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Endocrine Two > Konorev - Diabetes > Flashcards

Konorev - Diabetes Flashcards

1
Q

Describe the general insulin pathway that has effects on glucose, lipid and protein metabolism, primarily via regulation of enzyme activities.

A

IR —> IRS —> PI3K —> AKT

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2
Q

Describe the general insulin pathway that regulates gene transcription and cell proliferation.

A

IR —> IRS —> MAP kinases

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3
Q

Regulation of carbohydrate metabolism: glucose transport

A

IR —> IRS —> PI3K —> AKT —> GLUT4 (sk m, cardiac myocytes, adipocytes)

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4
Q

Regulation of carbohydrate metabolism: activation of glycogen syntehsis

A

IR —> IRS —> PI3K —> AKT —> decreased glycogen-synthase-kinase-3 –> increased glycogen synthase —> more glycogen

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5
Q

Regulation of carbohydrate metabolism: (1)inhibition of gluconeogenesis and (2) inhibition of glycogenolysis

A

IR —> IRS —> PI3K —> AKT —> increased PDE —> decreased cAMP —>

  1. decreased fructose -1,6-BP (inhibition of gluconeogenesis)
  2. decreased glycogen phosphorylase (inhibition of glycogenolysis)
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6
Q

Regulation of lipid metabolism by insulin

A

IR —> IRS —> increased PDE —> decreased cAMP —> decreased hormone-sensitive lipase —> decreased triglyceride breakdown

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7
Q

Regulation of protein metabolism by insulin

A

IR —> IRS —> PI3K —> AKT —> increased mammalial target of rapamycin (mTOR) —> increased ribosome biogenesis —> increased mRNA transcription

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8
Q

List the three rapid-acting insulins. Clinical use.

A

Aspart, Lispro, Glulisine

Clinical: postprandial hyperglycemia (before meals)

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9
Q

List the one short-acting insulins. Clinical use.

A

regular insulin
Clinical: basal insulin maintenance, overnight coverage, if used for postprandial hyperglycemia inject 45 min prior to meal

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10
Q

List the one intermediate-acting insulins. Clinical use.

A

NPH (neutral protamine hagerdorn)

Clinical: basal insulin maintenance, overnight coverage - use is declining; replaced by long acting insulin

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11
Q

List the two long-acting insulins. Clinical use.

A

detemir, glargine

Clinical: Basal insulin mainenance (1-2 injections daily)

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12
Q

Which long acting insulin is peakless?

A

glargine

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13
Q

Clinical indications for insulin (four).

A
  • Type 1 diabetes
  • Type 2 (inadequately controlled by excercise, diet, non-insulin therapies)
  • Gestational diabetes
  • Severe hyperkalemia
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14
Q

Explain use of insulin in treatment of severe hyperkalemia

A

Severe Hyperkalemia
– Insulin + glucose (to prevent hypoglycemic shock) + furosemide
– Insulin (i.v.) rapidly activates Na/K-ATPase to shift K+ from extracellular fluid into cells
– Effect is transient (several hours)
– K+ is eliminated from the body using loop diuretics in the meantime

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15
Q

Five adverse effects of insulin

A

Hypoglycemia, lipodystrophy, resistance/develop insulin binding antibodies, allergic reacitons, hypOkalemia

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16
Q

What is hypoglycemia unawareness?

A

When a person with diabetes doesn’t experience the usual warning symptoms of hypoglycemia. Usually, when a person’s blood glucose drops, the body tries to raise it by releasing the hormones glucagon and epinephrine.

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17
Q

Signs and symptoms of hypoglycemia.

A
  • CNS/behavioral - confusion, seizures, coma, weird behavior
  • Hyperactive SNS (tachycardia, palpitations, sweating, tremor)
  • Hyperactive PSNS (hunger/nausea)
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18
Q

treatment of hypoglycemia

A
  • Diazoxide (K-channel opener - to decrease insulin release)

- **Glucagon

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19
Q

What is amylin and what about its MOA is useful for tx of diabetes?

A

Pancreatic hormone synthesized by B-cells.
MOA: inhibits glucagon secretion, enhances insulin sensitivity, decreases gastric emptying (slow rate of glucose absorption), causes satiety

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20
Q

Clinical use of pramlintide (amylin analog).

A

TI and TII - For postprandial hyperglycemia. Taken before meals, short acting.

21
Q

AE of pramlintide

A

GI - N/V/D/anorexia

Severe hypoglycemia

22
Q

What are the two types of incretin mimetics (insulin secretagogues)

A

GLP-1 agonists and DDP-4 inhibitors

23
Q

Name the two GLP-1 receptor agonists.

A

exenatide and liraglutide

24
Q

MOA of long acting GLP-1 receptor agonists

A

increasing GLP-1/GLP-1R action increased cAMPincreased PKA upregulated insulin gene transcription.

25
Q

What drug is clinically used for -

Type 2 pts not adequately controlled by metformin, sulfonylureas, thiazolidineodiones

A

Clinical use of long acting GLP-1 receptor agonists

26
Q

AE of what?
GI - N/V/D/anorexia
-hypoglycemia, but lower risk than pramlintide (amylin analog)
-possible pancreatitis, and pancreatic/thyroid cancer

A

long acting GLP-1 receptor agonists

27
Q

Name the four DPP-4 inhibitors

A

Sitagliptin
Linagliptin
Saxagliptin
Alogliptin

28
Q

MOA of DPP-4 inhibitors

A

By inhibiting the DPP-4 protease, it slows the degradation of GLP-1 and other secretins, thus allowing for greater insulin stimulation and greater decreases in blood glucose levels.

29
Q

What is used as adjunctive ORAL therapy to diet and exercise in people with Type 2 diabetes.

A

Clinical use of DPP-4 inhibitors

30
Q 
A person has:
-a URI and nasopharyngitis OR
-acute pancreatitis OR
-hypoglycemia
What is this person taking?
A

DPP-4 inhibitor

31
Q

What are differentiating factors between first and second generation sulfonylureas (K-ATP channel blockers). Which is DOC?

A
  • First generation - cheaper, more SE, need higher dosing

- Second generation - DOC! more potent, less SE

32
Q

Name the second generation sulfonylureas

A

Gl~ides: glipizide, glyburide, glimepriride

33
Q

MOA of sulfonylureas

A

Bind to SUR (sulfonylurea receptor). Block the K+ current thorugh Kir6.2, inwardly rectifying potassium channel

34
Q

Clinical use of sulfonylureas

A

type 2

35
Q

AE of what drugs?

-hypoglycemia, wt gain, alcohol induced flushing, secondary failure

A

sulfonylureas

36
Q

What class has major drug interactions?

A

sulfonylureas

37
Q

What is the main use of meglitinides drugs?

A

present postprandial hyperglycemia in type 2

38
Q

what drug has MOA with activation of AMP-dependent protein kinase. And some type of inhibition of respiratory complex I in mitochondria

A

Metformin

39
Q

Clinical use of metformin (biguanides).

A

Most commonly used oral agent for type 2 treatment - first line!
DOC

40
Q

MOA of thiazolinidediones

A

ligands of PPAR-gamma, bind to PPRA-gamma nuclear receptor

41
Q

Effects of thazolidinediones on gene expression (5)

A
  • Increased GLUT4 in skeletal muscle and adipocytes – GLUT4 is an insulin dependent glucose transporter – increased glucose transport into skeletal muscle and fat cells
  • Increased IRS1, IRS2, PI3K – proteins that all function in the insulin post-receptor signaling pathway
  • Increased adiponectin – insulin mimetic
  • Decreased PEPCK – rate limiting enzyme in hepatic gluconeogenic pathway. So it decreases gluconeogenesis.
  • Decreased NF-kB, AP-1 – proinflammatory
42
Q

Metabolization of thazolidineodiones

A

hepatic CYP

43
Q

Name of two thazolidineodiones

A

Pioglitazone, Rosiglutazone

44
Q

Name the newest class of antidiabetic drugs

A

SGLT2 inhibitors - ~gliflozin

-decrease renal reabsorption of glucose

45
Q

Name of the three SGLT2 inhibitors

A

~gliflozin
Canagliflozin
Dapagliflozin
Empagliflozin

46
Q

Name of the two alpha-glycosidases

A

acarbose, miglitol

47
Q

MOA of alpha-glycosidases

A

competitive inhibtion of alpha-glycosidases - **brush border

-lowers postprandial hyperglycemia to create an insulin sparing effect

48
Q

Special characterisitc about clinical use of alpha-glycosidases

A

used for Type 2, but does not cause hypoglycemia when used alone and does not cause weight gain.

49
Q

Drug interaction with amylin

A

anticholinergics

Endocrine Two (16 decks)

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