Module 15 - Part 2 Flashcards
The effects of insluin were discovered by this guy.
Sir Frederick Banting (Canadian)
Insulin is an ________ hormone.
This means the actions of insulin promote energy _______ and _________.
Anabolic
storage and conservation
(glucose –> glycogen)
Describe the actions of insulin on the liver, muscle cells and adipose tissue.
Glucose uptake and glycogen formation in the liver; decreased hepatic gluconeogeneis
Triglyceride formation in adipose tissue
Cellular uptake of amino acids and protein synthesis in muscle
Insulin deficiency puts the body into a _______ state.
Catabolic - favours the breakdown of complex macromolecules into simpler ones
What are the catabolic effects of insulin deficiency?
Glycogenolysis
Gluconeogenesis
Decreased glucose utilization
There are __ main types of insulin available to treat diabetes.
The different types can be separated into four categories based on their time course of action.
What are they.
7 Short-duration, rapid acting Short duration, slower acting Intermediate duration Long duration
Insulin types in short duration-rapid acting.
Insulin lispro, aspart, glusiline
This class of insulin is administered in association with meals to control postprandial rises in glucose.
Short duration-rapid acting
also short duration - slower acting if injected before meals
Route of administration of short duration-rapid acting insulin.
Solution colour?
SC
clear solution
The only type of short duration slower acting insulin.
Unmodified human insulin
Can be injected before meals to control postprandial rises in glucose or infused to provide basal control of blood glucose.
Short duration - slower acting
Administration of short-duration, slower acting.
Why are they slower acting?
Solution colour?
SC, or IM (rare)
After injection, form small aggregates/dimers, slowing absorption
Clear solution
Intermediate duration insulins.
NPH (neutral protamine hormone) insulin
Insulin determir
Onset of action is delayed and may not be used to control postrprandial rises in blood glucose.
Are instead injected once or twice daily to control blood glucose between meals and in the evenings.
Intermediate duration insulin
Why are the actions of NPH insulin and detemir delayed?
NPH - insulin conjugated to protamine (large protein), decreasing solubility and absorption
Detemir - molecules have high affinity for each other, delaying absorption
Administration of intermediate duration insulin.
Colour of intermediate duraiton insulins?
SC injection
NPH - cloudy
detemir - clear
Only type of long acting insulin.
Insulin glargine
What is the main advantage of insulin glargine?
Long duration of action
Administration of insulin glargine
SC, once daily at bedtime
What is the long duration of insulin glargine attributed to?
Low solubility at physiological pH.
When injected, it forms microprecipitates that slowly dissolve and release it over an extended amount of time.
Colour of insulin glargine solution
Clear
Describe insulin mixing
Optimal to mix insulins into one syringe (good for 28 days)
Short acting insulin drawn into syringe first
Only NPH insulin can be mixed with short acting insulins
Primary complication of insulin treatment.
Hypoglycemia
Rapid decreaes in blood glucose result in activation of the sympathetic NS, causing these symptoms.
Tachycardia, palpitations, sweating, nervousness
Slow decreases in blood glucose result in these CNS symptoms.
Headache, confusion, drowsiness and fatigue
If hypoglycemia is severe, these symptoms may occur.
Coma, convulsions (remember insulin used to be used to induce seizures), and perhaps death
Rapid treatment of hypoglycemia is crucial to prevent irreversible _____ damage.
If patients are conscious, fast acting _____ sugar should be used.
if patients are unconscious, ____ glucose may be required.
Diabetic patients are also recommended to keep _____ on hand
brain damage
fast acting oral sugar - orange juice, glucose tablets, corn syrup, and pop (not diet)
IV glucose
glucagon
Hormone produced by the alpha cells of the islets of langerhans.
Glucagon
Describe why glucagon is effective in treating hypoglycemia. Describe in which case it would not be effective.
Causes the conversion of glycogen to glucose.
Contraindicated if the person is starving or malnourished as glycogen stores will be empty.
Glucagon is most often used in the _______ when the patient is ________.
community
unconscious
What is preferred for unconscious, hypoglycemic patients?
IV glucose, but this is impractical outside the hospital
Oral antidiabetic drugs are used to treat type __ diabeties, and are for the most part ineffective in type _ diabetes. Why is this?
Type II - gucci
Type 1 - useless
This is because they rely on having some insulin in the body
Often the drug of choice for treating type II diabetes.
Biguanides
How do biguanides decrease blood glucose (3)?
1 - Increase the sensitivity and number of insulin receptors (1° mechanism)
2 - Decreases hepatic gluconeogensis
3 - Reduced intestinal glucose absorption
What is the major advantage of biguanides?
Do not increase insulin levels and thus do not pose a risk for hypoglyemia
What are the adverse effects of biguanides?
Nausea, decreased appetite, decreased aborption of vitamin B12 and folic acid, diarrhea lactic acidosis (rare, but serious)
Mechanism of action of sulfonylureas.
Stimulating release of insulin
Inhibit glycogenolysis
Describe the difference between 1st generation and second generation sulfonylureas.
Second generation are much more potent (~1000x) and cause fewer drug interactions
What are the major sides of sulfonylureas?
Hypoglycemia
Pancreatic burnout after prolonged used
The pancreas has reduced capacity to synthesize insulin.
Pancreatic burnout
These have the same mechanism of action as sulfonylureas, but differ in a specific way. Describe.
Meglitinides
Differ in that they have a shorter half-life and are effective in treating postprandial rises in blood glucose
are less likely to cause hypoglycemia and pancreatic burnout
Describe the mechanism of action of glitazones.
Activate the PPAR gamma receptor (intracellular), which results in transcription of genes regulating carbohydrate metabolism
the result is increased insulin sensitivity, through increased glucose transporters
Glitazones act by increasing ________ sensitivity in target tissues and decreasing ________ ___________.
insulin
hepatic gluconeogenesis
Glitazones also affect another receptor. Describe.
Also activate PPAR alpha, which causes an increase in HDL and a decrease in triglyceride levels
What are the adverse effects of Glitazones?
Fluid retenion/edema (contraindicated in pts with CHF)
Headache
Myalgia
Describe the mechanism of action of alpha-glucosidase inhibitors.
Inhibit alpha-glucosidase, which is needed to digest complex carbs into simple ones, thereby decreasing carbohydrate absorption in the intestine
Describe the adverse effects of alpha-glucosidase inhibitors.
Restricted to the intestine
Flatulence, cramps, abdominal distension, diarrhea, decreased iron absorption
Describe the mechanism of action of Gliptins.
Gliptins inhibit DPP-4, which thus reduces the breakdown of incretin hormones, GLP-1 and GIP.
These incretin hormones are released from the GI tract after a meal and:
increase insulin release
Decrease glucagon levels
What are the adverse affects of gliptins?
Good safety profile, no major sides
Describe incretin mimetics.
Synthetic incretin analogs that mimic the actions of incretin homrones –> increase insulin release and decrease release of glucagon
How are incretin mimetics administered?
NOT ORALLY
administered by SC injection.
used as an adjunct therapy to biguanides or sulfonylureas
Incretin mimetics are used along with what drugs?
sulfonylureas or biguanides
What are the adverse effects of incretin mimetics?
Hypoglycemia
Pancreatitis
