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Clinical Pharmacology > "Older" Non-insulin Analogues > Flashcards

"Older" Non-insulin Analogues Flashcards

1
Q

List the 5 “older” options for non-insulin analogues.

A
  • Biguanides
  • Sulfonylurea
  • Meglitinides
  • Thiazolidinediones
  • Alpha-glucosidase inhibitors
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2
Q

What is the main biguanide used? What’s the MOA?

A

Metformin

MOA:

  • decrease hepatic glucose production
  • increase secretion of GLP-1

may also:

  • decrease intestinal absorption of glucose
  • increase peripheral glucose uptake
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3
Q

What are the three indications for using biguanides (Metformin)?

A
  1. Prediabetes
  2. T2DM (1st line - every pt should be on metformin as long as no C.I.)
    - monotherapy
    - combotherapy
  3. Insulin resistance in PCOS pt
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4
Q

When should you use metformin in a prediabetic?

A

A1c 5.7-6.4 or FBG 100-125

especially:
- < 60yo
- BMI > 35
- h/o gestational DM

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5
Q

How would you dose a patient for metformin?

A

Start: 250-500 mg/d
Titrate by 250-500mg q1-2wk as tolerated

Usual effective dose = 2g**

Do NOT titrate too fast and scare patient away with ADRs.

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6
Q

What are three clinical pearls related to Metformin?

A
  1. RARELY causes hypoglycemia
  2. Associated w/decreased micro/macrovascular complications (mostly micro)
  3. Lipid lowering activity
    - decrease TG, FFA, LDL
    - increase HDL
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7
Q

What are the two things you should monitor for patient on metformin?

A
  1. H/H & RBC indices
    - beware of B12 def
    - monitor initially & at least annually
  2. eGFR
    - baseline & at least annually
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8
Q

Which comorbidity has Metformin been proven safe in? Which comorbidity should you avoid Metformin in?

A

Safe: Stable HF
- hold during exacerbation

Avoid: Renal dysf (GFR <30)
- decreased clearance of lactate –> increased risk for lactic acidosis

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9
Q

Monitor eGFR with your metformin patient. What do you need to know about the values?

A

> 60: no real concerns

45-60: continue dose, routine f/u

30-45: do NOT initiate therapy at this stage
- continue if already on, should reduce dose 1/2 for CKD

< 30: do NOT use**

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10
Q

What are the Pk and Pd for metformin?

A

Pk: no CYP interactions (not metabolized)

Pd:

  • concomitant hypoglycemic agent
  • hyperglycemic-inducing agent (counteracts)
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11
Q

What do you need to do with metformin if your patient is having a radiologic procedure involving IV iodinated contrast?

A

D/c immediately prior to & for 48hr

Contrast may cause AKI w/increase risk of lactic acidosis

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12
Q

What are 3 ADRs of metformin?

A
  1. GI intolerance (MC)
    - Metallic taste*, mild anorexia, NVD, abd discomfort
  2. Macrocytic anemia & peripheral neuropathy
  3. Lactic acidosis
    - more serious LA accumulation occurs w/conditions leading to hypoxemia (e.g. AKI or CKD)
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13
Q

Metformin may decrease Vit B12 absorption. Who should you check [B12] and what do you recommend your patient?

A

Check [B12]

  • new or worsening peripheral neuropathy or macrocytic anemia
  • at risk pt (vegetarian, PPI user, elderly)

Recommend: daily complete multivitamin for all pt on metformin**

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14
Q

What are the three 2nd gen sulfonylurea? Which is generally the best option to use?

A
  • glyburide (not recommended in ANYONE)
  • glimepiride (not recommended in ELDERLY)
    • glipizide **
  • generally best option to use
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15
Q

What are the sulfonylurea MOA?

A

Stimulate insulin secretion

Sulfonylurea binds to pancreatic beta cell and insulin is released.

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16
Q

What is the half life of ‘regular’ glipizide? How do you dose it?

A

2-5 hours

BID dosing
- typically started w/low dose before breakfast

17
Q

What are the clinical indications of Sulfonylureas?

A

T2DM

  • monotherapy
  • combination therapy

Falling out of favor.

18
Q

What are clinical pearls of metformin?

A
  • decrease A1c 1-1.5%
  • needs insulin to work**
  • promotes modest weight reduction or at least weight stabilization
19
Q

Name 3 clinical pearls regarding Sulfonylureas?

A
  • decrease A1c 1-1.5%
  • promotes wt gain**
  • Glyburide C.I. for eGFR < 50 and also has an active metabolite **
20
Q

What allergic reaction may occur with Sulfonylurea use?

A

“Sulfonamide” allergy**

21
Q

What is the Pk and Pd related to Sulfonylureas?

A

Pk: 2C9 substrates

Pd:

  • concomitant hypoglycemia agent
  • hyperglycemia-inducing agent
22
Q

What are the two most common ADRs related to Sulfonylureas?

A

**Wt gain & hypoglycemia (glyburide > glimepiride > glipizide)

No CV harm, but No CV benefit either

23
Q

After metronidazole, what is the next drug you should think of for “disulfiram-like reaction”? Especially after ETOH ingestion.

A

Glyburide

24
Q

What are the two Meglitinides? What is the MOA of Meg Zoooot?

A

Nateglinide & Repaglinide

MOA: increase insulin secretion

  • structurally different and exert effects via different receptors compared to sulfonylureas
25
Q

What are the clinical indications for Meglitinides?

A

T2DM

  • monotherapy
  • combo therapy
26
Q

What should you know regarding the dosing of Meglitinides?

A
  • take prior to meal (e.g. TID)

- dose should be skipped if meal is missed**

27
Q

Meglitinide clinical pearls?

A
  • A1c reduction 0.5-1%
  • weight neutral
  • no micro/macrovascular data

main role: “be a sulfonylurea for CKD pt –> mostly repaglinide” **

28
Q

What is the one ADR related to Meglitinides?

A

MC is hypoglycemia

less than Sulfonylureas?

29
Q

What are the two Thiazolidinediones (TZDs)? MOA?

A
  • Pioglitazone > `rosiglitazone
  • MOA: increased insulin sensitivity by acting on adipose, muscle, and liver to increase glucose utilization and decrease glucose production
30
Q

TZD indications

A
  • Don’t use unless forced to!
  • Monotherapy DMII or combo
  • Insulin resistance in PCOS (metformin first)
31
Q

TZD Pearls

A
  • Dec A1c 1-1.5%, no hypoglycemia
  • **Does not inc pancreatic secretion–> needs insulin
  • **May take 6-14 wks for max effect
  • **Don’t use in pts who have/had bladder CA
32
Q

TZD warnings/ADR

A
  • CI in pts w/ NYHA III/IV
  • BBW for inc risk of angina or AMI, removed in 2014
  • LFT monitoring
  • Weight gain, **fluid retention
  • **dec bone dens, inc fracture risk
33
Q

What are the alpha-glucosidase inhibitors? MOA?

A
  • Acarbose, Miglitol

- MOA: Interfere with hydrolysis of carbs in SI, delay absorption of glucose

34
Q

Alpha-glucosidase indications

A
  • Monotherapy or combo

- Dose TID and take before meals

35
Q

Alpha-glucosidase Pearls

A
  • No hypoglycemia, dec A1c 0.5-1.0%

- **CI in pts with intestinal or bowel dz, intestinal obstruction

36
Q

Alpha-glucosidase Pearls

A
  • Abd pain, diarrhea, rancid farts
  • **Pts often d/c med due to this
  • Begin with lose dose and titrate up to avoid

Clinical Pharmacology (54 decks)

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