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Pharm: Endocrine and Derm > Diabetes > Flashcards

Diabetes Flashcards

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1
Q

Short term meds for weight loss

A

Phentermine(Lomaira)

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2
Q

Long term meds for weight loss

A

Orlistat (Alli or Xenical), Lorcaserin (Belviq), phenetermine/topiramate ER (Qysymia), Naltrexone/bupropion (Contrave), Liraglutide (Saxenda)

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3
Q

Surgery for weight loss requirements

A

Considered in BMI > 40 kg/m2 regardless of control or

BMI 30-34.9 kg/m2 if hyperglycemia is inadequately control despite optimal medical care

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4
Q

Biguanide Drug name and MOA

A

1st line for T2DM

Metformin

MOA:
Primary – dec. hepatic glucose output

Secondary – inc. peripheral glucose uptake and utilization

Mild anorexia effect may promote weight loss

Does NOT affect insulin secretion

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5
Q

Biguanides Efficacy and Pharmacokinetics

A

Efficacy

  • dec. fasting blood glucose by 50-70 mg/dL
  • dec. A1c by 1-2%
  • dec. LDL, dec. TG, inc. HDL
  • Weight loss
  • Only oral agent shown to improve mortality

Pharmacokinetics:
Eliminated entirely by the kidney

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6
Q

Biguanides ADE

A

Anorexia and nausea on initiation (20-30%)

Abdominal discomfort and diarrhea

Decreased serum vitamin B12 levels over time- risk for peripheral neuropathy

Metallic taste (3%)

BBW for Lactic acidosis – (Rare) occurs in 3 per 100,000 patients/year:

  • Fatal in approximately 50% of cases
  • Signs and symptoms are nausea, shallow/labored breathing, mental confusion
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7
Q

Biguanides Contraindications/Precautions

A

Renal impairment:

  • CrCl < 30 ml/min
  • Starting NOT recommended if CrCl between 30-45 ml/min
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8
Q

Biguanides Drug-Drug Interactions

A

Alcohol

Iodinated contrast agents (Discontinue metformin prior to exposure and withhold for 48 hours after, SCr should be checked prior to restarting)

Cimetidine may increase metformin levels

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9
Q

Biguanides Dosing

A

Initial IR dose: 500 mg BID or 850 mg daily
Titrate in increments of 500 mg weekly or 850 mg every other week

IR: 500 mg to 850 mg TID with meals
To minimize GI effects

Max dose:
Immediate Release: 2,550 mg/day
Extended Release: 2,000 mg once daily

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10
Q

Sulfonylureas Drugs

A

Glipizide (Glucotrol®, Glucotrol® XL)
Glimepiride (Amaryl®)

Glyburide (Micronase®, Diabeta®, Glynase®) - No longer recommended by guidelines, increased risk of hypoglycemia especially in elderly. However, still used for gestational diabetes.

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11
Q

Sulfonylureas MOA

A

stimulate insulin secretion from beta cells of pancreas

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12
Q

Sulfonylurease Pharmacokinetics

A

Glipizide, glimepiride: Metabolized in liver to inactive or mildly active metabolites

Glyburide: 50% of metabolites eliminated in kidney, 50% feces

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13
Q

Sulfonylureas ADE

A

Hypoglycemia – most common

Weight gain (5-20 lb)

Gastrointestinal disturbances: Nausea, dyspepsia, vomiting, abnormal liver function tests

Dermatologic reactions: Rash, photosensitivity reactions, pruritus, hypersensitivity reactions

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14
Q

Sulfonylurea Contraindications/Precautions

A 
Pregnancy
Renal Insufficiency (Glyburide)
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15
Q

Sulfonylurea Drug-Drug Interactions

A

↑ SU effect: antacids, fluconazole, gemfibrozil, salicylates

↓ SU effect: rifampin (glyburide), cyclosporine

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16
Q

Sulfonylureas place in therapy

A

Fasting BG < 200 mg/dL

Patients who develop diabetes after the age of 40

Have diabetes < 5 years

No previous treatment with insulin

Glipizide and glimepiride preferred with CrCl < 50 mL/min

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17
Q

Meglitinides Drugs and MOA

A

Repaglinide (Prandin®)
Nateglinide (Starlix®)

Mechanism of action:
Stimulates insulin secretion in glucose dependent manner -> less hypoglycemia

Lowers PPBG*
Do not take if miss a meal

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18
Q

Meglitinides Pharmacokinetics

A

Onset of action: 15 minutes

Peak response: 60-90 min

Duration of action: <4 hrs

Metabolism: via cytochrome P450 enzymes (CYP 3A4)

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19
Q

Meglitinides ADE (less than SU)

A

Hypoglycemia (repaglinide > nateglinide)

Weight gain

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20
Q

Meglitinides Contraindications/Precautions

A

Use with caution in patients w/ hepatic dysfunction

Pregnancy Category C

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21
Q

Meglitinides Drug Interactions

A

Dec. hypoglycemic effect
Cytochrome P3A4 inducers: Rifampin, Carbamazepine, Phenobarbital

Inc. hypoglycemic effect:
Cytochrome P3A4 inhibitors
Erythromycin
Azole antifungals (ketoconazole, fluconazole, itraconazole)
Gemfibrozil – severe hypoglycemia w/ repaglinide (KNOW)

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22
Q

Thiazolidinediones (TZD) Drugs and MOA

A

Pioglitazone (Actos®)
Rosiglitazone (Avandia®)

MOA:
Peroxisome proliferator activated receptor (PPAR) agonist to promote glucose uptake into target cells:
- Increase insulin sensitivity 
- Decrease hepatic glucose output 
- No effect on insulin secretion
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23
Q

TZDs Safety Concerns

A

TZDs are contraindicated in patients with NYHA Stage III-IV CHF and should be avoided in patients with symptomatic CHF on nitrates.

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24
Q

TZDs Efficacy

A

Dec A1c approximately 0.6-1.3%, FBG by 30-60 mg/dL
Rosiglitazone: inc HDL and LDL cholesterol
Pioglitazone: Dec. triglyceride levels 10%

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25
Q

TZDs Pharmacokinetics

A

Hepatic metabolism

Onset of action is slow:
Several weeks
4 months - maximum effect

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26
Q

TZDs ADE

A

Weight gain (>2-6 kg)

Hepatotoxicity :
Baseline liver function tests
Do not initiate therapy if ALT >2.5 times ULN
ALT >3x ULN, discontinue therapy
ALT >1.5 but <2x ULN, repeat and weekly until normal

Peripheral Edema (5%):
Worse if combined with insulin (risk of CHF)

Mild anemia (1-2%)

Macular Edema (3-6 times more likely to develop)

Risk of proximal fractures

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27
Q

TZDs Contraindications/Precautions

A

Do not use in NYHA Class III or IV heart failure (KNOW)

Contraindicated in pregnancy

Avoid in patients with active liver disease

Caution in patients with anemia, edema

MI (Rosi) – although FDA restrictions removed

Bladder cancer (Pio)

Mild fracture risk

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28
Q

TZDs Drug Interactions

A

Pioglitazone (induces CYP3A4)–↓ effect:
- Cyclosporine, tacrolimus, HMG-CoA reductase inhibitors, oral contraceptives containing ethinyl estradiol and norethindrone

Ketoconazole-inhibits pio metabolism

Rosiglitazone:
- Does not affect PK of oral contraceptives

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29
Q

DPP-4 Inhibitors MOA

A

Inhibits dipeptidyl peptidase-4 enzyme (DPP-4), which inactivates the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP)

↑insulin release and ↓ glucagon levels in a glucose- dependent manner in patients with T2DM

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30
Q

DPP-4 Inhibitors Pharmacokinetics

A

Pharmacokinetics:
Primarily renal elimination
Half-life = 12.4 hours

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31
Q

DPP-4 Inhibitors ADE

A

Headache
Acute pancreatitis
Upper Respiratory Tract Infections
Severe Joint Pain (FDA warning, most w/ Sita)

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32
Q

Saxagliptin ADE

A

Urinary Tract Infections

Skin reactions

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33
Q

Linagliptin ADE

A

Hypoglycemia, arthralgia and back pain

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34
Q

Saxagliptin FDA Warning

A

Increased rate of heart failure hospitalizations, still being reviewed.
Patients should not stop taking saxagliptin
Health care professionals should continue to follow the prescribing recommendations

35
Q

DPP-4 Inhibitors Contraindications/precautions

A

Sita:
Cases of acute Pancreatitis reported, caution in starting in patients with history of or active pancreatitis (FDA warning)

Saxa:
Caution in patients with heart failure and concurrent elevation in BNP, CKD.

Alo:
Post-marketing reports of hepatic failure

Alo,sita,saxa:
Dose adjustment in renal dysfunction

36
Q

DPP-4 Inhibitors Drug Interactions

A

Digoxin: oral sitagliptin caused small (11%) increase in AUC and plasma Cmax (18%) of digoxin at 0.25 mg/day. Dose adjustment of digoxin not recommended, but monitor closely.

37
Q

SGLT-2 Inhibitors MOA

A

Inhibits glucose and sodium reabsorption in renal proximal tubule
SGLT2: ~90% of renal glucose reabsorption
Increases urinary glucose excretion

38
Q

SGLT-2 Inhibitors Efficacy

A

decrease A1c 0.6-1.2%
decrease FBG and PPG
Reduction in weight (1.6-3.8%) and BP

39
Q

SGLT-2 Inhibitors Pharmacokinetics

A

Hepatic metabolism
Excretion: fecal and renal
Renal: Dapagliflozin > Canagliflozin

40
Q

SGLT-2 Inhibitors ADE

A 
Polyuria (4-5%)
UTI (4-6%)
Genital mycosis: Female (10-11%), Male  (3-4%) 
Hypotension (2-3%)
Dapaglifozin: Nasopharyngitis (6-7%)
41
Q

SGLT-2 Inhibitors Contraindications/Precautions

A

Renal impairment (eGFR < 30mL/min) or ESRD
Dialysis
Caution in the elderly or hepatic impairment

42
Q

SGLT-2 Inhibitors Drug interactions

A

Rifampin, phenytoin, phenobarbital, and ritonavir decrease canagliflozin concentration

Canagliflozin increase digoxin concentration

43
Q

What is an important health benefit of SGLT-2 Inhibitors

A

decreasing ASCVD/CHF risks

Empagliflozin received FDA approval for this!

44
Q

Alpha-Glucosidase Inhibitors MOA

A

Potent competitive inhibitor of brush border alpha-glucosidases necessary for the breakdown of complex carbohydrates
Slows intestinal carbohydrate digestion/absorption

45
Q

Alpha-Glucosidase Inhibitors Efficacy

A

Decrease postprandial hyperglycemia 30-60mg/dL
Not effective in lowering blood glucose levels throughout the rest of the day
Small improvements in A1c

46
Q

Alpha-Glucosidase Inhibitors ADE

A

Gastrointestinal side effects (up to 70%)
Acarbose – increased LFTs at doses >100 mg TID
No hypoglycemia as monotherapy

47
Q

Alpha-Glucosidase Inhibitors Contraindications/precautions

A

GI disorders including inflammatory bowel disease, chronic ulceration, and partial obstruction

Renal impairment: avoid acarbose if Scr > 2 mg/dL; not studied

Hypoglycemia -Treat with glucose ,dextrose, lactose only ( why?…MOA prevents breakdown of table sugar)

Contraindicated in pregnancy

48
Q

Alpha-Glucosidase Inhibitors Drug interactions

A

Acarbose and miglitol may decrease digoxin levels

Miglitol may decrease propranolol and ranitidine concentrations

49
Q

Bile Acid Sequestrant (BAS) MOA

A

Thought to be an antagonist to the farnesoid X receptor (FXR), which subsequently reduces hepatic gluconeogenesis
Used in conjunction with insulin or oral DM medications

50
Q

Bile Acid Sequestrant (BAS) Adverse Effects:

A

Constipation, dyspepsia, nausea, myalgia

51
Q

Bile Acid Sequestrant (BAS) Contraindications and precautions

A

Contraindicated in patients with a history of bowel obstruction, serum TG concentration greater than 500 mg/dL
Caution in patients with swallowing disorders (large pill), dysphasia, gastric mobility disor- ders, and serum TG concentrations greater than 300 mg/dL

52
Q

Are GLP-1 Receptor Agonists monotherapy?

A

This injectable agent is not indicated as monotherapy!

53
Q

GLP-1 Receptor Agonists MOA

A

Mimics the effects of an incretin hormone called glucagon-like peptide-1 (GLP-1):
Stress response to high BG levels
Inhibits release of glucagon after meals
Slows the rate of gastric emptying-> DDIs
Promotes satiety -> less intake -> weight loss
stimulates production of insulin

54
Q

GLP-1 Receptor Agonists ADE

A 
Mild to moderate:
Hypoglycemia (14–36%)-more commonly in patients receiving a sulfonylurea
Nausea (40-50%)
Vomiting (13%)
Diarrhea (13%)
Dizziness (9%)
Immunogenicity may occur – exenatide is a protein
Injection-site reactions
55
Q

GLP-1 Receptor Agonists Black Box Warning

A

Can cause dose-dependent and treatment duration–dependent thyroid C-cell tumors at clinically relevant exposures in rodents.

Unknown in humans

56
Q

GLP-1 Receptor Agonists Drug Interactions

A

Slows gastric emptying – may alter rate and extent of absorption of oral drugs
Take oral meds at least one hour before injecting a GLP-1 RA

57
Q

GLP-1 Receptor Agonists Precautions

A

Should not be used in patients with severe renal impairment (CrCl < 30 mL/min) or those with ESRD (Exenatide ONLY)

Should not be used in patients with severe GI disease including gastroparesis

Cases of acute pancreatitis have been reported. Consider alternatives in patients w/ history of pancreatitis

58
Q

GLP-1 Receptor Agonists Indication

A

Adjunctive therapy to improve glycemic control in patients with T2DM who are not adequately controlled with metformin, a sulfonylurea, or a combination of both

59
Q

Pramlintide (Symlin®) MOA

A

Synthetic analog of amylin, an endogenous hormone produced in the pancreas to assist in postprandial glucose control
Decrease glucagon secretion
Delays gastric emptying, increases the feeling of satiety

60
Q

Pramlintide (Symlin) Indications

A

Approved for use in patients with either type 1 or type 2 diabetes

Type 1 diabetes:
Approved as an adjunctive treatment in patients who use mealtime insulin and who have failed to achieve glucose control despite optimal insulin therapy

Type 2 diabetes:
Approved as an adjunct to mealtime insulin in patients who have failed to achieve optimal glucose control with insulin therapy, with or without concurrent sulfonylureas and/or metformin

61
Q

Pramlintide (Symlin) ADE

A

Does not cause hypoglycemia when used alone

Can cause severe, insulin-induced hypoglycemia when used in combination with insulin:
Type 1 diabetes
Occurs within 3 hours after a dose

Gastrointestinal:
Nausea especially upon initiation of therapy (28-48%)
Loss of appetite
Vomiting
Headache
62
Q

Pramlintide (Symlin) has a REMS for what?

A

risk for severe hypoglycemia with concurrent use of pramlintide and insulin.

*Need to reduce insulin doses when initiating pramlintide

63
Q

Pramlintide (Symlin) Contraindications

A

Patients with confirmed diagnosis of gastroparesis or hypoglycemia awareness

Should not be used in patients who have had recurrent severe hypoglycemia, have poor compliance with insulin regimens or SMBG instructions

64
Q

Pramlintide (Symlin) Drug interactions

A

Should not be used in patients who are taking medications that affect gastric motility such as anticholinergic medications or agents that slow intestinal absorption of nutrients such as the alpha-glucosidase inhibitors

May slow the absorption of drugs taken orally
Take oral medication 1 hour before pramlintide

65
Q

What are the Insulin Indications for T2DM

A

Severe Hyperglycemia at Dx
Overcoming glucose toxicity
A1c> goal despite max doses of 2 oral agents
Pregnancy, surgery

66
Q

Insulin Pharmacokinetics

A

Route of administration: IV > IM > SC

Clearance:
Renal Function (failure decreases clearance)
Insulin antibodies – IgG antibodies bind insulin and release it slowly

Absorption:
Injection site, exercise, temperature, massage, dose

67
Q

How does thyroid function effect insulin clearance?

A

Hyperthyroidism increases insulin clearance but also delays action

68
Q

Basal Insulin Characteristics

A

Suppresses hepatic glucose production b/w meals and overnight
Stimulates lipid and protein synthesis
Use intermediate or long-acting insulin
50 % of daily needs

69
Q

Bolus Insulin Characteristics

A

Controls hyperglycemia after meals (stores nutrients)
Use rapid (best) or regular insulin
10-20 % of daily insulin requirement for each meal

70
Q

Basal Insulin Long Acting Drugs

A 
Insulin Glargine (Lantus®)
Insulin Detemir (Levemir®)
Insulin Degludec (Tresiba®)
71
Q

Bolus Insulin Rapid Acting Drugs and how to use

A 
Insulin lispro (Humalog®)
Aspart insulin (Novolog®)
Insulin glulisine (Apidra®)

Inject just before meals (15 min)

72
Q

Bolus Insulin Short Acting Drugs and how to use

A

Regular insulin (Humulin R)

Must be administered 30-45 minutes before meals

73
Q

Afrezza Administration and Contraindication

A

Shorting acting and
Regular Inhaled Insulin

Contraindicated in patients w/ chronic lung disease such as asthma or COPD

74
Q

What is a problem with premixed insulin?

A

Problematic for hospitalized patients

Inflexible dosing

75
Q

What is the recommended initial insulin dosing therapy for T1DM

A

Initially, start total daily insulin at 0.4-0.5 units/kg/day

76
Q

Steps for Initiating Insulin in T2DM

A

Step 1: ODA + Basal Insulin

After 3 months, if target A1C is not reached…

Step 2: Consider GLP-1 OR Add prandial (bolus) insulin

After 3 months, if target A1C is not reached…

Step 3: Add prandial (Bolus) insulin to the next meal

After 3 months, if target A1C is not reached…

Step 4: Add prandial (Bolus) insulin to the last meal

77
Q

What are the BG goals for pre-meal, bedtime, and post-meal for T2DM?

A

Pre-meal & bedtime glucose = 80-130 mg/dL

1-2 hour post-prandial = <180 mg/dL

78
Q

Patients on multiple-dose insulin or insulin pump therapy should perform SMBG when?

A 
Prior to meals and snacks
Occasionally post-prandially
At bedtime
Prior to exercise
When they suspect hypoglycemia 
Prior to critical tasks such as driving
79
Q

When should A1C testing be done?

A

At least two times a year in patients who are meeting treatment goals (and who have stable glycemic control)
OR
Test quarterly in patients whose therapy has changed or who are not meeting glycemic goals

80
Q

Insulin ADE

A

Hypoglycemia

Weight gain

Injection site discomfort or redness:
Lipohypertrophy- Repeated injection in the same site causing fatty build up. Stress importance of rotating injection sites
Lipoatrophy- Pitting of skin (immune response to impure insulin)

Local allergic reactions & hypersensitivity

81
Q

Hypoglycemia Types (Levels) and General Tx

A

< 70mg/dL = Hypoglycemia alert value (level 1)
-Treat w/ fast acting carbohydrate, dose adjustment

<54mg/dL = Clinically significant hypoglycemia (level 2)
-Give Glucagon

No level but severe cognitive impairment = Severe (level 3)
-Requires assistance from another person for recovery

Values associated with Symptoms
BG < 50 mg/dL; patient may or may not be symptomatic
BG < 40 mg/dL; patient generally symptomatic
BG < 20 mg/dL; can be associated with seizures and coma

82
Q

Hypoglycemia Clinical Considerations

A

Irregular eating patterns
Increased physical exercise
Gastroparesis (delayed gastric emptying time)
Medications (including oral sulfonylureas)

83
Q

Hypoglycemia Tx

A

15-20 g rapidly absorbed carbohydrate
Repeat in 15-20 min of glucose concentration <60 mg/dl or if patient symptomatic
Follow with complex carbohydrate/protein snack
15-15-15 Rule

84
Q

What do you use to treat a patient who is unconscious as a result of hypoglycemia?

A

Glucagon 1 mg SC, IM, or IV – mean response time 6.5 minutes – must reconstitute

Pharm: Endocrine and Derm (6 decks)

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