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Pharm: Endocrine and Derm > Diabetes > Flashcards

Diabetes Flashcards

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
TZDs Pharmacokinetics
Hepatic metabolism Onset of action is slow: Several weeks 4 months - maximum effect
26
TZDs ADE
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
27
TZDs Contraindications/Precautions
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
28
TZDs Drug Interactions
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
29
DPP-4 Inhibitors MOA
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
30
DPP-4 Inhibitors Pharmacokinetics
Pharmacokinetics: Primarily renal elimination Half-life = 12.4 hours
31
DPP-4 Inhibitors ADE
Headache Acute pancreatitis Upper Respiratory Tract Infections Severe Joint Pain (FDA warning, most w/ Sita)
32
Saxagliptin ADE
Urinary Tract Infections | Skin reactions
33
Linagliptin ADE
Hypoglycemia, arthralgia and back pain
34
Saxagliptin FDA Warning
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
DPP-4 Inhibitors Contraindications/precautions
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
DPP-4 Inhibitors Drug Interactions
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
SGLT-2 Inhibitors MOA
Inhibits glucose and sodium reabsorption in renal proximal tubule SGLT2: ~90% of renal glucose reabsorption Increases urinary glucose excretion
38
SGLT-2 Inhibitors Efficacy
decrease A1c 0.6-1.2% decrease FBG and PPG Reduction in weight (1.6-3.8%) and BP
39
SGLT-2 Inhibitors Pharmacokinetics
Hepatic metabolism Excretion: fecal and renal Renal: Dapagliflozin > Canagliflozin
40
SGLT-2 Inhibitors ADE
``` Polyuria (4-5%) UTI (4-6%) Genital mycosis: Female (10-11%), Male (3-4%) Hypotension (2-3%) Dapaglifozin: Nasopharyngitis (6-7%) ```
41
SGLT-2 Inhibitors Contraindications/Precautions
Renal impairment (eGFR < 30mL/min) or ESRD Dialysis Caution in the elderly or hepatic impairment
42
SGLT-2 Inhibitors Drug interactions
Rifampin, phenytoin, phenobarbital, and ritonavir decrease canagliflozin concentration Canagliflozin increase digoxin concentration
43
What is an important health benefit of SGLT-2 Inhibitors
decreasing ASCVD/CHF risks | Empagliflozin received FDA approval for this!
44
Alpha-Glucosidase Inhibitors MOA
Potent competitive inhibitor of brush border alpha-glucosidases necessary for the breakdown of complex carbohydrates Slows intestinal carbohydrate digestion/absorption
45
Alpha-Glucosidase Inhibitors Efficacy
Decrease postprandial hyperglycemia 30-60mg/dL Not effective in lowering blood glucose levels throughout the rest of the day Small improvements in A1c
46
Alpha-Glucosidase Inhibitors ADE
Gastrointestinal side effects (up to 70%) Acarbose – increased LFTs at doses >100 mg TID No hypoglycemia as monotherapy
47
Alpha-Glucosidase Inhibitors Contraindications/precautions
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
Alpha-Glucosidase Inhibitors Drug interactions
Acarbose and miglitol may decrease digoxin levels Miglitol may decrease propranolol and ranitidine concentrations
49
Bile Acid Sequestrant (BAS) MOA
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
Bile Acid Sequestrant (BAS) Adverse Effects:
Constipation, dyspepsia, nausea, myalgia
51
Bile Acid Sequestrant (BAS) Contraindications and precautions
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
Are GLP-1 Receptor Agonists monotherapy?
This injectable agent is not indicated as monotherapy!
53
GLP-1 Receptor Agonists MOA
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
GLP-1 Receptor Agonists ADE
``` 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
GLP-1 Receptor Agonists Black Box Warning
Can cause dose-dependent and treatment duration–dependent thyroid C-cell tumors at clinically relevant exposures in rodents. Unknown in humans
56
GLP-1 Receptor Agonists Drug Interactions
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
GLP-1 Receptor Agonists Precautions
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
GLP-1 Receptor Agonists Indication
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
Pramlintide (Symlin®) MOA
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
Pramlintide (Symlin) Indications
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
Pramlintide (Symlin) ADE
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
Pramlintide (Symlin) has a REMS for what?
risk for severe hypoglycemia with concurrent use of pramlintide and insulin. *Need to reduce insulin doses when initiating pramlintide
63
Pramlintide (Symlin) Contraindications
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
Pramlintide (Symlin) Drug interactions
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
What are the Insulin Indications for T2DM
Severe Hyperglycemia at Dx Overcoming glucose toxicity A1c> goal despite max doses of 2 oral agents Pregnancy, surgery
66
Insulin Pharmacokinetics
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
How does thyroid function effect insulin clearance?
Hyperthyroidism increases insulin clearance but also delays action
68
Basal Insulin Characteristics
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
Bolus Insulin Characteristics
Controls hyperglycemia after meals (stores nutrients) Use rapid (best) or regular insulin 10-20 % of daily insulin requirement for each meal
70
Basal Insulin Long Acting Drugs
``` Insulin Glargine (Lantus®) Insulin Detemir (Levemir®) Insulin Degludec (Tresiba®) ```
71
Bolus Insulin Rapid Acting Drugs and how to use
``` Insulin lispro (Humalog®) Aspart insulin (Novolog®) Insulin glulisine (Apidra®) ``` Inject just before meals (15 min)
72
Bolus Insulin Short Acting Drugs and how to use
Regular insulin (Humulin R) Must be administered 30-45 minutes before meals
73
Afrezza Administration and Contraindication
Shorting acting and Regular Inhaled Insulin Contraindicated in patients w/ chronic lung disease such as asthma or COPD
74
What is a problem with premixed insulin?
Problematic for hospitalized patients | Inflexible dosing
75
What is the recommended initial insulin dosing therapy for T1DM
Initially, start total daily insulin at 0.4-0.5 units/kg/day
76
Steps for Initiating Insulin in T2DM
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
What are the BG goals for pre-meal, bedtime, and post-meal for T2DM?
Pre-meal & bedtime glucose = 80-130 mg/dL 1-2 hour post-prandial = <180 mg/dL
78
Patients on multiple-dose insulin or insulin pump therapy should perform SMBG when?
``` 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
When should A1C testing be done?
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
Insulin ADE
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
Hypoglycemia Types (Levels) and General Tx
< 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
Hypoglycemia Clinical Considerations
Irregular eating patterns Increased physical exercise Gastroparesis (delayed gastric emptying time) Medications (including oral sulfonylureas)
83
Hypoglycemia Tx
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
What do you use to treat a patient who is unconscious as a result of hypoglycemia?
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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