Exam 3: Antidiabetic Flashcards
1
Q
What are the 4 rapid acting insulins?
A
Insulin lispro, insulin aspart, insulin glulisine, and insulin inhaled
2
Q
What is the short acting insulin?
A
Regular insulin
3
Q
What is the intermediate acting insulin?
A
NPH insulin
4
Q
What are the 3 long acting insulins?
A
Insulin glargine, insulin detemir, insulin degludec
5
Q
What are the anabolic effects of insulin?
A
Decreased gluconeogenesis and increased glycogen synthesis in the liver. Increased glucose uptake in muscle and adipose
6
Q
Where is GLUT1 found?
A
All tissues, especially red cells and the brain
7
Q
Where is GLUT2 found?
A
B cells of the pancreas, liver, kidney, and gut
8
Q
Where is GLUT3 found?
A
Brain, kidney, and placenta
9
Q
Where is GLUT4 found?
A
Muscle and adipose
10
Q
What are the adverse effects of insulin?
A
- Hypoglycemia (tachycardia, confusion, sweats)
- Weight gain
11
Q
How can hyperinsulinism cause hypoglycemia?
A
- inadvertent administration of too much insulin
- Change in type of preparation
- failure to eat
- vigorous exercise
- spontaneous decrease in insulin requirement
12
Q
What kind of insulin is used in insulin pumps?
A
Rapid acting
13
Q
What type of insulin is first used in T2D?
A
Long acting
14
Q
What is the MOA of glucagon?
A
- Increased blood glucose level by mobilizing hepatic glycogen when available
- regulates glucose, amino acids, and possible free fatty acid homeostasis
15
Q
What are the therapeutic effects of glucagon?
A
- Potent inotropic and chronotropic effects on the heart (used in B blocker overdose)
- produces profound relaxation of the intestine
- not very effective in patients with reduced glycogen stores and juveniles respond less than adults
16
Q
How is glucagon administered?
A
Parenterally (SC, IM, IV)
17
Q
What kind of drug is Diazoxide?
A
A non diuretic thiazide, vasodilator, and hyperglycemic drug
18
Q
What is the MOA of Diazoxide?
A
Promotes hyperglycemia by directly inhibiting insulin secretion, decreasing peripheral glucose utilization, or stimulating hepatic glucose production
19
Q
When in Diazoxide used?
A
In patients with insulinoma
20
Q
How is Diazoxide administered?
A
Orally, long duration of action
21
Q
What does Metformin do?
A
Decrease glucose levels in a predominately insulin-independent manner
22
Q
What is the initial DOC for Type 2 DM if A1C is <10%?
A
Metformin
23
Q
What are the glycemic effects of Metformin?
A
Promotes a euglycemic state, but glucose is not lowered in non diabetics
24
Q
What are the cardiovascular effects of Metformin?
Any other effects?
A
- Decrease macrovascular events and decreased TGs
- decrease all cause mortality events
- weight neutral
25
What is the best pharmacologic therapy for diabetes prevention?
Metformin
26
How is Metformin administered and excreted?
Oral administration
Renal excretion
27
What are the adverse effects of Metformin?
- Hypoglycemia (rare)
- Diarrhea (most common)
- Lactic acidosis (most dangerous, dose dependent)
- Reversible vitamin B12 deficiency
28
What are the contraindications to Metformin?
Lactic acidosis conditions
- Kidney disease: C/I in renal failure or severe renal impairment (GFR <30)
- hepatic Disease
- alcoholism
- diseases predisposing to tissue hypoxia
29
Oral glucose stimulates the release of what?
Incretins: GLP1 and glucose dependent insulinotropic peptide (GIP)
30
GLP1 and GIP increase the release of what?
Insulin
31
GLP1 inhibits the release of what?
Glucagon
32
What are the 3 GLP receptor agonists?
Exenatide, liraglutide, and semaglutide
33
What is the MOA of the GLP1 receptor agonists?
GLP1 agonists that are resistant to DPP4 degradation
34
How are GLP1 receptor agonists administered? What is the exception to this?
S.C injections either twice a day, or once weekly
Semaglutide is oral
35
What is the compelling indication of Liraglutide?
It decreased macrovascular events
| -FDA approved to reduce risk of major CV events in T2D
36
What are the effects of GLP-1 receptor agonists?
- Slows gastric emptying so patient eats less
- Weight loss (compelling indication, only liraglutide)
- Potential increased B cell number and function
37
What are the adverse effects of GLP1 RA?
- Hypoglycemia (low risk)
- GI disturbance
- acute pancreatitis
38
What are the contraindications for GLP1 RA?
- History of, or acute, pancreatitis
- Thyroid cancer (can increase incident of thyroid CA)
- GI disease
- renal impairment
39
What are the two Dipeptidyl-peptidase-4 (DPP-4) inhibitors?
Sitagliptan and Linagliptan
40
What is the MOA of the DPP-4 inhibitors?
-Potentiates the effects of endogenous incretin hormones by inhibiting their breakdown by DPP4
41
How are DPP-4 inhibitors administered?
How are they excreted and what is the exception to this?
- Oral administration
| - Eliminated by the kidney, except Linagliptan is liver/GI
42
What are the therapeutic effects of DPP-4 inhibitors?
Cardiovascular: neutral
| -Weight neutral
43
What are the adverse effects of DPP-4 inhibitors?
- Hypoglycemia (low risk)
- Associated with acute pancreatitis
- joint pain
44
What are the contraindications of GPP-4 inhibitors?
- Renal impairment (except linagliptan)
- History of, or acute, pancreatitis
- Slow GI problems
45
What are the 3 SGLT inhibitors?
Canagliflozin, Dapagliflozin, and Empagliflozin
46
What is the MOA of SGLT2 inhibitors?
Inhibits the sodium-glucose co-transporter 2 (SGLT2) in the kidney, so more glucose is lost in the urine
47
How are SGLT2 inhibitors administered?
Orally
48
Which SGLT2 inhibitors are FDA approved to decreased CV events in T2D?
Empagliflozin and Canagliflozin
49
Which SGLT2 inhibitor decreases CKD progression?
Canagliflozin
50
Which SGLT2 inhibitors decrease the amount of HF hospitalizations?
Canagliflozin and Dapagliflozin
*** all can lower BP and promote weight loss
51
What are the adverse effects of SGLT2 inhibitors?
- Hypoglycemia (rare)
- female genital mycotic infections, UTI, and increased urinary frequency
- increased serum creatinine, decreased GFR, and rarely renal impairment and AKI
- increased LDL
- Increased bone fractures
52
What are the contraindications to SGLT2 inhibitors?
- Severe real impairment or dialysis
| - prone to UTIs are other GI infections
53
What are the two Thiazolidinediones (TZDs)?
Pioglitazone and Rosiglitazone
54
What is the MOA of TZDs?
Ligands to the nuclear PPAR-gamma receptor which can cause post-receptor insulin mimetic action
- increased glucose transport synthesis in adipose
- decrease hepatic glucose production
55
How are TZDs administered?
Orally
56
What are the therpeutic effects of TZDs?
Cardiovascular: decrease TGs, slight HDL increase
- Lower insulin resistance
- Potential benefit in reducing the development of T2D, but not as effective as Metformin
57
What are the adverse effects of TZDs?
- Hypoglycemia (rare)
- weight gain (possibly edema)
- edema (dont give in HF)
- increased bone fracture risk
58
What are the contraindications of TZDs?
- Hepatic disease (Troglitazone is hepatotoxic)
| - HF
59
What are the two Alpha-glucosidase inhibitors?
Acarbose and miglitol
60
What is unique about Alpha-glucosidase inhibitors?
They are used for both Type1 and 2 DM
61
What is the MOA of Alpha-glucosidase inhibitors (AGi)?
Inhibit alpha-glucosidase in the small intestine, leading to delayed carb digestion and absorption
62
How are a AGis administered?
Orally, pre prandially
63
What are the therapeutic effects of AGis?
- Decrease postprandial glucose only
| - weight neutral
64
What are the adverse effects of AGis?
- Hypoglycemia (rare)
- frequent GI effects, flatulence
- elevated hepatic enzymes
65
What are the C/I of AGis?
- GI disease, obstruction, ileus, IBD, hiatal hernia
- Hepatic disease
- renal impairment
66
What is the MOA of Sulfonylureas (SU)?
Binding to and blocking ATP sensitive K channels to cause membrane depolarization and increased Ca influx on B cells, leading to insulin release
***these are not commonly used
67
What are the therapeutic effects of SUs?
- Decreased risk of MI and microvascular disease in long term therapy
- Decrease all-cause mortality
- decrease serum glucagon
68
How are SUs administered?
Orally
69
What are the adverse effects of SUs?
- Hypoglycemia, highest risk of any non-insulin therapy and why they are not used often
- weight gain
- GI side effects
70
What are the contraindications of SUs?
- patients with allergies to sulfas
| - Caution in patients with severe renal disease or hepatic dysfunction
71
What are the 3 second generation SUs?
- Glyburide
- Glipizide
- Glimepiride
72
Out of the 3 second generation SUs, which causes the worst hypoglycemia? Which causes the least?
Worst: Glyburide
Least: Glipizide
73
What kind of drug is Repaglinide?
Metaglitinide (GLN)
74
What is the MOA of GLNs?
Same as SUs
75
What are the important pharmacokinetics of GLNs?
- Rapid action and short half life (mimics insulin)
- administered orally, preprandially
- Metabolized in the liver by CYP3A4
76
What are the therapeutic effects of GLNs?
- Decrease postprandial glucose only
| - weight neutral
77
What are the adverse effects of GLNs?
-Repaglinide can cause moderate hypoglycemia (less than 2nd generation SUs)
78
What are the contraindications to GLNs?
- Don’t combine with SUs
| - caution in liver impairment
79
What kind of drug is Colesevelam?
Bile acid binding resin
-Glycemic effect MOA is unknown
80
What are the therapeutic effects of Colesevelam?
- combo with other anti diabetic drugs can decrease basal plasma glucose
- reduces LDL
- weight neutral
81
What are the most common adverse effects of Colesevelam?
Constipation and bloating
82
What is the MOA of Bromocriptine?
Dopamine agonist that augments low hypothalamic dopamine levels, which inhibits excessive sympathetic tone within the CNS, which decreases postmeal plasma glucose levels due to enhance suppression of hepatic glucose production
83
What are the important pharmacokinetics of Bromocriptine?
Orally administered within 2 hours of awakening
| -metabolized by CYP3A4
84
What are the therapeutic effects of Bromocriptine?
- Decrease postprandial glucose levels
- decreased FFA and TGs
- decreased CV end point problems
- weight neutral
85
What are the contraindications to Bromocriptine?
Caution with CYP3A4 inhibitors, inducers, or substrates
86
What kind of drug is Pramlintide?
Amylin-like peptide
87
When is pramlintide use?
Only as an adjunct to insulin therapy in Type 1 and 2 DM
88
What is the MOA of Pramlintide?
-works with insulin to regulate postprandial glucose by decreases gastric emptying, supression of postprandial glucose secretion,and modulation of appetite to decrease calorie intake
89
How is Pramlintide administered?
S.C injection 3x per day
90
What are the therapeutic effects of pramlintide?
- In combo with insulin, decrease postprandial glucose
| - weight loss
91
What are the adverse effects of pramlintide?
Hypoglycemia (only with insulin)
| -GI disturbance
92
What is the contraindication to Pramlintide?
Slow GI problems (gastroparesis)
93
Which two insulin types can be used IV?
Rapid acting and short acting
94
Why is rapid acting insulin preferred over regular insulin?
Rapid acting causes less hypoglycemia
95
What are the 3 drugs approved fro ASCVD and DM?
Liraglutide, Empagliflozin, and canagliflozin
96
Whatclasses of anti diabetic drugs cause weight gain?
Insulin, SUs, and TZDs
97
What 3 classes of antidiabetic drugs cause weight loss?
GLP-1 RA, Pramlintide, and SGLT2 inhibitors
