Block 3: Diabetes II Flashcards
How does metformin work?
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
CI for metformin?
- T1DM/Ketoacidosis
- Hyperssensitivity
- Renal impairment requires a dosage adjustment
- Unstable HF
- Metabolic acidosis
- Hx of lactic acidosis
Metformin place in therapy?
- 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
Metformin
Brand, ADR, DDI, Dosing, Monitoring
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
Pharmacology of TZDs (Piaglitazone)
PPAR agonist that increases glucose uptake by muscle and fat
Insulin sensitizer in muscle, fat»_space; liver
Hepatically metabolized
CI of Pioglitazone?
- 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
Place in therapy TZDs?
- 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
Pioglitazone
Brand, ADR, DDI, DOsing, Monitoring
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
Types of sulfonylurea?
Glimepiride (Amaryl)
Glipizide (Glucotrol, Glucotrol XL)
Glyburide (Diabeta, Micronase)
Glyburide micronized (Glynase)
Pharmacology and PK of sulfonylurea?
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
CI of sulfonylurea?
- T1DM or Ketoacidosis*
- Hypersensitivity*
- Severe hepatic or renal impairment
- G6PD deficiency
- Illness that affect blood glucose levels
Place in therapy for sulfonylurea?
- 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)
Sulfonylurea
ADR, DDI, Dosing,
ADR: Hypoglycemia, weight gain
DDI: Warfarin, cimetidine
Dosing: QD w/ breakfast
Types of Short-acting Insulin Secretagogues?
Nateglinide (Starlix) and Repaglinide (Prandin)
Pharmacology of Short-acting Insulin Secretagogues?
- 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
CI of Short-acting Insulin Secretagogues?
- T1DM or Ketoacidosis*
- Hypersensitivity*
- Use with caution in severe hepatic or renal impairment
Short-acting Insulin Secretagogues Place in therapy?
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
Short-acting Insulin Secretagogues
ADR, Dosing, DDI
ADR: hypoglycemia, weight gain
Dosing: Take 30 minutes prior to each meal
DDI: Repaglinide/gemfibrozil
What is secondary b cell failure?
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
Types of Alpha-glucosidase Inhibitors?
Acarbose (Precose) and Miglitol (Glyset)
Pharmacology of a-glucosidase inhibitors?
Delays digestion of carbs
Acarbose is metabolized by amylases to inactive metabolites
Miglitol is excreted uncahnged in urine
CI of a-glucosidase inhibitor?
- T1DM or Ketoacidosis*
- Hypersensitivity*
- Hypoglycemia
- Severe renal impairment
- Cirrhosis
- GI conditions
a-glucosidase inhibitor place in therapy?
Adjunctive therapy:
1. Low effectiveness: A1c 0.5-1%
2. Low risk of hypoglycemia
3. Weight neutral
4. Avoid in patients with GI problems
ADRs of a-glucosidase inhibitors?
- Flatulense, diarrhea, abdominal pain
- Treat hypoglycemia with PO glucose or lactose NOT sucrose
How do you dose a-glucosidase inhibitors?
Start low, go slow
At the beginning of each meal
What are the types of BAS?
Colesevelam (Welchol)
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
BAS place in therapy?
- Lower effectiveness: <0.5%
- Not used in T2DM except in specific situations
- Lower LDL, increase TG
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
Dosing and monitoring of BAS?
Take with food and water
- Lipid panel
- May take 4-6 weeks to see effect
Types of dopamine agonists?
Bromocriptine (Cycloset)
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%