OADs, GLP-1, Amylinomimetics Flashcards
1
Q
How many generations of SU are there?
A
3
2
Q
What 2 agents are included in the meglitinide class?
A
- repaglinide (Prandin) - approved 1997
- nateglinide (Starlix) - approved 2000
3
Q
What combinations may SUs be used with?
A
- as monotherapy
- combined with metformin
- combined with insulin (glimepiride)
4
Q
What treatment regimens can the meglitinides be used with?
A
- indicated for monotherapy
- combined with metformin
- combined with TZD
5
Q
True or False: both the ADA and AACEA recommend SUs as a first-line treatment.
A
False, both recommend SU as a second or third line agent.
6
Q
According to AACE, who is the candidate for monotherapy?
A
7.5% A1c or lower
7
Q
According to AACE, who is a candidate for dual therapy?
A
patients with A1Cs 7.6-9.0%
8
Q
What is the MOA of an SU?
A
- SUs bind to SURs (SU Receptors) at the beta-cell potassium channels
- this closes the channel and blocks K+ ions from leaving the cell
- the membrane becomes depolarized and calcium channels open
- Ca2+ ions enter the cell and triggers the release of insulin
9
Q
What is the only first generation SU still in use?
A
chlorpropamide
10
Q
Second-generation SUs bind _____ tightly to proteins and are better able to penetrate cellular membranes. This makes them less likely to interact with other meds.
A
less
11
Q
How is glimepiride different from second generation SUs?
A
- it binds to a different part of the SUR
- binds less tightly to the SUR
- binds more quickly to the SUR (2-3 times faster)
- separates from the SUR more quickly (8-9 times faster)
12
Q
How often is glimepiride dosed?
A
once daily with first main meal
13
Q
What is the brand name of glimepiride?
A
Amaryl
14
Q
In general, SU monotherapy can be expected to lower A1C by _______%.
A
1.0-1.5%
15
Q
What are the limitations of SU therapy?
A
- hypoglycemia
- elimination through kidneys puts patients with decreased kidney function at greater risk of hypoglycemia
- Weight gain
- Some studies suggest that SUs may cause beta cell death.
16
Q
SUs are contraindicated in patients with __________________.
A
diabetic ketoacidosis.
17
Q
When does ADA recommend use of meglitinides?
A
they may be used in place of SUs, particularly in patients with irregular meal schedules or how develop late postprandial hypoglycemia on SUs
18
Q
When does AACE recommend use of meglitinides?
A
- only for patients with A1C levels between 6.5-7.5% as one of the last alternatives for the second component of dual therapy OR
- as a third medication in triple therapy
19
Q
What is the MOA of meglitinides?
A
- stimulate rapid, short-lived pancreatic secretion of insulin
- bind to a different site within the SUR on pancreatic beta cells and for a shorter time than SUs
- the mechanism of insulin release is otherwise the same as SU
20
Q
Is insulin release triggered by meglitinides glucose dependent?
A
Yes and it diminishes at low glucose concentrations.
21
Q
When taken before a meal, how long is the insulin-releasing effect of the meglitinides?
A
about 3 hours
22
Q
What is an advantage of Prandin (repaglinide)?
A
It is rapidly and completely absorbed and eliminated.
23
Q
When do peak plasma levels of Prandin occur?
A
within 1 hour of dosing
24
Q
A dose of nateglinide (Starlix) stimulates pancreatic insulin secretion within ___ minutes of dosing.
A
20 minutes
25
Prandin is metabolized exclusively in the \_\_\_\_\_\_\_\_, so a decrease in ________ function will ___________ its half-life and possibly cause hypoglycemia.
liver, liver, increase
26
What are the primary benefits of meglitinides?
* rapid onset
* short duration
* reduced hypoglycemia risk compared with some SUs
27
What is the average A1C reduction of Prandin?
1.5%
28
Which meglitinide causes the greatest A1C reduction?
Prandin has a greater effect on A1C than Starlix (1.5% vs. 0.5%).
29
What are the limitations of meglitinides?
* dosing frequency (up to 30 minutes before each meal)
* weight gain
30
Metformin may be used in patients ___ years old or older and extended release metformin may be used in patients ___ years old or older.
10, 17
31
According to the PIs of these drugs, metformin can be used in combination with what other agents?
1. TZDs
2. meglitinides
3. exenatide
4. liraglutide
5. acarbose
32
Both metformin and extended release metformin may be used in combination with SU or insulin in patients ___ years old or older.
17
33
What is the branded name of metformin?
Glucophage
34
What treatment regimen(s) are the TZDs indicated with?
* as monotherapy
* combination with an SU
* combination with metformin
* with insulin (pioglitazone only)
35
How does metformin affect glucose control?
* decreases the amount of glucose produced by the liver (impacts FPG)
* to a lesser degree it improveds cellular glucose uptake and utilization
36
On average, metformin lowers A1C values by how much?
1.5%
37
True or False: metformin appears to have a favorable effect on serum lipids.
True.
38
What is the maximum daily dose of immediate-release metformin and extended release metformin, respectively?
* Glucophage: 2550 mg
* Glucophage XR: 2000 mg
39
How often is XR metformin dosed compared to IR metformin?
XR metformin can be dosed once daily while IR metformin is dosed 2-3 times per day
40
What are the contraindications for metformin?
1. renal disease or dysfunction (plasma creatinine =\> 1.5 mg/dL in men or =\>1.4 mg/dL in women, or abnormal creatinine clearance)
2. hypersensitivity
3. acute or chronic metabolic acidosis
41
Who else should not use metformin besides those it is contraindicated for?
* patients undergoing radiologic studies with iodinated contrast materials
* CHF requiring drug treatment
* liver disease
* patients who are hypoxemic, dehydrated, or septic
42
What is the greatest danger associated with metformin?
Lactic Acidosis
43
True or False: since metformin is excreted unchanged through the urine, if a patient has kidney impairment, the drug may accumulate in the blood and produce acidosis.
True
44
How often should metformin users have their kidney function checked?
* before beginning therapy
* at least once a year after starting therapy
* more regularly if older or if kidney dysfunction is anticipated
45
Why should patients who drink alcohol excessively or have liver disease not take metformin?
Both conditions can create lactic acidosis.
46
What are the common side effects of metformin?
* Diarrhea
* Nausea and Vomiting
* Flatulence
47
What is the main effect of the TZDs?
* increase the sensitivity of muscle, fat, and liver tissue to insulin
48
How do the TZDs work?
by improving the insulin sensitivity of peripheral tissues (muscle and fat cells) and the liver when the drug is bound to them
49
What do TZDs bind to to initiate their MOA?
peroxisome proliferator-activated receptor-gamma (PPARy)
50
Which TZD is indicated for use with insulin?
pioglitazone (Actos)
51
What are the primary advantages of TZDs?
* efficacy
* low risk of hypoglycemia
* lipid improvements
* simplified dosing
52
What is the average A1C reduction with TZDs?
0.5% - 1.4%
53
How often is Avandia dosed?
once or twice daily
54
How often is Actos dosed?
once daily
55
What are the limitations associated with TZDs?
* edema and weight gain
* heart failure (has boxed warning)
* urinary bladder tumors (Actos)
* bone fractures in women
* liver toxicity (should be monitored)
56
Addition of Victoza to metformin, SU, insulin detemir, and/or TZD therapy has been shown to reduce A1C by \_\_\_\_\_\_\_%.
0.5-1.5%
57
What was the mean weight loss in the 52-week Victoza monotherapy trial in the 1.2 mg arm and 1.8 arm, respectively?
* 1.2 mg arm: 2.1 kg (4.6 lb)
* 1.8 mg arm: 2.5 kg (5.5 lb)
58
Where does ADA place DPP-4 inhibitos in the treatment spectrum?
as 2nd or 3rd line combination therapy
59
Where does AACE position the use of DPP4 inhibitors?
as monotherapy after metformin and in dual and triple therapy
60
Sitagliptin lowers A1C levels by \_\_% to \_\_% from baseline.
0.7%-0.8%
61
AGI stands for what?
Alpha-Glucosidase Inhibitors
62
What is the indication for AGIs?
* for use in monotherapy as an adjunct to diet
* The PI for acarbose reports clinical efficacy when used in combination with SU, metformin, or insulin
* Miglitol is indicated for monotherapy or in combination with SU
63
True or False: AGIs will be most effective in combination with other glucose lowering agents due to their distinct MOA.
True.
64
How do AGIs work?
They slow intestinal absorption of carbohydrates, and thus blunt the sharp postprandial rise in blood glucose.
65
What is the detailed MOA of the AGIs?
* they bind to and competitively inhibit the 2 types of enzymes - alpha-amylases and alpha-glucosidases - responsible for the breakdown of carbs in the small intestine
* this inhibition prolongs carbohydrate absorption, and thus blunts postprandial glucose spikes
66
What are the 2 types of enzymes that AGIs inhibit?
1. Alpha-amylases
2. Alpha-glucosidases
67
What are the main benefits of AGI therapy?
* not associated with hypoglycemia or weight gain in monotherapy
* only about 2% of acarbose is absorbed into the bloodstream, which reduces the possibility of drug interactions in the blood
68
What is the average A1C reduction of the AGIs?
0.5%-0.8%
69
What are the limitations with AGI therapy?
* modest efficacy
* dosing (at each meal)
* GI adverse events
* expensive
70
What are the common AEs associated with AGIs?
* bloating
* abdominal pain
* diarrhea
* flatulence
71
What are the predominant AGIs and their brand name?
* acarbose: Precose
* miglitol: Glyset
72
Which AGI may elevate liver enzymes?
acarbose (Precose)
73
True or False: Pramlintide can only be used in patients with type 1 diabetes.
False. Pramlintide can be used in patients with both type 1 and type 2 diabetes who are taking mealtime insulin.
74
When starting therapy with pramlintide, patients should reduce their insulin dose by \_\_\_% to reduce the risk of hypoglycemia.
50%
75
The average A1C reduction of pramlintide is how much?
0.5% - 0.7%
