Drugs Acting on Glucose Metabolism Flashcards
0
Q
Alpha cells produce what?
A
Glucagon
1
Q
Beta cells produce what?
A
Insulin
2
Q
Delta cells produce what?
A
Somatostatin
3
Q
F cells produce what?
A
Pancreatic polypeptide
4
Q
Is insulin amino acid sequence preserved across species?
A
Yes
5
Q
Insulation secretion has what effect on blood glucose?
A
Rise in blood glucose concentration.
6
Q
What 5 GI hormones can stimulate insulin secretion?
A
- Gastrin
- CCK
- Secretin
- Gastric Inhibitory Polypeptide
- Glucagon
7
Q
Amino acids and fatty acids in the GIT can stimulation the secretion of what?
A
Insulin
8
Q
Vagal stimulation affects what receptors?
A
M receptors
9
Q
Catecholamines act on what receptors?
A
Beta 2 receptors
10
Q
What are 3 things that inhibit insulin secretion?
A
- Decrease in blood glucose concentration
- Somatostatin
- Catecholamines (a2 or I3 receptors)
11
Q
What are 3 effects insulin has on storage and building?
A
- Stimulates glycogenesis
- Stimulates lipogenesis
- Stimulates protein synthesis
12
Q
What are 3 things insulin can inhibit?
A
- Glycogenolysis
- Gluconeogenesis
- Lipolysis
13
Q
Insulin can stimulate the uptake of what into cells?
A
Potassium
14
Q
What type of effect does insulin have in a fetus?
A
Anabolic
15
Q
What 3 parts of the body are involved in the metabolism of insulin?
A
- Liver
- Kidneys
- Muscle
16
Q
Too much insulin leads to what?
A
Hypoglycemia
17
Q
Too little insulin can lead to what?
A
Hyperglycemia
18
Q
What are 5 differential for hypoglycemia?
A
- Artifact
- Unable to make glucose
- Excessive consumption
- Exogenous hypoglycemic agents
- Endogenous hypoglycemic agents
19
Q
What are 5 reasons the body may be unable to make glucose?
A
- Liver failure/cirrhosis
- Portosystemic shunt
- Severe malnutrition (neonates/toy breeds)
- Hypoadrenocorticism (pituitary/GH deficiency)
- Glycogen storage diseases
20
Q
What are 2 examples of causes for excessive consumption of glucose that can cause hypoglycemia?
A
- Sepsis
- Extreme exertion
21
Q
What are 2 examples of exogenous hypoglycemic agents?
A
- Insulin overdose
- Overdose of other hypoglycemic agents
22
Q
What are 4 examples of endogenous hypoglycemic agents?
A
- Xylitol toxicity (dogs)
- Insulin-secreting islet cell neoplasia (insulinoma)
- Extrapancreatic neoplasias
- Islet cell hyperplasia
23
Q
What are 2 therapeutic considerations if not involving insulin?
A
- Give dextrose (if severe)
- Treat the underlying disease
24
What are 2 examples of therapeutic considerations if involving insulin?
- Iatrogenic
| - Endogenous
25
What are 3 types of pharmacologic treatment of hypoglycemia?
- Replacement
- Diet
- Anti-hypoglycemic agents
26
What are 2 examples of replacement pharmacologic treatment of hypoglycemia?
- Dextrose
| - Glucagon
27
What are 4 examples of anti-hypoglycemic agents?
- Glucocorticoids
- Diazoxide
- Somatostatin
- Streptozotocin
28
Is glucagon commonly used?
No
29
If administering glucagon, what is the initial dose and what dose follows?
How is the dose adjusted?
- Initial dose of 50ng/kg followed by 10-15ng/kg/min
| - Adjust based on blood glucose measurement.
30
What is the dose if using dextrose to treat acute hypoglycemia?
Maintenance of hypoglycemia?
- 1mL/kg of 50% dextrose diluted (1:4)
| - 2.5-5% dextrose IV adjusted based on blood glucose levels.
31
What are 2 consideration with the use of dextrose for the treatment of hypoglycemia?
- Hyperosmolality/irritation
| - Rising glucose stimulate insulin secretion.
32
What can be given to treat acute hypoglycemia?
Karo syrup/corn syrup
33
What are 4 consideration when using dietary management of chronic hypoglycemia?
- Frequent, small meals.
- Complex carbs (simple carbs may stimulate insulin secretion).
- Easily digestible.
- Moderate fate and protein.
34
What is the goal of therapy with hypoglycemia?
To eliminate/minimize clinical signs associated with hypoglycemia.
35
Is the goal of hypoglycemia treatment to maintain a "normal" blood glucose?
Not necessarily.
36
What are 2 examples of glucocorticoids?
- Prednisone
| - Prednisolone
37
What do glucocorticoids increase?
Decrease?
Stimulate?
- Increase gluconeogenesis
- Decrease glucose uptake into tissue
- Stimulate glucagon secretion
38
Do glucocorticoids have good bioavailability?
Yes
39
Where is prednisone metabolized to prednisolone?
| Is this required?
- Liver
| - Yes
40
Glucocorticoids are usually started at what dose?
About 0.5mg/kg/day, increase as needed.
41
What are 2 examples of side effects that can be seen with low doses of prednisone, prednisolone?
- Pu/pd
| - Panting
42
What happen to the side effects seen with prednisone/prednisolone as the dose is increased?
Get progressively more severe.
43
How is diazoxide administered?
Orally
44
T/F: With diazoxide, you should start at the higher end of the dose and decrease from there.
False - Start at lower end of dose and increase.
45
What can be used in place of glucocorticoids and diet if they are no longer working in the treatment of hypoglycemia?
Diazoxide
46
What are 4 side effects that can be seen with diazoxide?
| What are 4 less commonly seen side effects?
- Hypersalivation, anorexia, vomiting, diarrhea
| - Tachycardia, hematologic changes, diabetes, fluid retention
47
What does Diazoxide activate?
K+ channels in islet cells.
48
What channels does Diazoxide switch off?
| What does this inhibit?
- Voltage-gated Ca2+ channels.
| - To inhibit the release of insulin.
49
What does Diazoxide increase in the liver?
Glycogenolysis
50
What effect does Diazoxide have on glucose?
Inhibits tissue uptake of glucose.
51
Does Diazoxide alter synthesis of insulin?
No
52
Does Diazoxide treat the neoplasia?
No
53
What cells produce somatostatin?
Gamma cells of the Islets of Langerhans
54
What are 6 things somatostatin inhibits the release of?
- INsulin
- Glucagon
- Growth hormone
- CCK
- Secretin
- Gastrin
- VIP
55
What is an example of a somatostatin analogue?
Octreotide
56
Octreotide is sometimes used for what in dogs and ferrets?
Insulinomas
57
Octreotide is sometimes used for what in dogs and cats?
Gastrinomas and Chylothorax
58
Octreotide is sometimes used for what in dogs?
Acromegaly
59
How is Streptozotocin administered?
IV infusion
60
What is a chemotherapeutic drug that selectively destroys beta cells in the pancreas or metastatic sites?
Streptozotocin
61
Does Streptozotocin have a narrow or wide therapeutic index?
Narrow
62
Is Streptozotocin nephrotoxic?
Yes
63
What should be given prior to administration of Streptozotoocin?
Saline diuresis
64
What side effect can be seen in about 30% of patients administered Streptozotocin?
Vomiting
65
How does the median survival of patients on Streptozotocin compare to other therapies?
Median survival may not be significantly improved over other therapies.
66
Too much insulin can cause what?
Hypoglycemia
67
Too little insulin can cause what?
Hyperglycemia
68
What are 7 differentials to consider with hyperglycemia?
- Physiologic hyperglycemia
- Diabetes Mellitus
- Hyperadrenocorticism
- Pheochromocytoma
- Pancreatitis/Exocrine pancreatic neoplasia
- Some drugs/toxins
- Head trauma
69
What are 3 examples of causes physiologic hyperglycemia?
- Stress
- Postprandial
- Diestrus
70
What is an example of a drug that can cause hyperglycemia?
Amitraz
71
What are the 2 types of diabetes mellitus?
- Type I: Insulin-dependent (IDDM)
| - Type II: Non-insulin dependent (NIDDM)
72
What are 2 possible causes of diabetes mellitus?
- Insulin resistance
| - Insulin deficiency
73
Absolute deficiency of insulin from destruction (autoimmune) of pancreatic beta cells causes what type of diabetes mellitus?
Type I: Insulin-dependent (IDDM)
74
What type of diabetes mellitus is not generally seen in dogs?
Type II: Non-insulin dependent (NIDDM)
75
Which type of diabetes mellitus can be seen in cats, horses and humans?
Type II: Non-insulin dependent (NIDDM)
76
Relative insulin deficiency and insulin resistance can be seen with which type of diabetes mellitus?
Type II: Non-insulin dependent (NIDDM)
77
What are 3 things insulin stimulates?
- Glycogenesis
- Lipogenesis
- Protein synthesis
78
What are 3 processes that insulin inhibits?
- Glycogenolysis
- Gluconeogenesis
- Lipolysis
79
Cellular "starvation" is caused by what?
Lack of insulin.
80
What are 4 things that can be caused by lack of insulin?
- Decreased tissue utilization of glucose
- Stimulation of liver glycogenolysis
- Proteolysis - AAs - Gluconeogenesis
- Lipolysis - FFAs - Ketoacidossi, hepatic lipidosis
81
What are the 4 cardinal signs of diabetes?
- Muscle loss
- Weight loss
- Accumulation of glucose in the blood (PU/PD)
- Lack of glucose entering "satiety center" of the brain leads to polyphagia
82
What are 3 things that happen with accumulation of glucose in the blood?
- Exceeds renal tubular resorption
- About 100-220 mg/dL
- Glucose in urine causes osmotic diuresis (PU/PD)
83
What are 5 goals of hyperglycemia treatment?
- Reduce hyperglycemia
- Reverse catabolic effects
- Reverse ketosis
- Control clinical signs
- Maintain patient in a mild hyperglycemic state (150-200 mg/dL) for the most of the day.
84
What are 3 general forms of treatment for Diabetes Mellitus?
- General management
- Diet
- Pharmacologic management
85
What are 2 examples of general management practices when dealing with diabetes mellitus?
- Weight management
| - Exercise
86
What kind of a diet should a dog with diabetes mellitus be put on?
A cat?
- Dog: high fiber (Hill's R/D or W/D, Purina DCO)
| - Cat: low carb (Hill's M/D, Purina DM)
87
What are 3 examples of pharmacologic management for diabetes mellitus?
- Acarbose
- Oral hypoglycemic agents
- Insulin
88
Is Acarbose a hypoglycemic agent?
No
89
What does Acarbose inhibit?
Alpha amylases and brush border oligo/disaccharides.
90
How does Acarbose work?
- Digest starch and cleaves off glucose.
| - Inhibition delays absorption of glucose from the GI tract to decrease postprandial rise in glucose.
91
What does Acarbose reduce?
Postprandial hyperglycemia after carbohydrate intake.
92
Acarbose is sometimes used as an adjunct in what 2 species?
- Dogs
| - Cats
93
What are 2 possible side effects of Acarbose?
- Diarrhea
| - Weight loss
94
What are 3 categories of oral hypoglycemics?
- Sulfonylureas
- Biguanides
- Thiazolidinediones
95
Which oral hypoglycemic is a secretagogue?
Sulfonylureas
96
Which oral hypoglycemics are sensitizers?
- Biguanides
| - Thiazolidinediones
97
What are 6 examples of Sulfonylureas?
- Glipizide
- Glyburide
- Glicazide
- Glimepiride
- Chlorpropamide
- Toluamide
98
Which oral hypoglycemic agent stimulates insulin secretion by blocking potassium channels in the beta cells, increased Ca2+ and increases release of insulin?
Glipizide
99
What drug has the opposite effect of Glipizide?
Diazoxide
