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90 Cards in this Set
- Front
- Back
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In what form is insulin secreted?
What form is biologically active? |
Complex of 2 atoms of Zinc and 6 molecules of insulin.
Only monomeric insulin is biologically active (binds to insulin receptor) |
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How may insulin be administered and what type of administration is required for long-term treatment?
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May be administered intramuscularly or intravenously.
*Long-term treatments require subcutaneous administration |
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How are all insulin preparations the same and how are they different?
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All have the same mechanism of action
Differ in ability to enter systemic circulation --> changes onset and duration of action |
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Ultra-short-acting/ Rapid acting
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1. Insulin Lispro
2. Insulin aspart |
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What are the characteristics of insulin lispro and aspart?
How long does it take to be efficacious? |
(ultra-short-acting)
1. Recombinant 2. Low-propensity to form hexamers (due to point mutations in the C-terminus of the B-chain) *Efficacious after 10 minutes |
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How long is the duration of insulin lispro and aspart?
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About 3-4 hours
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What is the advantage of ultra-short-acting insulin preparations?
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The immediate onset and short duration of action enhance glycemic control
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Which insulin preparation is short-acting?
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Regular human insulin
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Regular human insulin is efficacious after how many minutes?
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30 minutes
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What is the biggest "problem" with regular human insulin?
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Patient must eat within 30 minutes or there is a risk of sever hypoglycemia
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Which type of insulin is the only for that can be administered IV and only under the direct supervision of a physician?
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Regular human insulin
(short-acting) |
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Which insulin preparation is a crystalline zinc insulin?
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Regular human insulin
(short-acting) |
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Which insulin preparation is intermediate-acting?
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NPH Insulin
(Neutral protamine Hagedon) |
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How is the onset of action delayed in NPH insulin?
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Delayed by combining insulin and protamine in a ratio so that neither is present in an uncomplexed form-- complex slowly dissociates.
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Which insulin preparation is long-lasting?
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Ultralente insulin
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What is the ratio of protamine:insulin in NPH insulin?
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1:10 (protamine:insulin) --by weight
1: 6 -- molar |
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Which insulin preparation is a bioengineered form of insulin that is soluble at pH 4, but precipitates at physiologic pH (7.4)?
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Glargine
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How often is Glargine administered?
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Once daily (with no peak activity)
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What is Novolin a mixture of?
Why is this mixture convenient? |
70% NPH/ 30% regular human insulin
*Most patient need a mixture for immediate and long-term glucose uptake |
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Why must care be taken when combining insulin preparations?
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Excess zinc and protamine may form undesired insulin complexes
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What was the complication of insulin purified from cows or pigs?
How has this problem been eliminated? |
Antigenicity
*DNA recombinant technology (gene for human DNA expressed in bacteria or yeast, expressed protein is purified) |
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What are the 3 insulin delivery systems.
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1. Injection of measured doses (subcutaneously)
2. Portable pen injectors 3. Continuous pumps |
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List 4 complications that can be associated with insulin therapy.
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1. Hypoglycemia
2. Lipodystrophy 3. Weight gain 4. Immunopathology |
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What is the treatment for Type I diabetes and what does the choice of insulin depend on?
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Insulin replacement
Choice depends on desired onset and duration of action |
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What are the 3 therapeutic goals of treatment of Type II diabetes?
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1. Insulin release
2. Increased sensitization to insulin 3. Decrease blood glucose |
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How do sulfonylureas work?
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1. Bind to sulfonylurea receptor that associates with ATP-sensitive K+ channel (inward-rectifying type)
2. Binding inhibits efflux of K+, resulting in membrane depolarization 3. Ca2+ voltage-gated channels open, allowing influx of Ca2+ 4. Ca2+ causes release of preformed insulin |
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What can be the result of chronic use of sulfonylureas?
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They also decrease serum glucagons, contributing to hypoglycemic effects
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Why are second generation sulfonylureas more commonly used?
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Increased potency
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What are the adverse effects of sulfonylureas?
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1. Hypoglycemia
2. Weight gain |
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List 3 first-generation sulfonylureas.
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1. Tolbutamide
2. Chlorpropamide 3. Tolazamide |
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What is Tolbutamide?
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First generation sulfonylurea
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What is Chlorpropamide?
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First generation sulfonylurea
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What is Tolazamide?
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First generation sulfonylurea
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Which of the first generation sulfonylureas has a rapid onset of action?
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Tolbutamide
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Where is Tolbutamide metabolized?
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Liver
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Where is Chlorpropamide metabolized?
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Liver
(20-30% excreted unchanged in kidney) |
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List 3 second-generation sulfonylureas.
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1. Glyburide
2. Glipizide 3. Glimepiride |
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What is Glyberide?
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Second generation sulfonylurea
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What is Glipizide?
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Second generation sulfonylurea
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What is Glimepiride?
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Second generation sulfonylurea
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Glyburide is contraindicated for what kind of patients?
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Those with hepatic impairment and renal insufficiency
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At what time should Glimepiride be taken?
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30 minutes before breakfast
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Which of the second generation sulfonylureas has the highest propensity for hypoglycemia?
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Glipizide
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How often is Glimepiride administered?
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Once a day
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Where is glimepiride metabolized?
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Liver
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How do meglitinides modulate insulin release?
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Decrease potassium channel efflux
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What type of onset-of-action do the meglitinides have?
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Rapid onset of action
(peaks within 1 hour) |
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List 2 Meglitinides.
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1. Repaglinide
2. Nategelinide |
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What is Repaglinide?
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Meglitinide (non-sulfonylurea secretagogue)
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What is Nateglinide?
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Meglitinide (non-sulfonylurea secretagogue)
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What are the meglitnides metabolized by?
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CYP3A4
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What are the two groups of insulin secretagogues?
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1. Sulfonylureas
2. Meglitinides |
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What are the 4 proposed mechanisms of biguanides?
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(insulin sensitizers)
1. Stimulation of glycolysis in tissues 2. Reduced hepatic and renal gluconeogenesis 3. Slowing of glucose absorption from GI tract 4. Reduction of plasma glucagon levels |
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Biguanides are useful for what type of patients?
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Those with refractory obesity whose hyperglycemia is due to ineffective insulin action ("insulin resistance syndrome")
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What group of drugs can be used with sulfonylureas when sulfonylureas alone are inadequate?
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Biguanides
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What type of side effects can result from biguanides?
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GI side effects:
1. Anorexia 2. Nausea 3. Vomiting 4. Abdominal discomfort 5. Diarrhea |
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Biguanides are contraindicated for what patients?
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Those with:
1. *Renal disease 2. *Alcoholism 3. Hepatic disease 4. Conditions predisposing to tissue anoxia |
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Name a drug in the class of biguanides.
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Metformin
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What are the benefits of Metformin?
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1. Can be used alone
2. Does not cause hypoglycemia 3. May produce modest weight loss |
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What is the bad news about Metformin?
How can these symptoms be reduced |
GI distress
(metallic taste, nausea, diarrhea, and abdominal pain) Lactic acidosis *Symptoms reduced by taking the drug slowly with food. |
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What is a potentially fatal complication of Metformin?
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Lactic acidosis
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How do Thiazolidinediones function?
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By enhancing insulin target tissue sensitivity by increasing activity of peroxisome proliferator-activated receptor-gamma (PPARy) nuclear receptor
*PPARy regulates expression of genes involved in glucose and lipid metabolism (functions only in adipose tissue, skeletal muscle, and liver) |
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How do Thiazolidinediones regularize blood glucose?
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By increasing glucose uptake into muscle and adipose tissue
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What is the result of Thiazolidinediones on body fat?
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Results in redistribution of body fat
(decreased visceral fat mass, increased peripheral small adipocytes) |
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How are the Thiazolidinediones metabolized?
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CYP450s in the liver
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List 2 examples of Thiazolidinediones.
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1. Pioglitazone
2. Rosiglitazone |
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What is Pioglitazone?
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Thiazolidinedione
(Insulin sensitizer) |
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What is Rosigitazone?
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Thiazolidinedione
(insulin sensitizer) |
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What are the two groups of insulin sensitizing drugs?
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1. Biguanides
2. Thiazolidinediones |
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What are the adverse effects of Thiazolidinediones?
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1. Weight gain
2. Fluid retention (These can lead to heart failure) 3. Retard fetal development--> not recommended during pregnancy |
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How do a-Glucosidase inhibitors work?
What is the goal of this treatment? |
Inhibit enteric enzymes of the brush border of the intestinal cells
*Minimize absorption and digestion of ingested starch |
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At what time should a-glucosidase inhibitors be taken (in respect to meals)?
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Should be taken WITH meals
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What are the adverse effects of a-glucosidase inhibitors?
How can these side effects be alleviated? |
GI distress:
1. SEVERE flatulence 2. Diarrhea 3. Abdominal pain *Leading cause of why patients stop taking these drugs *Slowly increasing dosages of drugs can help alleviate some of these side effects |
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a-Glucosidase inhibitors are contraindicated for what type of patients?
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Patients with:
1. Chronic intestinal disease 2. Inflammatory bowel disease 3. Colonic ulceration 4. Any degree of intestinal obstruction |
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Hypoglycemia caused by concurrent sulfonylurea and a-glucosidase inhibitor therapies should be treated with what?
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Dextrose
(NOT sucrose) |
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List 2 examples of a-Glucosidase inhibitors.
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1. Acarbose
2. Miglitol |
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What is Acarbose?
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a-Glucosidase inhibitor
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What is Miglitol?
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a-Glucosidase inhibitor
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Where is glucagon degraded?
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Liver
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What are the metabolic effects of glucagon?
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1. Increased cAMP production
2. Facilitates glycogenolysis 3. Increases gluconeogensis, ketogenesis *Infusion of glucagon increases blood glucose and decreases hepatic glycogen |
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What is the effect of glucagon on cardiac tissue?
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B-adrenergic receptor like effects
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What is the effect of glucagon on smooth muscle?
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Profound relaxation of the small intestines
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List 4 clinical uses of glucagon.
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1. Treatment of severe hypoglycemia
2. Diagnosis of endocrine disorders 3. B-blocker poisoning 4. Radiology of the bowel |
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How does glucagon correct hypoglycemia?
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Converts glycogen to glucose
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How can glucagon be used for diagnosing endocrine disorders?
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Glucagon is administerd ina bolus, resulting in the release of B-cell reserves. C-peptide levels are used to indicate B-cell function
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Why are C-peptide levels measures to check B-cell function rather than measuring insulin levels?
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Often insulin cannot be measured because the patient will produce antibodies to insulin which interferes with the assay for insulin levels
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How can glucagon be used to correct B-blocker poisoning?
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Glucagon has similar effect as B-adrenergic agonists-- it increases cAMP levels by stimulating adenylyl cyclase
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Why is glucagon useful for radiographic imaging of the bowel?
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Causes profound relaxation of the small intestines
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What is Acetohexamide?
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1st generation sulfonylurea
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What is the therapeutic goal of treating Type 1 diabetes?
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Insulin replacement
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