Lecture 7-Glucose Control Flashcards
What protein is released from the CNS when there is glucose in the bloodstream; released to give you a feeling of fullness after eating; works in the pancreas to have the pancreas release insulin from the beta islet cells; and works in the liver to go from glycogenolysis to gluconeogenesis?
Glucagon like peptide (GLP1)
What protein breaks down GLP1 to stop its activity?
Dipeptidylpeptidase (DPP4)
Type I diabetes–historically ___ (juvenile/older) onset; ___ (abrupt/slow) onset; ___ (does/does not) require exogenous insulin to treat; ___ (prone/not prone to) ketoacidosis; ___ (small/large) fluctuations in blood glucose concentration; ___ (thin/thicker) body habitus
type I diabetes–historically juvenile onset; abrupt onset; does require exogenous insulin to treat; prone to ketoacidosis; large fluctuations in blood glucose concentration; thin body habitus
Patients are genetically predisposed to type I diabetes–T/F?
True
Genetic predisposition to type I diabetes is caused by altered human lymphocyte antigen on the short arm of chromosome ___; this defect causes “___itis”
chromosome 6; this defect causes “insulinitis”
Autoantibodies may be detected at the time of type I diabetes diagnosis but may be absent years later–T/F?
True
What are the main signs and symptoms at time of type I diabetes diagnosis?–___glycemia; ___acidosis; 3 P’s
- Hyperglycemia
- Ketoacidosis
- 3 P’s–polyuria, polyphagia, polydypsia
Type II diabetes–historically ___ (juvenile/adult) onset; ___ (does/does not) require exogenous insulin; ___ (prone/not prone to) ketoacidosis; ___ (stable/unstable) blood glucose concentration; ___ (thin/obese) body habitus
Type II diabetes–historically adult onset; does not require exogenous insulin (patients may still be on it though); not prone to ketoacidosis; stable blood glucose concentration; obese body habitus
What are (3) signs and symptoms of type II diabetes?
3 P’s–polyuria, polydypsia, polyphagia
The younger a patient is when they develop type II diabetes, the more likely they will require exogenous insulin (in addition to oral hypoglycemics)–T/F?
True
(4) medication classes that can cause hyperglycemia–gluco___; anti___; ___ medications; ___
glucocorticoids; antipsychotics; HIV medications; octreotide
(3) stressful situations that can cause hyperglycemia
illness, trauma, pregnancy
Diagnosis of diabetes–fasting blood glucose ___ mg/dl or greater; random blood glucose > ___ mg/dl
fasting blood glucose 126 mg/dl or greater; random blood glucose > 200 mg/dl
By the time patients are diagnosed with type II diabetes, ~90% of their beta islet cells are gone–T/F?
True–early diagnosis/treatment is key
BG monitoring–ISO guideline 15197 suggests that for glucose levels < 75 mg/dl, a meter should read within ___ mg/dl of the reference sample, and for levels > 75 mg/dl, the reading should be within ___%. A meter should also be able to meet these targets in at least ___% of the samples tested
for glucose levels < 75 mg/dl, a meter should read within 15 mg/dl of the reference sample, and for levels > 75 mg/dl, the reading should be within 20%. A meter should also be able to meet these targets in at least 95% of the samples tested.
Normal HgA1C = ___-___%
4-6%
ADA recommends HgA1C < ___-___%, depending on the age of the diabetic patient
< 7-8.5%
HgA1C gives an idea of the degree of control of blood glucose levels over the past ___ months
3 months
HgA1C assesses the long-range effectiveness of glucose control–T/F?
True
Urinary ___ are assessed by reagent strips if patients develop symptoms of cold, flu, vomiting, abdominal pain, polyuria, or on finding an unexpectedly high glucose level
Urinary ketones
Urinary ketones can be used to monitor patients at risk of going into diabetic ___, type ___ diabetics
diabetic ketoacidosis, type I diabetics
Diabetes treatment–___ changes are first line treatment for pre-diabetics
dietary changes are first line treatment for pre-diabetics
Diabetes treatment–oral ___ agents for type II diabetics
oral hypoglycemic agents for type II diabetics
Diabetes treatment–___ for type I and advanced type II diabetics
insulin for type I and advanced type II diabetics
What does PI-3K do?–It moves a ___ into the cell wall of cells
It moves a glucose transporter into the cell wall of cells
Insulin MOA–binds to plasma membrane ___ receptors; phosphorylated receptor substrates then activate or inactivate numerous enzymes and other mediating molecules; translocation of ___ to plasma membranes
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
Glucose transporters facilitate ___ diffusion into cells; shift intracellular glucose metabolism toward ___ (glyco___); stimulate cellular uptake of ___ acids, ___ate, ___ium, and ___ium; stimulate protein ___ and inhibit proteo___; regulate ___ expression via insulin regulatory elements in target DNA
Glucose transporters facilitate glucose diffusion into cells; shift intracellular glucose metabolism toward storage (glycogenesis); stimulate cellular uptake of amino acids, phosphate, potassium, and magnesium; stimulate protein synthesis and inhibit proteolysis; regulate gene expression via insulin regulatory elements in target DNA
___ occurs when there is an impaired intracellular insulin signal that results in decreased recruitment of glucose transport proteins to the plasma membrane and subsequent decreased glucose uptake
Insulin resistance
Compensatory ___insulinemia occurs to overcome insulin resistance
Compensatory hyperinsulinemia occurs to overcome insulin resistance
Cells send signals to the CNS that they’re starving (because insulin signal is messed up and isn’t bringing glucose into the cells); body sends signals to the pancreas to make more glucose/release more insulin, resulting in hyperinsulinemia; hyperinsulinemia leads to eventual burnout of the pancreas and worsening of diabetes
Insulin receptor saturation occurs with ___ (low/high) circulating concentrations of insulin; ___ (more/less) insulin receptors are popped into the cell walls as a result
Insulin receptor saturation occurs with low circulating concentrations of insulin; more insulin receptors are popped into the cell walls as a result
The number of insulin receptors in a cell wall is ___ (inversely/directly) related to the plasma concentration of insulin
The number of insulin receptors in a cell wall is inversely related to the plasma concentration of insulin
The higher the plasma concentration of insulin, the ___ (less/more) insulin receptors in the cell wall
The higher the plasma concentration of insulin, the less insulin receptors in the cell wall
The lower the plasma concentration of insulin, the ___ (less/more) insulin receptors in the cell wall
The lower the plasma concentration of insulin, the more insulin receptors in the cell wall
Insulin can up or down regulate its number of receptors in cell walls in response to circulating concentrations of insulin–T/F?
True
Elimination half-life of insulin is ___-___ minutes
5-10 minutes
Insulin is metabolized by the ___ and ___
kidneys and liver
___% of the insulin that reaches the liver via the portal circulation is metabolized on a single pass through the liver
50% of the insulin that reaches the liver via the portal circulation is metabolized on a single pass through the liver
What prolongs the elimination half-life of insulin more–kidney or liver disease?
Kidney disease prolongs the elimination half-life of insulin more than liver disease
Despite rapid clearance from the plasma, there is a sustained pharmacologic effect of insulin for ___-___ minutes because insulin is tightly bound to ___ receptors
Despite rapid clearance from the plasma, there is a sustained pharmacologic effect of insulin for 30-90 minutes because insulin is tightly bound to tissue receptors
Insulin administered subQ is released ___ (slowly/quickly) into the circulation to produce a sustained biological effect
Insulin administered subQ is released slowly into the circulation to produce a sustained biological effect
Basal rate of insulin secretion by the pancreas is ___ unit/hr
Basal rate of insulin secretion by the pancreas is 1 unit/hr
Food prompts a ___-___ fold increase in insulin secretion
Food prompts a 5-10 fold increase in insulin secretion
Total daily secretion of insulin is approximately ___ units/day
Total daily secretion of insulin is approximately 40 units/day
Insulin response to glucose is greater for IV infusion than oral ingestion–T/F?
FALSE–insulin response to glucose is greater for oral ingestion than IV infusion
Long acting insulins should be used for acute diabetic attacks–T/F?
FALSE–long acting insulins should NOT be used for acute diabetic attacks
What long acting insulin acts just like basal rate insulin; is sgiven once a day; good for people who have very brittle diabetes/lots of swings in glucose levels; also good for patients who are not good at keeping a schedule for giving themselves insulin?
Degludec (Tresiba)
Rates of hypoglycemia with Degludec (Tresiba) are no greater than any other insulins–T/F?
True
What insulin is given at bedtime and helps to counteract the morning burst of hormones?
Glargine (Lantus)
Insulin preparations–newer agents are produced by ___ technology
recombinant technology
What is the advantage of newer insulin preparations?–___ or ___ that could accompany administration of animal insulins is no longer a significant problem
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
only short acting insulin may be given IV/via pump
Side effects of insulin–___glycemia; ___kalemia; ___magnesemia; ___phosphatemia; ___ reactions; ___dystrophy; insulin ___; drug ___
hypoglycemia; hypokalemia; hypomagnesemia; hypophosphatemia; allergic reactions; lipodystrophy; insulin resistance; drug interactions
Hypokalemia/hypomagnesemia that may occur with insulin administration puts patients at risk for ___
arrhythmias
Hypophosphatemia that may occur with insulin administration puts patients at risk for respiratory ___
respiratory depression
___ syndrome can occur in patients who have been NPO for awhile; get ___ (up/down) regulation of insulin receptors because the cells are hungry and waiting for more glucose to be introduced into the body
Refeeding syndrome can occur in patients who have been NPO for awhile; get up regulation of insulin receptors because the cells are hungry and waiting for more glucose to be introduced into the body
What happens if you give someone who has been NPO for so long 100% of their caloric requirements for the day?
Refeeding syndrome–they will get massive rush of insulin release from the pancreas; insulin will bind to all of the up regulated receptors; and there will be a rush of potassium, magnesium, and phosphate into the cells
What is the most serious side effect of insulin?
Hypoglycemia
Symptoms of hypoglycemia reflect the compensatory effects of increased ___–___esis, ___cardia, ___tension
increased epinephrine–diaphoresis, tachycardia, hypertension
Epi is released in response to hypoglycemia because it kickstarts gluconeogenesis/glycogenolysis to increase blood glucose levels
Rebound ___glycemia caused by ___ (sympathetic/parasympathetic) nervous system activity in response to hypoglycemia may mask the correct diagnosis–this is known as the ___ Effect
Rebound hyperglycemia caused by sympathetic nervous system activity in response to hypoglycemia may mask the correct diagnosis–this is known as the Somogyi Effect
CNS symptoms of hypoglycemia include mental ___ progressing to ___ and ___
mental confusion progressing to seizures and coma
Diagnosis of hypoglycemia under general anesthesia is ___ (easy/difficult)
difficult
Treatment of hypoglycemia–___ and ___ IV
dextrose and glucagon IV
Use of human insulin has eliminated the problem with systemic allergic reactions that could be associated with animal preparations of insulin–T/F?
True
Local allergic reactions to insulin are red hardened areas that develop at the site of injection; they are due to non insulin materials in the preparation–T/F?
True
Chronic NPH administration may lead to the development of antibodies to ___
protamine
Lipodystrophy is atrophy of fat at sites of ___
subQ insulin injection
Lipodystrophy occurs if you continue to inject in the ___ spot
same spot
Lipodystrophy is minimized by ___ the site of injection
rotating the site of injection
Insulin resistance occurs in patients requiring > ___ units/day (remember avg daily insulin release from the body is ~___ units/day)
Insulin resistance occurs in patients requiring > 100 units/day (remember the avg daily insulin release from the body is ~40 units/day)
Acute insulin resistance is associated with ___, ___, and ___
trauma, surgery, and infection
___resistance has been eliminated with the switch from animal insulin to human insulin
Immunoresistance
Hypoglycemic effects of insulin are countered by ___ or ___ steroids; ___en; ___on
ACTH or glucocorticoid steroids; estrogen; glucagon
Insulin drug interactions–hypoglycemic effects of insulin are countered by ___ or ___ steroids; ___en; ___on
ACTH or glucocorticoid steroids; estrogen; glucagon
Insulin drug interactions–epinephrine ___ (inhibits/stimulates) the secretion of insulin; ___ (inhibits/stimulates) glycogenolysis
epinephrine inhibits the secretion of insulin; stimulates glycogenolysis
Insulin pumps are only for ___/___ insulins (___/___ acting)
regular/analog insulins (rapid/short acting)
Methods of insulin administration–multiple SQ insulin injections–administer 70% of total insulin dose as ___ or ___ acting at ___ (basal insulin); type I diabetics may require ___ or ___ acting insulin in the ___ as well
administer 70% of total insulin dose as intermediate or long acting at bedtime (basal insulin); type I diabetics may require intermediate or long acting insulin in the morning as well
Methods of insulin administration–multiple SQ insulin injections–administer a ___ acting insulin prep before each meal or snack; doses should be adjusted based on blood ___ level and/or anticipated ___ intake
administer a rapid acting insulin prep before each meal or snack; doses should be adjusted based on blood glucose level and/or anticipated carbohydrate intake
Methods of insulin administration–insulin pumps–pump site is changed every ___-___ days; use a ___ acting insulin (___ or ___); administer a ___ rate with preprandial ___; basal rate is usually ___-___ unit/hr
pump site is changed every 2-4 days; use a rapid acting insulin (regular or lispro); administer a basal rate with preprandial boluses; basal rate is usually 0.5-1 unit/hr
Inhaled insulin = ___
Afreeza
Inhaled insulin (Afreeza) is ___ (rapid/long) acting; onset ___-___ minutes; duration ___ hours; available as single use cartridges of ___, ___, and ___ units
Inhaled insulin (Afreeza) is rapid acting; onset 10-15 minutes; duration 3 hours; available as single use cartridges of 4, 8, and 12 units
Basal bolus insulin administration matches the ___ process
physiologic process
Basal bolus insulin administration–___% long acting, ___% divided to AC/HS
70% long acting, 30% divided to AC/HS
Insulin sliding scales should be used alone–T/F?
FALSE–should NOT be used alone…need some sort of basal glucose control
Rapid acting insulin only temporarily corrects elevated blood glucose–T/F?
True
Goals of insulin therapy = maintain blood glucose levels as close to ___ as possible; delay or minimize long term complications of ___
maintain blood glucose levels as close to normal as possible; delay or minimize long term complications of diabetes
Long term complications of diabetes = athero___; ___pathy; ___pathy; ___pathy
atherosclerosis; neuropathy; nephropathy; retinopathy
Risks of hyperglycemia in the perioperative period = micro___; impaired ___ function; cerebral ___; impaired ___ healing; postoperative ___; ___natremia
microangiopathy; impaired leukocyte function; cerebral edema; impaired wound healing; postoperative sepsis; hyponatremia
Microangiopathy = disease of the capillaries–walls become so thick/weak and bleed, leak protein, and slow the flow of blood
The key to managing blood glucose levels perioperatively = set ___ goals, monitor blood glucose ___, and ___ therapy to achieve these goals
set clear goals, monitor blood glucose frequently, and adjust therapy to achieve these goals
What is desired under general anesthesia–higher or lower blood glucose? Why?
Higher blood glucose because general anesthesia can mask signs of low blood glucose
Perioperative management of blood glucose–optimal blood glucose levels ___-___ mg/dl; < ___ mg/dl for total joints; glucose infusion if blood glucose decreases to < ___ mg/dl
optimal blood glucose levels 110-180 mg/dl; < 150 mg/dl for total joints; glucose infusion if blood glucose decreases to < 80 mg/dl
Surgical stress may alter the expected blood glucose–T/F?
True
It is important to maintain optimal glucose levels in the intraoperative period and ___-___ hours postoperatively
24-72 hours postoperatively
Ideally, diabetic patients should be scheduled for surgery as ___
as the first case of the morning
“Non-tight” control regimen–give ___ to ___ the dose of intermediate or long acting insulin as the last dose prior to procedure; if the procedure is short, may give ___ daily dose
give 1/4 to 1/2 the dose of intermediate or long acting insulin as the last dose prior to procedure; if the procedure is short, may give regular daily dose
“Non-tight” control regimen–if patient is on tresiba (degludec), ___ dose
if patient is on tresiba (degludec), hold dose
“Non-tight” control regimen–small dose of short acting or rapid acting insulin ___ (can/cannot) be administered as needed
small dose of short acting or rapid acting insulin can be administered as needed
“Non-tight” control regimen–coverage with short or rapid acting insulin is based on blood ___ concentrations; should give ___ unit regular for every ___-___ mg/dl blood glucose
coverage with short or rapid acting insulin is based on blood glucose concentrations; should give 1 unit regular for every 50-60 mg/dl blood glucose
For longer/serious procedures, follow the “___” regimen
“tight control” regimen
“Tight control” regimen–continuous IV ___ infusion to maintain target glucose level; ___ units/kg/hr (___-___ unit/hour)
continuous IV insulin infusion to maintain target glucose level
“Tight control” regimen–start insulin drip at plasma glucose level/___ (divide by ___ if patient is on steroids)
start insulin drip at plasma glucose level/150 (divide by 100 if patient is on steroids…allows for tighter control)
“Tight control” regimen–maintenance fluid ___/electrolytes IV at ___ ml/hr/70 kg body weight
maintenance fluid D5W/electrolytes IV at 50 ml/hr/70 kg body weight
“Tight control” regimen–IV boluses of regular insulin can create dangerous ___ of glucose levels because regular insulin has a half-life of ___-___ minutes with a biological half-life of ___-___ minutes, resulting in short, but high levels of insulin
IV boluses of regular insulin can create dangerous swings of glucose levels because regular insulin has a half-life of 4-5 minutes with a biological half-life of 15-20 minutes, resulting in short, but high levels of insulin
Perioperative management for patients with insulin pumps–prior to surgery, can have ___ liquids with or without sugar; maintain ___ infusion rate; turn off ___; measure blood glucose every ___; know the typical bolus for the patient to decrease blood glucose by ___ mg/dl
patients with insulin pumps–prior to surgery, can have clear liquids with or without sugar; maintain basal infusion rate; turn off preprandial boluses; measure blood glucose every hour; know the typical bolus for the patient to decrease blood glucose by 50 mg/dl
What are the (8) classes of oral hypoglycemics?–___ureas; ___ inhibitors; ___nides; ___nides; ___diones; ___ inhibitors; ___ mimetics; ___inhibitor
- Sulfonylureas
- Alpha-glucosidase inhibitors
- Meglitanides
- Biguanides
- Thiazolidinediones
- DPP4 inhibitors
- Incretin mimetics
- SLGT2 inhibitor
Sulfonylureas MOA–act at ___ cells to stimulate release of ___
act at pancreatic beta cells to stimulate release of insulin
Sulfonylureas were traditionally a ___ dosing schedule; newest generation dosed ___
traditionally a meal time dosing schedule; newest generation dose once daily
In order for sulfonylureas to work, you need to have a functioning ___
pancreas
Sulfonylureas are orally effective in ___ (lowering/raising) blood glucose levels even to the point of ___glycemia
lowering blood glucose levels even to the point of hypoglycemia
Sulfonylureas have high ___ rates
high failure rates
20% primary failures (1 in 5 patients they won’t work for at all); each year 10-15% secondary failures
Sulfonylureas should be avoided in patients with allergy to ___ drugs
sulfa drugs
If patient took their sulfonylurea the morning of surgery, he/she will be at high risk for ___glycemia; have ___ or ___ available
he/she will be at high risk for hypoglycemia; have D50 or glucagon available
Sulfonlyureas are primarily metabolized by the ___ and excreted by the ___; have ___ and ___ metabolites
Sulfonylureas are primarily metabolized by the liver and excreted by the kidneys; have active and inactive metabolites
___ patients are at high risk of hypoglycemia from sulfonylureas
Renal failure patients are at high risk of hypoglycemia from sulfonylureas (because they are renally eliminated…renal failure prolongs their duration of action)
Most common severe complication of sulfonylureas is ___
hypoglycemia
Risk of hypoglycemia from sulfonylureas is highest with ___ and ___
glyburide and chlorpropamide (because they have the longest elimination half-life)
Duration of action of a sulfonylurea is up to ___ days
up to 7 days
Hypoglycemia from sulfonylureas is ___ (more/less) frequent than with insulin; it is often ___ and more ___ than hypoglycemia due to insulin
Hypoglycemia from sulfonlyureas is less frequent than with insulin; it is often prolonged and more dangerous than hypoglycemia due to insulin
Do sulfonylureas cross the placenta?
Yes–can cause fetal hypoglycemia
Other side effects of sulfonlyureas–weight ___ (gain/loss)/___; ___ disturbances in 1-3%–___/___; abnormal ___s; ___stasis
weight gain/edema; GI disturbances in 1-3%–nausea/vomiting; abnormal LFTs; cholestasis
Avoid sulfonylureas (except ___) in patients with ___ disease
Avoid sulfonylureas (except acetohexamide) in patients with liver disease
Contraindications/precautions for sulfonylurea use–hypersensitivity to ___; patients with ___glycemic unawareness; poor ___ function
hypersensitivity to sulfonamides; patients with hypoglycemic unawareness; poor renal function
What are (3) 2nd generation sulfonylureas?
- Glyburide (DiaBeta, Micronase)
- Glipizide (Glucotrol)
- Glimepiride (Amaryl)
Glyburide (DiaBeta, Micronase) is given as a ___ daily dose for 24 hour effects; cleared from plasma in ___ hours
Glyburide (DiaBeta, Micronase) is given as a single daily dose for 24 hour effects; cleared from plasma in 36 hours
What sulfonylurea is safest to use in patients with poor kidney function?
Glipizide (Glucotrol)
Glipizide (Glucotrol) stimulates insulin secretion over a ___ hour period; effects persist for prolonged periods (at least ___ years) without evidence of tolerance; ___ (does/does not) have active metabolites
Glipizide (Glucotrol) stimulates insulin secretion over a 12 hour period; effects persist for prolonged periods (at least 3 years) without evidence of tolerance; does not have active metabolites
If CrCl is above 10, it ___ (is/is not) safe for the patient to take glipizide
it is safe for the patient to take glipizide
If someone took a sulfonylurea the morning of surgery, they are at risk for ___, especially if they took ___
they are at risk for hypoglycemia, especially if they took glyburide
What are (3) 1st generation sulfonylureas?
- Tolbutamide (Orinase)
- Acetohexamide
- Chlorpropamide (Diabinese)
Which 1st generation sulfonylurea is the shortest acting and least potent and is associated with the fewest side effects?
Tolbutamide (Orinase)
Most of the hypoglycemic action from acetohexamide is due to its principle metabolite, ___; ___ excrete the active metabolite
Most of the hypoglycemic action from acetohexamide is due to its principle metabolite, uricosuric; kidneys excrete the active metabolite
Which 1st generation sulfonylurea is the longest acting?
Chlorpropamide (Diabinese)
Chlorpropamide (Diabinese) duration of action may approach ___ hours; 20% of the drug is excreted unchanged by the ___; it is associated with ___-like reactions; can cause severe ___natremia
duration of action may approach 72 hours; 20% of the drug is excreted unchanged by the kidneys; it is associated with disulfiram-like reactions; can cause severe hyponatremia (< 129)
Disulfiram = drug that causes an adverse reaction to alcohol, leading to nausea, vomiting, flushing, dizziness, throbbing headache, chest/abdominal discomfort, and general hangover-like symptoms
Effects and risk of hypoglycemia from chlorpropamide (Diabinese) can be prolonged in impaired ___ function
can be prolonged in impaired renal function
(2) alpha-glucosidase inhibitors = ___ and ___
acarbose (precose) and miglitol (glyset)
Alpha-glucosidase inhibitors MOA–decreased intestinal hydrolysis of ___
decreased intestinal hydrolysis of complex carbohydrates
Side effects of alpha-glucosidase inhibitors = GI ___; increased ___s; avoid in ___ disease and ___
GI upset; increased LFTs; avoid in inflammatory bowel disease and obstructions
Once complex carbohydrates are broken down into glucose, alpha-glucosidase inhibitors are ineffective–T/F?
True
(2) meglitinides = ___ and ___
Repaglinide (Prandin) Nateglinide (Starlix)
Meglitinides MOA–increase ___ secretion from islet cells like ___ (what other drug class?)
increase insulin secretion from islet cells like sulfonylureas
Meglitinides have a ___ (slower/faster) onset and ___ (shorter/longer) duration of action than sulfonylureas
faster onset (1 hour) and shorter duration of action (4 hours)
Meglitinides should be administered ___-___ minutes before meals
15-30 minutes before meals
Meglitinides can be administered while fasting–T.F?
FALSE–NEVER administer while fasting
Meglitinides are active only in the presence of ___; this decreases the risk of prolonged ___glycemic episodes
active only in the presence of glucose; this decreases the risk of prolonged hypoglycemic episodes
Side effects of meglitinides–___glycemia (___ (more/less) than sulfonlyureas); weight ___ (gain/loss); ___ infection
hypoglycemia (less than sulfonylureas); weight gain; upper respiratory infection
What is the name of (1) biguanide that is the #1 medication in type 2 diabetes treatment guidelines?
Metformin (Glucophage)
Metformin (Glucophage) decreases blood glucose concentrations with a very ___ (low/high) risk of hypoglycemia; has a positive effect on ___ concentrations; and leads to mild weight ___ in obese patients
very low risk of hypoglycemia; has a positive effect on lipid concentrations; and leads to mild weight loss in obese patients (unlike sulfonlyureas and meglitinides, which both cause weight gain)
Metformin MOA–___ (increased/decreased) hepatic glucose production [gluconeogenesis]; ___ (increases/decreases) glucose absorption from the intestine [similar to acarbose]; and ___ (increases/decreases) insulin sensitivity at the skeletal muscle cells
decreased hepatic glucose production [gluconeogenesis]; decreases glucose absorption from the intestine [similar to acarbose]; and increases insulin sensitivity at the skeletal muscle cells
Metformin produces satisfactory results in 50% of sulfonylurea failures–T/F?
True
Why should type 2 diabetics continue their metformin even if they are started on insulin?
Because metformin enhances the action of insulin at skeletal muscle cells
Metformin gut microbiota changes–___ (increases/decreases) bacteroides fragilis; higher rates of bacteroides fragilis are linked to ___ity, glucose ___, and ___ (increased/decreased) insulin sensitivity
decreases bacteroides fragilis; higher rates of bacteroides fragilis are linked to obesity, glucose intolerance, and decreased insulin sensitivity
Also…metformin increases GUDCA (FXR antagonist) and inhibits FXR, which regulates bile acid associated with metabolic disease
Common side effects of metformin = ___, ___, and ___
anorexia, nausea, and diarrhea
Rare side effect of metformin = ___
lactic acidosis
Black box warning for metformin
Signs of lactic acidosis from metformin–___/___; ___ (increased/decreased) RR, HR; ___ pain; ___
nausea/vomiting; increased RR, HR; abdominal pain; shock
Metformin can exaggerate post-op nausea/vomiting–T/F?
True
Starting regular dose of metformin post-op can make patient very sick after surgery
Discontinue metformin ___ hours prior to elective surgery d/t risk of lactic acidosis in the intraoperative period
48 hours prior to elective surgery
Metformin and IV contrast = increased risk of ___toxicity; hold ___ hours prior to and after dye, check ___ levels
increased risk of nephrotoxicity; hold 48 hours prior to and after dye, check creatinine levels
Metformin contraindications/precautions–new recommendations for renal impairment–contraindicated in patients with eGFR < ___ ml/min; do not initiate or re-evaluate patients with eGFR < ___ ml/min
contraindicated in patients with eGFR < 30 ml/min; do not initiate or re-evaluate patients with eGFR < 45 ml/min
Metformin contraindications/precautions–age > ___ years old; ___ impairment; ___
age > 80 years old; hepatic impairment; CHF
(2) thiazolidinediones–___ and ___
rosiglitazone (Avandia) and pioglitazone (actos)
Thiazolidinediones MOA–___ (increase/decrease) insulin resistance; ___ (increase/decrease) hepatic glucose output
decrease insulin resistance; decrease hepatic glucose output
Thiazolidinediones require the presence of ___ and are especially effective in ___ patients
require the presence of insulin and are especially effective in obese patients
Thiazolidinediones side effects–weight ___ (loss/gain); ___toxicity; peripheral ___; ___ exacerbations; risk of ___
weight gain; hepatotoxicity; peripheral edema; CHF exacerbations; risk of bone fractures
Why was rosiglitazone (avandia) pulled from the market?
Controversial increase in MI and CV death
(4) DPP4 inhibitors
- Sitagliptin (Januvia)
- Saxagliptin (Onglyza)
- Linagliptin (Tradjenta)
- Alogliptin (Nesina)
DPP4 inhibitors MOA–___ (increase/decrease) pancreatic insulin secretion; ___ (limit/enhance) glucagon secretion; ___ (slow/speed up) gastric emptying; ___ (promote/inhibit) satiety
increase pancreatic insulin secretion; limit glucagon secretion; slow gastric emptying; promote satiety
How do DPP4 inhibitors specifically work though? They slow down metabolism of what protein?
slow down metabolism of GLP-1
Side effects of DPP4 inhibitors–___ infection and ___ infections; ___ache; weight ___ (loss/gain/neutral); ___ (lower/higher) risk of hypoglycemia…___ (increased/decreased) risk of hypoglycemia if using in combo with other agents
upper respiratory infection and urinary tract infections; headache; weight neutral; lower risk of hypoglycemia…increased risk of hypoglycemia if using in combo with other agents
Post-marketing, DPP4 inhibitors were found to cause ___titis, ___edema, ___ syndrome, ___laxis
pancreatitis, angioedema, Stevens Johnson syndrome, anaphylaxis
DPP4 inhibitors 08/2015 FDA safety warning for ___
joint pain
Incretin mimetics are also known as ___ analogs and ___ analogs
GLP-1 analogs and amylin analogs
(4) incretin mimetics–GLP-1 analogs
- Exanatide (Byetta, Bydureon)
- Liraglutide (Victoza)
- Albiglutide (Tanzeum)
- Dulaglutide (Trulicity)
^ These are injectables
GLP-1 analogs ___ (slow/speed up) gastric emptying; ___ (reduce/enhance) postprandial glucagon secretion
slow gastric emptying; reduce postprandial glucagon secretion
Amylin analogs ___ (increase/decrease) insulin secretion; ___ (slow/speed up) gastric emptying; ___ (increase/decrease) beta cell growth; ___ (suppress/stimulate) central appetite
increase insulin secretion; slow gastric emptying; increase beta cell growth; suppress central appetite
What is (1) amylin analog? Why is it not really used?
Pramlinide (Symlin)–too expensive
Where does pramlinide (symlin) come from?
Gila monsters
What is a risk postoperatively if the patient takes a GLP-1 analog?
Postop nausea/vomiting because GLP-1 analogs slow down the GI tract
Side effects of GLP-1 analogs–___/___/___; ___titis; acute ___ failure; weight ___ (loss/gain)
nausea/vomiting/diarrhea; pancreatitis; acute renal failure; weight loss
Specific GLP-1 analog precautions–avoid Byetta in ___ failure; avoid Victoza in ___ carcinoma
avoid Byetta in renal failure; avoid Victoza in thyroid carcinoma
Side effects of amylin analogs–black box warning: ___glycemia, especially in type ___ diabetics; ___/___; ___rexia; ___ache; gastro___
black box warning: hypoglycemia, especially in type I diabetics; nausea/vomiting; anorexia; headache; gastroparesis
(3) SGLT2 inhibitors
- Canagliflozin (Invokana)
- Dapagliflozin (Farxiga)
- Empagliflozin (Jardiance)
SGLT2 inhibitors MOA–___ (increased/decreased) urinary glucose excretion from the ___ tubule
increased urinary glucose excretion from the proximal tubule
Contraindications for SGLT2 inhibitors–CrCl < ___ ml/min, end stage ___ disease, patients on hemo___
CrCl < 30 ml/min, end stage renal disease, patients on hemodialysis
Warnings for SGLT2 inhibitors–___tension, ___ side effects
hypotension, urinary side effects
Increased risk of ___ and ___ with SGLT2 inhibitors
gangrene and amputations, primarily toe
What does SGLT2 inhibitor mean?
sodium glucose transporter 2 inhibitor
SGLT2 inhibitors–increased risk of perioperative ___glycemic keto___
euglycemic ketoacidosis
Thyroid gland hormones review–hypothalamus releases ___; pituitary releases ___; thyroid releases ___ and ___
hypothalamus releases thyroid releasing hormone (TRH); pituitary releases thyroid stimulating hormone (TSH); thyroid releases T3 ad T4
Clinical presentation of HYPOthyroid (Hashimoto disease)–___ (cold/heat) intolerance; ___ (moist/dry) skin; ___ness; weight ___ (loss/gain); ___cardia; ___ (slow/fast) reflexes; ___ (coarse/fine) skin and hair; periorbital ___; painful/heavy ___; ___ coma
cold intolerance; dry skin; weakness; weight gain; bradycardia; slow reflexes; coarse skin and hair; periorbital swelling; painful/heavy menstruation; myxedema coma
Clinical presentation of HYPERthyroid (Graves disease)–weight ___ (loss/gain); ___ (increased/decreased) appetite; ___ (cold/heat) intolerance; ___er; ___ (coarse/fine) hair; ___cardia; ___iety; ___nia; ___ (lighter/heavier) periods/___menorrhea; ___ (cold/warm) skin; ___thalmos; ___ storm
weight loss; increased appetite; heat intolerance; goiter; fine hair; tachycardia; anxiety; insomnia; lighter periods/amenorrhea; warm skin; exophthalmos; thyroid storm
Armour thyroid composition ratio of T4 to T3 is ___:___
4:1
Effectiveness of armour thyroid therapy is demonstrated by the return of TSH to normal and decrease in the size of the goiter–T/F?
True
Armour thyroid suppresses the responsiveness and causes regression of TSH sensitive malignant tumors–T/F?
True
T4 = ___ (active/inactive)
T4 = inactive
T3 = ___ (active/inactive)
T3 = active
What is the most frequently administered drug for the treatment of diseases requiring thyroid hormone replacement (i.e.: hypothyroidism)?
Levothyroxine (T4) (Synthroid)
What mechanism of administration is preferred for levothyroxine?
Oral (but IV is available)
If a patient is on PO Synthroid and is unable to take oral meds for several days, do they need immediate IV replacement of Synthroid? Why?
No because Synthroid has a long elimination half-life (7 days)
After 7 days, if patient is still not able to take PO, you can administer half the oral dose IV
The elimination half-life of Synthroid is ___ days
7 days
In the body, Synthroid is deiodinated and converted to ___
T3
Liothyronine (Cytomel) is a levorotatory isomer of ___
T3
Liothyronine (T3) (Cytomel) is __-__x as potent as levothyroxine
2.5-3x as potent as levothyroxine
Liothyronine (T3) (Cytomel) is usually added on if someone is on a max dose of Synthroid and their body isn’t responding appropriately to it–T/F?
True
Liothyronine (T3) (Cytomel) has a ___ (slow/rapid) onset and ___ (short/long) duration of action
rapid onset and short duration of action
Hypothyroidism anesthetic implications–___ (increased/decreased) sensitivity to depressant drugs, including inhaled anesthetics; ___dynamic (hyper/hypo) CV system; ___ (increased/decreased) CO d/t ___ (increased/decreased) HR and SV; ___ (slow/fast) metabolism of drugs, particularly opioids; unresponsive ___ reflexes; ___ (increased/decreased) intravascular fluid volume; impaired ventilatory response to ___ (low/high) PaO2 and/or ___ (increased/decreased) PaCO2; ___ (delayed/enhanced) gastric emptying; ___natremic; ___thermic; ___nemic; ___glycemic; primary ___ insufficiency
increased sensitivity to depressant drugs, including inhaled anesthetics; hypodynamic CV system; decreased CO d/t decreased HR and SV; slow metabolism of drugs, particularly opioids; unresponsive baroreceptor reflexes; decreased intravascular fluid volume; impaired ventilatory response to low PaO2 and/or increased PaCO2; delayed gastric emptying; hyponatremic; hypothermic; anemic; hypoglycemic; primary adrenal insufficiency
Two antithyroid drugs to treat hyperthyroidism–___ and ___
propylthiouracil (PTU) and methimazole (tapazole)
Methimazole MOA–inhibit the formation of ___ hormone
thyroid hormone
PTU blocks the peripheral deiodination of ___ to ___
T4 to T3
PTU and methimazole are useful in treating ___thyroidism (including thyroid ___) before elective ___
useful in treating hyperthyroidism (including thyroid storm) before elective thyroidectomy
PTU and methimazole are only available ___
orally
PTU and methimazole require several days for full effect because pre-formed hormone must be depleted–T/F?
True
Antithyroid medication side effects–transient ___penia; ___; ___gias; ___-like symptoms; ___; ___cytosis early in therapy
transient leukopenia; rash; arthralgias; lupus-like symptoms; fever; granulocytosis early in therapy
What is the oldest effective treatment for hyperthyroidism?
Iodines–Lugol’s solution, saturated KI (potassium iodide) solution
Iodines inhibit the release of ___ hormone into the circulation
inhibit the release of thyroid hormone into the circulation
Iodines are combined with ___olol to treat hyperthyroidism before thyroidectomy
propranolol
___ is a severe exacerbation of hyperthyroidism due to a sudden excessive release of thyroid hormone
Thyroid storm (thyrotoxicosis)
Signs of thyroid storm–___thermia, ___cardia, ___, ___hydration, and ___
hyperthermia, tachycardia, CHF, dehydration, and shock
Thyroid storm resembles ___
malignant hyperthermia
Thyroid storm is more likely to occur in the first ___-___ hours postop than intraop
first 6-19 hours postop
Thyroid storm has a/an ___ (abrupt/delayed) onset
an abrupt onset
Treatment of thyroid storm–IV infusion of ___ (warm/cold) crystalloid solutions; sodium ___ IV to reduce the release of active hormones from the thyroid gland; ___ IV to treat acute primary adrenal insufficiency from increased metabolism and use of corticosteroids; ___ IV to alleviate the CV effects of thyroid hormones; ___ PO to reduce synthesis of new thyroid hormone
IV infusion of cold crystalloid solutions; sodium iodide IV to reduce the release of active hormones from the thyroid gland; cortisol IV to treat acute primary adrenal insufficiency from increased metabolism and use of corticosteroids; propranolol IV to alleviate the CV effects of thyroid hormones; PTU PO to reduce synthesis of new thyroid hormone
Avoid ___ for elevated temperature because it may displace thyroxine from carrier proteins
Avoid aspirin for elevated temperature because it may displace thyroxine from carrier proteins (so then there will be more circulating thyroxine)
