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Advanced Pharmacology > Diabetes > Flashcards

Diabetes Flashcards

1
Q

Alpha cells make_____

A

glucagon

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2
Q

Beta cells make _____

A

insulin

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3
Q

Delta cells make ______

A

somatostatin

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4
Q

Epsilon cells make _______

A

ghrelin

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5
Q

Diabetes mellitus is____

A

lack of insulin

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6
Q

Type I DM

A

-insulin dependent
Cause by: autoimmune mediated that can be triggered by virus or other toxic process in the environment
-In Type I DM—because there is no beta cell function—there is no basal insulin secreted nor is there a prandial [food related] response

TREATMENT: exogenous insulin

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7
Q

Type II DM

A

-Lack of sensitivity of target organs to insulin

-Pancreas has some beta cell function intact [at least—early on in the
disease process], but the secretion and action is not sufficient to keep
blood sugar normal

-Obese states contribute to the insulin resistance

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8
Q

Pathogenesis of type II diabetes

A
  • Decreased insulin secretion
  • Ineffective glucose uptake [skeletal muscle]
  • Increased hepatic glucose production
  • Decreased incretin effect
  • Increased free fatty acid production
  • Neurotransmitter dysfunction
  • Increased glucose reabsorption
  • Diminished beta cell response (insulin deficiency)
  • Increased stimulus needed for beta cell function (insulin resistance)
  • Decreased muscle uptake of glucose
  • Impaired insulin secretion
  • Increased hepatic glucose production

all of the above lead to hyperglycemia

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9
Q

Pancreas produces which peptide hormones

A

insulin
glucagon
somatostatin

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10
Q

4 categories of diabetes

A
  1. type 1
  2. type 2
  3. gestational
  4. diabetes d/t other causes
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11
Q

What can can type 2 cause

A
  1. Postprandial hyperglycemia
  2. Hyperinsulinemia from slow release
    of insulin
  3. Impaired insulin secretion—glucose
    toxicity can occur
  4. Increased hepatic glucose
    production
  5. Insensitivity to insulin in tissues
    [hallmark of this disease]
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12
Q

Insulin resistance-causes and associated conditions

A
  1. aging
  2. obesity
  3. medications
  4. rare d/o
  5. genetics
  6. type 2 dm
  7. htn
  8. dyslipidemia
  9. atherosclerosis
  10. PCOS
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13
Q

Other Defects Do Occur—β

Cells vs. Tissue Receptors

A
  • β cells in pancreas sense glucose levels→ leads to the production and release of insulin
  • Receptors in tissue are part of auto-regulationsystem located in all organs
  • Insulin on the receptors allow glucose transport into cells for utilization
  • Defects in the receptors or defects in receptor response to insulin can lead to tissue insensitivity to insulin and increased glucose levels
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14
Q

Type I DM

A
  • usually during childhood and puberty
  • commonly undernourished
  • moderate genetic predisposition
  • beta cells are destroyed, eliminating the production of insulin
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15
Q

TYPE II DM

A
  • commonly over age 35
  • obesity usually present
  • strong genetic predisposition
  • inability of beta cells to produce appropriate quantities of insulin; insulin resistance; other defects
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16
Q

What medications are not 1st line for gestational DM bc they cross the placenta?

A

metformin and glyburide

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17
Q

Other less common type of diabetes

A 
Diabetes related to disease of
the exocrine pancreas—cystic
fibrosis
Diabetes from other endocrine
dysfunction—Cushing syndrome,
acromegaly, chromocytoma
Drug induced diabetes—high
dose corticosteroids
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18
Q

Causes of type II DM

A

-Lack of sensitivity of target organs to insulin
-Pancreas has some beta cell function intact [at least—early on in the disease process], but the secretion and action is not sufficient to keep
blood sugar normal
-Obese states contribute to the insulin resistance

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19
Q

Glucogenesis

A

is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates.

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20
Q

Glycolyisis

A

breaks down glucose into two three-carbon compounds and generates energy

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21
Q

What happens in insulin resistance?

A
  • not enough insulin
  • loss of insulin receptors
  • loss of insulin receptor function
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22
Q

Downstream effects of insulin resistance?

A
  • increased fatty acids in blood
  • lipolysis for glucose
  • decreased protein storage
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23
Q

What is lipolysis

A

metabolic process through which triacylglycerols (TAGs) break down via hydrolysis into their constituent molecules: glycerol and free fatty acids (FFAs)

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24
Q

DM + HTN + dyslipidemia are risk factors for?

A

ASCVD-atherosclerotic cardiovascular disease

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25
Q

What meds work best for DM with heart failure?

A

SGLTs inhibitors-have a diuretic effect and lower the risk of HF in diabetics who are at risk

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26
Q

SGLT inhibitors are?

A

inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes.

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27
Q

Examples of SGLT2 inihibitors

A

canagliflozin, dapagliflozin, and empagliflozin

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28
Q

Consequences of diabetes and insulin restistance

A

lower HDL and icnreases LDL and triglycerides

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29
Q

LDL levels

A

50-100

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30
Q

HDL levels

A

> 40

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31
Q

Triglycerides

A

<150

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32
Q

If a diabetic with ASCVD is on a maximally tolerated statin and LD Is >70 what should you add to their meds

A

PCSK-9 inhibitor or Ezetimibe to help reduce LDL more

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33
Q

Moderate intensity statins

A 
Simvastatin 20/40 mg
Pravastatin 40/80 mg
Atorvastatin 10/20 mg
Lovastatin 40 mg
Fluvastatin XL 80 mg
Rosuvastatin 5.10 mg
Pitavastatin 1/2/4 mg
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34
Q

High Intensity Statins

A

Atorvastatin 40/80 mg

Rosuvastatin 20/40 mg

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35
Q

Risk for ASCVD

A
  • obestiy
  • htn
  • dyslipidemia
  • smoking
  • FH of CAD
  • CKD
  • albuminuria
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36
Q

Aspirin in DM with risk of ASCVD

A

-ADA now recommends that ASA 72-162
mg/day be used for secondary
prevention in diabetics with ASCVD

-ASA can be considered for primary
prevention in diabetics who are at
increased risk of ASCVD

-ASA is not recommended for diabetics
with low ASCVD risk—diabetics less than
age 50 and have no other ASCVD risk
factors are considered low risk

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37
Q

When should we screen for DM?

A

All adults >45 should be screened every 3 years—or every 2 years if they have risk factors
All comers—regardless of age who are at risk or are suspected of having DM should be screened

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38
Q

Diagnostic Criteria for DM

A

DIAGNOSIS REQUIRES 2 ABNORMAL TEST RESULTS:

-FPG ≥126 mg/dL ; Fasting is defined as no caloric intake for at least 8 h.*
OR
-2-h PG ≥200 mg/dL during OGTT. The test should be performed as
described by WHO, using a glucose load containing the equivalent of 75 g
anhydrous glucose dissolved in water.*
OR
-A1C ≥6.5% ; The test should be performed in a laboratory using a method
that is certified and standardized to the DCCT assay.*
OR
-In a patient with classic symptoms of hyperglycemia or hyperglycemic
crisis, a random plasma glucose ≥200 mg/dL.

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39
Q

What is insulin

A

polypeptide hormone made of 2 peptide chains connected by disulfide bonds. Synthesized as a prodrug that
undergoes cleavage to form insulin and c-peptide—both of which are secreted by the Beta cells of the pancreas

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40
Q

What triggers insulin secretion

A

increased blood sugar

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41
Q

MOA of insulin

A
  • Exogenous insulin is given to replace
    absent insulin in Type I Diabetes Mellitus
  • Exogenous insulin is given to supplement
    insulin secretion in Type II Diabetes Mellitus
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42
Q

ADE of insulin

A

Low blood sugar
Weight gain
Local injection site reactions, lipodystrophy
Bronchospasm can occur with inhaled insulin—those with COPD and smokers should not use this form of insulin

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43
Q

Meal insulin bolus

A

is determined by the amount of CHO to be
ingested; this amount is divided by the insulin-to-CHO ratio [the number of grams of CHO that 1 unit of insulin covers]—this ratio is individualized and will vary from
patient to patient

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44
Q

Correction insulin bolus

A

is used to quickly reduce BS back to

normal; the dose is determined by the sensitivity factor [the amount the BS will decrease with 1 unit of insulin]

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45
Q

Goal of cholesterol in DM

A

lower LDL by 50%

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46
Q

Basal Insulin

A
  • This is the steady background insulin that controls BS in the fasting state [overnight and in between meals]
  • Basal insulin enables stored fat and glucose to be released in appropriate amounts to sustain metabolism during time when fuel is not being consumed and metabolized
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47
Q

What does insulin promote

A

fat storage and amino acid conversion to
proteins; promotes transport and storage of
glucose as triglyceride into fat cells

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48
Q

What does insulin lower?

A

Lowers serum blood sugar by enhancing transport of glucose into tissues; inhibits release of fatty acids
into blood

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49
Q

Normal action of insulin

A

Increases nitric oxide [NO] production in blood vessels
Acts as a vasodilator; inhibits platelet aggregation
A person with normal insulin sensitivity—insulin can be considered
antiatherogenic

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50
Q

What can decrease GLUT 1-5 transporter affinity for insulin

A

Corticosteroids, obesity, chronic high blood glucose

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51
Q

Insulin Lispro

A

RAPID ACTING

Ex: Ademlog, Humalog, Lyumjev

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52
Q

Insulin Aspart

A

RAPID ACTING

Ex: NovaLog, Fiasp

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53
Q

Insulin Glulisine

A

RAPID ACTING

Ex: Apidra

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54
Q

Regular Insulin

A

SHORT ACTING

Ex: Humulin R u-100, Humulin R u-500, Novolin R

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55
Q

Inhaled Insulin

A

SHORT ACTING

EX: Afrezza

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56
Q

Insulin Aspart

A
  • Given within 15 minutes before or 15 minutes after the person starts eating
  • Onset is quick—5-15 minutes; peaks at 60 minutes; effective duration is about 2 hours
  • Comes in 10 cc vials and prefilled and cartridge pens [cartridge pens are being phased out]
  • Once opened, drug is good for 28 days
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57
Q

Insulin Lispro

A
  • Given within 15 minutes before or 15 minutes after the person starts eating
  • Onset is quick—15-30 minutes; peaks at 60-90 minutes; effective duration is about 3 hours
  • Comes in 10 cc vials and prefilled and cartridge pens [cartridge pens are being phased out]
  • Once opened, drug is good for 28 days
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58
Q

Insulin Glulisine

A
  • Given within 15 minutes before or 15 minutes after the person starts eating
  • Onset is quick—5-30 minutes; peaks at 90-120 minutes; effective duration
    is about 3 hours
  • Comes in 10 cc vials and prefilled SoloStar pen
  • Can be refrigerated or stored at room temperature
  • Once opened, drug is good for 28 days
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59
Q

Inhaled Insulin—Afrezza

A

Short-acting human insulin powder for inhalation
Can be used in both types of DM [in those >18 years]—use with basal in the Type I diabetic
Insulin is delivered in microparticles; absorbed & eliminated more rapidly
Provides higher insulin levels with peak effects in about 2 hours
4-, 8- and 12-unit single use cartridges
Dosed beginning with largest meal
Interactions and side effects—same as regular insulin
Can affect lung function—contraindicated in COPD [risk acute bronchospasm]
Patient must have baseline PFTs, then repeated every 6- 12 months
Should not be used in smokers or in those with severe asthma

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60
Q

Regular Insulin

A
  • Short acting soluble crystalline zinc
    insulin
  • Both forms will begin to work in 30
    minutes, but peak in 2-3 hours, and
    duration of action is 6-12 hours—it
    hangs around a long time…
  • Humulin R is made from nonpathogenic
    E. coli and is zinc-insulin crystals
    dissolved in a clear fluid—it is available
    in U100 and U500 concentrations
  • expires 31 days after opened
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61
Q

Intermediate Acting Insulin

A

Only one formulation available in US
Formed by adding zinc and protamine to regular insulin
Used for basal in Type I or Type II diabetes—is usually given with rapid or short acting insulin to cover mealtime—it can only be given SQ—and it should never be used when rapid BS lowering in needed

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62
Q

Neutral Protamine Hagedorn [NPH]

A
  • Manufactured as Novolin N or Humulin N
  • Both are zinc suspension that includes
    protamine
  • Both come in U100 concentrations and are
    cloudy suspensions
  • NPH is made from noninfectious E. coli
  • Comes in 10 cc vials and prefilled pens
  • Onset of action—2 hours; peaks in 5-6 hours and duration of action is 12 hours
  • should be room temp before injecting
  • can be mixed with aspart, lispro, and glulisine
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63
Q

Long Acting insulin

A

Long-acting insulins are used for basal control and should only be given SQ—and they should not be mixed with any other insulin
Lantus is the prototype in the class

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64
Q

Insulin Glargine

A

LONG ACTING

EX: Basaglar, Lantus, ZSemglee, Toujeo

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65
Q

Insulin Detemir

A

LONG ACTING

EX: Levemir

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66
Q

Insulin Degludec

A

ULTRA LONG ACTING

EX: Triseba

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67
Q

Insulin Glargine

A
  • The isoelectric point of insulin glargine is lower than that of human insulin leading to a formation of a precipitate at the injection stie that releases the insulin over an extended time—it has a slower onset than NPH, and a flat prolonged blood sugar lowering effect with no peak
  • Available in 10 cc U100 vials and Solostar pen
  • Onset of action in 2-3 hours; duration of near 24 hours
  • No difference in absorption regardless of site used
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68
Q

How to initiate Insulin Glargine-Lantus

A 
Adding to oral agents—start 10 units 
evening dose—14 hours before first 
meal of the day
Converting from once daily NPH—
Insulin glargine dose remains the same 
Converting from BID NPH to glargine—
take total NPH dose & decrease by 
20% for starting dose
*****↑Glargine until fasting glucose target 
of 100 mg/dL reached; then stop—that 
is the maximum dose
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69
Q

Insulin GLargine U300 (Toujeo)

A
  • Brand name Toujeo—duration is >24 hours
  • Once a day at the same time—may take up to 5 days before maximum effect is seen
  • When switching from Lantus—it is a 1:1 unit conversion
    Comes in 1.5 and 3 cc SoloStar pens-
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70
Q

Insulin Detemir

A
  • This insulin has a fatty acid chain that enhances association to albumin—slow dissociation from albumin results in long-
    acting properties, much like that of insulin glargine
  • Used as basal insulin in both Type I and Type II diabetics
  • Onset of action is 3-8 hours, no peak, and duration of 6-23 hours [depends on the dose]—usually given as a BID insulin
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71
Q

Insulin Degludec

A

Ultra long-acting insulin
Brand name is Tresiba
Duration of action is 42 hours; given SQ once per day any time of the day
Comes in U100 vial and FlexTouch pen; also comes in U200 FlexTouch pen
When converting from glargine or detemir—it is a 1:1 unit conversion—however, Triseba is about 70% as potent—so expect
to have to increase the dose over the first few weeks by 30%

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72
Q

Side effects of long acting insulin

A 
The greatest risk is low BS—s/sx include 
headache, anxiety, tachycardia, 
confusion, vertigo, sweating, 
shakiness, increased appetite, blurred 
vision, weakness/fatigue
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73
Q

RAPID ACTING: LISPRO (HUMOLOG)

A

ONSET: 5-15 MIN
PEAK:30-90 MIN
DURATION:2-4 HR

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74
Q

RAPID ACTING: ASPART (NOVOLOG)

A

ONSET: 5-15 MI
PEAK: 1-3 HRS
DURATION: 3-4 HRS

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75
Q

RAPID ACTING: GLUILISINE (APIDRA)

A

ONSET: 5-15 MIN
PEAK: 30-90 MIN
DURATION: 3-4 HRS

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76
Q

SHORT: REGULAR

A

ONSET: 30-60 MIM
PEAK: 2-4 HRS
DURATION:6-12 HRS

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77
Q

INTERMEDIATE INSULIN: NPH

A

ONSET: 2-4 HRS
PEAK: 6-10 HRS
DURATION:10-16 HRS

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78
Q

LONG ACTING: GLARGINE (LANTUS)

A

ONSET: 2 HR
PEAK: NO PEAK
DURATION: 20-24 HR

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79
Q

LONG ACTING: DETEMIR (LEVEMIR)

A

ONSET: 1 HR
PEAK: NO PEAK
DURATION:6-24 HR

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80
Q

INSULIN MIXES:
70/30 (NPH + REGULAR)
HUMULIN + NOVILIN

A

ONSET: 30-60 MIN
PEAK: 3-8 HR
DURATION: 10-18 HR

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81
Q

INSULIN MIXES:

HUMILIN 50/50 (NPH + REGULAR)

A

ONSET: 30 MIN
PEAK: 3-5 HR
DURATION: 10-18 HR

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82
Q

INSULIN MIXES:

HUMALOG 50/50 (NPH-LIKE +LISPRO)

A

ONSET: 15 MI
PEAK: 2-4 HR
DURATION:10-16 HR

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83
Q

INSULIN MIXES:
HUMALOG 75/25
(NPH-LIKE + LISPRO)

A

ONSET: 15 MIN
PEAK: 2-4 HR
DURATION: 10-16

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84
Q

INSULIN MIXES:

NOVOLOG 70/30

A

ONSET: 15 MIN
PEAK: 2-4 HR
DURATION: 10-16 HR

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85
Q

standard insulin treatment

A

injections twice a day

86
Q

intensive insulin treatment

A

3 or more injections per day
- But those on intensive therapy have less
retinopathy, nephropathy and neuropathy

  • But intensive therapy is not for everyone—
    those with long-standing disease, those with
    significant microvascular complications,
    those with advanced age and those with
    hypoglycemic unawareness should not be
    on intensive treatment regimens
87
Q

Starting dose of insulin for adults

A

0.6U/kg/day for adults

88
Q

Starting dose of insulin for children

A

0.25-0.5 U/kg/day

89
Q

2 units of insulin covers how many grams of CHO

A

40

90
Q

Guide to Type I DM dosing

A

Determine total insulin needed for the day
Long-acting Lantus®™or Levemir®™
Use 50% of total insulin dose at bedtime
Taken regardless of meals
Regular, Aspart , Lispro or Glulisine
-50% of total insulin dose is divided by 3 for pre-meal bolus
- Omit bolus if meal not taken

91
Q

Guide to Type II DM dosing

A

Basal insulin with oral agents

  • When starting Lantus or Levemir START with 10 units or 0.2 unit/kg at supper or bedtime; increase by 2-4 units every 3-5 days to achieve fasting glucose of 100-120
    [DO NOT dose the long-acting insulin to have a fasting morning glucose <100 mg/dL]
  • Start NPH 10 units at supper or bedtime; increase by 1- 2 units every 3-5 days to achieve fasting glucose goal
92
Q

Guide to Type II DM Dosing—if using Split/Mixed Regimens

A

Premixed insulin

  • Start 70/30 at supper or NPH/Regular at supper especially if glucose high at bedtime and fasting
  • Increase dose by 10-20% every 3-5 days to
    achieve glucose goal, or
  • Start 70/30 at breakfast and supper especially if glucose high throughout day and not candidate for oral therapy
93
Q

Guide to Type II DM Specific Dosing if
Prescribing Split/Mixed Regimens:

NPH/Regular before breakfast and dinner—or NPH-like + a fast-acting insulin

A

 Use 0.6 units/kg/day as total insulin dose
 2/3 total dose ac breakfast; 1/3 ac supper
 Divide each morning and evening dose so that 2/3 is NPH [or NPH-Like] and 1/3 is Regular [or fast acting]

94
Q

How often should you monitor Hbg A1c

A

baseline and every 3 months

95
Q

Continuous Insulin Delivery—Insulin Pumps

A

Currently we used Lispro, Aspart or buffered regular [formulated to reduce aggregation—Velosulin®™]Synthetic

96
Q

Synthetic Amylin Analogs

A

Amylin is a hormone that is co-secreted with insulin from the beta cells after food is eaten
Amylin delays gastric emptying, decreases
postprandial glucagon secretion and improvessatiety—its production is decreased in diabetes
Amylin, GLP-1 and DPP-4 are a group of endocrine hormones referred to an incretins

97
Q

General Considerations—for all

Incretins

A
  • stimulate glucose dependent insulin secretion
  • suppresses inappropriate glucagon secretion
  • thought to increase ℬ cell growth and replication
  • slows gastric empyting
98
Q

Incretin Hormones—GIP and GLP-1

A

GLP-1 secreted from L cells in the small intestine

  • Stimulated by oral nutrients
  • Stimulates insulin secretion
  • Suppresses secretion of glucagon
  • Slows gastric emptying; reduces food intake & promotes weight loss

➢ In Type 2 diabetes, they lack the glucose lowering response; circulating levels of postprandial GLP-1 are deficient

99
Q

Incretin Hormones- Pramlintide [Symlin]

A 
Approved by FDA in 2005, a
synthetic amylin analogue that is
indicated as an add on to
mealtime insulin therapy in those
with Type I or Type II DM
It is given SQ right before meals
When started—the dose of
mealtime insulin should be
decreased by 50% to avoid
severe low BS
100
Q

Side effects: Pramlintide [Symlin]

A

ADEs—nausea, anorexia, vomiting, dizziness, pharyngitis
Avoid in those with gastroparesis or hypoglycemic unawareness
It can potentially cause weight loss—as it slows gastric emptying, and effect that last for about 3 hours after each dose—it reduces the initial postprandial increase
in BS, but does not alter the absorption of CHOs, fats or other nutrients

101
Q

Primary Action of Insulin

A

Promotes glucose storage and
metabolism

Promotes peripheral glucose uptake

Promotes protein and fat synthesis

102
Q

Primary Action of Amylin

A

Regulates rate of gastric emptying

Regulates hypersecretion of postprandial glucagon

Promotes reduction of food intake

103
Q

Primary Action of Glucagon

A

Stimulates breakdown of liver glycogen

Promotes hepatic gluconeogenesis

Promotes hepatic ketogenesis

104
Q

Primary Action of GLP-1 (Glucagon-like peptide)

A

Stimulate glucose-dependent insulin
secretion

Regulates rate of gastric emptying

Regulates hypersecretion of
postprandial glucagon

Promotes reduction of food intake

Inhibits gastric acid secretion

105
Q

Primary Action of GIP (gastric inhibitory peptide)

A

Stimulate glucose-dependent insulin
secretion

Inhibits gastric acid secretion

106
Q

GLP-1 Agonists—General Considerations

A
  • Oral intake of glucose causes higher secretion of insulin than what occurs when and equal load of glucose is given IV—this is called the “incretin effect”—and is markedly reduced in Type II DM
  • This “incretin effect” occurs because the gut releases incretinm hormones—glucagon-like peptide-1 [GLP-1] and glucosedependent-insulinotropic polypeptide [GIP] in response to a meal
  • Incretin hormones are responsible for 60-70% of postprandial insulin
    release

Injectable GLP-1 receptor agonists are used to treat Type II DM—and Liraglutide is also approved to reduce the risk of CV events and CV deaths in those with Type II DM
and cardiovascular disease
Exenatide [Byetta]—prototype

107
Q

Examples of GLP- 1 Agonists

A

Aligulutie (Tanzeum)
Dulaglutide(Trulicity)
Lixisenatie (Adlxin)

108
Q

MOA GLP-1 agonists

A

These drugs exert their activity by improving glucosedependent insulin secretion, slowing gastric emptying time, reducing food intake as they increase satiety, decrease the postprandial glucagon secretion and promoting beta cell proliferation

Postprandial elevated BS is reduced; weight is reduced; and weight loss occurs

109
Q

Pharmacokinetics GLP-1 agonists

A
  • Most are given SQ as they are polypeptides
    Abiglutide, Dulaglutide and Semaglutide are given SQ weekly
  • Liraglutide is given SQ once daily
  • Lixisenatide is also given SQ daily, but is considered a short acting agent, as is
  • Exenatide—which is given SQ twice daily
    • Semaglutide comes in a short-acting oral form
  • Exenatide does come in an ER form—that is given once weekly
    • Exenatide should not be used in those with renal impairment
110
Q

ADEs of GLP-1 Agonists

A

Nausea, vomiting, diarrhea, constipation [constipation is very common]

Prototype drug has been associated with pancreatitis—so do not prescribe to those who have a history of pancreatitis

In the animal trials, there was an association with thyroid C-cell
cancers, so do not prescribe to those with history of medullary
thyroid cancer or multiple endocrine neoplasia type II

111
Q

Exenatide— Prototype Drug

GLP 1 agonist

A
  • First GLP-1 analog FDA approved [2005], but not usedas often as some of the newer agents, as the CV data are not as compelling
  • Exenatide enhances insulin secretion by pancreatic beta cells, slows gastric emptying, and suppresses glucagon secretion—it binds to and activates GLP-1
    receptor, which increases synthesis and secretion of
    insulin
112
Q

Exenatide-antidiabetic RX

GLP 1 agonist

A

onset: 30 minutes
duration: 10 hrs
SE: n/diarrhea/constipation/dizziness/headache/dyspepsia

DO NOT USE IN RENAL DISEASE, HX PANCREATITIS, USE CAUTION IN THOSE WITH SEVERE GASTROPARESIS

113
Q

Liraglutide-antidiabetic RX

GLP 1 agonist

A
  • helping the pancreas to release the right amount of insulin when blood sugar levels are high.
  • It is a long-acting GLP-1 agonist with the same MOA as Exenatide—branded as Victoza
  • Like Exenatide, is causes weight loss—and in high dose [as Saxenda] it is approved as a weight loss agent
  • Also thought to improve beta cell function and rejuvenation
  • Has FDA labeling—shown to reduce CV events i nadults
    Peak 8-12 hrs and 1/2 life is 13 hours
  • High dose Liraglutide—3 mg SQ daily is approved for adults and children aged 12 and older for
    long-term treatment of obesity in non-diabetics
    DO NOT USE IN PREGNANCY
114
Q

Albiglutide (Tanzeum) GLP -1 AGONIST

A

Another once per week GLP-1— but did not capture a large market share, so production in the US halted—and no longer available here

115
Q

Dulaglutide (Trulicity) GLP 1 agonist

A
  • for DM II
  • no for pregnancy
  • subQ one a week
116
Q

Lixisenatide (Adlyxn) GLP 1 agonist

A
  • for adults
  • do not use with GFR <15
  • only agent in family without a BB for medullary thyroid cancer in Men
  • subQ after 1st meal of day within 1 hour
117
Q

Semaglutie (Ozempic-injection) (Rybelsus-PO) GLP 1 agonist

A

–SQ weekly for DM II
- nausea big SE
-caution with those with retinopathy
-When added to Metformin, 14 mg
of oral Semaglutide (oral) lowered A1C
more than did adding a SGLT2
agent

118
Q

Sulfonylureas

A

 Classed as insulin secretagogues, as the promote insulin release from the beta cells of the pancreas

119
Q

Candidate for sulfonylureas

A

Type II diabetic without severe dyslipidemia
Diabetic of normal weight
Diabetic having elevated BS, in spite of meal planning and exercise
Patient who is willing and able to follow LSM
Has had disease <5 years
Older than age 30

120
Q

MOA of sulfonylureas

A
  • Stimulate insulin release from the beta cells of the pancreas
  • May reduce hepatic glucose production and increase peripheral insulin sensitivity
  • will lower A1C by about 1%
121
Q

Pharmacokinetics of sulfonylureas

A

-Given orally, these agents bind to serum
proteins, are metabolized by the liver, and areexcreted in the urine and feces

-Duration of action is from 12-24 hours

122
Q

ADEs of sulfonylureas

A
  • Hypoglycemia and weight gain
  • Hyperinsulinemia
  • Use with caution in renal and liver disease

-Glipizide or Glimepiride are better
options in older adults and in those with
renal disease

123
Q

First Generation Sulfonylureas

A
  • Tolbutamide is dosed at 500-3000 mg per day in divided doses
  • Onset of action is 1 hour; ½ life is 6-8 hours; duration of action is 12-18 hours
  • Metabolized in the liver and excreted via the renal system
  • Again, difficult to find, as it is not prescribed often in the US
124
Q

Second generation sulfonylureas: GLYBURIDE - prototype

A

With the regular preparation, start with 2.5-5 mg per day, which can be increased weekly up to 20 mg/day
With the micronized preparation, start with 1.5-3 mg per day, which can be titrated up weekly up to 12 mg/day
Onset of action in 90 minutes, with maximum effect seen in 60 minutes; ½ life is 10 hours [regardless of the preparation]; duration of action is 12-24 hours [micronized] or 16-24 hours [nonmicronized]
Not approved for use in children; it does cross the placenta, so use caution in women of childbearing age

125
Q

Glimepiride-sulfonylureas

A

-Prescribed in 1-4 mg per day; with a maximum dose of 8 mg per day
=Taken with breakfast [or 1st meal of the day
-Onset of action is 2-3 hours; ½ life is 5-9 hours; maximum effect is seen in 2-6 hours; duration of action is 24 hours
-Can be used in children aged 8 years and older
-Also crosses placenta, so use caution in women of child-bearing age

126
Q

Glipizide -sulfonylureas

A

Start at 2.5 mg; can be titrated up to 40 mg per day for standard preparation or 20 mg per day of the extended-release preparation
•Standard preparation is prescribed 3 times per day
•ER preparation is taken once per day

Onset of action for both preparations is 3.5-6 hours; maximum effect is obtained within 1 hour; duration of action if 12-24 hours; ½ life is 2-5 hours

Not approved for use in children; does cross the placenta and can affect a fetus

127
Q

SEs of sulfonylureas

A
  • Low blood sugar and weight gain
  • Less common ADEs—skin rash, GI disturbances
  • Use care when treating malnourished, debilitated and older adults—as these groups are particular risk for hypoglycemia
128
Q

Timing of Sulfonylureas

A
  • Most sulfonylureas should be taken with
    breakfast or with the first main meal of the
    day to obtain the maximum effect and
    safety
  • Patients on this type of medication should
    carry a rapid-acting glucose source—such
    as tablets or gel, in order to swiftly treat
    hypoglycemia—at the initial signs of low BS
  • Advise these patient regarding safe use of
    alcohol—it lowers BS
129
Q

Drugs that my effect sulfonylureas, leading to loss of glucose control

A
  • atypical antipsychotics
  • corticosteroids
  • diuretics
  • niacin
  • phenothiazines
  • sympathomimetics
130
Q

Drugs that my potentiate the effects of sulfonylureas leading to hypoglycemia

A
  • azole antifungals
  • B blockers
  • chlorampheimcol
  • clarithromycin
  • monoamine oxidase inhibitors
  • probenecid
  • salicylates
  • sulfonamides
131
Q

Nonsulfonylurea Secretagogues

A

It inhibits the amount of glucose produced by the liver, increases the insulin-receptor binding and stimulates tissue uptake of glucose.

132
Q

Candidate for Nonsulfonylurea Secretagogues

A

a Type II diabetic, for which LSM alone or in combination with another agent has not obtained normoglycemia

**These agents are not for use in Type I diabetes,ketoacidosis, severe infections, surgical or trauma patients

133
Q

MOA of Nonsulfonylurea Secretagogues—

A

Short-acting insulin secretagogues
Stimulate insulin release rapidly and have a short duration of action
Very effective in the early release of insulin that occurs after a meal—they are known as
postprandial glucose regulators
Should NOT be used with sulfonylureas

134
Q

Pharmacokinetics of Nonsulfonylurea Secretagogues—

A

Taken prior to a meal; are well metabolized after oral administration

If the patient is not going to consume 70 grams of CHO with the meal—the
drug should be skipped

135
Q

ADEs of Nonsulfonylurea Secretagogues—

A

Hypoglycemia and weight gain—but to a lesser degree than do sulfonylureas

Do NOT prescribe Gemfibrozil with the agents—can markedly increase their effects

Use with caution in those with
liver disease

136
Q

Repaglinide—Prototype

Nonsulfonylurea Secretagogues

A

-Closes ATP dependent K+ channels in the beta cell membrane, which
depolarizes the beta cell and leads to opening of calcium channels—
resulting in increased Ca++ influx causing insulin secretion

-Action of this agent is highly tissue selective, with low affinity for heart
and skeletal muscle

-Best results occur when drug is taken within 15-30 minutes of a meal—
leading to greater insulin release during the 1st phase

  • Onset of action is 15-60 minutes; ½ life is 1 hour; duration 4 hours
  • It is excreted in the feces
  • Can be used as monotherapy or with Metformin, TZD or both
137
Q

Nonsulfonylurea Secretagogues-Natelinide

A

Rapid acting amino-acid derivative known as Dphenylalanine
MOA is similar to the prototype
Like Repaglinide, the extent of insulin release is glucose dependent—and it diminishes with low glucose levels
Rapidly absorbed after oral ingestion—onset is within 20 minutes; ½ life is 90 minutes; duration of action 4 hours
Like the prototype, it is excreted in the feces; can be used alone, with Metformin or TZD or both
- not safe for pregnancy
-SEs:bronchitis, rhinitis, nausea,
vomiting, diarrhea or constipation, headache, chest pain, UTI, back pain, dizziness

138
Q

Nonsulfonylurea Secretagogues

Biguanides

A

Considered an insulin sensitizer
Metformin increases glucose uptake and use bytarget tissues, thereby decreasing insulin secretion
Also used in the treatment of PCOS

139
Q

MOA of Biguanides

A

Reduces hepatic gluconeogenesis—the liver is a major source of high BS in Type II DM, accounting for high fasting BS

Metformin slows intestinal absorption of sugars and improves peripheral glucose uptake and utilization

Weight loss can occur as it causes loss of appetite

The drug does not cause low BS—unless the patient is taking insulin or another secretagogue

140
Q

Pharmacokinetics of Biguanides

A

Well absorbed after oral ingestion, is not bound toserum proteins, and is not
metabolized

Excreted via the urine

141
Q

ADEs of Biguanides

A

Mainly GI—diarrhea, nausea, vomiting
These ADEs can be muted by slow titration—and use of the ER version of the drug, which causes far fewer GI SE
Should be taken with food to reduce ADEs
Metallic taste—when initiating
Contraindicated in renal dysfunction—due to risk of lactic acidosis

142
Q

When should you stop Biguanides?

A

acute MI, exacerbation of HF, sepsis or other d/o that could cause acute RF

143
Q

Use Biguanides in caution with

A

patients >80 years and those with HF or alcohol use

144
Q

When should you hold Biguanides?

A

Procedures requiring IV contrast

145
Q

What is long term Biguanides associated with

A

What is long term Biguanides associated with

146
Q

Biguanides:

METFORMIN what does it do?

A
  • Preferred 1st line agent in those with Type II DM—it lowers both basal and
    postprandial glucoses and improves glucose tolerance
  • Metformin inhibits hepatic glucose production and intestinal absorption of
    glucose; it also increases peripheral glucose uptake and utilization
  • It does not cause elevated insulin levels
  • Again, it causes weight loss—and it is associated with a lower risk of CV
    events in diabetics with reduced renal function—compared to sulfonylureas
147
Q

Candidates for metformin

A

The ideal candidate has Type II DM, is obese, has dyslipidemia and has elevated BS

 It is approved for adults and children aged 10 and older; it can be used in pregnancy

148
Q

Metformin (Biguanides)

A

The drug should always be started with the evening meal and titrated upwards—it is most often given in 2 divided doses

Onset of action is within days, but peak effect is within 4 hours
[for both SA and ER formulations]

Duration of action is 6 hours for the SA and 24 hours for the ER

½ life of both formulations is 4-9 hours

Not metabolized by the liver; renal tubular secretion is route of
elimination

149
Q

Metformin Extended Release

A

This drug—same compound, but with a different release mechanism, that essentially prevents most of the GI side effects
Currently, it is priced the same as the SA
formulation—and is preferred—as it allows for titration up to the 2000 mg per day dosing that is needed for full therapeutic effect
At this dosing—A1C reduction is 1-1.5%
 ER product is ALWAYS preferred—it is dosed the same as the SA
product—no difference in efficacy—but unlikely to reach full therapeutic dose with SA formula—as the GI SE are dose dependent and do not abate with duration of use of the SA formula
 Will LOWER cholesterol, triglycerides and LDL and causes weight loss in
most

150
Q

With Metformin, watch for…

A
  • Hold for situations that cause dehydration—as this predisposes the patient to lactic acidosis [acute illness, gastroenteritis, NPO for procedures, etc.]
  • Hold for 48 hours after radiology testing that utilized iodinated contrast
  • This drug is contraindicated in men with creatinine 1.5 mg/dL or greater and women with creatinine of 1.4 mg/dL or more
  • Should not be started in those with creatinine clearance <46 cc/min;
    and in those on the drug, if the creatinine clearance falls to <30 cc/min, the drug must be stopped
  • Calculate eGFR before starting the drug—do not start if this value is between 30-45 cc/minute
  • Check creatinine and calculate eGFR annually in all patients on Metformin—more frequently in those at risk, such as the older adult
  • In those on the drug—assess the risk/benefit ratio if the eGFR falls below 46 cc/minute to decide upon continuation—but stop when eGFR is 30 cc/minute or less
  • At risk patients—those with liver dysfunction; those with a history of alcohol abuse or binge drinking; those with COPD or unstable HF should not receive Metformin due to lactate accumulation in these
    hypoxic states
  • Lactic acidosis—rare—but deadly
151
Q

Thiazolidinediones

A

-Pioglitazone—Actos [not really the prototype—but only agent left on
the market in US that is prescribed commonly in the class]

  • Rosiglitazone—Avandia [rarely prescribed, and usually only by endo in the US—b/c of increased risk of MI and angina with this agent]
  • Drugs in this class are also considered insulin sensitizers
  • Insulin is required for their action—TZDs do not promote insulin release
These agents do not cause
hypoglycemia
These agents reduce BS, insulin
levels and triglyceride levels
There is increased responsiveness
of insulin-dependent tissues
Can be used as monotherapy or
with Metformin, a SU, a
secretagogue and/or insulin
152
Q

MOA of Thiazolidinediones—also known as TZDs

A

Decrease insulin resistance by acting as an agonist for peroxisome proliferator-activated receptor gamma [PPARγ]—a nuclear receptor
Activating PPARγ causes increased insulin sensitivity in adipose tissues, liver and skeletal muscles
These are 2nd or 3rd line agents that can lower A1C about 1%

153
Q

Pharmacokinetics of Thiazolidinediones—also known as TZDs

A

Well absorbed after oral administration

Extensively bound to serum albumin

154
Q

ADEs of Thiazolidinediones—also known as TZDs

A
  • Liver toxicity—but rare
  • Baseline and periodic management of LFTs is required
  • Weight gain—these drugs increase SQ fat
    and they cause fluid retention
  • Should not be used in those with HF
  • Osteopenia and increased fracture in
    women
  • Increased risk of bladder cancer with Actos
155
Q

Thiazolidinediones : Pioglitazone

A
  • Approved for adults and children >15 years with Type II diabetes; avoid in pregnancy
  • Contraindicated in—active liver disease or ALT levels greater than 2.5 times ULN; NYH class III or class IV HF [BB warning]; jaundice; Type I diabetes; DKA
  • Onset of action is not known; peak effect is in 2 hours [this is delayed by food]; ½ life is 16-24 hours
  • Excreted into the bile unchanged and eliminated in the feces
156
Q

With Pioglitazone watch for…

A

Weight gain
Increased total cholesterol
Fluid retention; headache; arthralgias; back pain; nausea and diarrhea
Atorvastatin—can decrease effectiveness of both Atorvastatin and Actos
Actos reduces effectiveness of OCP
Ketoconazole inhibits the breakdown of Actos
Change—elevation of LFTs

157
Q

Alpha-Glucosidase Inhibitors

A
  • Acarbose—Precose—prototype
  • Miglitol—Glyset
  • Ideal candidate for one of these drugs is a Type II diabetic who is obese, has dyslipidemia and postprandial hyperglycemia
  • These drugs reduce insulinotropic and weight increasing effects of
    SU
158
Q

MOA Alpha-Glucosidase Inhibitors

A

Located in the brush border of the intestine—alpha-glucosidase enzymes breakdown CHO into glucose and other simple sugars that can be absorbed

  • These drugs reversibly inhibit alpha-glucosidase enzymes—thus
    delaying the digesting of CHOs leading to lower postprandial BS levels
  • Taken at the start of a meal; these drugs do not cause hypoglycemia
    [unless used with insulin or a secretagogue—and remember if low BS were to occur in this scenario—must use glucose—NOT sucrose [as its breakdown is inhibited by these drugs]
159
Q

Pharmacokinetics of Alpha-Glucosidase Inhibitors

A
  • Acarbose poorly absorbed—excreted in the urine
  • Miglitol is very well absorbed—but no systemic effects—excreted unchanged by the kidney
  • In the US, these drugs lower A1C by .5% —while in other countries— where these agents are used more commonly, lower A1C by 1%
160
Q

ADEs of Alpha-Glucosidase Inhibitors

A

Flatulence, diarrhea, abdominal cramping

These limit the use of these agents in the US

Do not use in those with inflammatory bowel disease, colonic ulceration or intestinal obstruction, cirrhosis, creatine levels of >2 mg

Avoid use in pregnancy or lactation

161
Q

Alpha-Glucosidase Inhibitors –Acarbose

A

-prototype
Taken right before each meal
Onset of action is immediate; peaks in 1 hour; duration is near 6 hours; ½ life of the drug is 2 hours

162
Q

Alpha-Glucosidase Inhibitors–Miglitol

A
  • take before each meal

- rapid onset of action; peaks in 2 hours; duration of action is near 4 hours

163
Q

With Alpha-Glucosidase Inhibitors watch for….

A

Effects of these drugs are altered by
charcoal products

These drugs reduce bioavailability of
Ranitidine, Propranolol and Digoxin

These drugs reduce the efficacy of—
CCBs, corticosteroids, estrogens, INH,
nicotinic acid, Phenytoin [and its
derivatives], thiazides

164
Q

Timing considerations of Alpha-Glucosidase Inhibitors

A

Must take—essentially, with the first bite of food with each meal

If the patient is on insulin or a SU and one of these agents—and low BS occurs—treat with simple sugar sources—glucose tablets or gels—they should always have these on hand if the patient is on a secretagogue and an alpha-glucosidase inhibitor

165
Q

Dipeptidyl Peptidase-4 Inhibitors [DPP-4

Inhibitors]—also known as Gliptins

A

These agents slow the inactivation of incretin hormones

166
Q

Examples of Dipeptidyl Peptidase-4 Inhibitors

A

Sitagliptin—Januvia [prototype]
Saxagliptin—Onglyza
Linagliptin—Tradjenta
Alogliptin—Nesina

167
Q

MOA Dipeptidyl Peptidase-4 Inhibitors

A

 Well absorbed after oral administration
 Alogliptin and Sitagliptin are excreted unchanged in the urine
 Linagliptin eliminated by enterohepatic system
 Saxagliptin metabolized by CYP450-3A4/5 to an active metabolite; metabolite is excreted renally
 All gliptins except Linagliptin [Tradjenta] require dose adjustments for renal disease

168
Q

ADEs of Dipeptidyl Peptidase-4 Inhibitors

A

Generally, well tolerated

Can cause nasopharyngitis, headache and pancreatitis, severe joint pain

Alogliptin and Saxagliptin have been shown to increase the risk of

HF hospitalizations

Do not use in those with HF or at risk for such; do not use in those with a history of pancreatitis; not to be used in pregnancy or in children

169
Q

Pharmacokinetics of Dipeptidyl Peptidase-4 Inhibitors

A

 Well absorbed after oral administration
 Alogliptin and Sitagliptin are excreted unchanged in the urine
 Linagliptin eliminated by enterohepatic system
 Saxagliptin metabolized by CYP450-3A4/5 to an active metabolite; metabolite is excreted renally
 All gliptins except Linagliptin [Tradjenta] require dose adjustments for renal disease

170
Q

Dipeptidyl Peptidase-4 Inhibitors [DPP-4
Inhibitors]

SITAGLIPTIN (PROTYPE)

A

Given once per day at 100 mg per day; if eGFR is 30-50 cc/minute, the dose is 50 mg per day; and if eGFR is <30 cc/minute the dose is 25 mg per day

Rapidly absorbed, with peak action in 1-4 hours; duration of action is 24 hours; ½ life is 12 hours

Most common side effects are nasopharyngitis or URI; headache;
abdominal pain; diarrhea or nausea

Severe necrotizing pancreatitis has been reported—this agent is thought to double the risk of developing pancreatitis for all who take it

171
Q

What is Sitagliptin associated with/

A
  • precanerous cellular changes of the pancreas

- pancreatitis

172
Q

Dipeptidyl Peptidase-4 Inhibitors [DPP-4
Inhibitors]

Saxagliptin

A

Dosed as 5 mg per day; 2.5 mg dose is used in those with moderate-severe renal disease

Peaks in 2 hours; duration of action is 24 hours; metabolized hepatically

Common SE and ADEs are the same as the prototype

Latest FDA safety review found that this agent can increase the risk of HF, particularly in those with CV or renal disease

173
Q

Dipeptidyl Peptidase-4 Inhibitors [DPP-4
Inhibitors]

Linagliptin

A

Approved by FDA in 2011

If given with a secretagogue, the dose of the secretagogue should be reduced—to prevent low BS

Rapidly absorbed after oral administration—onset of action 90 minutes; duration of action is 24 hours

No dosage change in liver or renal disease
Common SE and ADEs same as prototype

174
Q

Dipeptidyl Peptidase-4 Inhibitors [DPP-4
Inhibitors]

Alogliptin

A

-Approved by FDA in 2013—given once daily
as a 25 mg tablet or 12.5 mg if the patient
has renal disease
- Common SE and ADEs are the same as the
prototype
- In 2016, FDA found that this agent may
increase the risk of HF in diabetics with heart or renal disease

175
Q

Timing considerations of Dipeptidyl Peptidase-4 Inhibitors [DPP-4
Inhibitors]

A

These agents can be taken any time during the day—regardless of food intake

176
Q

Sodium-Glucose Cotransporter 2

Inhibitors [SGLT2 Inhibitors]—also known as Flozins

A

Sodium-Glucose Cotransporter 2

Inhibitors [SGLT2 Inhibitors]—also known as Flozins

177
Q

Examples of Sodium-Glucose Cotransporter 2 Inhibitors [SGLT2 Inhibitors]—

A

 Canagliflozin—Invokana [prototype]
 Dapagliflozin—Farxiga
 Empagliflozin—Jardiance
 Ertugliflozin—Steglatro

178
Q

MOA Sodium-Glucose Cotransporter 2

Inhibitors aka Flozins

A

By inhibiting SGLT2, these drugs decrease the resorption of glucose, increase urinary glucose excretion and lower BS

Inhibition of SGLT2 also decreases resorption of sodium and causes
osmotic diuresis—in some this will lower blood pressure

Approved for adults; should avoid in pregnancy

Will lower A1C 1%

179
Q

Pharmacokinetics Sodium-Glucose Cotransporter 2 Inhibitors aka Flozins

A
  • Given once daily in the morning
  • Canagliflozin should be taken before the first meal of the day
  • All are metabolized by glucuronidation to inactive metabolites
  • Avoid these drugs in those with renal disease, history of UTIs or at risk
    of them [those with renal stones, neurogenic bladder and BPH]
180
Q

ADEs of Sodium-Glucose Cotransporter 2 Inhibitors aka Flozins

A

Genital mycotic infections, severe UTIs, urinary frequency, low blood pressure in older patients and in those on diuretics, ketoacidosis without elevated BS,
Fournier’s gangrene**, increased risk of LE
amputation*, bone fractures, acute kidney injury, electrolyte abnormalities

**should NOT use this family of drugs in patients who have decreased arterial
flow below the femoral vessels [as assessed by poor or absent pulses]

181
Q

Sodium-Glucose Cotransporter 2 Inhibitors [SGLT2 Inhibitors]—

Canagliflozin—Invokana [prototype]

A

100 or 300 mg tablets
Take before 1st meal of the day; use 100 mg per day if
eGFR <60 cc/minute
Do not use in eGFR <30 cc/minute; do not use in severe liver disease
Highest risk of LE amputation with this SGLT2 inhibitor
Some beneficial effects for risk reduction of CV events in diabetics with CV disease and progression of renal disease to ESRD
Hold for 3 days before procedures and surgery

182
Q

Sodium-Glucose Cotransporter 2 Inhibitors [SGLT2 Inhibitors]—

Dapagliflozin—Farxiga

A

 10 and 25 mg tablets
 Once a day in the AM—with or without food
 Do not give if eGFR is <45 cc/minute
 Robust data for prevention of hospitalization from HF in those
with risk factors or those with a HF diagnosis—diabetic and nondiabetic
 Evaluate volume status before initiating; stop for 3 days before surgery and procedures that could cause
dehydration and alcohol abuse—all of these scenarios predispose the diabetic to ketoacidosis without an elevated
blood sugar

183
Q

Sodium-Glucose Cotransporter 2 Inhibitors [SGLT2 Inhibitors]—

Empagliflozin—Jardiance

A
  • 5 and 10 mg tablets
  • Once a day in the AM—with or without food
  • Do not give if eGFR is <45 cc/minute
  • Strong data for reduced risk of adverse CV events—including death in diabetics with CV
    disease
  • Evaluate volume status before initiating; stop for 3 days before surgery and proceduresm that could cause dehydration and alcohol abuse—all of these scenarios predispose them diabetic to ketoacidosis without an elevated blood sugar
184
Q

Sodium-Glucose Cotransporter 2 Inhibitors [SGLT2 Inhibitors]—

Ertugliflozin—Steglatro

A

 5 and 15 mg tablets
 Once a day in the AM—with or without food
 Do not give if eGFR is <60 cc/minute
 No specific data for cardiovascular, renal or HF risk reduction for this agent, at this time
 Evaluate volume status before initiating; stop for 3 days before surgery and procedures that could cause
dehydration and alcohol abuse—all of these scenarios predispose the diabetic to ketoacidosis without an elevated
blood sugar

185
Q

With Sodium-Glucose Cotransporter 2 Inhibitors [SGLT2 Inhibitors]—watch for..

A

Elevated potassium
Renal insufficiency [from the diuretic effect]
Ketoacidosis with BS < 250 mg/dL [yes, ketoacidosis in Type II diabetic—which is not something that is seen—and true mechanism is not well understood]
Severe UTIs
Genital yeast infections

186
Q

Bromocriptine—Cycloset

A

Ergot derivative that stimulates the dopamine receptors—MOA in diabetes is unknown

Start with 0.8 mg each AM with food; increase by 0.8 mg per week [diabetic dose is 1.6 – 4.8 mg per day]

Contraindications—syncope, migraines, pregnancy, lactation, psychosis

Common side effects—GI upset, nausea, headache, orthostatic
hypotension

187
Q

Combination Preparations—General

Considerations

A

Ideal patient for combination preparations is being treated with 2 separate families of antidiabetic medications

But combination therapy is not totally risk free—contraindications and ADEs of both agents must be considered

Combination medications are only available in fixed dosages and may not meet the needs of every patient—and sometimes the
combinations are more expensive than the 2 separate agents

188
Q

Sulfyonylureas

  1. glimepiride
  2. glipizide
  3. glyburide
A

MOA: stimulates insulin secretion
Effect on plasma insulin: increases
Risk of Hypoglycemia: yes
Comments: well established hx of effectiveness. Weight gain can occur. Hypoglycemia most common with this class of oral agents

189
Q

GLINIDES

  1. Nateglinide
  2. Repaglinide
A

MOA: stimulates insulin secretion
Effect on Plasma Insulin: increase
Risk of Hypoglycemia: yes (rare)
Comments: taken with meals. short action with less hypoglycemia. postprandial effect.

190
Q

BIGUANIDES

1. Metformin

A

MOA: decrease hepatic production of glucose
Effect on Plasma Insulin: decrease
Risk of Hypoglycemia: no
Comments: preferred agent for type 2 DM. well est. hx of effectivness. weight loss my occur. Monitor renal function and Vit B12 levels.

191
Q

THIAZOLIDNESDIONES

  1. Pioglitazone
  2. Rosiglitazone
A

MOA: binds to peroxisome proliferator-activated receptor in muscle, fat, and liver to decrease insulin resistance
Effect on Plasma Insulin: decrease
Risk of Hypoglycemia: no
Comments: Effective i highly insulin-resistant patients. Once daily dosing for pioglitazone. Check liver function before initiation. Avoid in liver disease or heart failure.

192
Q

⍺ Glucosidase Inhibitors

  1. Acarbose
  2. Miglitol
A

MOA: decease glucose absorption
Effect on Plasma Insulin: same
Risk of Hypoglycemia: No
Comments: taken with meals. Adverse gastrointestinal effects. Not a preferred therapy. .Reserve for pts unablet o tolerate other agents.

193
Q 
DPP 4 inhibitors
1 . Alogliptin
2. Linagliptin
3. Sitagliptin
4. Saxaogliptin
A

MOA: increase glucose dependent insulin insulin release; decrease secretion of glucagon
Effect on Plasma Insulin: increase
Risk of Hypoglycemia: no
Comments: once daily dosing. may be taken with or without food. Well tolerated. Risk of pancreatitis.

194
Q

SGLT2 inhibitors

  1. Canagliflozin
  2. Dapagliflozin
  3. Dmpagliflozin
  4. Ertugliflozin
A

MOA: increase urinary glucose secretion
Effect on Plasma Insulin: same
Risk of Hypoglycemia: no
Comments: once daily dosing in the morning. Risk of hypotension, genitourinary infections. Avoid in severe renal impairment. Empagliflozin is approved to reduce cardiovascular evens in pts with DM II

195
Q

GLP-1 receptor agonist

  1. Albiglutide
  2. Dulaglutide
  3. Exenatide
  4. Liraglutide
  5. Lixisenatide
  6. Semaglutide
A

MOA: increase glucose-dependent insulin release; decrease secretion of glucagon; slows gastric emptying; increase satiety
Effect on Plasma Insulin: increase
Risk of Hypoglycemia: no
Comments: Injection formulation. Liraglutide and Lixisenatide are dose once daily. Albiglutide, dulaglutide, and semaglutdie are dosed once weekly.

Liraglutide is approved to reduce cardiovascular events in pts with DM II

Weight loss my occur. Risk of pancreatitis.

Contraindicated in pts with hx of medullary thyroid carcinoma

196
Q

Advantage and Disadvantage of

METFORMIN

A 
AD: 
Weight neutral
No hypoglycemia
Improve lipids
Dec micro-macro risks
Dec hyperinsulinemia
DISAD:
Number of
contraindications
Adverse GI effects
Rarely, lactic acidosis
B12 deficiency
197
Q

Advantage and Disadvantage SULFONYLUREAS

A

AD:
Convenient dosing
Inexpensive
Well-established efficacy

DISAD:
Hypoglycemia
Weight gain

198
Q

Advantage and Disadvantage

TZDs

A 
AD: 
No hypoglycemia
Improved lipids
Improved endothelial function
Increased fibrinolysis
Convenient dosing
DISAD:
Inc risk for CHF
Edema
Weight gain
Liver function monitoring
Other adverse effects
199
Q

Advantage and Disadvantage

GLINIDES

A 
AD:
Short duration of action
Low incidence of
hypoglycemia
Less wt gain than SUs

DISAD:
Frequent dosing
Expensive

200
Q

Advantage and Disadvantage

ALPHA GLUCOSIDASE INHIBITORS

A 
AD:
No weight gain
Targets PP glycemia
No hypoglycemia
Nonsystemic

DISAD:
Frequent GI adverse effects
Frequent dosing
Expensive

201
Q

Advantage and Disadvantage

DPP-4 INHIBITORS

A

AD:
Low rate of Adv effects
Convenient dosing
No weight gain

DISAD:
Minimal reduction in A1C
Pancreatitis risk
Expensive

202
Q

Advantage and Disadvantage

GLP-1 AGONIST

A

AD:
Weight loss

DISAD:
Injections
Slight risk of pancreatitis
GI adverse effects
Expensive
203
Q

Herbs that can lower CBG

A

Aloe Vera, Ginseng, Ginger, Turmeric
Bilberry, Cinnamon Bark, Milk Thistle
Kudzu, Blond Psyllium

204
Q

Herbs that can increase CBG

A

Ma Huang
Licorice
Rosemary

205
Q

Cautions with these herbs:

A 
 Garlic
 Ginger
 Ginseng
 Hawthorn
 Ma Huang
 Nettle
 Licorice
 Rosemary
 Saw Palmetto
 Valerian
 Tea Tree Oil
 Primrose
 Turmeric
 Stevia
206
Q

• If ASCVD predominates—

A

reach for a GLP-1 agonist; best evidence is for Liraglutide, Semaglutide or ER Exenatide [in order of strongest to weakest
evidence]

207
Q

• If HF or chronic kidney disease predominates

A

reach for SGLT2 inhibitor; best evidence is for Dapagliflozin, Empagliflozin or Canagliflozin [in order of strongest to weakest]

208
Q

General considerations for prescribing antidiabetic meds

A
  • If the patient does not have established ASCVD, HF or renal disease, the
    recommendations are driven by factors such as weight gain, risk of low BS or cost
  • If hypoglycemia prevention is the most compelling concern—then add a
    GLP-1 agonist, or an SGLT2 inhibitor, a TZD or a DPP-4 inhibitor
  • If you need the patient to lose weight—then go to the GLP-1 agonist,
    followed by a SGLT2 inhibitor—as both of these cause weight loss
  • If cost is a large issue—then the next agent to add is
    a SU or a TZD
209
Q

Insulin Therapy Updates—Consider GLP-1

Agonists before Insulin in Type II Diabetes

A

Most recent diabetic standards recommend that most patients with Type II diabetes who continue tohave elevated A1C in spite treatment with 2 or 3 drugs—should receive a GLP-1 agonist BEFORE insulin

GLP-1s are as good or better than insulin at lowering A1C, they cause weight loss and do not cause low BS

Insulin, of course, is still used without a trial of a GLP-1 agonist in Type I diabetes and in the Type II diabetics with A1C values >11%
Insulin can also be used in Type II diabetes already on a GLP-1 who are still not controlled [insulin is added]; those
who cannot take a GLP-1 and for those who prefer insulin over a GLP-1

210
Q

Geriatric considerations-less is more

A

The latest diabetes guidelines also recommend a deintensification [or simplification] of therapy in those older than
65 years

Recent evidence revealed that patients >50 years with an A1C less than 9% while on Metformin gained only modest benefits
from intensifying treatment [adding insulin]—while the patient’s perception of treatment burden has a large impact on the net
benefit of therapy

In those >75 years, the increased treatment
burden—including an increased risk of low BS—of more intensive therapy resulted in a net effect of harm rather than benefit.

Given the risk of low BS and the medication burden that older adults may have, the ADA now provides formal guidance on deintensifying therapy

211
Q

Risks for ASCVD:

A 
Obesity
HTN
dyslipidemia
soking
FH of CAD
CKD
Albuminuria

Advanced Pharmacology (18 decks)

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