Pharm Chapter 32
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T/F: Pancreas functions as endocrine and exocrine gland.
- Exocrine: excretes digestive enzymes into duodenum via pancreatic duct
- Endocrine: Insulin and glucagon regulate blood glucose (Insulin also plays a role in protein and lipid metabolism and several aspects of growth and development)
What synthesizes and secretes pancreatic hormones?
- Islets of Landerhans
- Four primary cell types
- 1. Alpha (A) cells: produce glucagon
- 2. Beta (B) cells: produce insulin
- 3. Delta (D) cells: produce somatostatin (regulates GI absorption and motility)
- 4. F cells: produce pancreatic polypeptide
What is the primary effect of insulin?
- Lower blood glucose by facilitating entry of glucose into peripheral tissues
- Stored in liver: Hepatic cells permeable to glucose, even w/o insulin
- Stored in other tissues: Most relatively impermeable to glucose and need facilitated diffusion
How does insulin effect the glucokinase system?
- Stimulates it!
- Phosphorylates glucose and traps molecule in hepatic cell
- ↑ activity of enzymes promoting glycogen synthesis, inhibits those promoting glycogen breakdown
How does insulin promote storeage of protein and lipid in muscle and adipose tissue?
- Protein: stimulates aa uptake, ↑ DNA/RNA activity, inhibits protein breakdown
- Adipose: stimulates TG synthesis, inhibits hormone sensitive lipase (which breks down stored lipids)
What is the hormonal antagonist of insulin, and what is its primary effect?
- Increases blood glucose to maintain levels and prevent hypoglycemia
- Produces ↑ in glycogen breakdown in liver (glycogenolysis)
- Stimulates ↑ in hepatic glucose production (gluconeogenesis) to sustain blood glucose levels
How does Glucagon affect the cAMP system in the liver cells?
- Binds to hepatic cell membrane and stimulates activity of adenyl cyclase enzyme
- Transforms ATP to cAMP (this stimulates enzymes to ↑ glycogen breakdown and stimulates gluconeogenesis)
What is normal blood glucose levels? What maintains these levels? What happens if it gets too high/low?
- 80-90mg/100mL of blood
- Insulin and glucagon maintain blood glucose withing finite range
- Hypoglycemia: can result in coma or death
- Hyperglycemia: can result in neural and vascular changes
What is the primary factor affecting pancreatic hormone release?
- Level of glucose in the bloodstream
- Blood glucose rises: insulin released from beta cells
- Blood glucose falls: glucagon released from alpha cells
What is type 1 diabetes?
- Unable to synthesize enough insulin
- Destruction of beta cells
- Need exogenous insulin to survive
What is diabetes mellitus and what are the types?
- Insufficient insulin secretion or decrease in peripheral effects of insulin
- Type I: Insulin-dependent diabetes mellitus (IDDM)/ Juvenile diabetes
- Type II: Non-insulin dependent diabetes mellitus (NIDDM)
What causes Type II diabetes?
- Genetic predisposition
- Poor diet, obesity, lack of exercise
- Usually in older individuals
What is the primary problem in type II diabetes?
- Decreased sensitivity of peripheral tissues to circulating insulin (insulin resistance)
- Target cell defect causes decreased resonse of cell to insulin
- Cellular response is inadequate
What is a secondary problem in type II diabetes aside from insulin resistance?
- Pancreatic beta cells intact, can produce insulin
- Insulin is release continuously, even when fasting
- After meal, beta cells don't ↑ insulin release in proportion to ↑ glucose levels
What are complications of DM?
- Most common: hyperglycemia
- Glycosuria: ↑ glucose excretion by kidneys (kidneys can't adequately resorb glucose)
- Dehydration/electrolyte imbalance: osmotic force promotes fluid excretion
- Ketoacidosis: Loss of glucose in urine causes shift towards fat and protein mobilization for energy
- Microangiopathy: Abnormalities in small blood vessels leads to occlusion (can damage retina and kidneys)--->poor wound healing and ulcers!!
T/F: Exogenous insulin is used for both type I and type II diabetes.
TRUE: used in type 2 b/c other interventions may not be adequate to control disease
What is a type of insulin preparation?
- Lispro (Humalog)
- Slower than endogenous insulin
- Preparations can be fast or slow acting; slow acting allows more sustained levels
What are ways of administering insulin?
- Nasal spray (Exubera)
- IV in emergency
T/F: Insulin is often administered orally.
FALSE: b/c of large polypeptide structure
What is done in intensive insulin therapy?
- Self-administering 3 or more dosages/day
- Monitor blood glucose levels
- Reduces long-term complications
What are adverse effects of Insulin Therapy?
- Primary problem: hypoglycemia
- Strenuous activity can cause this by having insulin-like effect
- Avoid by decreasing insulin by 30-35%
- 10-15 g D-glucose restores blood glucose in early hypoglycemia
T/F: Oral antidiabetic drugs are effective for type I and type II diabetes.
FALSE: only type 2 (by mouth)
What do Sulfonylureas do? Examples?
- Act on beta cells to stimulate release of insulin
- Released into hepatic portal vein to liver to inhibit glucose production
- Early stages of type II
- Glipizide (Glucotrol)
- Glyburide (DiaBeta)
- Type of Immunosuppressant
- Minimizes beta cell loss
- Type of Glucagon-like Peptide 1
- Released after meal
- Increases after meal
- ↑ ability of blood glucose to stimulate insulin release from beta cells
What is sometimes used to Rx acute hypoglycemia?
Nonpharmacologic Intervention in DM
- Diet, weight loss
- Tissue transplants and gene therapy of pancreas
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