Block 3: Diabetes II Flashcards
1
Q
How does metformin work?
A
Lowers glucose level by:
1. Decreasing hepatic glucose production
2. Decreases intestinal absoprtion of glucose
3. Increasing peripheral insulin sensitivity
Liver»_space; Muscle
Does NOT directly effect beta-cells
Eliminated by kidneys
2
Q
CI for metformin?
A
- T1DM/Ketoacidosis
- Hyperssensitivity
- Renal impairment requires a dosage adjustment
- Unstable HF
- Metabolic acidosis
- Hx of lactic acidosis
3
Q
Metformin place in therapy?
A
- Highly effective: Decreases A1c 1-1.5%
- Lower risk of hypoglycemia
- Modest to neutral weight
- Low cost
- Avoid renal insufficiency
- Approved for pediatrics as young as 10
4
Q
Metformin
Brand, ADR, DDI, Dosing, Monitoring
A
Glucophage, Glucophage XR
ADR:
1. GI upset stomach, diarrhea
2. Decreased B12 absorption
3. Induction of ovulation
4. Lactic acidosis
CI: Alcohol, Cimetidine, Constrast dye (hold metformin 48 hrs after procedure)
Dosing: Take with food and titrate slowly (weekly) to minimize GI problems
Monitoring: Srcr, hepatic function, B12 levels, H&H yearly
5
Q
Pharmacology of TZDs (Piaglitazone)
A
PPAR agonist that increases glucose uptake by muscle and fat
Insulin sensitizer in muscle, fat»_space; liver
Hepatically metabolized
6
Q
CI of Pioglitazone?
A
- T1DM or Ketoacidosis
- Hypersensitivity
- Hepatic Impairment* (Baseline ALT >2.5 X NL) or Cirrhosis
- Severe CHF (NYHA Class III and IV)
- Premenopausal Anovulatory Woman
- ACS
- Monitor Mucular edema
- Increased risk of fractures in women
7
Q
Place in therapy TZDs?
A
- High effectiveness for glucose lowering: Decreases A1c 1.0-1.5%
- alternative to metformin
- Low risk of hypoglycemia
- Risk reduction in patients with ASCVD: add-on to SGLT2 and/or GLP-1
- Weight gain/edema
- Low cost
- Avoid in patients with ALT > 2.5 times normal at baseline; STOP if ALT 3 times normal while on therapy
8
Q
Pioglitazone
Brand, ADR, DDI, DOsing, Monitoring
A
Actos
ADRs: Hepatotoxicity, macular edema, fluid retention, weight gain, Resumption of ovulation in premenopausal anovulatory women, fracture risk in women, bladder cancer
DDI: Strong CYP2C8 inhibitor, Pioglitazone induces CYP3A4, oral contraceptives
Dosing: Take with or without food
Monitoring: Hepatic function, ADRs, may take 4-8 weeks to see effect
9
Q
Types of sulfonylurea?
A
Glimepiride (Amaryl)
Glipizide (Glucotrol, Glucotrol XL)
Glyburide (Diabeta, Micronase)
Glyburide micronized (Glynase)
10
Q
Pharmacology and PK of sulfonylurea?
A
Lowers glucose levels by:
1. Increasing insulin secretion from beta cell (Requires functioning B cells)
2. Normalizing hepatic glucose production
3. Partially reversing insulin resistance in the peripheral tissues
Dose adjust in renal insufficiency
Increased half-life -> increased accumulation -> increased risk of hypoglycemia
11
Q
CI of sulfonylurea?
A
- T1DM or Ketoacidosis*
- Hypersensitivity*
- Severe hepatic or renal impairment
- G6PD deficiency
- Illness that affect blood glucose levels
12
Q
Place in therapy for sulfonylurea?
A
- High effectiveness for glucose lowering: Decreases A1c 1.0-1.5%
- High risk of hypoglycemia
- Weight gain
- Low cost
- Avoid in patients with significant renal insufficiency
- More useful in long standing DM
- Avoid in patients where hypoglycemia is a problem (i.e., elderly)
* Especially glyburide (long ½ life)
13
Q
Sulfonylurea
ADR, DDI, Dosing,
A
ADR: Hypoglycemia, weight gain
DDI: Warfarin, cimetidine
Dosing: QD w/ breakfast
14
Q
Types of Short-acting Insulin Secretagogues?
A
Nateglinide (Starlix) and Repaglinide (Prandin)
15
Q
Pharmacology of Short-acting Insulin Secretagogues?
A
- Lowers glucose levels
- Increasing insulin secretion from the beta cells in the pancreas in the presence of glucose
- Requires functioning B cells
Short half-life
16
Q
CI of Short-acting Insulin Secretagogues?
A
- T1DM or Ketoacidosis*
- Hypersensitivity*
- Use with caution in severe hepatic or renal impairment
17
Q
Short-acting Insulin Secretagogues Place in therapy?
A
Less effective for glucose lowering than sulfonylureas: Decreases A1c 1%
* post-prandial glucose levels (taken with meals: “oral insulin”)
May be used as an alternative to sulfonylureas in patients with renal insufficiency
* Do NOT use with sulfonylureas
Low cost
18
Q
Short-acting Insulin Secretagogues
ADR, Dosing, DDI
A
ADR: hypoglycemia, weight gain
Dosing: Take 30 minutes prior to each meal
DDI: Repaglinide/gemfibrozil
19
Q
What is secondary b cell failure?
A
Oral secretagogues, i.e., sulfonylureas, which increase insulin secretion are effective initially
Over time:
1. ß cell failure
2. Insulin secretion declines
3. Secondary failure of oral secretagogues and increased blood glucose levels
20
Q
Types of Alpha-glucosidase Inhibitors?
A
Acarbose (Precose) and Miglitol (Glyset)
21
Q
Pharmacology of a-glucosidase inhibitors?
A
Delays digestion of carbs
Acarbose is metabolized by amylases to inactive metabolites
Miglitol is excreted uncahnged in urine
22
Q
CI of a-glucosidase inhibitor?
A
- T1DM or Ketoacidosis*
- Hypersensitivity*
- Hypoglycemia
- Severe renal impairment
- Cirrhosis
- GI conditions
23
Q
a-glucosidase inhibitor place in therapy?
A
Adjunctive therapy:
1. Low effectiveness: A1c 0.5-1%
2. Low risk of hypoglycemia
3. Weight neutral
4. Avoid in patients with GI problems
24
Q
ADRs of a-glucosidase inhibitors?
A
- Flatulense, diarrhea, abdominal pain
- Treat hypoglycemia with PO glucose or lactose NOT sucrose
25
How do you dose a-glucosidase inhibitors?
**Start low, go slow**
At the beginning of each meal
26
What are the types of BAS?
Colesevelam (Welchol)
27
What is the caution using Welchol?
CI:
1. Bowel obstruction
2. TG >500, precation >300
3. High TG
4. T1DM
5. Hypersensitivity
6. ADEK def
28
BAS place in therapy?
1. Lower effectiveness: <0.5%
2. Not used in T2DM except in specific situations
3. Lower LDL, increase TG
29
ADR and DDI of Colesevelam?
**ADR:** GI effects, hyperTG, pancreatitis
**DDI:**
* Separate by 4 hours from drugs with narrow therapeutic index i.e., warfarin, phenytoin, digoxin
* Decreases levels of many drugs (levothyroxine, phenytoin, OC, warfarin, ADEK, glyburide
30
Dosing and monitoring of BAS?
Take with food and water
1. Lipid panel
2. May take 4-6 weeks to see effect
31
Types of dopamine agonists?
Bromocriptine (Cycloset)
32
Place in therapy and CI of Bromocriptine?
**CI:**
1. Hypersensitivity to ergots and drug
2. T1DM
3. Don't use in lactating mothers (decreases lactation)
4. Renal and hepatic impairment
Lower effectiveness decreases A1C 0.5%
33
Bromocriptine
| ADR, Monitoring Dosing
**ADR:**
1. Somnolence
2. Hypotension
3. Syncope
**DOsing:**
1. Take first thing in the morning with food, within two hours of rising
2. Use of ergots within 6 hours of bromocriptine is NOT recommended
**Monitoring:**
1. BP and HR
2. Vision
3. Melanoma skin exam
4. Prolactin levels
34
Type of SGLT2 inhibitor?
Canagliflozin (Invokana)
Dapagliflozin (Forxiga)
Empagliflozin (Jardiance)
Ertugliflozin (Steglatro)
Bexaglifozin (Brenzavvy)*
35
SGLT2 inhibitor MOA and PK?
Lowers glucose levels by:
1. Reduces glucose reabsopriton
2. Increases urinary glucose excretion
3. Lowers blood glucose levels
Urine and feces
36
CI of SGLT2i?
1. T1 DM or Ketoacidosis*
2. Hypersensitivity*
3. Avoid in patients with significant renal insufficiency
4. Use with caution in patients with a history of bladder CA
5. Ensure patients are NOT volume depleted before initiating therapy
37
SGLT2 place in therapy?
1. Intermediate: A1c 0.5-1%
2. Low risk of hypoglycemia
3. Risk reduction in ASCVD, HF, CKD
4. Weight loss
5. High cost
6. Avoid renal insufficiency
7. Empaglifozin is approved in pediatric patients as young as 10 years of age
38
SGLT2I indication
| Indications, DDI, ADR
**Indication:** ASCVD, HF, DKD, T2DM (Canagliflozin, Empagliflozin)
**DDI:** UGT inducer, digoxin
**ADR:** Fungal infection, UTI, Polyuria (hypovolemia), Hypotension w/ elederly, diuretics, ACEIs or ARBs, Hetoacidosis, Increased risk of lower limb amputations
**Dosing:** Take in morning with or without food
* Canagliflozin: CI in eGFR < 30
* Dapagliflozin: CI in eGFR < 45
39
DPP4 inhibitor types?
Sitagliptin (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)
40
MOA and PK of DPP inhibitors?
**MOA:** Decreases the breakdown of incretins by DDP4
**PK:** Excreted in feces and urine
41
DPP4 inhibitors CI
1. T1DM or Ketoacidosis*
1. Hypersensitivity*
1. Hx of pancreatitis
1. Adjust doses in renal impairment (not linagliptin)
42
Place in therapy DPP4 inhibitors?
1. Intermediate: A1C 0.5-1%
2. Low risk of hypoglycemia
3. Risk of HF with saxagliptin
4. Weight neutral
5. High cost
6. MAY be used in renal impairment
7. No GI effects
43
DPP4 inhibitors?
| ADR, DDI, Dosing, Monitoring
**ADR:** Pancreatitis, bullous pemphigoid
**DDI:** GLP1 inhibitors
**Dosing:**
* Sitagliptin: 100 mg QD: Reduce dose in moderate to severe renal insufficiency (50 mg: GFR <45, 25 mg: <30
* Saxagliptin: Moderate to severe renal insufficiency (eGFR < 45 ml/min/1.73 m2)
* Alogliptin: Reduce dose in renal insufficiency (CrCl 30 to 59 ml/min: 12.5 mg daily, CrCl < 30 ml/min: 6.25 mg daily)
**Monitoring:**
* Renal function
* HF sx (saxagliptin)
* Pancreatitis
* Dermatological conditions
44
Injectable meds?
Incretin Mimetics (GLP-1 Agonists) (Type 2 DM)
GIP-GLP-1 Agonists (Type 2 DM)
Amylin Analogs (Type 1 & 2 DM)
Insulin (Type 1 & 2 DM)
45
Incretin mimetics types?
Semaglutide (Ozempic [SC]; Rybelsus [PO])
Liraglutide (Victoza)
Dulaglutide (Trulicity)
Lixisenatide (Adlyxin)
Exenatide (Byetta, Bydureon BCise)
46
MOA and PK of GLI agonists?
Activates glucsgon-like-peptide-1 (GLP-1) receptors:
1. Enhances glucose-dependent insulin secretion by the pancreatic beta-cell
2. Suppresses inappropriately elevated glucagon secretion
3. Slows gastric emptying
4. Improves glycemic control by reducing fasting and postprandial glucose concentrations
**PK:** feces and urine
47
CI GLP1 agonists?
1. T1DM
2. Hypersensitivity
3. Pregnancy, lactation
4. GI dx
5. Pancreatitis
6. Thyroid C-cel tumors, MTC, MENS2
48
Place in therapy GLP1 agonists?
1. HIGH effectiveness for glucose lowering: Decreases A1c by 1.0% to 1.5%
2. Low risk of hypoglycemia
3. Weight loss
4. Avoid in patients with significant renal insufficiency
5. Do NOT use with DPP-4s
49
GLP1 agonist
| Indications,
**Indications:** ASCVD, DKD, T2DM (Dulagutide, Liraglutide, Semaglutide)
**ADR:** GI, weight loss, pancreatitis, AKI, acute gallbladder disease
**DI:** Medications that may be affected by delay in gastric emptying (OC)
**Dosing:**
* DO NOT mix with insulin or inject into an area adjacent to insulin
* SubQ injection: thigh, abdomen, or upper arm
* Give daily injections WITH food; weekly injections may be given WITH or WITHOUT food
* Exenatide (Bydueron BCise): injected immediately after mixing
* Exenatide (Byetta): Increase dose after 1 month, 60 minutes before 2 main meals, not after meals
* Lixisenatide: 60 minutes before meal
50
How do you administer Rybelsus?
1. Take at least 30 minutes BEFORE first food, beverage, or other oral medications of the day
2. Take with a sip (no more than 4 ounces) of PLAIN Water only
51
Tizepatide MOA
GIP/GLP1 receptor agonists:
1. Enhances glucose-dependent insulin secretion by the pancreatic beta-cell
2. Suppresses inappropriately elevated glucagon secretion
3. Slows gastric emptying
4. Improves glycemic control by reducing fasting and postprandial glucose concentrations
52
CI of Mounjaro?
1. Severe GI disease (i.e., Crohn's disease, gastroparesis)
2. Hx of pancreatitis
3. T c-cell tumor, MTC, MENS2
4. Caution with gallbladder dx and diabetic retinopathy
5. T1DM, Hypersensitivity
6. Pregnancy and lactation
7. Renal insufficiency
53
Mounjaro place in therapy?
1. High effectivenss: 1.5%
2. Low risk of hypoglycemia
3. Weight loss
4. High cose
5. Avoid patients with renal insufficiency
54
Mounjaro
| ADR, DDI,
**ADR:** GI, weight loss, pancreatitis, AKI, acute gallbladder disease
**DDI:** Slows gastric emptyin (OC), DPP4i
**Dosing:**
* DO NOT mix with insulin or inject into an area adjacent to insulin
* Increase dosea fter 4 weeks (max 15 mg)
* SubQ injection: thigh, abdomen, or upper arm
* May be given with or without food
55
What are the amylin analogs? MOA?
Pramlintide (Symlin):
1. Slows gastric emptying
2. Suppressing glucagon secretion
3. Satiety
56
CI with Symlin?
1. Hypoglycemia unawareness
2. Severe hypoglycemia in the past 6 months
3. Gastroparesis
57
Place in therapy of Pramlinitide?
1. Decreases A1c 1.0%
2. Hypoglycemia risk
3. Insulin dose reduction required when initiating pramlintide to avoid SEVERE HYPOglycemia
4. Weight loss
5. Relative high cost
58
Amylin analog
| ADR,
**ADR:** Hypoglycemia
**DDI:** Delayed absorption
**Admin:**
* Take immediately before major meals containing at least 250 calories or 30 grams of carbohydrate
* Do NOT take if the meal has less than 250 calories or 30 grams of carbohydrates
* When first starting reduce the amount of mealtime insulin by 50% to reduce the risk of HYPOglycemia
* SC, don't inject in arm
* Rotate injection site or 2 inches from
* Don't mix with insulin
* Refrigerate, room temp (30 days)
59
Amylin dosing?
60
MOA of insulin? PK?
1. Anabolic and anticatabolic hormone
2. Major role in protein, carbohydrate and fat metabolism
3. Lowers blood glucose levels by: Stimulating peripheral glucose uptake, Inhibits lipolysis and proteolysis, Enhances protein synthesis
**PK:**
Absorption:
1. Concentration
2. Insulin source
3. Additives
4. Injection site (abdomen >> arms >> thighs >> buttocks)
5. Blood flow to injection site
61
Insulin is categorized by what factors?
1. Source
2. Strenfth
3. Onset
4. Peak
5. DOA
62
URA insulin types?
| Place in therapy, Admin
U-100 Insulin Lispro-aabc (Lyumjev)
U-100 Insulin Aspart (Fiasp)
Oral Inhaled Insulin (Afreeza)
**Place:** Lower post-prandial glucose levels
**Admin:** Immediately before meals
63
Rapid acting insulins?
| Types, Place in therapy, Admin
U-100 Insulin Lispro (Humalog)
U-200 Insulin Lispro (Humalog)
U-100 Insulin Aspart (Novolog)
U-100 Insulin Glulisine (Apidra)
**Place:** Lower post-prandial glucose levels
**Admin:** 15 minutes to immediately before meals
64
SA insulin
| Types, Place in therapy, Admin
U-100 Humulin R
U-100 Novolin R
U-500 Humulin R (Concentrated)
**Place:** Lower post-prandial glucose levels
**Admin:** 30 minutes prior to meals
65
Intermediate acting insulins?
| Type, Place in therapy, admin
NPH:
U-100 Humulin N
U-100 Novolin N
**Place:** basal or bolus
**Admin:** Given once or twice daily, Can be used alone or in combination with rapid or short acting insulin
66
Long acting insulins?
| Types, place in therapy, admin
U-100 Insulin Glargine (Lantus, Toujeo)
U-100 Insulin Glargine Equivalent (Basaglar)
U-100 Insulin Detemir (Levemir)
U-100 Insulin Degludec (Tresiba)
U-200 Insulin Degludec (Tresiba)
U-300 Insulin Glargine (Toujeo Max)
**Place:** Basal
**Admin:** QHS, Lantus and Levemir CANNOT be mixed with other insulin products
67
Insulin
| CI, ADR
**CI:** hypoglycemia, hypersensitivity
**ADR:** hypoglycemia, weight gain, hypokalemia, lipodystrophy
68
RF of lipodystrophy? Types?
1. Reusing needles
2. Not rotating injection site
**Lipohypertrophy:** increased mass, Caused by repeat injections of insulin
**Lipoatrophy:** decreased mass from insulin antibodies
69
DDI of insulin?
**Drugs that affect glucose control:**
1. Steroids
2. Diuretics
3. Beta-blockers
4. Alcohol
70
What is the initial insulin dose for T1DM?
Initial dose: 0.5-0.6 units/kg/day in divided doses
Honeymoon phase: lower dose
Ketosis, growth, illness: higher dodes
71
Basal insulin is about ___ of the total daily requirements?
50%
72
What is the initial dose for T2DM?
Start with low doses of basal insulin and titrate up based on response
* 10 units of intermediate or long acting at bedtime
73
Types of insulin admin devices?
1. Insulin syringe
2. Insulin pen
3. I-Port
4. Insulin pump
5. Inhaler
74
What is the least expensive insulin admin device?
Syringe:
Requires more visual acuity and physical manipulation
75
Pros and cons of insulin pens?
1. Disposible
2. Convenient and portable
3. Accurate
More expensive than syringe and vial
76
Pros of I port?
1. Device for multiple insulin injections
1. Can be worn for up to 72 hours (75 injections)
1. Good for patients with needle phobia
2. Comes with inserter
77
Pros and Cons of insulin pump?
Use rapid or ultra rapid acting insulin in pumps:
* Program pump for basal and bolus
78
Afreeza
| Indications, CI, ADR, Admin, Storage
**Indications:** Lowers postprandial BG
**CI:** COPD, asthma
**ADR:** Less weight gain
**Admin:** Administered at the start of a meal, and dissolves immediately upon inhalation delivering insulin to the blood stream.
**Storage:** Sealed foil package (10 days room temp), opened (used within 3 days)
79
How do you dose Afrezza?
**Insulin naive:** 4 units/meal
**Conversion from SubQ pre-meal rapid acting insulin:** # units SubQ injected with each meal = # units inhaled with each meal
**Conversion from SubQ BID premixed insulin:**
* Estimate the mealtime injected dose by dividing ½ of the total daily injected premixed dose equally among the three meals of the day.
* Convert each injected mealtime dose to a mealtime inhalation dose using the scale above.
* Administer ½ of the injected premixed dose as an injected basal insulin dose.
80
What is the goals of intensive insulin therapy?
1. Goal of tight glycemic control
2. Multiple insulin injections or pump
3. Frequent FSBS monitoring or CGM
4. Alternation of insulin therapy based on BS results
81
What dis Diabetes Control and Complications Trial (DCCT) reveal?
Intensive therapy:
1. Reduces microvascular complications in T1DM (retinopathy, neuropathy, nephropathy)
2. Increases risk of hypoglycemia and weight gain
82
What did United Kingdom Prospective Diabetes Study (UKPDS) reveal?
1. Tight glycemic control in T2DM helps microvascular complications
2. Sulfonylurea/insulin does not increase macrovascular risk
3. Metformin reduces macrovascular risk in obese patients
4. Aggressive blood pressure control reduces microvascular and macrovascular events
