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ILE I U2 PO Flashcards

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1
Q

glipizide, glyburide and glimepiride are what types of drugs? Which generations are these?

A

Sulfonylureas, 2nd and 3rd gen

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2
Q

Sulfonylurea MoA on pancreas

A

Inhibit efflux of K from beta cells through SUR receptor, which causes Ca channels to open, releasing Ca, which binds to calmodulin, and releases granules containing insulin

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3
Q

Name of the K-ATP channel in beta cells

A

Kir6.2

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4
Q

Glipizide in excretion

A

85% renal - patients MUST have renal function!

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5
Q

Glyburide in excretion

A

50:50 renal:fecal

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6
Q

When should you use a sulfonylurea?

A

Patients >40, duration of disease <5 years, no prior treatment with insulin

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7
Q

Combination sulfonylurea therapy

A

Okay with other anti diabetics, but cannot be used with meglitinides

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8
Q

Rosiglitazone/Glimepiride brand

A

Avandaryl

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9
Q

Pioglitazone/Glimepiride brand

A

Duetact

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10
Q

Glyburide/Metformin brand

A

Glucovance

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11
Q

Glipizide/Metformin brand

A

Metaglip

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12
Q

Sulfonylurea ADRs

A
  1. Weight GAIN

2. Hypoglycemia

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13
Q

Sulfonylurea considerations

A
  1. Cannot use with meglitinides
  2. Cannot use with gestational diabetes
  3. Cannot use with renal failure patients
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14
Q

Glipizide brand

A

Glucotrol

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15
Q

Glyburide brand

A

Glycron, Diabeta

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16
Q

Sulfonylurea advantages over other drugs

A

Extensive experience, decreases microvascular risk

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17
Q

Beta blockers and sulfonylureas

A

these drugs block the counter-regulatory response that prevents a dangerous hypo or–if it cannot prevent the hypo–at least gives the victim some warning that one is coming by causing shakes and pounding pulse.

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18
Q

Repaglinide and nateglinide are what kinds of drugs?

A

Meglitinides

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19
Q

Repaglinide brand

A

Prandin

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20
Q

Nateglinide brand

A

Starlix

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21
Q

Meglitinide MoA

A

Similar to sulfonylurea MoA, but different site. Block ATP-K channels, Ca influx induces insulin secretion.
Stimulate pancreatic insulin secretion: decrease glucose rise after a meal, however insulin is glucose dependent and thus diminishes at low blood glucose concentrations.

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22
Q

Meglitinide MoA is dependent on

A

functional pancreatic islet cells

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23
Q

Meglitinide vs suflonylurea: which has a faster “on/off” effect, and is more tissue selective?

A

Meglitinides. Therefore, these are less effective at a lower state of hypoglycemia

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24
Q

Meglitinide ADRs

A
  1. hypoglycemia (less than 8% A1C), less than SU due to glucose sensitive release of insulin
  2. slight weight GAIN
  3. Headache.
  4. GI disturbances.
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25
Meglitinide excretion
1. Renal | 2. Bile
26
When to use meglitinides
patients that have postpranadial hyperglycemia and are close to glycemic goals.
27
Meglitinide combination therapies:
1. Effective with metformin 2. Can be used with other drugs 3. Can NOT be used with SUs
28
Replaglinide/Metformin brand
PrandiMet
29
Additional meglitinide considerations
1. Must be taken 30 min before meal 2. Causes hypoglycemia in patients less than 8% A1C 3. More flexible dosing and less weight gain than SU
30
Repaglinide and erythromycin
Causes increased serum concentrations
31
Drugs that ____ decrease effect of repaglinide
induce the CYP 3A4 (i.e. rifampin, phenytoin, barbiturates, carbamazepine)
32
Rosiglitazone and pioglitazone are what type of drugs?
TZDs (Thiazolidinediones)
33
Rosiglitazone brand
Avandia
34
Pioglitazone brand
Actos
35
TZD onset
4-6 weeks
36
TZD target tissues
adipose, some skeletal/liver
37
TZD MoA
By acting on PPAR-gamma (which regulates insulin responsive genes), they increase glucose and fatty acid uptake into adipose tissue and act on liver to decrease hepatic glucose production. IMPROVED INSULIN SENSITIVITY
38
TZDs lower A1C by
.5-1.5%
39
Rosiglitazone/Metformin brand
Avandamet
40
Pioglitazone/Metformin brand
Actoplus Met
41
Rosiglitazone/Glimepiride brand
Avandaryl
42
Pioglitazone/Glimepiride brand
DuetAct
43
TZD compatibility with other drugs
Can be used with all other antidiabetic drugs!
44
TZD ADRs
1. Can cause MI in patients with preexisting cardiovascular conditions
45
Advantages of TZDs
1. Less hypoglycemia 2. durable 3. Can be used with other anti diabetic meds 4. decreases triglycerides 5. Positive effect on lipid profiles!
46
Disadvantages of TZDs
1. Expensive 2. Weight gain 3. Edema 4. Bone fractures 5. Increased LDL 6. MI possibility (rosi) 7. Bladder cancer (pio)
47
Which TZD was removed from the market? Why?
Rosiglitazone, because it causes MI in patients with a history of CVD.
48
What kind of drugs are metformin, phenformin and buformin?
biguanide
49
metformin brand
glucophage
50
Why was phenformin removed from the market?
it caused lactic acidosis
51
GIP synthesized from
K cells small intestines
52
GLP-1 synthesized from
L cells of bowel/colon
53
GLP-1 function
increased insulin secretion increase uptake of glucose decreased gastric emptying increased satiety
54
GIP function
induces insulin secretion
55
limitation of GIP and GLP-1
quick degradation by DPP4
56
DPP4 function
degrades GIP and GLP4
57
GIP degradation time
7.3 min
58
GLP-4 degradation time
2 min
59
Exenatide found in
Gila monster saliva
60
Exenatide MoA
Exenatide enhances insulin secretion in aglucose-dependent manner, suppressing inappropriately high postprandial glucagon secretion resulting in decreased hepatic glucose production. It increases satiety, slows gastric emptying, and promotes weight loss.
61
GLP-1 agonists are dependent on
the presence of elevated circulating glucose levels.
62
GLP-1 vs exenatide; which is more potent?
exenatide
63
exenatide with metformin
Fine
64
exenatide with SU
reduce the SU dose to reduce risk of hypoglycemia
65
Liraglutide is a
GLP-1 A
66
Exenatide is
GLP-1 A
67
How does dosing a GLP-1 A differ from dosing a SU?
Give SU after, give GLP-1 A before meals
68
Why give GLP-1 A before a meal?
Dependent on increase of glucose to work
69
victoza
liraglutide
70
advantage of victoza
plasma protein bound, lasts longer
71
Problems with GLP-1 A
``` GI upset, injectable, anti-exenatide antibodies, ACUTE PANCREATITIS THYROID TUMORS ```
72
DDP-4 inhibitor MoA
inhibits the enzyme that breaks apart GLP-1 and GIP,
73
DDP4 inhibitor drug
sitagliptin
74
Sitagliptin should be decreased when treating with another drug in combination
no
75
GLP-1 A examples
``` EXENATIDE (Bydureon, Byetta) LIRAGLUTIDE (Victoza) Albiglutide (Tanzeum) Dulaglutide (Trulicity) Lixisenatide(Adlyxin) ```
76
DDP4 examples
``` LINAGLIPTIN (Tradjenta) Saxagliptin (Onglyza) SINAGLIPTIN (Januvia) Alogliptin (Nesina) Vildagliptin(dialiptin, equa, galvus) ```
77
Problems with DD4 inhibitors
Urticaria/angioedema, heart problems, PANCREATITIS
78
Advantages of GLP-1A
weight loss, no hypoglycemia, CVD reduction
79
Advantages of DD4 inhibitors
well tolerated, no hypoglycemia
80
Antidiabetics that cause weight gain
Glinides Insulin Sulfonylureas Thiazolidinediones
81
Antidiabetics that cause weight loss
``` α-Glucosidase inhibitors DPP-4 inhibitors GLP-1 receptor agonists Metformin SLGT2 inhibitors ```
82
Which drugs most likely to cause hypoglycemia
SU, some meglitinides, rarely glitazones (TZDs)
83
Which drugs will NOT cause hypoglycemia?
metformin, acarbose
84
How much glucose is filtered each day?
180 g (SLGT2 90%, SLGT1 10%)
85
SLGT2 inhibitor advantages
Weight loss, decreased BP, all stages of T2D
86
SLGT2 inhibitor disadvantages
GI INFECTIONS, polyuria, LDL-C increase hypotension
87
SLGT2 inhibitor examples
Canagliflozin (Invokana) Dapagliflozin (Farxiga) Empagliflozin(Jardiance)

ILE I (18 decks)

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