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Pharmacology -- Test #5 > Insulin and Diabetes > Flashcards

Insulin and Diabetes Flashcards

1
Q

Potential adverse effects of sulfonylureas

A

Lasting, Prolonged Hypoglycemia
GI Porbs
Weight Gain

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2
Q

Drugs that increase the risk of developing hypoglycemia from sulfonylurea use. Why?

A 
Salicyclates
Phenylbutazone
Sulfonamide
Clofibrate
These drugs displace sulfonylureas from carrier proteins nd may decrease liver metabolism.
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3
Q

Drugs with independent hypoglycemic effects that may be additive to the sulfonylureas

A

Alcohol

High Dose Salicyclates

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4
Q

Some major drugs that cause hyperglycemia and may oppose sulfonylureas

A

Oral contraceptives, epinephrine, corticosteroids

Thiazides, thyroid hormone

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5
Q

What is the Incretin effect all about

A

Oral glucose stimulates a larger insulin response than IV glucose due to incretin activity

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6
Q

Two important Incretins

A

GIP, GLP-1

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7
Q

Two pathways involved in Incretin Activity and what they do

A

cAMP – Increase Insulin Secretion

ERK1/2 - Increas in beta cell prolif

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8
Q

Important ways that GLP-1 may support diabetic patients

A
  • Stimulates Insulin, suppresses Glucagon
  • Slows gastric emptying
  • Improved Satiety
  • Increased beta-cell mass
  • Inc. insulin sensitivity
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9
Q

GLP stimulation of insulin secretion is dependent upon

A

presence of glucose

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10
Q

What strategies are used to raise GLP-1 levels in T2Diabetics? Biggest perk of GLPs over sulfonylureas?

A

Make GLP that is longer lasting or prevent breakdown of what is already there. Very low risk of hypglycemia

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11
Q

Name the GLP-1 analogs

A

Exenatide
Victoza
Tanzeum
Dulaglutide

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12
Q

Important details on Exenatide

A

Gila Monster Saliva
Longer halflife than GLP-1
Co-admin w/ metformin, TzDs, sulfonylureas

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13
Q

Risks assocaited with Exenatide

A

Nausea, Vomiting
Pancreatitis
Thyroid Cancer in Rats

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14
Q

How is Victoza different from Exenatide

A

Fatty acid added on to increase serum protein binding

This slows the release of the drug

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15
Q

What is DPP-IV

A

The protease that cleaves GLP-1 to make it inactive

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16
Q

How is Tanzeum different than normal GLP

A

DDP-IV resistant
GLP-1 Dimer Fused to Albumin (very long half life)
Injected only once/week

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17
Q

How is Dulaglutide different from normal GLP

A

Injected once/week

Agonist proteins slowly released from IgG Fc domain by reduction of disulfide linker region

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18
Q

Which drugs work by inhibiting DPP-IV

A

Januvia
Onglyza
Tradjenta
Nesina

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19
Q

How are the DPP-IV inhibitors metabolized?

A

Januvia+Nesina –> Not, Just excreted in Urine
Tradjenta –> Not, Just excreted in Feces
Onglyza –> CYP 3A4/5, Metab active

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20
Q

Most important side effects of the DPP-IV inhibitors

A

Severe Skin Reactions
Reduced WBC count (Infections)
Theoretical Increased Risk of Cancers

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21
Q

What is Symlin?

A

An Amylin Analog
Slows gastric emptying, increases satiety, blunts postprandial rise in glu
Helps Type I and II

22
Q

How do alpha-glucosidase inhibitors work?

A

They decrease the absorption of carbohydrates from the intestine via inhibition of glucosidases on the brush border (such as sucrase, maltase, or glucoamylase).

23
Q

Two examples of alpha-glucosidase inhibitors

A

Acarbose

Miglitol

24
Q

Adverse effects of alpha-glucosidase inhibitors?

A

Diarrhea, Nausea, Flatulence

Acarbose can cause liver damage at really high doses

25
Q

What strategy is being used with a patient is given SLGT2 meds for their diabetes

A

Sodium Glucose Transporter 2 inhibitors are used to decrease the threshold for glucose excretion in the urine

26
Q

Name the most signifciant SLGT2 inhibitors

A

Empagliflozin (Jardiance)
Depagliflozin (Farxiga)
Canagliflozin (Invokana)

27
Q

Risks associated with SLGT2 inhibitors

A

UTI
Increased Urine Flow
Risk of Hypoglycemia
Contraindicated w/ renal impairment or bladder cancer

28
Q

Effects of Insulin Resistance on Skeletal muscle, Adipose, and Liver

A

Muscle – Impaired Glucose Uptake
Adipose – Impaired Uptake, Impaired inhib of lipolysis
Liver – Impaired inhibition of glucose output

29
Q

Relationship of FFAs and insulin

A

Acutely raising FFAs –> Insulin Resistance
Acutely Lowering reduced chronic IR
Mostly effects insulin-stimulated glucose transport

30
Q

What happens at the molecular level in Insulin Resistance

A

Polymorphisms in the insulin receptor make serine phosphate act on IR and IRS proteins, which inhibits signalling.

Degradation of IRS instead of p13K recruitment

31
Q

Explain the whole obesity induced inflammation thing

A

Hypertrophied adipocytes secrete Monocyte chemoattractant protein-1 (MCP-1) to draw in more macrophages. This causes increased secretions of circulating TNFa and IL6 that will trigger insulin resistance in the Liver and muscle. Lean folks secrete IL-10 and keep the inflam down.

32
Q

How does Metformin work?

A

Activator of AMP-activated Kinase (AMPK)
this Increases the efficiency/sensitivity to insulin of the liver (decresaing gluconeogenesis), fat, and muscle (increasing glycolysis and uptake

33
Q

Advantages of biguanides (Metformin) over sulfonylureas

A

Rarely causes hypoglycemia

Rarely causes weight gain

34
Q

Steps of metformin action in the liver

A
  1. Inhibition of Mitochondrial Resp. via complex 1
  2. This decreases energy availability
  3. This increases AMPK activity while decreasing Glucagon receptor-cAMP and gluconeogenic enzyme activity
  4. Decreased Glucose production and lipid cholesterol synthesis
35
Q

How does Metformin act on the skeletal muscle

A

AMPK activity phosp. TBC1D1/4, which promotes GTPase activity of Rab. This knocks Rab off of GLUT4, allowing translocation

36
Q

Contraindications for Metformin

A

Disorders with a tendency toward lactic acidosis

Causes decreased Vit B12 Absorpt.

37
Q

Effects of Metformin on blood lipid profile

A

decreased serum triglycerides

decreased serum LDL

38
Q

How do Thiazolidinediones work

A

Activation of PPARgamma, a transcription factor

39
Q

What do Thiazolidinediones do with the transcriptional changes (fat, liver, and muscle)

A

Adipocytes – Enhanced adi. differentiation, which enhanced the FFA uptake
Liver – Enhanced Glucose Uptake, reduced hepatic production
Sk Muscle – Enhanced Glucose Uptake

40
Q

Name Thiazolidinedione drugs

A

Rosiglitazone

Pioglitazone

41
Q

Whats the problem with Thiazolidinediones?

A

CV Toxicity
Pio has bladder cancer risk
Contraindicated in CHF (due to fluid retention)

42
Q

Three factors regulated by PPAR gamma

A

Resistin
Adiponectin
TNFa

43
Q

Important details about Resistin in T2D

A

Elevated in T2D
Stimulates glucose export by liver and insulin resistance.
Protein produced, secreted by WAT

44
Q

Important details about adiponectin in T2D

A

Decreased in T2D
Reduced Blood glucose and insulin resistance
Produced, secreted by WAT

45
Q

TNFa in T2D?

A

Increased

Stimulates lipolysis in WAT and insulin resistance in skele.

46
Q

Adipokines elevated in T2D

A

Leptin, Angiotensinogen, Plasminogen Activator Inhibitor 1 (PAI1)

47
Q

What does Leptin do?

A

Signals fed state to the brain, reduces appetite

48
Q

What does Angiotensinogen do?

A

Contributes to HTN and excess WAT proliferation

49
Q

What does Plasminogen Activator Inhibitor 1 do?

A

Visceral WAT secretes, could cause increased emboli in obesity

50
Q

Met or Thiazolidinediones. Which has periph edema risk?

A

Thia

51
Q

Met or Thiazolidinediones. which decreases mineral deposits in bone?

A

thia

Pharmacology -- Test #5 (12 decks)

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