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

Insulin and Diabetes Flashcards

(51 cards)

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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?

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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?

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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

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A

Acarbose

Miglitol

24
Q

Adverse effects of alpha-glucosidase inhibitors?

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A

Diarrhea, Nausea, Flatulence

Acarbose can cause liver damage at really high doses

25
What strategy is being used with a patient is given SLGT2 meds for their diabetes
Sodium Glucose Transporter 2 inhibitors are used to decrease the threshold for glucose excretion in the urine
26
Name the most signifciant SLGT2 inhibitors
Empagliflozin (Jardiance) Depagliflozin (Farxiga) Canagliflozin (Invokana)
27
Risks associated with SLGT2 inhibitors
UTI Increased Urine Flow Risk of Hypoglycemia Contraindicated w/ renal impairment or bladder cancer
28
Effects of Insulin Resistance on Skeletal muscle, Adipose, and Liver
Muscle -- Impaired Glucose Uptake Adipose -- Impaired Uptake, Impaired inhib of lipolysis Liver -- Impaired inhibition of glucose output
29
Relationship of FFAs and insulin
Acutely raising FFAs --> Insulin Resistance Acutely Lowering reduced chronic IR Mostly effects insulin-stimulated glucose transport
30
What happens at the molecular level in Insulin Resistance
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
Explain the whole obesity induced inflammation thing
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
How does Metformin work?
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
Advantages of biguanides (Metformin) over sulfonylureas
Rarely causes hypoglycemia | Rarely causes weight gain
34
Steps of metformin action in the liver
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
How does Metformin act on the skeletal muscle
AMPK activity phosp. TBC1D1/4, which promotes GTPase activity of Rab. This knocks Rab off of GLUT4, allowing translocation
36
Contraindications for Metformin
Disorders with a tendency toward lactic acidosis | Causes decreased Vit B12 Absorpt.
37
Effects of Metformin on blood lipid profile
decreased serum triglycerides | decreased serum LDL
38
How do Thiazolidinediones work
Activation of PPARgamma, a transcription factor
39
What do Thiazolidinediones do with the transcriptional changes (fat, liver, and muscle)
Adipocytes -- Enhanced adi. differentiation, which enhanced the FFA uptake Liver -- Enhanced Glucose Uptake, reduced hepatic production Sk Muscle -- Enhanced Glucose Uptake
40
Name Thiazolidinedione drugs
Rosiglitazone | Pioglitazone
41
Whats the problem with Thiazolidinediones?
CV Toxicity Pio has bladder cancer risk Contraindicated in CHF (due to fluid retention)
42
Three factors regulated by PPAR gamma
Resistin Adiponectin TNFa
43
Important details about Resistin in T2D
Elevated in T2D Stimulates glucose export by liver and insulin resistance. Protein produced, secreted by WAT
44
Important details about adiponectin in T2D
Decreased in T2D Reduced Blood glucose and insulin resistance Produced, secreted by WAT
45
TNFa in T2D?
Increased | Stimulates lipolysis in WAT and insulin resistance in skele.
46
Adipokines elevated in T2D
Leptin, Angiotensinogen, Plasminogen Activator Inhibitor 1 (PAI1)
47
What does Leptin do?
Signals fed state to the brain, reduces appetite
48
What does Angiotensinogen do?
Contributes to HTN and excess WAT proliferation
49
What does Plasminogen Activator Inhibitor 1 do?
Visceral WAT secretes, could cause increased emboli in obesity
50
Met or Thiazolidinediones. Which has periph edema risk?
Thia
51
Met or Thiazolidinediones. which decreases mineral deposits in bone?
thia

Pharmacology -- Test #5 (12 decks)

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