Diabetic Meds Flashcards
What substance is released from the intestine in response to eating that goes up to brain and provides satiety?
GLP-1 (Glucagon Like Peptide
What substance is released from the intestine in response to eating that goes up to brain and provides satiety?
GLP-1 (Glucagon Like Peptide
What substance sends signals to pancreas that starts the release of insulin in response to elevated glucose after eating?
GLP-1
What cells in the pancreas release insulin?
Beta islet cells
GLP cause the liver to slow down ____ and start storing ____
- gluconeogenesis - glycogen
3 P’s of DM
- Polydyspia - Polyuria - Polyphagia
Difference in body habitus b/w DM I and DM II
DM I are thin, DM II are obese
DM Type I is a genetically predisposed disease that causes an alteration on which chromosome?
Altered Human Lymphocyte Antigen on the short arm of chromosome 6
At time of diagnoses of DM type II, ___% of beta islet cells are destroyed
90%
What meds can induced hyperglycemia?
- Glucocorticoids (Long term prednisone) - Antipsychotics (esp Risperadal, Haldol, Zyprexa) - HIV medications - Octreotide
What 3 conditions can cause stress-induced hyperglycemia
Illness Trauma Pregnancy all increase release of epi and cortisol
What two ways is DM diagnosed?
Fasting BG > 126 x 2 occasions Random BG > 200mg/dl
4 ways glucose is monitored
- Blood Glucose (BG) Monitor - Blood or Plasma Glucose - Glycosylated Hgb (HgA1C) - Urinary Ketones
For BG monitoring levels <75 mg/dl, a meter should read within ___ mg/dl
15
For BG monitoring levels >70 mg/dl, a meter should read within ___%
20%
What is the advantage and disadvantage of blood plasma glucose levels?
- more accurate -takes longer and requires more blood
Normal HgA1C?
4-6%
ADA recommended HgA1C level?
<7-8.5% (depends on age of diabetic patient)
HgA1C provides a average reading based on BG over the past __ months
3
What happens if you aggressively try to drive down BG levels?
PONV, feel worse after outcomes will be actually worse
BG level of ___ is ok to go to OR and under ___ for most procedures
175 180
T/F Only Type II DM will show urinary ketones
FALSE only type I
Type II DM will start on oral hyperglycemic meds, but most will require insulin esp if their first HgA1C is > __
10
Pro-insulin (storage) molecule is small amino acids chained together with cleavages between ___ and ___
31-32 and 64-65
What type of reaction takes place after insulin bind to alpha and beta receptors?
Phosphorylates, and then different types of cascades begin
Besides glucose, What substances are pulled into the cell by insulin through the GLUT-4 molecule?
Amino acids Phosphate Potassium Magnesium
What insulin-stimulated intracellular pathway causes cell growth, proliferation, and gene expression?
MAP Kinase signaling pathway
What insulin-stimulated intracellular pathway causes synthesis of lipids, proteins, glcogen, along with cell survival/proliferation and GLTU-4 molecule activation?
PI-3K signaling pathway
To prevent refeeding syndrome, what % of normal caloric intake should they start at
25% Too much results in massive release of insulin, leads to massive drops in phos, K, mag –> arrhythmias, respects failure, death
MOA of insulin
- Binds to plasma membrane insulin receptors - Phosphorylated receptor substrates then activate or inactivate numerous enzymes and other mediating molecules. - Translocation of glucose transporters to plasma membranes
What do Glucose transport molecules (GLUT-4) do?
- Facilitate glucose diffusion into cells - Shift intracellular glucose metabolism toward storage (Glycogenesis) - Stimulate cellular uptake of amino acids, phosphate, potassium and magnesium
When does insulin resistance occur?
Occurs when there is an impaired intracellular insulin signal that results in decreased recruitment of glucose transport proteins to the plasma membrane and subsequent decrease glucose uptake.
What is the body’s response to insulin resistance ?
Compensatory hyperinsulinemia
T/F Insulin can regulate the population of receptors
True
What is the relationship between insulin and the number of insulin receptors
Inversely related The more circulating insulin, the less number of insulin receptors on the cell
What is the t1/2 of IV insulin?
5-10 mins but the duration of effect is longer
What is the DOA of insulin?
30-90 mins
Where is insulin metabolized?
liver and kidneys
How much insulin that reaches the liver is metabolized on a single pass?
50%
What prolongs the half life of insulin more, liver or renal disease?
Renal disease
Insulin administered SQ is released ____ into the circulation
slowly
Basal rate of insulin secretion by the pancreas is _ unit/hr.
1
Food prompts a _ - _ fold increase in secretion
5-10x
Total daily secretion of insulin is approx. __ units/day
40
T/F Insulin response to glucose is greater for oral ingestion than for I.V. infusion
True eat a sandwich - better insulin response than glucose
What is the peak of long acting insulins?
There is no peak
Regarding insulin types, there duration of action correlates with ___
onset of action
Long acting insulins are also known as ____
glargine
What is the longest acting insulin?
Degludec (Tresiba), up to 42 hrs good for people that aren’t good at remembering to take insulin
What is the only time you would give lantus BID?
If the volume is too much to handle in one dose. Otherwise its pointless
Onset, peak, and duration of regular insulin
30mins 2-4 hrs 6-8 hrs
what is the DOA of Levemir?
6-23 hours It’s intermediate like NPH
What types of insulin are considered “basal rate insulins”?
Long and intermediate acting (long is given once daily, intermediate BID)
In premixed insulin, which number is the longer acting one?
First number ex. humulin 70/30 (70% is NPH, 30% is regular
T/F Insulin is one of the top 5 drugs that send people to ER
True
Whats a drawback to rapid acting insulins?
With the rapid acting - Wild swings in glucose can make people feel sick, dizzy
Newer insulin agents are produced from ___ Older agents were produced from ___
recombinant technology animal (beef and pork)
What is the benefit of recombinant technology insulins?
Allergy or immunoresistance that could accompany administration of animal insulins is no longer a significant problem
Only ___ acting insulin may be given IV/ via pump
short no NPH or long acting
T/F All insulins can be given SQ
True
Side effects of insulin
- Hypoglycemia - Hypokalemia (also hypo phos and mag) - Allergic Reactions - Lipodystrophy - Insulin Resistance - Drug Interactions
What is the most severe side effect of insulin?
hypoglycemia
what is lipodystrophy?
injecting in same site over and over again results in atrophy of fat at site of SQ injection, get hard bumps.
How can lipodystrophy be minimized?
Minimized by rotating the site of injection every 3 days
Signs and symptoms of hypoglycemia
Diaphoresis Tachycardia Hypertension
Hypoglycemia symptoms reflect the compensatory effects of increased ____
epinephrine
What is Somogyi effect?
Rebound hyperglycemia caused by sympathetic nervous system activity in response to hypoglycemia may mask the correct diagnosis
What is the most significant risk factor for developing insulin resistance?
If the diabetic patient doesn’t change their lifestyle and diet “ex. I took my insulin, so now I can eat a whole cake”
At what level would you begin to worry about hypoglycemia intra-op?
80 Diagnosis under GA is difficult
Chronic NPH administration may lead to the development of antibodies to _____
protamine
what type of currently available type of insulin is most likely to cause an allergic reaction?
NPH (due to protamine)
A patient is considered to be insulin resistant if they require > ___ units/day
100 Battling DOWN REGULATIOn of insulin receptors
Acute insulin resistance is associated with what 3 things?
trauma surgery infection
What meds can counter the effects of insulin?
Epinephrine ACTH/glucocortocoids estrogen Glucagon
How does epinephrine counter insulin?
- Inhibits the secretion of insulin - Stimulates glycogenolysis
What does epinephrine stimulate ?
Glycogenolysis
With multiple SQ injection insulin management, what percent is given at intermediate or long acting? Versus how much is given in additional dosages with meals and sugar checks?
70% as intermediate or long acting at bedtime. 30% as additional doses with rapid acting
How often should insulin pump injection site be changed?
every 2-4 days
What type of insulin is typically used in insulin pumps?
Regular or Lispro
What is afreeza?
Rapid acting Inhaled Insulin with onset 10-15 min and duration 3 hours. “a hot steaming pile of garbage” per Emily
In what situation would insulin sliding scale be used as sole treatment method?
When someone is on a steroid that is causing hyperglycemia Otherwise SS’s should e NOT be used alone, need some sort of basal coverage as well
What are the four main long term complications of diabetes mellitus?
- Atherosclerosis 2. Neuropathy 3. Nephropathy 4. Retinopathy
Diabetes is the number one cause of….?
1 cause of: 1. Dialysis 2. Blindness 3. Amputation due to large size of a glucose molecule that destroy tiny capillaries/nephrons
What electrolyte abnormality can have an increased risk with perioperative hyperglycemia?
Hyponatremia As glucose goes up, Na+ begins to come down
T/F: High rather than low blood glucose is desired under general anesthesia?
True; because GA can mask signs of low blood glucose
What is optimal blood glucose levels perioperatively? Total joints?
80-180mg/dl Total joints 80-150mg/dl
What is included in “non-tight control regimen”?
1/4 to 1/2 dose intermediate or long acting prior to surgery. Coverage based on BG concentrations. Initiate IV insulin infusion based on continued need for correction.
1 unit of regular insulin will decrease BG by how many mg/dl?
50-60mg/dl per 1 unit regular insulin
What is included in “Tight Control regimen”?
- Maintenance D5W at 50ml/hr/70kg body weight 2. Insulin at 0.05u/kg/hr (0.5-1u/hr) 3. Check BG Q1-2hrs 4. Adjust drip as needed to obtain targeted goal
If “tight control regimen” being used and 4 hours into a case the BG is 300mg/dl, should you bolus regular insulin?
No; bolusing regular insulin can create dangerous swings of glucose levels. Better to titrate gtt accordingly
What is perioperative management of patients with insulin pumps?
- Prior to surgery= clear liquids with or without sugar 2. Maintain basal infusion rate 3. Turn off preprandial boluses 4. Measure BG Q1hr 5. Question patient how much insulin is typically required to decrease BG by 50mg/dl
Which oral hypoglycemic medication 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 sulfnylureas?
- Glyburide ( Diabeta, Micronase) 2. Glipizide (Glucotrol) 3. Glimepiride (Amaryl).
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 2. Weight gain 3. GI disturbances (PONV can be common)
What are contraindications/precautions with sulfonylureas?
- Sulfa drug allergy 2. Patients with hypoglycemia unawareness 3. Poor renal function 4. 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) 2. 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) 2. 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) 2. Weight gain 3. 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) 2. Increase glycoursodeoxylcholic acid (GUDCA) 3. Inhibit signaling of intestinal farnesoid X receptor (FXR)
What are side effects of metformin?
- Common: anorexia, nausea, diarrhea 2. 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 2. Hold 48hrs prior to and after IV dye, check Cr levels 3. Do not restart too quickly after surgery d/t worsening PONV
Contraindications/precations with metformin?
- Renal impairment 2. Age >80years old 3. Hepatic impairment 4. 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) 2. pioglitazone (Actos) “glitazone”’s
MOA of TZDs?
- Decrease insulin resistance 2. Decrease hepatic glucose output Require the presence of insulin and are especially effective in obese patients. If insulins resistant, not going to work
Side effects of TZDs?
- Weight gain 2/ Hepatotoxicity 3. Peripheral edema 4. CHF exacerbation 5.Risk of bone fractures 6. *controversial MI or CV death with avandia*
What are examples of DPP-4 Inhibitors?
- sitagliptin (Januvia) 2. saxagliptin (Onglyza) 3. linagliptin (Tradjenta) 4. 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: 1. Increase pancreatic insulin secretion 2. Limits glucagon secretion 3. Slows gastric emptying 4. Promotes satiety “Results in more GLP1 available”
Side effects of DPP-4 Inhibitors?
- URI/UTIs (esp if catheter is in place) 2. HA 3. Weight neutral 4. Low(ish) risk of hypoglycemia 5. *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) 2. liraglutide (Victoza) 3. albiglutide (Tanzeum) 4. dulaglutide (Trulicity)
MOA of GLP-1 analogs?
- Prolong gastric emptying 2. Reduce post-prandial gluacagon secretion
MOA of Amylin analogs?
“like super GLP-1” 1. Increase insulin secretions 2. Prolong gastric emptying 3. increase beta cell growth 4. Central appetite suppression
Side effects of GLP-1 analogs?
- N/V/D 2. Pancreatitis 3. ARF 4. 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
Side effects of Amylin Analogs?
- Black box=hypoglycemia with Type 1
- N/V
- Anorexia
- HA
- Gastroparesis
Which hypoglycemic agent 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 1. canagliflozin (Invokana) 2. dapagliflozin (Farxiga 3. 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)
Afreeza (inhaled insulin) comes is single use cartridges of __, __, and __ units
4,8,12
Prior to giving insulin during the operative period, what should you do first?
Start D5W (or at least have it available) Def start if glucose is < 80
For surgery, should Tresiba be held all together?
Yes, b/c it is sooo long acting its recommended to just hold it all together
For “Tight control” IV insulin, how would you figure out the starting rate
Start drip @ plasma glucose/150 (100 if patient on steroids
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 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 2. Low risk hypoglycemia 3. Potentially these UTIs that could develop 4. 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
Which two drug classes cause URI’s?
DPP-4 Inhibitors and meglitinides
Which two drug classes cause UTIs?
DPP-4 Inhibitors and SLGT2 Inhibitors
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)
