ANTIDIABETIC AGENTSINSULIN INSULIN

ORAL HYPOGLYCEMICSORAL HYPOGLYCEMICS

Fall 2013

INSULIN

Insulin is a hormone produced in the beta cells of the pancreas, secreted at a rate of 0.5 to 1 unit per hour. Average insulin secretion in adult is 30-50 Units per day.

Insulin is required for entry of glucose into skeletal and heart muscle and fat.

Insulin is important in protein and lipid metabolism.

Decrease in insulin = decrease in glucose into cell = hyperglycemia

Beef and pork discontinued in US in 2005Biosynthetic insulins are now available for

most patients

INSULIN CONCENTRATION

100 Units per mL

Regular insulin may come 100 Units / mL or

500 Units / mL for IV use

ONLY USE INSULIN SYRINGE

Exogenous insulin works the same as endogenous insulin

Transports glucose FROMFROM the blood to the INSIDEINSIDE of cells and

Takes excess glucose to the liver for storage This results in LOWERINGLOWERING of the blood blood

glucoseglucose level

Mechanism of Action

THERAPEUTIC USES

Insulin is the drug of choice for type 1 and type 2 uncontrolled by diet, exercise or oral hypoglycemic agents

Hormonal replacement - remember insulin is a hormone

GoalGoal - maintain stable blood glucose levels

ADMINISTRATION

Subcutaneous injectionSyringe and needlePen injectors Jet injectorsInhalationExuberaSubcutaneous infusionPortable insulin pumps Implantable insulin pumpsIntravenous infusion

ADVERSE EFFECTS

The most significant adverse effect is HYPOGLYCEMIAHYPOGLYCEMIA

The signs & symptoms are the same for any hypoglycemic reaction / state

BLOOD GLUCOSE MUST BE BLOOD GLUCOSE MUST BE MONITOREDMONITORED

DOSAGE

INDIVIDUALIZEDINDIVIDUALIZEDInsulin dosage is “tailored”

to each patient specifics metabolic needs to achieve stable blood glucose levels

INSULIN PEAK / ONSET / DURATION

It is important to know the insulin’s onset, peak and duration

Onset- time required for the med to have an initial effect

Peak – when agent will have the maximum effect

Duration – length of time the agent remains active in the body

RAPID ACTINGHumalog (lispro) or (Novolog) aspart

Synthetic formClear solutionCan be given separately or mixed with

intermediate or long acting insulinsMore rapid and shorter acting than human regular

InsulinOnset / Peak / Duration = 10 min / 1 -3 hr / 3-6 hrsAdminister within 10 – 15 minutes of a meal

Apidra (insulin glulisine)Onset / Peak / Duration = 10-15 min / 1-1.5 hr / 3-5

hrsGive within 15 min before mealCan be used in insulin pumpCan be mixed with NPH for subcutaneous injection

SHORT DURATIONRegular InsulinHumulin R, Novolin R

Onset / Peak / Duration = 30 to 60 min / 1-5 / 6-10 hrs

Can be given Sub Q and IV Routes: IV, sub Q, IM, inhalationAdminister no sooner than 30 minutes before meal

Exubera – inhaled insulin Onset / Peak / Duration = 15 to 30 min / 0.5-1.5 hrs /

6.5 hrs

Fine powder of regular insulin

NPH (Neutral protamine Hagedorn)

Onset / Peak / Duration 2-4 / 4-12 / 16-20 hrs

Contains specific amounts of regular insulin and protamine

Onset is delayed and action is extended.

Cloudy solution, must be gently agitated before drawing up.

Usually administered twice daily

Intermediate Acting Insulins

PREMIXED INSULIN COMBINATIONS

Humalog Mix 75 – 25 (75% Lispro protamine solution with 25 % Lispro solution)

Rapid onset with intermediate durationOnset / Peak / Duration 15-30 min / 1-6.5 /12-24 hrs

Humulin 50/50 (R=50, N=50)Humulin 70/30, Novolin 70/30, (N=70,

R=30)30 min / 2-12 hr / 24 hr

LONG ACTING INSULINSInsulin detemir (Levemir)Onset / Peak / Duration / 6-8 / 12-24Slow onset and dose dependent durationProvides basal glycemic controlAs compared with NPH, has slower onset

and longer durationClear solutionAdministered once or twice daily

Long Acting

Humulin U (Ultralente)Onset / Peak / Duration

6-8 / 12-16 / 20-30

VERY LONG ACTING INSULIN

Very Long Acting

Insulin glargine (Lantus)Onset 1 hour no pronounced peak Duration 24 hours

LANTUS

NOT to be confused with LENTELong lasting basal insulinSlow steady release of insulin needed to

control blood glucose & keep cells supplied with energy when no food is being digested

ONCE-A-DAY - AT BEDTIME usuallySteady absorption - NO PRONOUNCED

PEAKWorks twice as long as NPH (Lantus 24

hrs, NPH 14.5 hrs)Used for adults with Type 2 or children

and adults with Type 1

LANTUS

Does NOT replace short-acting insulins

Can be used with oral anti-diabetic medications

MUST NOT be diluted or mixed with any other insulin or solution

MUST use U-100 syringe

NOT intended for IV use

Patients experience same side effects (hypoglycemia & injection-site reactions)

STOP AND THINK

if you administer 10 units of regular insulin at 7:00 am when should you observe for hypoglycemia?

if you administer 5 units of Humulin R insulin and 22 units of Humulin N at 7:30 am when will you observe for hypoglycemia?

if you administer 7 units of Humulin R at 11:30 am when will you observe for hypoglycemia?

if your patient is NPO for breakfast and is due insulin at 7:30 am what should you do?

INSULIN STORAGE

Insulin should not be allowed to freeze, nor be heated above room temperature.

Insulin should be stored in the refrigerator until opened, then may be stored at room temperature until gone.

At sustained temperatures above room temperature, insulins lose potency rapidly.

Excess agitation should be avoided to prevent loss of potency, clumping or precipitation.

All insulins except Regular, Lispro and Aspart should be gently rolled in the palms to resuspend solution. (Do not shake)

NURSING IMPLICATIONS

when mixing insulins - CLEAR TO CLOUDYCLEAR TO CLOUDY

do not “shake” insulin vial to resuspend cloudy mixtures - gently rotate / roll vial in palm of hand or swirl, avoids bubbles

insulin must be stored in a stable temperature, refrigeration prolongs shelf life, in clinical settings - opened vial MUST be dated & initialed

schedule snacks to coincide with insulin PEAK’sPEAK’s

SAFE PRACTICE FOR INSULIN ADMINISTRATION

BEFORE ADMINISTERINGBEFORE ADMINISTERING:

Check the original doctor’s order

KNOWKNOW your patient’s blood sugar and “trends or patterns”

Check the last time your patient ate (what & how much)

Check other drugs patient is taking and question yourself about interactions

REVIEW ADMINISTRATION

ADMINISTERED SUBQADMINISTERED SUBQ (unless emergency and then ONLY Short ACTING insulin can be given IV)

45 or 90 degree angle

27 - 25 G needle (microfine) (Only administer in an insulin syringe)

5/8 inch

do not have to aspirate

NURSING IMPLICATIONS

ALL insulin dosages ALL insulin dosages MUSTMUST be be DOUBLE CHECKED by a second DOUBLE CHECKED by a second LISCENED personLISCENED person

administer insulin only with an insulin syringe calibrated for that concentration of insulin

BEFORE ADMINISTERINGBEFORE ADMINISTERING:

check the original doctor’s order KNOWKNOW your patient’s blood sugar and “trends or patterns”

Check the last time your patient ate Check other drugs patient is taking and question yourself about interactions

SITE ROTATION

Diabetics should be taught to ROTATEROTATE their injection sites

This is done to prevent “lipoatrophy” / scarring at the injection site - which results in variable insulin absorption

SUBCUTANEOUS

INSULIN ADMINISTRATION: METHODS OF DELIVERY: INSULIN PENS

INSULINS THAT CAN BE USED IN PUMPS: REGULAR, LISPRO, ASPART, GLULISINE

INSULIN ADMINISTRATION: METHODS OF DELIVERY: INSULIN INJECTORS

COMPLICATIONS OF INSULIN THERAPY

Local Reactions

Redness, tenderness, swelling, induration

1-2 hours after insulin administration

May occur at beginning of therapy and resolve

COMPLICATIONS OF INSULIN THERAPY: INSULIN LIPODYSTROPHY

Localized reaction

Lipoatrophy loss of subcutaneous fat, appears as dimpling or pitting in of

subcutaneous fat

Lipohypertrophy the development of fibrofatty masses at the injections site. Caused by repeated use of same injections site. Insulin injected into scarred areas, absorption is delayed

DIABETICS IN THE HOSPITAL SETTING

Hospitalization may drastically affect insulin requirements because of stress (infections, surgery, acute illness, inactivity, variable food intake)

It is often used to monitor patients on hyperalimentation

Blood glucose checks are ordered at specific intervals - most often ac & at bedtime

The insulin dose is then adjusted to a predetermined “scale” ordered by the physician

The ONLY type of insulin used in sliding scale is

Short Acting (Regular Insulin) Acting (Regular Insulin)

SLIDING SCALE

Method of insulin “dosing”

Dose is adjusted according to blood glucose results

This method of dosing is most often used for hospitalized diabetics

Sliding Scale OrderBlood glucose < 200 - give 0 units Regular

Insulin

Blood glucose 201 - 249 give 4 units Regular Insulin

Blood glucose 250 - 299 give 6 units Regular Insulin

Blood glucose > 300 call Dr.

At 0730 your patient is scheduled to receive 20 units of Humulin N and 5 units of Humulin R, their blood sugar level is 247, what will you give?

SLIDING SCALE ORDER

EXAMPLE:EXAMPLE:

Blood glucose < 200 - give 0 units Regular Insulin

Blood glucose 201 - 249 give 4 units Regular Insulin

Blood glucose 250 - 299 give 6 units Regular Insulin

Blood glucose > 300 call Dr.

At 1130 your patient’s blood sugar is 284, how much insulin will you give?

What type of Insulin is ordered for sliding Scale?

Sliding Scale Order

Blood glucose < 200 - give 0 u

Blood glucose 201 - 249 give 4 u

Blood glucose 250 - 299 give 6 u

Blood glucose > 300 call Dr.

Order: Regular Insulin per sliding scale AC & HS

Order: Lantus 10 Units sub Q at bedtime.

Your patient’s blood glucose at 2100 is 278, how much insulin will you give?

How would you administer it?

ORAL HYPOGLYCEMICS

Oral hypoglycemic agents work in one of three ways:

STIMULATESTIMULATE the pancreas to produce more insulin

DECREASEDECREASE glucose production

INCREASEINCREASE glucose uptake by the cell by enhancing the effectiveness of insulin

Oral hypoglycemics are usually only given to Type II diabeticsType II diabetics

SULFONYLUREA ORAL HYPOGLYCEMICS: SECOND GENERATION

EXAMPLES EXAMPLES Diabeta, Micronase (glyburide); Glucotrol (glipizide), Amaryl (glimepiride)

Action: LowersAction: Lowers blood sugar by stimulating the release of insulin from beta cells of the pancreas

Adverse reactions: hypoglycemiahypoglycemia, nausea, heartburn, bloating, flatulence, anorexia, skin reactions, photosensitivity, allergic reaction, CNS - paresthesia, tinnitus, dizziness, wt gain, edema

Contraindicated with Sulfonamide allergy

Monitor for hepatotoxicity, blood dyscrasias, dermatologic reactions

Drug interactions: Beta Blockers may mask hypoglycemic reactions, alcohol may result in Anabuse like reaction

BIGUANIDE ORAL HYPOGLYCEMIC AGENTS

metformin (GLUCOPHAGE)Action:Action:Decreases glucose released from liverDecreases intestinal absorption of glucose, metforminImproves insulin sensitivityResulting in improved blood glucose controlUSES:Type II diabetesMay be combined with other antidiabetic agentsSIDE / ADVERSE EFFECTS:Primarily GI effects - bloating, nausea, cramping, diarrheaAdvantage: Does not cause hypoglycemia, does not cause

wt gain, favorable effect on triglyceridesIncreased risk for lactic acidosis and renal failure, Stop

Metformin 48 h prior to and 48 h after diagnostic procedures using a contrast agent.

ALPHA-GLUCOSIDASE INHIBITORS

accarbose (Precose), miglitol (Glyset)

Action: Delay absorption of complex carbohydrates in intestine, slow entry of glucose into systemic circulation, does not increase insulin secretion.

SE: hypoglycemia, GI affects

Administration: taken with first bite of food

Monitor: LFT

Not systemically absorbed

NON-SULFONYREA INSULIN SECRETAGOGUES Examples◦Repaglinide (Prandin) (SE – hypoglycemia)

◦Nateglinide (Starlix) Action: Stimulate release of insulin

from beta cells in the pancreas Rapid action and short half life Taken before each meal

THIAZOLIDINEDIONE ORAL HYPOGLYCEMICS (TZD)(THIGH-A-ZOE-LID-EEN-DIE-OWN)Rosiglitazone (row-sih-GLIT-uh-zone) AvandiaPioglitazone (pie-oh-GLIT-uh-zone) Actos

ActionAction: Increases sensitivity of muscle and fat tissue to

insulin, allowing more glucose to enter the cells

May inhibit hepatic glycogenesis and decrease hepatic glucose output

SE Expected: N/V, anorexia, Abd crampsSE unexpected: hypoglycemia, hepatotoxicity,

wt. gainDrug Interactions: Beta Blockers ay ask signs of

hypoglycemia, may cause BC pills to be ineffective

DRUG INTERACTIONS

There are SIGNIFICANT SIGNIFICANT potential drug interactions between oral hypoglycemics and multiple classifications

Sulfonylureas: alcohol, oral anticoagulants, antibiotics (sulfa), corticosteroids, thiazides, furosemide, thyroid drugs

Biguanides: furosemide, digoxin, nifedipine, cimetidine

Thiazolidinediones: reduces effectiveness of BC

TEACHING PLAN

HBA1C: GLYCOSYLATED HEMOGLOBIN A1C

Monitor lab test to determine BS control

An accurate long term index of the patient’s average blood glucose level

Reflects the average blood glucose level over the past 100-120 days

Good control = 2.5 – 5.9 %

Fair Control = 6-8% Poor control = > 8%

GLUCOSE TESTING

Using the Glucometer – (Measures capillary blood glucose)

• Wash hands• Sterile 2x2, alcohol swab,

towel, Glucometer, non-sterile gloves

• Open sterile packages, place in reach, Don gloves

• Select finger – lateral aspect of fingertips

• Apply warm compress if cold fingers

• Place towel under hand• Cleanse and allow to air dry• Puncture finger and squeeze• Wipe off 1st drop with 2x2• Collect blood on strip – cover

entire area. 2x2 to site

TEST YOUR KNOWLEDGE

A patient in the ICU requires intravenous insulin. The nurse is aware that:

A. insulin aspart or glargine can be administered IV.

B. any form of insulin can be used IV at the same dose ordered for subcutaneous administration.

C. insulin should never be given IV, and this order should be questioned.

D. only regular insulin can be administered IV.

TEST YOUR KNOWLEDGE

A type 1 diabetic patient on insulin reports taking propranolol for hypertension. This provokes the concern that:

A. the beta blocker can produce insulin resistance.

B. the two agents used together will increase the risk of ketoacidosis.

C. propranolol will increase insulin requirements because of receptor blocking.

D. the beta blocker can mask the symptoms of hypoglycemia.

TEST YOUR KNOWLEDGE

A nurse counsels a diabetic patient starting therapy with an alpha-glucosidase inhibitor. The patient should be educated about the potential for which adverse reaction(s)? You may select more than one answer.

A. Hypoglycemia

B. Flatulence

C. Elevated iron levels in the blood

D. Fluid retention

E. Diarrhea

TEST YOUR KNOWLEDGE

A diabetic client taking daily NPH insulin has been started on therapy with dexamethasone (Decadron). The nurse anticipates that which of the following adjustments in medication dosage will be made?

1. Decreased NPH insulin

2. Increased NPH insulin

3. Lower dose of dexamethasone (Decadron) than usual

4. Higher dose of dexamethasone (Decadron) than usual

TEST YOUR KNOWLEDGE

The nurse monitors the blood glucose level of the client who received NPH insulin at 7 AM knowing that the client may experience a hypoglycemic reaction between:

A. 9 to 11 AM

B. 1 to 7 PM

C. 7 to 11 PM

D. Midnight to 6 AM