Professional Documents
Culture Documents
NURP423 Exam 1
NURP423 Exam 1
What Is Asthma?
Reversible, Intermittent, possibly allergic inflammation of the airway which accompanied by wheezing,
cough, chest tightness mostly during the night.
Complex and characterized by variable and recurring symptoms
Caused by:
o Bronchoconstrictionbronchial smooth muscle contraction
o IgE mediated
o Non-IgE mediated (aspirin, exercise, cold air)
o Airway edema
o May or may not be sensed
o Airway hyperreponsiveness
o Airway remodeling
o COPD state
Triad of Asthma: Airflow obstruction, (smooth muscle) bronchial hyperresponsiveness/ hyperplasia,
and inflammation
Types:
o Atopic or extrinsic
o Allergenic asthma, needs to be triggered by allergends
o Non-Atopic or intrinsic
o Viral Infection, Aspirin, exercises, stress, cold, occupations- toxins
NIH Revisions in 2007
Conduct severity rating when/if no long-term control medications are needed
Incorporate number of oral steroid courses needed per year into severity
Go up and down on treatment by "steps" based on level needed to maintain control
o Step 1 (mild) to Step 6
After establishing a step and severity rating, use validated tools to measure control and quality of life
Comorbidities
Prior to/concurrent with assessing severity and starting pharmacologic therapy, must assess for/rule out
comorbidities/complicating factors
If present, must treat
Sx
Noc Sx
Lung Function
Long term
Quick relief
1 mild intermittent
< 2 wk
2 month
None
SABA (albuterol-INH)
2 Mild persistent
>2wk
>2month
SABA (albuterol-INH)
Daily
Continua
l
>1/wk
Frequent
60-80%
<60%
Inhaled Corticosteroid
and Leukotriene INH (po)
Steroid + LABA
Steroid + LABA + PO
steroids
SABA (albuterol-INH)
SABA (albuterol-INH)
Classifying asthma severity in patients after asthma becomes well controlled, by lowest level of treatment
required to maintain control---Need to know
Levalbuterol
R-isomer of racemic albuterol
Side effects = tachycardia, palpitations, tremor, insomnia, nervousness, nausea, headache
As effective as albuterol with fewer cardiac side effects
o Same side effect but use less amount, hence small dose fewer side effects
Dosing not equivalent
o 0.31 to 0.63 mg levalbuterol ~ equal to 2.5 mg of albuterol
Systemic Corticosteroids
Should be used in all moderate to severe exacerbations
Risk of adverse effects related to dose and length of treatment hence the term "steroid burst"
"Steroid burst": short-term (five to seven days), must be tapered off
No consensus on increments or timeline
a. 60/4040/6020/80 0/100
Dosing Memorize
o Prednisone/prednisolone 12 mg/kg/day, max 4080 mg/day outpatient
o COPD 40 mg/day
o Asthma 60 mg/day
Asthma Medications form Leik book
Rescue Medicine
Only one drug class used for rescue: short-acting B2 agonists
Short-acting B2 agonists metered-dose inhalers (MDI) or by nebulizer.
Albuterol (Ventolin HFA) or pirbuterol (Maxair): 2 inhalations q4-6hrs PRN
Levalbuterol (Xopenex HFA): ): 2 inhalations q4-6hrs PRN
Quick onset (15 to 39 minutes) and lasts about 4 to 6 hours.
Used for quick relief of wheezing, but does not treat underlying inflammation
Long-Term Control Medications
These drugs act as anti-inflammatoreis. Must be taken every day to be effective.
Long-acting B2 agonists (LABAs) are not rescue drugs. Must be taken BID
LABAs increase the risk of death from asthma.
Oral thrush: prevent with use of spacer and rinsing after use
o
Monitor for thrush and treat if occurs
Linear growth velocity: may slow linear growth velocity but uncontrolled asthma may also slow growth
o
Studies show loss in height small, nonprogressive and may be reversible (??).
Bone mineral density: doses >2000 mcg of beclomethasone a day and age >18 years old
o
Consider biphosphonates and monitoring bone density q 12 years if at high risk
o
High-dose inhaled corticosteroids
o
Increased rate of bone fractures with COPD
Only adjunctive therapy to demonstrate added efficacy to high dose ICS+LABA in patients who
have severe persistent allergic asthma
Approved for patients aged 12 and over known to have inhaled allergen sensitivities
Adverse effects: injection site pain, bruising, urticaria, anaphylaxis, risk of malignancy
Leukotriene Modifiers
Alternative but not preferred treatment for mild persistent asthma
Or adjunct to ICS (12 and over use LABA first)
Leukotrienes: powerful biochemicals released from mast cells, eosinophils, and basophils that
contract smooth muscle, increase vascular permeability, increase mucus secretions, attract
inflammatory cells
Adjuct to inhaled corticosteroids
Leukotriene Inhibitors
5-lipoxygenase pathway inhibitors (Zileuton = Zyflo)
o Approved age 12+
o Need to check LFTs regularly
o Cytochrome P450 inhibitor increase level to Theophyline
o Side effects: headache, nausea, dyspepsia, abd pain
Leukotriene Inhibitors: Side Effects
Vasculitis (rare)
Insomnia
Dream abnormalities
Nausea/vomiting/diarrhea
Elevated liver enzymes
Eosinophilia
Muscle cramps
Cough/rhinorrhea
Leukotriene Receptor Antagonists (LTRAs)
Montelukast (Singulair)
o Can use in children 6 months and older
o Cytochrome P450 substrate
o Benefit of once-daily dosing
Zafirlukast (Accolate)
o Can be used in children 5 years and older
o Cytochrome P450 substrate and inhibitor
o Requires BID dosing
Singulair and Behavior Changes
FDA released alert in 2008
Singulair may increase risk of:
o Mood/behavior changes
o Suicidal thinking/behavior
o Suicide
Cautions all health care providers to review patients on Singulair and assess for behavior changes and
suicidality
Methylxanthines
Theophylline and SR theophylline
Alternative but not preferred treatment for mild persistent asthma and COPD
Alternative but not preferred adjunct to ICS
Provides mild to moderate bronchodilation
Caffeine, in the same family, produces similar effects
Nonselective phosphodiesterase inhibitor
Less effective than ICS, use when pt has aversion to inhaled meds or cost is issue
Methylxanthines: Side Effects
Toxicity an issue: monitor serum levels!
S/S toxicity:
o Severe headache
o Tachycardia, PVCs
o Nausea and vomiting
Many drug interactions
GI upset
GER
Diarrhea
N,v
Abd pain
Nervousness
Insomnia
Muscle cramps
Tremor
Asthma: Long-Term Control Medications
Drug Class
Brand Name
Inhaled Corticosteroid
LABA combination
Leukotriene Inhibitors
Mast Cell stabilizers
Methylxanthines
Immunomodulators
Chronic bronchitis: chronic cough for three months in each of two successive years; when other causes
have been ruled out (bronchiectasis).
Emphysema: abnormal and permanent enlargement of airspaces distal to the terminal bronchioles, with
associated destruction of the airspace walls, without fibrosis (however, fibrosis is seen with pneumonia
as well as in the early stages of emphysema).
Asthma: chronic inflammation associated with airway responsiveness, with wheezing, breathlessness,
chest tightness. Airflow obstruction in asthma is usually reversible.
Pathophysiology of COPD
Airway abnormalities in COPD:
Chronic inflammation
Excessive lysis of elastin and other structural proteins in the lung matrix
Protease from neutrophils, macrophages
Elastase
Mononuclear cells
Atrophy (occurring from bronchoconstriction)
Lung parenchyma abnormalities:
Normal structures comprising the acinar include:
Respiratory bronchiole, alveolar ducts, sacs, and alveoli. These structures along with the associated
capillaries, and interstitium form the parenchyma of the lungs.
The part of the acinar affected by permanent dilation or destruction. This helps to name the subtype of
emphysema (proximal acinar; panacinarseen in alpha-1 antitrypsin deficiency; distal acinar).
Pulmonary vasculature:
Changes include intimal hyperplasia
Smooth muscle hypertrophy/hyperplasia, likely due to hypoxic vasoconstriction of small pulmonary
arteries
Destruction of alveoli from emphysema = loss of pulmonary capillary bed
Diagnoses
Be sure of your diagnosis: concurrent dx or differentials
o Asthma
o Bronchiectasis
o Congestive heart failure
o Diffuse panbronchiolitis
o Obliterative bronchiolitis
o Pulmonary hypertension
o Tuberculosis
o Pneumonia
o Pleural effusion
Goals of Management
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent disease progression
Prevent and treat exacerbations
Reduce mortality
All with minimal side effects of treatment, if possible
Spirometer Parameters
-Green Zone: 80% to 100% of expected volume
Maintain or reduce medications
-Yellow Zone: 50%-80% of expected volume
Maintenance therapy needs to be increased
or patient is having an acute exacerbation.
-Red Zone: Below 50% of expected volume
If after treatment patients PEFR is still
below 50% expected, call 911. If in
respiratory distress, give epinephrine
injection. Call 911
Managing COPD Exacerbations
How do we know it's an exacerbation?
GOLD guidelines define an exacerbation of COPD as
o "an event in the natural course of the disease characterized by a change in the patient's baseline
dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and
may warrant a change in regular medication in the patient with underlying COPD." GOLD
(2014) p. 40
Exacerbations
Cardinal symptoms of COPD exacerbation:
o Increase in dyspnea
Causes
Infection, CHF, PE
Common organisms: viruses, H. flu, M. catarrhalis, S. pneumonia
Air pollution
Approx. 1/3 of severe exacerbations cannot be identified
Arterial blood gas (in hospital)
EKG
O2 saturation
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using spirometry
Assess risk of exacerbations
Evaluation
CXR
Pulse oximetry
Management of Exacerbations: Outpatient
Bronchodilators
Oral steroids
Oxygen PRN
Antibiotics
o Patients with exacerbation with two of the cardinal symptoms if increased purulence of sputum is
one of the two symptoms
o For patients with severe exacerbation requiring mechanical ventilation
Inhaled Glucocorticoids in COPD
Help to reduce inflammation in the airways
May help to reduce exacerbations
Possibly slow the progression of respiratory symptoms
Have little effect on altering lung function
Not to be used alone in treating COPD
Combined with bronchodilators (LABA), in advanced COPD
o GOLD stages C and D
Phosphodiesterase-4 Inhibitor
Roflumilast
Mechanism of action: Roflumilast and its active N-oxide metabolite selectively inhibit
phosphodiesterase-4 (PDE4).
Diabetes Overview
Diabetes Mellitus Types
Type 1: an absolute deficiency of insulin secretion
Type 2: a combination of resistance to insulin action and inadequate compensatory insulin secretory
response
o Patients do not make enough insulin to keep blood glucose levels within target range
Diabetes Mellitus
Characterized by hyperglycemia
o Blood glucose levels in the high 100s, 200s, or 300s
Associated with major abnormalities in carbohydrate, fat, and protein metabolism
Poor glycemic control can lead to the development of long-term complications
o E.g., retinopathy, neuropathy, nephropathy, and cardiovascular disease
Diabetes Mellitus: Classification
Type 1: insulin dependent (~1020%)
o Most common in youth, can be diagnosed at any age
Type 2: insulin resistance (~8090%)
o Most common in adults, on the rise in youth
Sedentary lifestyle, diet, refined foods, and rising rates of obesity
Obesity could be associated with either type 1 or type 2 diabetes
Gestational (25% of all pregnancies)
o Ends after delivery but 4050% are at risk for type 2 diabetes
Secondary and other forms
o Maturity-onset diabetes of youth (MODY)
o Cystic fibrosisrelated diabetes (CFRD)
Multidisciplinary team: endocrinologist, nurse, nurse practitioner, dietician, and mental health
support
Hemoglobin A1C
A glycoprotein formed when glucose binds to hemoglobin A in the blood
Typically measured 3 or 4 times a year
A1C goals are age-specific
o
Long acting
o To maintain basal insulin
Administered subcutaneously via syringe, pen, or continuous subcutaneous infusion insulin pump
Some providers still mix insulin but less common
o When drawing insulin in a syringe, draw the clear insulin and then the cloudy.
Insulin Analogs
Insulin Lispro (Humalog) (1996)
Insulin Aspart (NovoLog) (2000)
Insulin Glargine (Lantus) (2002)
Insulin Detemir (Levemir) (2005)
Insulin Glulisine (Apidra) (2006)
Rapid-Acting Insulin
Matches the way insulin reacts in the body
Better match of food to insulin
Shorter duration of activity
Decreased frequency of hypoglycemia
Administered 15 minutes before meals
o Some situations may lead to insulin after a meal, e.g., a picky toddler
Can give half before meal and another half during the meal.
Clear insulin
Short-Acting Insulin
Regular insulin
Primarily used to treat diabetic ketoacidosis (DKA) as an IV insulin
Longer duration and onset
Usability not as flexible for patients and families
Administered 3060 minutes before meals
Less flexible than the rapid-acting insulin because it takes longer to be come effective
Insulin Types:
Rapid Acting and Short Acting
Insulin Type
Onset
Peak
Duration
Administration
Rapid Acting
Aspart (Novolog)
510 min
13 hr
35 hr
Glulisine (Apidra)
15 min
3090 min
35 hr
hyperglycemia.
Lispro (Humalog)
Short Acting
Regular (Humulin,
Novolin)
15 min
14 hr
35 hr
3060 min
25 hr
612 hr
Intermediate-Acting Insulin
NPH insulin
Lasts 12 hours
o BID- good option for schoolers who have nobody to give them med during the day
Not commonly used now
Cloudy insulin
o When mixed, must be second insulin drawn up in syringe
Intermediate Acting Onset
NPH
12 hr
Peak
414 hr
Duration
Administration
1024 hr
Insulin Mixes
Referred to in terms such as 70/30 or 75/25
Rapid-acting insulin
Then part of it is buffered so it acts like an intermediate insulin
Typically administered as two daily doses, morning and evening, to cover all the meals and snacks
Not used as first treatment choice because it is not intensive
Insulin Types: Mixes
Onset
Peak
Duration
Administration
15 min
17 hr
620 hr
15 min
15 hr
612 hr
1030 min
13 hr
Up to 24 hr
30 min
212 hr
24+ hr
3060 min
212 hr
1824 hr
Long-Acting Insulin
Basal insulin
Typically injected once daily
Allows more flexibility for patients and families
Insulin Types: Long-Acting
Long-Acting
Onset
Peak
Duration
None
624 hr
Administration
Duration varies with dosage.
Use once or twice daily.
None
24 hr
Insulin Dosing
Initial Insulin Dosing
Based on pubertal stage of development and weight
Various regimens to adopt: BID dosing, TID dosing, and mixed regimens
Hypoglycemia
Primary side effect of insulin
Patients should expect at least one episode per week
Patients and families fear dead-in-bed syndrome
Frequent blood glucose monitoring and looking for patterns help prevent this and provide
reassurance
Non-DKA patient:
Prepubertal 0.250.5 units/kg/day
Pubertal 0.50.75 units/kg/day
Post-DKA patient:
Prepubertal 0.75 units/kg/day
Pubertal 1 unit/kg/day
Total daily dose should be divided as follows:
TID injection regimen:
o 2/3 of TDD is given before breakfast (2/3 as NPH and 1/3 as rapid-acting insulin; 1/3 of the
remaining TDD is given as predinner rapid-acting insulin (1/3) and prebedtime NPH(2/3)
BID injection regimen: Daily dosage: 0.5U/Kg
o 2/3 of TDD is given before breakfast and 1/3 of TDD is given before dinner
o 2/3 of each dose should be given as NPH and 1/3 as rapid-acting insulin
For example: Mr. Smith weights 247 pounds (112kg)
o He will take 56 U throughout the day (112 kg x 0.5U/kg = 56 U)
In the morning, he will take 37.2 U of 75/25 preparation
In the evening. He will take 18.7 U of 50/50 preparation
Insulin Side Effects
Primary symptoms of hypoglycemia:
Cardiovascular: pallor, palpitation, tachycardia
Central nervous system: fatigue, headache, hypothermia, loss of consciousness, mental confusion
Dermatologic: redness, urticaria
Endocrine and metabolic: hypoglycemia, hypokalemia
Gastrointestinal: hunger, nausea, numbness of mouth
Local: atrophy or hypertrophy of SubQ fat tissue; edema, itching, pain, or warmth at injection site;
stinging
Neuromuscular and skeletal: muscle weakness, paresthesia, tremor
Ocular: transient presbyopia or blurred vision
Miscellaneous: anaphylaxis, diaphoresis, local, and/or systemic hypersensitivity reactions
Drug Interactions
Increase hypoglycemic effect of insulin
Alcohol, anabolic steroids, beta blockers, chloroquine guanethidine, lithium carbonate, MAOI,
mebendazole, octreotide, pentamidine, phenylbutazone, pyridoxine, salicylates, sulfinpyrazone,
sulfonamides, tetracyclines
Decrease hypoglycemic effect
Insulin Regimens
Fixed doses
Sliding scales
BID injections
TID injections
Basal-bolus regimen
Modified basal-bolus regimen: uses long-acting, rapid-acting, and NPH insulin
Most intensive regimen is typically basal-bolus
Insulin Regimens
Regimens
Fixed doses
Sliding scales
BID injections
TID injections
Basal-bolus regime
Modified basal-bolus
Insulin Effect
Diluted Insulin
Used for patients who are very sensitive to insulin (even a 0.5 unit dose may be too much)
Often used for toddlers
Typically delivered in doses of 0.10 or 0.25 units
Referred to as U10: each line on the syringe is 0.10 of a unit
Humulin R U500
May be considered in people requiring more than 200 units a day
Allows 1/5 of the volume of insulin to be injected
Used in extreme insulin resistance
o Type 2 diabetes, diabetes patients being treated with long-term high-dose steroids
o Humulin R U-500 vial contains 20 ml
Insulin Algorithm
Algorithm for insulin therapy based on units of insulin administered per dose
Recognize that insulin choice is driven by insurance and can change frequently.
http://www.disetronic.com
Criteria for Successful Pump Management
Child must want pump; not only parents or health care team
Good family and school support
Demonstrated comfort level with conventional management tools
Diabetes team with 24-hour support system
Ability to count carbohydrates
Insulin Pumps
o Animas Ping
o Medtronic MiniMed
o OmniPod
o AccuChek Spirit Combo
t: slim
Pump Benefits
Improvement in blood glucose levels is possible with pump
Greater flexibility, including flexibility of timing and size of
Meals and snacks (less/more)
Exercise (timing, duration and intensity)
Ability to intensify blood sugar control
Fewer severe low blood sugars
Immediate access to insulin
Ease at delivering insulin
More predictable insulin absorption from a continuous insulin depot
Dawn Phenomenon effects are easier to manage with the basal rate and can be set to accommodate
the rise in insulin requirements overnight
Basal insulin rates can be quickly changed to accommodate growth spurts in children or increased
insulin needs during pregnancy
Improvement in the safety profile is possible
Reducing the basal rate during periods of low physiological requirements can minimize
nocturnal or daytime hypoglycemia
Using a temp basal rate to meet short-term physiological needs
o
Pump Challenges
Increased frequency of monitoring
Increased chance of hyperglycemia and DKA due to crimped infusion sets, air bubbles, and
dislodged cannula
Only uses rapid-acting insulin, not long-acting insulin
Therefore, if mechanical failure, air in the tubing, or other issues occur, ketones can start to
develop within hours
Potential for skin abscess
Change in hypoglycemic symptoms
Constant attachment to pump
Technical or mechanical failure is possible with a pump
Weight gain is possible with improved glycemic control
Cost of insulin pumps usually almost $6,000 not including cost for supplies
Tools to Pump Success
Professional diabetes support team including school nurse in place
Regular medical follow-up
Parents' ability and willingness to manage the pump
Troubleshooting Hyperglycemia Insulin Pump Therapy
Red, tender, and swollen catheter site: the insulin not being absorbed correctly and adds to high
blood glucose
Seen only in rapid acting insulin
Leakage, breakage, or kinking of tubing
Battery failure
Empty reservoir or cartridge
Mechanical failure
Improper basal rate programming
Air in tubing
Illness
Menstrual cycle fluctuations
Insulin resistant before menses
Omitted bolus or improper dosing
Crimping of cannula
o
o
o
Minidose Glucagon
Used when a child or adolescent with type 1 diabetes is unable to consume or absorb oral
carbohydrate because of nausea and vomiting associated with gastroenteritis
Used to prevent impending hypoglycemia
Drawn up in a standard U-100 insulin syringe
Two "units" on the insulin syringe for children ages 2 years and one unit per each year of age in children
ages 215 years (150 mg)
Patients ages >15 years receive only 15 units
Monitor blood glucose q 30 minutes for the first hour, then hourly until blood glucose is at 100 mg/dl
If blood glucose unchanged after 30 minutes, may repeat and double the dose
Summary
Significantly more patients today practice intensive diabetes Rx as evidenced by
o More patients receiving 3 injections/day
o More patients performing BG monitoring 4/day
o More patients using CSII
Intensification of therapy leads to
o Improved glycemic control (lower A1C)
o No significant increase in z-BMI
o 50% fewer hypoglycemic events, 25% fewer ER visits
Future: CGM and closing the loop to improve and normalize glycemic control
Diabetic Control
DCCT (type 1 diabetes)
Tight control decreased microvascular and neurological complications, increased risk of hypglycemia
EDIC: control early in diabetes has positive long-term effects
UKPDS (type 2 diabetes)
Tight control decreased microvascular complications, but no change in macrovascular complications
Lowering BP decreased microvascular and further decreased macrovascular complications
ACCORD
Tight control for those with CAD risk; may not be beneficial
Normal
Goal
100
70130
23 hr postprandial
Bedtime glucose
90150
Glycohemoglobin (A1C)(%)
Type 1 Diabetes
o 10% of diabetes patients have type 1.
Autoimmune destruction of beta cells
+GAD (glutamic acid decarboxylase) antibodies
Ketone production
Injected insulin necessary
Multiple injections give better control
Onset often sudden
Increased thirst (polydipsea), increased hunger (polyphagia), increased urination (polyurea),
weight loss
LADA (latent autoimmune diabetes in adults) can mimic type 2 diabetes
Type 2 Diabetes
90% of diabetes patients have type 2.
Resistance to endogenous and exogenous insulin
75% of patients are obese at diagnosis
Impaired first- and second-phase insulin secretion. Insulin levels can start high and then drop off to
normal and low levels.
Increased hepatic glucose production
Ketosis is unlikely
Onset often insidious with no or mild "polys." 50% of patients are diagnosed at their first cardiac event,
and diagnoses are increasing in children.
Natural History of Type 2 Diabetes
Insulin Resistance
o Normally, insulin binds to specific receptors on cell surface, which activates glucose transport.
Insulin resistance = post binding defects
Occurs in hepatic and muscle tissue
Decreased glucose transport
Decreased glycogen synthesis
Choosing the Right Treatment
Diabetes Assessment
Complete history with emphasis on:
Confirmation of diagnosis
Review of treatments, outcomes, education
Factors that affect glucose control
Current lifestyle/psychosocial issues
Medications
Complications of diabetes
Complete exam: emphasis on complications
Labs and Goals
Lab assessment
o Glucose, glycohemoglobin
o Lipids
o Renal and liver functions
Establish goals
o SBGM/glycohemoglobin
o Weight, meal plan, activity plan
Pharmacologic treatment
Algorithm for Treatment
Insulin Sensitizers
o Biguanides
o Metformin (Glucophage)
o Metformin extended release
o Thiazolidinediones
o Rosiglitazone (Avandia)
o Pioglitazone (Actos)
Biguanides
Used as first-line therapy unless contraindicated, and in the obese (insulin resistant) with normal
liver and renal functions.
Decrease hepatic glucose production
Inhibit gluconeogenesis
Stimulate glucose uptake in skeletal muscle and adipocytes
Cell receptors
Glucose transport GLUT 4
Associated with 1- to 2-kg weight loss
Usually do not cause hypoglycemia
Thiazolidinediones (TZDs)
TZDs increase risk for new or worsening macular edema and may increase risk of bone fracture.
TZDs decrease hepatic glucose production, do not cause hypoglycemia, and are associated with weight
gain. Pioglitazone may improve lipid profile.
Rosiglitazone (Avandia)
No significant drug interactions
Starting dose: 4 mg qd or 2 mg bid
Adjust dose after 812 weeks
Maximum dose: 8 mg qd in single or divided doses
Pioglitazone (Actos)
Drug interactions: OCs not studied; may interact with ketoconazole
Starting dose: 1530 mg qd
Adjust at 4- to 6-week intervals
Maximum dose: 45 mg
Thiazolidinediones: Who and How
Typically used in obese patients without liver disease or severe heart disease.
LFTs should be at baseline, then check periodically.
TZDs can cause or worsen CHF. Risk increases with addition of insulin. Do not use rosiglitazone
with insulin.
Contraindicated in Class III or IV heart failure.
TZDs improve glucose transport into cells by binding to peroxisome proliferator-activated receptors
(PPARs), and affect multiple genes. Protein production affects insulin sensitivity, perhaps inflammation
(increases apidonectin).
Rosiglitazone Update
1. Usage may be associated with increased risk of MI, but not CV, mortality.
2. Compared to pioglitazone, rosiglitazone use may be associated with increased risk of stroke, CHF, and
all cause mortality. Both TZDs increase risk of CHF.
3. Most of these data are derived from meta-analyses and uncontrolled studies. In November 2013 the FDA
announced it is considering removing restrictions.
Risk Evaluation and Mitigation Strategy for Rosiglitazone
HCPs must now enroll in the REMS program to prescribe rosiglitazone, pharmacists must enroll to
dispense it, and patients must be enrolled by their physicians to begin or continue receiving it.
HCPs have to attest to and document the patient's eligibility if they believe the patient is a candidate for
rosiglitazone.
Patients must review statements describing CV safety concerns and sign acknowledgement of
their understanding.
Current users can only continue usage if they acknowledge and document they understand the
risks.
Patients not already taking rosiglitazone can receive it only if they're unable to achieve glycemic control
on other meds, and, in consultation with their HCP, decide not to take pioglitazone for medical reasons.
Pioglitazone Update
May be associated with increased risk for bladder cancer, but most data are derived from meta-analyses
and uncontrolled studies.
Do not use in people with active bladder cancer, and use caution in people with a history of bladder
cancer.
Metformin vs. TZD
Metformin can affect GI.
Metformin is less expensive.
Metformin is associated with weight loss; TZDs are associated with weight gain.
Metformin can't be used with renal disease; TZDs can.
Metformin doesn't cause edema; TZDs can.
Insulin Secretagogues
Classes of Secretagogues
Meglitinides: repaglinide (Prandin)
Amino acid derivatives: nateglinide (Starlix)
Sulfonylureas: long and short acting
Insulin Secretagogues: Who and How
Intended for the "less obese" patient with type 2 diabetes of longer duration, and decreased insulin
production
How they work:
Stimulate release of insulin from beta cells
Bind to cell receptor, inhibit potassium efflux, depolarize beta cell
Decrease hepatic glucose production
Potential for hypoglycemia
Avoid/use with caution in patients with liver and renal disease to prevent prolonged hypoglycemia.
Long-Acting Sulfonylureas
Generic/Trade
Glyburide/Micronase or Diabeta
Micronized Glyburide/Glynase
Glimepiride/Amaryl
Glipizide Extended Release/Glucotrol XL
Short-Acting Sulfonylureas
Glipizide/Glucotrol
Usually bid
2.540 mg qd (5, 10 mg)
30 minutes before meal
For lowering glucose, a small amount
Less potential for prolonged hypoglycemia
Meglitinides: Repaglinide (Prandin)
Chemically unrelated to sulfonylureas, making it an important tool for patients with sulfa allergies.
They stimulate the release of insulin from beta cells. The binding that occurs differs from sulfonylureas,
and the action is shorter. There is risk for hypoglycemia.
Can be taken 030 minutes before mealtime, 24 times/day. If a meal is skipped or added, dose should
be skipped or added as well.
SGLT2 Inhibitors
SGLT2 inhibitor is short for sodium-glucose cotransporter 2 inhibitor. There are two types:
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)Action of SGLT2 Inhibitors
SGLT2 inhibitors block reabsorption of glucose by the kidney and increase excretion of glucose in urine
by inhibiting SGLT2. The mechanism of action results in a positive test for urine glucose.
Side effects include hypotension (especially in older patients), dehydration, hyperkalemia, decreased
renal function, genital mycotic infections, UTI, increased LDL cholesterol, and weight loss.
Canagliflozin (Invokana)
Used as monotherapy or with metformin, sulfonylureas, pioglitazone, and insulin.
Dosing
If GFR < 45 mL/min: do not initiate use and discontinue use if already on drug.
If GFR > 45mL/min: start with 100 mg daily with first meal of day.
If GFR between 45 and 60 mL/min: limit to 100 mg daily.
If GFR 60mL/min: increase to 300 mg daily.
Interactions
UGT enzyme inducers (rifampin, phenytoin, ritonavir, phenobarb) may decrease canagliflozin
efficacy.
Canagliflozin increases digoxin concentration.
Dapagliflozin (Farxiga)
Used as monotherapy or with metformin, sulfonylureas, sitagliptin, pioglitazone, and insulin. Do not use
in bladder cancer, and use caution if the patient has a history of bladder cancer.
Dosing
If GFR < 60 mL/min: do not initiate use and discontinue use if already on drug.
If GFR 60 mL/min: start with 5 mg daily in morning, increasing to 10 mg daily if needed.
Effects of GLP-1
Upon food ingestion, GLP-1 is secreted into the circulation from L cells of the small intestine.
GLP-1 increases beta-cell response by enhancing glucose-dependent insulin secretion.
GLP-1 decreases beta-cell workloadhence the demand for insulin secretionby
Regulating the rate of gastric emptying such that meal nutrients are delivered to the small
intestine and, in turn, absorbed into the circulation more smoothly, reducing peak nutrient
absorption and insulin demand (beta-cell workload)
Decreasing postprandial glucagon secretion from pancreatic alpha cells, which helps to maintain
the counterregulatory balance between insulin and glucagon
Affecting the central nervous system, resulting in increased satiety (sensation of satisfaction with
food intake) and a reduction of food intake
Reducing postprandial glucagon secretion
GLP-1 has an indirect benefit on beta-cell workload since decreased glucagon secretion will produce
decreased postprandial hepatic glucose output. By decreasing beta-cell workload and improving betacell response, GLP-1 is an important regulator of glucose homeostasis.
Exenatide (Byetta)
Incretin mimetic
Incretin: glucagon-like peptide-1 (GLP-1)
Action
Enhances glucose dependent insulin secretion
Decreases gastric motility
Decreases hepatic glucose production
Increases satiety and causes modest ongoing weight loss
Insulin glargine can be used with exenatide.
Side effects include nausea. There have been recent reports of pancreatitis and renal failure.
Dosing
5 mcg bid subcutaneously at or within 60 minutes before meals for one month
After one month, increase to 10 mcg bid (prefilled pen)
Cut sulfonylurea dose in half to prevent hypoglycemia
Exenatide Extended-Release (Bydureon)
Bydureon caused thyroid C-cell tumors in rodents. Thus, the drug is contraindicated with personal or
family history of medullary thyroid carcinoma or MEN 2.
Side effects include nausea. A risk of pancreatitis is unclear.
Dosing
o 2 mg subcutaneously, once weekly
o Decrease sulfonylurea dose to prevent hypoglycemia
Liraglutide (Victoza)
Incretin mimetic
Incretin: glucagon-like peptide-1 (GLP-1)
Action
Enhances glucose-dependent insulin secretion
Decreases gastric motility
Decreases hepatic glucose production
Increases satiety and leads to modest ongoing weight loss
Use as type 2 diabetes as adjunct therapy if not optimally controlled on a thiazolidinedione, metformin, a
sulfonylurea, or metformin and a sulfonylurea.
Liraglutide has caused thyroid C-cell tumors in rodents, and thus is contraindicated in setting of personal
or family history of medullary thyroid carcinoma or MEN 2.
Side effects include nausea. A risk of pancreatitis is unclear.
Dosing
0.6 mg subcutaneously, once daily, for one week
After one week, increase to 1.2 mg daily
Further increase to 1.8 mg subcutaneously
Decrease sulfonylurea dose to prevent hypoglycemia