS UP!