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Describe Type 2 diabetes and its stages with regard to pharmacological intervention
Gradual β-cell deterioration
Early stages: Diet and Oral agents
Late-stage: Insulin therapy
DM is defined as what
is characterized by elevated blood sugar levels due to absolute or relative lack of insulin
How do we monitor the plasma glucose concentration over prolonged periods of time (4-6 weeks)
Glycosylated hemoglobin Hb-A1c test
Proinsulin is converted to what 2 products? Why does this matter?
Proinsulin is converted to insulin and C-peptide. If you find C peptide then the pancreas is producing insulin.
Alpha-2 agonists do what with regard to insulin
Alpha-2 agonist decrease insulin secretion and is the dominant regulator in sympathetic nervous system
What is the mechanism of action
Insulin binds to insulin receptors on the plasma membrane and activates tyrosine kinase - primarily in adipose tissue and skeletal muscle
What 3 organs will have different sorbitol types of pathway
nerves (neuropathy), kidneys and eyes (retinopathy).
What does insulin do in the adipose tissue
increase storage of triglycerides in fatty acids in the adipose tissue
When do oral insulin secretion activators not work
increase insulin secretion doesnt work in type 1 diabetes
Insulin is not active ________and it is inactivated by ________ found mainly in __________
orally: insulinase:liver and kidney
What drugs should be given with caution in diabetic patients?
Beta Blockers may cause hypoglycemia and if you must use a Beta 1 blocker is best.
Which of the insulins are rapid and short acting and also available as an IV?
Lispro and regular Crystalline insulin
When an insulin regimen is designed what types of insulin are used
both a slow acting and a fast acting that mimics physioligical rates.
Long acting or intermediate acting provide insulin during which physiological period
insulin levels during basal periods or rates
Rapid acting or short acting provide insulin during which physiological period
correct the postprandial hyperglycemia or short acting
Type II diabetes drugs include which 4 drugs
Biguanides, Sulfonylureas, Meglitinides, Thiazolindinediones
What are drugs known as sulfonylures?
Glipizide, Glyburide Glimiperide - more potent, more efficacious and fewer adverse effects.
Mechanism of action of Sulfonylureas and how do they treat diabetes?
Sulfonylureas stimulate the release of insulin by indirectly blocking β-cell K/ATP ase channel by binding to a specific site SUR (sulfonylurea receptor) on it
What are the side effects of the sulfonylreas
Hypoglycemia because it increases insulin and weight gain becuause it is an anabolic hormone.
How does metformin work or it's mechanism of action
It blocks gluconeogenesis via activation of AMP activated TK. It also increases muscle uptake
How does metformin or Biguanides better than other diabetic drugs
It upregulates insulin sensitivity no weight gain
What does pioglitazone (actos) do?
acts on gamma and alpha PPAR but specifically in the gamma PPAR it enhances glucose and lipid metabolism and sensitivity to insulin in the fat and muscle by increasing GLUT 4 receptors
What protein will be upregulated with pioglitazone use?
Increased Adiponectin and increase numbers of GLUT 4 receptors.
When the Thiazolindinediones were introduced what was the big side effect
increased liver enzymes and hepatitis although they are now not associated with the new drugs.
Thiazolindinediones like pioglitazone are black boxed with a warning of what side effect?
Fluid retention and weight gain, so not good in CHF
rosiglitazone also have what major side effects that have caused it to go out of favor
high risk of cardiovascular events and bladder cancer.
Alpha-glucosidase inhibitors work by what mechanism ......
inhibiting alpha glucosidase which converts dietary starch and complex carbohydrates into simple sugars so that they aren't absorbed
Alpha-glucosidase inhibitors cause what bad side effect that limit its use
Bloating, Diarrhea and flatulence
Sulfonylureas, how do they work
close K+ channel in beta-cell membrane, resulting in depolarization of cell triggering insulin release via Ca2+ influx; first generation [Tolbutamide, Cholorpropamide] disulfiram like effects, second generation [Glyburide, Glimepiride, Glipizide] can cause hypoglycemia
What is the major side effect in metformin
Serious concern about lactic acidocis especially in alchoholics and Renal patients
Why is Metformin such a breakthrough drug for Type II diabetes?
Does not promote insulin secretion so it does not cause hypoglycemia
How long is the half life of GLP 1 and what enzyme degrades it
Half life is 3 minutes and DPPIV degrades it which is why we need inhibitors of DPP-IV and stimulators of GLP-1
Exenatide and liraglutide are what type of drugs
GLP-1 agonist that tries to stimulate the pancreas to make insulin and suppress glucagon release and suppress appetite.
Sitagliptin and Saxagliptin are what type of drugs and used for what?
an oral drug that is used as an adjunct therapy used to block the enzyme DPP-4 that breaks down GLP-1
Pramlintide is used to do what
increase hypoglycemia by slowing gastric emptying and slows inappropriate glucagon secretion while improving blood sugar levels
Glucagon as a physiological drug does what
It has a positive inotropic action and increase the heart rate while stimulating glucagon receptors but not at the
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