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Pharmacology II > Therapeutic Approaches to Diabetes > Flashcards

Therapeutic Approaches to Diabetes Flashcards

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1
Q

primary energy source for all tissues?

A

Glucose

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2
Q

Uptake of blood glucose for energy utilization is in which two tissues?

A

Skeletal muscle

Brain

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3
Q

Uptake of blood glucose for energy storage is in which tissues?

A

Liver

Adipose

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4
Q

Blood glucose excretion is in which tissue?

A

Kidney

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5
Q

What happens to glucose in a calorie deficit? (2)

A 
Glycogen breakdown (glycogenolysis)
Glucose synthesis (gluconeogenesis)
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6
Q

Blood glucose:
variable or non-variable?
wide or narrow range?

A

Variable

Narrow range

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7
Q

What tissue is critical for glucose homeostasis?

A

Pancreas

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8
Q

The pancreatic islet of langerhans contains which two cells? They release which hormone/substance and under what condition (high or low glucose)

A

alpha : glucagon at low blood glucose levels

beta : insulin at high blood glucose levels

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9
Q

Primary target or alpha cells? (1)

A

hepatocytes

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10
Q

Primary target for beta cells? (3)

A

Liver
Fat
Skeletal muscle

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11
Q

Insulin is what type of hormone?

A

Anabolic polypeptide

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12
Q

Insulin is cleaved by intracellular ______ to generate which two chains? They remain linked by what?

A

proteases
A chain and B chain
Linked by 2 disulfide bridges

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13
Q

4 steps leading to glucose-stimulated insulin secretion (GSIS)

A
  1. Glucose enters via GLUT2 and is metabolized, elevates [ATP]
  2. Elevated ATP inhibits ATP-sensitive K+ channels
  3. Depolarization and opening and voltage-gated Ca2+ channel
  4. Increased intracellular Ca2+ results in exocytic secretion of insulin from storage vesicles into the blood
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14
Q

GLUT2 only transports glucose under what condition?

A

low affinity

>6mM

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15
Q

Blood insulin levels parallel _______ levels

A

blood glucose

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16
Q

Diabetes Mellitus causes what? (2)

What does DIABETES and MELLITUS reference to in this disease?

A

Rapid weight loss
Excessive urination
Diabetes : copious amounts of urine production
Mellitus: sweet taste or smell of urine produced

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17
Q

Diabetes Mellitus disorders are all characterized by what?

A

high blood glucose

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18
Q

Two primary causes of diabetes mellitus?

A

Inadequate insulin secretion

Impairment of insulin action

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19
Q

type I diabetes is the most or least common type of diabetes?
It is the destruction of what?
there is reduced/absence of ________

A

Least common
Pancreatic beta cells
insulin secretion

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20
Q

Type II diabetes is the most or least common type of diabetes?
The tissues are ______ to insulin
Advanced stages associated with __________ insulin secretion

A

Most common
resistant
insufficient

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21
Q 
Type I diabetes is the loss of insulin production and GSIS : 
\_\_\_\_\_\_ glucose uptake
\_\_\_\_\_\_ glucose storage
Failure to inhibit \_\_\_\_\_ production
Low or high levels of blood glucose?
A

Reduced
Reduced
Glucose production
Elevated blood glucose

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22
Q

Acute effects of Type I and Type II diabetes? (5)

A 
Excessive urine production
Extreme thirst/hunger
Rapid HR
Nausea, dizziness, confusion
Weakness, shaking, fainting
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23
Q

Chronic Complications of Type I and Type II diabetes? (8)

A
  1. Weight loss
  2. Damage to blood vessels in eyes
  3. Damage to blood vessels in extremities
  4. Kidney damage
  5. Peripheral nerve damage
  6. Hyperlipidemia
  7. Hypertension
  8. CV disease
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24
Q

Treatments of Type I diabetes? (2)

Even with good management of hyperglycemia, is there still risk of chronic complications?

A

Diet
Insulin replacement
Yes

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25
Type II diabetes is characterized by insulin resistance by the tissues: ____ glucose uptake and energy storage ____ liver glucose synthesis and release Chronic _______
Reduced Increased Hyperglycemia
26
Lifestyle changes to treat Type II diabetes? (3)
Diet Exercise Weight loss
27
6 drugs to treat type II diabetes?
``` Metformin Insulin secretagogues Incretin agents Gliflozins Thiazolidinediones Insulin ```
28
4 types of insulin/insulin analogues?
Regular insulin Insulin ispro NPH insulin Insulin Glargine
29
2 insulin secretagogues?
Glyburide (sulfonylurea) | Rapaglinide (meglitinide)
30
2 Incretin agents?
Sitagliptin | Exetanide
31
2 Gliflozins?
Dapagliflozin | Canagliflozin
32
2 Thiazolidinediones?
Avandia (rosiglitazone) | Actos (pioglitazone)
33
Insulin replacement therapy is always required in type ____ diabetes
I
34
When is Insulin replacement therapy only used on type II diabetics? Most common in severe cases where what happens?
When other therapies fail to provide adequate blood glucose control Chronic hyperglycemia leads to beta cell destruction and impaired insulin secretion
35
Only mode of insulin administration?
Injection
36
Insulin pharmacokinetics are primarily determined by what?
absorption
37
Steps of pharmacokinetics of insulin injection/absorption? (3)
1. Injection creates subcutaneous depot of insulin at injection site 2. Natural insulin molecules self-associate to form hexamers 3. Hexamer dissociation for absorption
38
Rate of insulin absorption determines what? (3)
Onset of action Peak activity Duration of action
39
Slow insulin absorption: Slow/long onset of action? Slow/long duration?
Slow | Long
40
Rapid insulin absorption: Slow/long onset of action? Slow/long duration?
Rapid | Short
41
Natural insulin: What configuration? slow, normal or rapid absorption? Onset is how long? peak? duration?
``` •Hexamer “Normal” absorption • Onset: 30 min • Peak: 2 hr • Duration: 6-8 hr ```
42
Insulin Lispro: What configuration? slow, normal or rapid absorption? Onset is how long? peak? duration?
``` Dimers Rapid 15min 30min 4hr ```
43
Insulin analogues are amino acid substitutions. These substitutions affect what? (3)
Quaternary structure Crystallization properties Solubility
44
Which has slower absorption between the following: Dimer vs. Hexamer Crystallization High vs. Low Solubility High vs. Low
Hexamer High Low
45
NPH : rapid, short, intermediate or long PK?
Intermediate
46
Glargine : rapid, short, intermediate or long PK?
Long
47
Example of GSIS replacement drug that will induce rapid/regular acting insulin? What do these mimic?
Lispro | Mimics beta cell release of insulin in response to nutrient load
48
Example of basal insulin replacement drug that will induce intermediate/long acting insulin? This provides constant ____ levels Important to prevent _____ release from liver during fasting
NPH Insulin glucose release
49
The dosage of GSIS/basal replacement depends on what? (2) | If not, there is risk for what disease?
Carb intake and physical activity | Risk for hypoglycemia
50
Insulin infusion devices: | which two manually monitor glucose?
Traditional Insulin Replacement | Insulin Infusion Pump
51
Insulin infusion devices: | Which one requires manual injection?
Traditional insulin replacement
52
Insulin Infusion devices: | Which two have automated delivery?
Insulin Infusion Pump | Artificial Pancreas
53
Insulin Infusion devices: | Which one has automated glucose monitoring?
Artificial Pancreas
54
Most common and severe adverse effect associated with insulin replacement therapy?
Hypoglycemia
55
Common causes of hypoglycemia? (3) | What is the treatment for acute hypoglycemia?
Inadequate carb intake, unusual physical activity, insulin dose too large Treatment : glucose
56
What is the most common adverse effect of insulin replacement therapy? Why?
Weight gain | Because insulin is an anabolic hormone and promotes energy storage
57
What is the drug of choice for type II diabetes?
Metformin
58
Metformin activates which enzyme? This increases insulin sensitivity in which tissues? What effect does this have?
AMP-dependent kinase (AMPK) Liver, Fat, Skeletal muscle Decreases basal and post-prandial blood glucose
59
Most common adverse effect of metformin? Most severe? Has low risk for ________
GI irritation Lactic acidosis Hypoglycemia
60
MOA of insulin secretagogues? (4)
1. Inhibits ATP-sensitive K+ channels in pancreatic B-cells 2. Cell depolarization 3. Opening of voltage-sensitive Ca2+ channels 4. Exocytic insulin secretion (Compensates for insulin resistance)
61
Two insulin secretagogues?
Sulfonylureas | Meglitinides
62
Incretins regulate the release of what? (2)
Pancreatic insulin and glucagon
63
MOA of glucose before administration of incretins? | *remember it acts of a-cells and B-cells
After oral intake: 1. Release of GLP-1 from GIT into bloodstream 2. GLP-1 acts on receptors on a cells or B cells 3. a cells : decrease in glucagon, decreased glucose production in liver 4. B cells: Increase in insulin, increased glucose uptake in fat and muscle
64
Dose GLP-1 promote BASAL or GLUCOSE-STIMULATED insulin secretion?
Glucose-stimulated
65
Temporal and Contextual control of GLP-1?
Temporal : released from intestine in response to glucose ingestion, degraded by DDP-4 Contextual : insulin release only when glucose is >4mmol
66
What degrades GLP-1?
DPP-4 : Dipeptidyl peptidase-4
67
What type of incretin agents can reduce GLP-1 degradation? | Example?
DPP-4 inhibitors | Ex : Sitagliptin
68
What is the effect of DPP-4 Inhibitors AND Incretin Mimetics on pancreatic GSIS insulin release and glucagon release?
Increases pancreatic GSIS insulin release | Reduces glucagon release
69
DPP-4 inhibitors and Incretin Mimetics are used in combination with what drugs? (2)
Metformin | Secretagogues
70
What type of incretin agents can activate pancreas GLP-1 receptors? Example?
Incretin mimetics | Ex : Exenatide
71
Administration of: DPP-4 inhibitors? Incretin mimetics?
DPP : oral | Mimetics : subcutaneous injection
72
Major role of Gliflozins? | Two examples of this drug?
Inhibits Renal Glucose Reabsorption Dapagliflozin Canagliflozin
73
MOA of gliflozins? | Effects under normoglycemic conditions and hyperglycemic conditions?
Inhibition of sodium-glucose transporter linked transporter 2 (SGLT2) - Normoglycemic : almost all glucose filtered at glomerulus is reabsorbed from renal proximal tubule by SGLT2 - Hyperglycemic: SGLT2 can be saturated leading to glucose excretion in urine

Pharmacology II (21 decks)

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