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MSII - Unit 5 > Diabetes Drugs > Flashcards

Diabetes Drugs Flashcards

1
Q

MOA of Metformin?

A 
Decrease hepatic glucose 
production
Activate hepatic AMP-kinase
 and inhibit mitochondrial isoform of glycerophosphate 
dehydrogenase
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2
Q

Benefits of Metformin?

A

Weight neutral
No hypoglycemia
Possibly fewer CVD events and cancer

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3
Q

What are the common side effects of Metformin?

A 
GI problems: 
diarrhea (usually but 
not always transient)
abdominal discomfort, 
nausea, vomiting, anorexia
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4
Q

What are the rare side effects of Metformin?

A

lactic acidosis

Vitamin B12 deficiency

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5
Q

Glyburide, Glipizide, Glimepiride are what class of drugs?

A

Oral Sulfonylurea agents (promote insulin secretion)

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6
Q

What is the MAO of oral sulfonylurea agents?

A

Block K(atp) chennels in pancreatic beta-cells which stimulates insulin and C-peptide secretion

(serum glucose enters beta-cells via Glut2 bidirectional glucose transporters. ^[Glucose] increases glycolysis and produces ATP => ATP DEACTIVATES K+ channels, which depolarize beta cell membrane triggering the opening of voltage gated Ca2+ channels, and Ca2+ mediated excocytosis of insulin and C-peptide. (pre-formed pro-insulin is stored in secretory granules - C-peptide is just part of the pro-insulin molecule)

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7
Q

What are the side effects of Sulfonylurea drugs?

A

Hypoglycemia
Weight gain

*May adversely affect
ischemic preconditioning

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8
Q

What kind of drugs are Repaglinide and Nateglinide?

A

Oral meglitinides

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9
Q

What is the MOA of Oral meglitinides?

A

Same as Sulfonylurea drugs - Block K+(ATP) channels to stimulate insulin and C-peptide secretion

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10
Q

What are advantages/disadvantages of meglitinides vs Sulfonylurea drugs? (i.e. Side effects / dosing)

A

Both cause hypoglycemia and weight gain but meglitinides (repaglinide, nateglinide) cause less hypoglycemia than the sulfonylurea drugs (glyburide, glipizide, glimepiride)

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11
Q

Drugs that activate PPAR-gamma ?

A

Thiazolidinediones “-litazone” Pioglitazone Rosiglitazone

PPAR-y = paraxazome proliferator-activated receptor

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12
Q

What is the MAO of Pioglitazone?

A

activates PPAR-gamma

Decreases insulin resistance

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13
Q

Why do the Rides, Zides, and Glinides cause weight gain?

A

All increase insulin secretion and activate its endogenous anabolic responses - increase glycogen and triglyceride sysnthesis, decrease lypolysis/ inhibit glucogon release)

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14
Q

What is the consequence activating PPAR-gamma?

A

decreases insulin resistance

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15
Q

What are the specific benefits and disadvantages of pioglitazone?

A

Possible decrease in
myocardial infarctions

Increase in bladder cancer

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16
Q

What are the side effects/disadvantages of Thiazolidinediones?

A

(Pioglitazone Rosiglitazone) sides effects:

Weight gain
Edema
Congestive heart failure
Bone fractures
Macular edema

EXPENSIVE!

17
Q

What is the shared benefit of Pioglitazone and Rosiglitazone?

A

No hypoglycemia

18
Q

What is the MOA for Acarbose and Miglitol?

A

Oral Alpha-Glucosidase (competitive)
Inhibitors

usually oligosaccarides - acarbose may also inhibit pancreatic amylase

19
Q

What does inhibiting Alpha-Glucosidase do?

A

Delays carbohydrate
absorption which results in
decreased postprandial
glucose levels

20
Q

What are the benefits of acarbose and miglitol?

A 
No hypoglycemia
Weight neutral 
Moderate efficacy in 
lowering 
postprandial glucose 
levels
21
Q

What are the side effects of acarbose and miglitol?

A

GI symptoms:
flatulence, diarrhea,
abdominal fullness and
discomfort

Dosing issues: Need to take with each
carbohydrate containing
meal

Efficacy issues:
only modest ↓ in A1c

22
Q

What is the MOA?

Exenatide
Liraglutide
Dulaglutide
Albiglutide

A

GLP-1 Receptor Agonists

23
Q

what does a GLP-1 Receptor Agonist do? (4 functions)

A

Increases glucose-stimulated insulin
secretion,

decreases glucagon secretion,

slows
gastric motility,

increases
satiety

24
Q

What are the major benefits of GLP-1R agonists?

A

Promote weight loss

No hypoglycemia

25
Q

Disadvantages of GLP-1R agonists?

A

Risk of pancreatitis

GI side effects (nausea,
vomiting, diarrhea)

Hypoglycemia (less than
sulfonylureas)

Caution with renal
insufficiency

Have to inject
subcutaneously 
(Byetta twice daily, 
Bydureon 
Albiglutide, 
Dulaglutide 
once weekly, 
Victoza once daily)

C-cell
hyperplasia/medullary
thyroid tumors in animals

Expensive!

26
Q

What drugs inhibit the metabolism of GLP-1 (glucagon-like-peptide 1)?

A

the DPP-4 inhibitors

“-gliptins”

27
Q

What are the benefits of the DDP-4 inhibitors?

A

Weight neutral
No hypoglycemia
Well-tolerated

28
Q

What are the side effects of DDP-4 inhibitors?

A

Risk of pancreatitis
Possible runny nose, URIs,
headache

29
Q

What is the MOA of these drugs?

Canagliflozin

Dapagliflozin

Empagliflozin

A

oral SGLT2 Inhibitors (“-gliflozin” - GLucose In FLow cauZes INfections)

30
Q

What is SGLT2?

A

Sodium/Glucose cotransporter-2 facilitates re-absorption of glucose and sodium

Inhibition of SGLT2 reduces glucose reabsorption in the kidney;
increases urinary glucose excretion

31
Q

Side effects of canagliflozin, Dapagliflozin, and Empagliflozin?

A 
Genital mycotic infections,  
urinary tract infections, 
hypotension, impaired renal function, hyperkalemia,
hypersensitivity, increased 
LDL-cholesterol
32
Q

Which drugs share increased risk of pancreatitis?

A

GLP-1 agonists and DPP4 inhibitors (“tides” and “gliptins”)— both function along same pathway leading to endogenous insulin secretion but GLP-1 agonists are upstream so these drugs are more potent stimulators of insulin

  • GLP1/GIP/Glucagon are agonists for GLP1R increases insulin secretion
  • DPP4 is enzyme that breaks down GLP1 so blocking DPP4 also increases insulin secretion by activation of GLP1R

Insulin cases the kidney to increase Na+ reabsorption so more insulin (e.g. GLP1R agonists) forces the kidney to work harder

33
Q

Which class of drugs cases UTI’s and gentical mycoses as a side effect? Why doe they do this?

A

gliflozin drugs (SGLT-2 inhibitors) - Increased urinary exretion of glucose (from blocked reabsorption) acts as a growth medium for fungi and bacteria

MSII - Unit 5 (16 decks)

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