Oral Hypoglycemics Flashcards
Which class of oral hypoglycemic medications has the highest risk of hypoglycemia?
Sulfonylureas
Esp if used with insulin
MOA of sulfonylureas?
Act at pancreatice beta cells to stimulate release of insulin
What are examples of sulfonylureas?
- Glyburide ( Diabeta, Micronase)
- Glipizide (Glucotrol)
- Glimepiride (Amaryl).
1st Generation:
- Tolbutamide (Orinase)
- Acetehexamide
- Chlorpropamide (Diabinese)
Sulfonylureas should be avoided in patients with what allergy?
Sulfa drugs
Where are sulfonylureas metabolized?
Liver and excreted by kidneys
Which patients are at an even higher risk of hypoglycemia with sulfonylureas?
Patients with renal failure
Do sulfonylureas cross the placenta?
May cross and may cause fetal hypoglycemia
What is duration of action of sulfonylureas?
Up to seven days and patients may require prolonged infusions of glucose-containing solutions
Side effects of sulfonylureas?
- (most common) Hypoglycemia
- Weight gain
- GI disturbances (PONV can be common)
What are contraindications/precautions with sulfonylureas?
- Sulfa drug allergy
- Patients with hypoglycemia unawareness
- Poor renal function
- Liver disease (except acetohexamide)
T/F: Sulfonylureas have metabolites that can be of concern with renal patients; however, Glipizide is safe ?
True; Glipizide is safe down to CrCl of 10 and has NO active metabolite
Which class of hypoglycemic drugs can cause severe GI upset and is intolerable for many patients?
Alpha-Glucosidase inhibitors
What are examples of Alpha Glucosidase Inhibitors?
- acarbose (Precose)
- miglitol (Glyset)
MOA of Alpha-Glucosidase Inhibitors?
Decrease intestinal hydrolysis of complex carbs
Which patients should Alpha-glucosidase inhibitors be avoided in?
IBS and bowel obstructions
T/F: Meglitinides have mostly replaced sulfonylureas as hypoglycemic agents?
False; Meglitinides have mostly been replaced by sulfonylureas
MOA of Meglitinides?
Increase insulin secretion from islet cells like sulfonylureas
What are examples of Meglitinides?
- repaglinide (Prandin)
- nateglinide (Starlix)
Why is there a reduced risk of prolonged hypoglycemic episodes with meglitinides ?
**Only active in the presence of glucose**
If they are NPO or not eating a lot, should be withheld until back to regular food intake
Meglitinides versus sulfonylureas, how does onset/duration compare?
Meglitinides have faster onset (1hr) and shorter duration of action (4hrs)
Administer 15-30 minutes a.c. and NEVER while fasting
What are adverse effects of Meglitinides?
- Hypoglycemia (less than sulfonylureas)
- Weight gain
- URI
What is the most widely prescribed oral hypoglycemic?
Metformin (Glucophage)
What drug class does metformin belong to?
Biguanides
MOA of Metformin?
- Dec hepatic glucose production
- Dec glucose absorption from intestine
- Increase insulin sensitivity
In what ways do gut microbiota change with metformin?
- Reduced bacteroides fragilis (this organism has high rates linked to obesity, glucose intolerance, reduced insulin sensitivity)
- Increase glycoursodeoxylcholic acid (GUDCA)
- Inhibit signaling of intestinal farnesoid X receptor (FXR)
What are side effects of metformin?
- Common: anorexia, nausea, diarrhea
- Rare: Lactic acidosis (black box warning) - N/V, inc RR/HR, abd pain, shock
What specific side effect can be seen if metformin restarted immediately after surgery?
worsen PONV
What are perioperative metformin administration considerations?
- Risk of lactic acidosis- should be d/c 48hrs prior to surgery
- Hold 48hrs prior to and after IV dye, check Cr levels
- Do not restart too quickly after surgery d/t worsening PONV
Contraindications/precations with metformin?
- Renal impairment
- Age >80years old
- Hepatic impairment
- CHF
How are old and new contraindications defined for metformin in renal impairment?
Old: Contraindicated SCr >1.5 males or >1.4 females New: Contraindicated eGFR <30ml/min. Can consider/evaluate with eGFR <45ml/min
Which hypoglycemic med class requires the presence of insulin and are especially effective in obese patients?
Thiazolidinediones (TZDs)
What are examples of thiazolidinediones (TZDs)
- rosiglitazone (Avandia)
- pioglitazone (Actos)
“glitazone”’s
MOA of TZDs?
- Decrease insulin resistance
- Decrease hepatic glucose output
Require the presence of insulin and are especially effective in obese patients. If insulin resistant, not going to work
Side effects of TZDs?
- Weight gain
- Hepatotoxicity
- Peripheral edema
- CHF exacerbation
- Risk of bone fractures
- *controversial MI or CV death with avandia*
What are examples of DPP-4 Inhibitors?
- sitagliptin (Januvia)
- saxagliptin (Onglyza)
- linagliptin (Tradjenta)
- alogliptin (Aloglitpin)
“gliptin’s”
MOA of DPP-4 Inhibitors?
GLP 1 released from the gut and goes to brain and tell you to stop eating. DDP enzyme breaks down GLP1.
Inhibiting DDP results in more GLP1 available, so:
- Increase pancreatic insulin secretion
- Limits glucagon secretion
- Slows gastric emptying
- Promotes satiety
Side effects of DPP-4 Inhibitors?
- URI
- *UTIs (esp if catheter is in place)*
- HA
- Weight neutral
- Low(ish) risk of hypoglycemia
- *rare but possible- pancreatitis, angioedema, Steven Johnsons, anaphylaxis
Which medication is produced from the spit of a gila monster?
the fuck if i care. (amylin analogs like pramlinide/Symlin)
What are the two subclasses of incretin mimetics?
- GLP-1 Analogs 2. Amylyn Analogs
What are examples of GLP-1 analogs?
- exanatide(Byetta, Bydureon)
- liraglutide (Victoza)
- albiglutide (Tanzeum)
- dulaglutide (Trulicity)
MOA of GLP-1 analogs?
- Prolong gastric emptying
- Reduce post-prandial glucagon secretion
MOA of Amylin analogs?
“like super GLP-1”
- Increase insulin secretions
- Prolong gastric emptying
- increase beta cell growth
- Central appetite suppression
Side effects of GLP-1 analogs?
- N/V/D
- Pancreatitis
- ARF
- Weight loss
Precautions of Byetta? for Victoza?
Byetta should be avoided in renal failure, leads to severe gastroparesis Victoza should be avoided in thyroid carcinoma
Which class of hypoglycemic agenst has shown promising results as they improve CV health as well as control glucose?
SLGT2 Inhibitors
What are examples of SLGT2 Inhibitors?
the “flozin”s
- canagliflozin (Invokana)
- dapagliflozin (Farxiga)
- empagliflozin (Jardiance)
Precautions/Contraindications of SLGT2 inhibitors (the flozins)?
- Increased urinary glucose excretion
- Contraindicated CrCl<30ml/min, ESRD, or HD
- Associated with Hypotension and urinary side effects like UTIs
- Increased risk of toe amputations (esp if there is poor circulation)
- Perioperative euglycemic ketoacidosis (esp in obese patients)
For surgery, should Tresiba be held all together?
Yes, b/c it is sooo long acting its recommended to just hold it all together
Suflonylureas have a primary failure rate of __%
20%
each year 10-15% secondary failure rate
Which sulfonylurea has the highest risk of hypoglycmemia if the pt also takes insulin?
Glyburide (DOA is up to 7 days)
Is hypoglycemia more frequent with insulin or sulfonylureas?
Insulin
However, hypoglycemia due to sulfonylureas is often PROLONGED and MORE DANGEROUS than that due to insulin
What is the most commonly prescribed sulfonylurea?
Glipizide
Which sulfonylurea has the highest risk of hypoglycemia in renal patients if there is even a slight shift in their kidney function?
Glyburide
starts to buildup with CrCl <50
T/F Metformin has a positive effect on lipid concentrations
True
b/c CAD and DM go hand in hand
T/F Metformin will cause weight gain just like Sulfonylureas and meglitinides
FASLE Metformin can cause small weight loss whereas sulfonylureas and meglitinides can cause weight gain
T/F If a patient becomes insulin dependent, metformin will be d/c
FALSE Will keep the metformin because it has not only some other positive benefits for diabetics but it it also improves they way your cells are using insulin.
Which oral hypoglycemic med has a controversial increase in MI and CV death?
Rosiglitazone (Avandia)
Its a blackbox warning and requires special dispensing
According to Emily, what do we need to know about DDP-4 inhibitors?
- No hold recommendations
- Low risk hypoglycemia
- Potentially these UTIs that could develop
- Pancreatitis, skin changes, anaphylaxis
T/F Incretin mimetics (GLP-1 analogs and Amylin Analogs) are all taken orally
FALSE are all injectable
MOA of SLGT2 Inhibitors
Sodium glucose transporter 2 enzyme co-transports Na and glucose from urine back into blood stream in the proximal tubule.
Blocking this enzyme leads to more leads to increased urinary Na and glucose excretion
High risk of dehyrdration (“b/c water follows sodium”)
T/F SLGT2 inhibitors have improved CV benefits in diabetic patients
True
With Glipizide, tolerance usually does not develop for at least __ years
3
Which sulfonylurea is associated with severe hyponatremia (<129) and disulfiram-like reactions?
Chlorpropramide (Diabinese)
Which sulfonylurea is the shortest acting, least potent, and associated with the fewest side effects?
Tolbutamide (Orinase)