What is the difference between regular insulin and NPH insulin?
Regular Insulin – clear solution, Only form to be used IV
NPH - “cloudy” more dense, 12-14 hour duration
What is the insulin that should be used for immediate action at meal time?
Lispro insulin
Insulin Aspart
– Works more quickly than native insulin injected due to monomers, rather than pentamers
What insulins are used for basal insulin levels?
- Insulin Glargine
- Insulin Determir
How are the mechanisms different for Glargine and Determir?
Glargine – long acting, precipitates at pH7, so takes the body longer to break it down into the blood stream.
Determir – long acting binds to albumin in plasma (remember only free is functional!)
What is the most common regimen to give insulin?
Usually a combination of intermediate/long acting and short acting pre-meal time. 70/30 mix
What are the goals for insulin and blood sugar management?
- Fasting glucose/post meal – 70-130
- 2 hour post meal time – less than 180
- HbA1c - less than 7%
How does the patient judge how much insulin to give themselves before a meal?
– Pre-meal stick, give 10 units base, then +1 for every 40 glucose over 120 before the meal.
– Also carb count and base insulin on % carbs in the meal
What are the best foods for a snack before bedtime?
- complex carbs
- proteins
- fats
What are the most common side effects of insulin?
- Hypoglycemia
- Lipohypertrophy
- High doses = cancer, weight gain, atherosclerosis
What is the mechanism of Sulfonylureas and who are they used for?
- Interacts with the K+ channel inhibiting it’s function and depolarizing the B-cell membrane, causing influx of Ca+2 into the cell and secretion of granules of insulin.
- Used for DM2, to increase their insulin levels –
If a patient had DM2 and had renal insufficiency, what would be the best drug to increase insulin levels?
Meglitinide
– Must be dosed 3 times per day, but is not have renal excretion and is to be used in patients with renal damage.
What sulfonylurea has the fastest action and shortest half life?
Glipizide
What are the sulfonylureas that have longer action and half lives?
Glyburide
Glimepiride
What are the most common side effects of sulfonylureas?
- hypoglycemia
- - GI symptoms
What is a first line therapy to a newly diagnosed patient with DM2?
Metformin (Biguanide)
What are contraindications for giving Metformin?
- Renal insufficiency
- Old (80+)
- liver dysfunction
How does Metformin help with DM2 patients?
- increases sensitivity of the Liver to insulin
- - decreases gluconeogenesis of the liver to lower glucose levels
What are the drugs that upregulate PPAR in peripheral tissues that increase glucose uptake by fat and muscle cells?
- Rosiglitazone
- - Pioglitazone
What are known side effects of Thiazolidinediones?
- Rosiglitazone – increased cardiac events
- - Pioglitazone – incrased bladder cancer, more commonly used
If a patient continually has difficulty removing carbohydrates out of his diet to manage his blood sugar, what might be a good option?
Acarbose – inhibits GI brush border enzymes preventing the break down of carbohydrates partially. Induced malabsorption.
Side effects: GI effects and bloating
What drugs can be used to augment insulin secretion and inhibit glucagon release similar to eating a meal?
Exenatide – GLP-1 analog, long acting, promotes insulin secretion and glucagon inhibition. Increases B-cell mass.
++ Liraglutide (same as above)
Instead of using GLP-1 analogs, how else can insulin be stimulated and glucagon be inhibited?
Sitagliptin – DPP-4 inhibits break down of GLP1 increasing the endogenous proteins effects.
If a patient has known DM2 and is taking her medications are prescribed, but keeps returning to the clinic with yeast infections, what drug could be causing this?
Canagliflozin – inhibits Sodium-Glucose transporter in the proximal tubule. Increases glucose in the urine and risk of urinary tract infections.
Which treatment methods lower the HbA1c the most?
Sulfonylureas / Metformin / Thiazolidinediones – lower 1.5%
What is a commonly used combination therapy for DM2?
Increase Insulin Secretion + Sensitizing agent - Sitagliptin -- DPP4 inhibitor - Exenatide -- GLP1 analog - Liraglutide -- GLP1 analog - Glipizide -- Sulfonylurea \+ - Metformin - Rosiglitazone - Pioglitazone
If a patient is found to have hypocalcemia with very high PTH levels and low phosphate, what should be the first line of treatment?
– Supplement Vitamin D (or in diet)
– Supplement Ca+2
Most likely osteomalacia due to VitD/Ca insufficiency
If a patient needs to be on a calcium supplement, Calcium carbonate or calcium citrate a better option?
Calcium Carbonate – more calcium present per gram consumed.
What is the mechanism of bisphosphonate and what is it used for?
Inhibits the conversion of mevalonate to farnesyl
- inducing apoptosis in osteoclasts
- Used for osteoporosis in preventing fractures
What bisphosphonate can be used to treat glucocorticoid induced osteoporosis?
Risedronate
Zoledronate
What is the most common side effect of Pamidronate and Zoledronate?
Hypocalcemia, since they are very potent at preventing bone reabsorption, should only be used in patients with hypercalcemia
What three bisphosphonate can be used to treat post-menopausal osteoporosis without hypercalcemia?
- Ibandronate
- Alendronate
- Risendronate
What is problematic about giving Calcitonin to a patient with osteoporosis?
–inhibits osteoclasts from functioning properly, however tolerance develops very quickly not longer providing benefits. – Last resort drug–
What osteoporosis treatment has benefits of added breast cancer prevention?
- Tamoxifen, prevents Breast CA proliferation and increases bone density.
- Raloxifene, prevents fractures and protects against cancer
What is a key side effect of selective estrogen receptor modulaters?
Increases thromboembolic risk
What are the most significant risk factors for low trauma fractures?
- Osteoporosis/BMD
- Past Fractures
- Female Sex
- Glucocorticoid Use
How does Denosumab prevent osteoclast activity?
– binds RankL preventing interaction with Rank receptor and stops differentiation of Macros into osteoclasts
What technique needs to be employed to use Teriparatide?
Teriparatide is a partial PTH fragment.
– When constantly infused it causes bone resorption, but when intermittently doses increases bone mass.
What are the most common causes for osteomalacia?
- nutritional deficiency
- renal disease or mutation of 1-hydroxylase
- GI malabsorption – celiac
- low vitamin D
What is FGF23 and its function?
- secreted from osteocytes
- Promotes excretion of PO3-4
- Inhibits expression of 1-Hydroxylase to prevent Vitamin D from absorbing anymore
- increases activity of 24-hydroxylase to deactivate VitD
- inhibits PTH secretion
- Prevents bone mineralization
What was commonly used in post menapausal women to prevent osteoporosis?
Estrogen
