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86 Cards in this Set
- Front
- Back
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Insulin
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hormone that is needed to convert sugar, starches & other food into energy needed for daily life
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Type 1 DM
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Autoimmune process.
Results in complete destruction of b cells of pancreas so no insulin can be produced. |
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Type 2 DM
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Wide variety of disorders cause this.
Characterized by insulin resistance, impaired insulin production and increased glucose production in liver. Preceded by period of deranged glucose homeostasis. Can have a long asymptomatic period before it is diagnosis. |
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Criteria for Diagnosis of DM
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Symptoms of diabetes plus a random plasma glucose >200mg/dl
Fasting plasma glucose >126 mg/dl Two hour plasma glucose >200mg/dl (some authorities list between 140-200 mg/dl as “prediabetes”)during an oral glucose tolerance test. |
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Screening for T2DM
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DM may be present for up to 10 yrs before it is diagnoses.
The ADA recommends screening individuals >45 years old, every 3 years for T2DM. |
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Insulin: Secretion
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Produced by the beta cells of the islets of Langerhans in the pancreas.
Glucose levels > 70 mg/dl stimulate release of insulin. Released in pulsatile bursts, occurring about every 10 minutes. Meals stimulate larger bursts that last for 2-3 hours. |
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Insulin: Action
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Released by pancreas into portal circulation.
At cellular level, insulin binds with a protein on the cell surface, an insulin receptor. This creates a complex series of reactions, but the outcome is the stimulation of the glucose transporter. Each reaction is controlled by a different enzyme. The end result is the formation of a protein, the glucose transporter. The glucose transporter then moves the glucose molecule into the cell. When the glucose moves into the cell, K is also moved into the cell. |
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Insulin: Actions
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Primary function of insulin is to regulate the metabolism of glucose and ensure that the body has a constant supply.
Insulin has different effects on different tissues. Insulin causes the cellular uptake of food components into the cell. Insulin also impacts the metabolism of fats and proteins. Under the influence of insulin fat stores are increased and the breakdown of fats and proteins is decreased. |
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Glycolysis
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the breakdown of glucose so the cell can form ATP-energy currency of the cell.
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Glycogenesis
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formation of glucogen in the liver and skeletal muscles
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Glycogenolysis
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breakdown of stored glucose or glycogen.
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Glyconeogenesis
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formation of new glucose from fat and amino acids.
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Signs and Symptoms of T1DM
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Polyphagia
Polyuria Polydipsia |
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Signs and Sx Common to Both (DM1 + 2)
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Fatigue.
Perineal itching and irritation-due to yeast infections that commonly occur with the hyperglycemia of undiagnosed DM. Irritability. Blurred vision. Recurring skin, gum or bladder infections. Bruises, or cuts that are slow to heal. Impotence. Nocturia. Dizziness. Weakness. |
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T2DM is characterized by three abnormalities
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Peripheral insulin resistance.
Impaired insulin production. Excessive hepatic glucose production. |
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Complications of T2DM
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Macrovascular
Microvascular Neurologic |
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Treatment for DM
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Type 1
Insulin therapy Type 2 Lifestyle changes Oral drug therapy Insulin when the above no longer provide glycemic control |
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Human-Based Insulins
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Rapid-acting
Insulin lispro (Humalog) Insulin aspart (NovoLog) Insulin glulisine (Apidra) Short-acting (regular) Intermediate-acting (NPH) Long-acting (glargine (Lantus), detemir (Levemir)) |
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Sliding-Scale Insulin Dosing
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SC short-acting or regular insulin doses adjusted according to blood glucose test results
Typically used in hospitalized diabetic patients or those on TPN or enteral tube feedings Subcutaneous insulin is ordered in an amount that increases as the blood glucose increases Disadvantage: delays insulin administration until hyperglycemia occurs; results in large swings in glucose control |
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Complications of Insulin Therapy: Hypoglycemia
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Occurs when the blood sugar falls to levels below 50-60 mg/dl.
Results from an imbalance between food intake and insulin. Can be caused by too much insulin, too little food or increased exercise. Delayed snacks or meals can be a common cause, as can a change in insulin needs. Increased exercise is one of the more common reasons for hypoglycemic reactions. Drinking ETOH can also cause symptom of hypoglycemia, particularly if taken alone, without food. |
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Significant Drug Interactions
Hypoglycemic agents |
Sulfonylureas
Alcohol Beta blockers |
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Significant Drug Interactions
Hyperglycemic agents |
Thiazide diuretics
Glucocorticoids Sympathomimetics |
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Symptoms of Hypoglycemia
Sympathetic Nervous System |
Sweating
Tremors Tachycardia & Palpitations Hunger Nervousness |
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Symptoms of Hypoglycemia
Central Nervous System |
Inability to concentrate
Headache Lightheadedness Confusion Slurred speech Impaired Coordination Emotional changes Irrational or Combative behavior Double vision |
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Biguanides/Metformin
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Metformin (currently only drug classified as a biguanide)-moderates insulin resistance.
Increases the utilization of glucose by the peripheral skeletal muscle. Endogenous insulin has to be present in order for the metformin to be effective. Metformin also lowers the level of production of hepatic glucose, it also reduces the absorption of glucose through the gut. Less stimulation of pancreas to produce insulin, helps to prevent burnout of the beta cells. |
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Metformin
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Most commonly used drug for T2DM
Does not stimulate insulin secretion (like sulfonylureas) so is not associated with hypoglycemia & weight gain Causes moderate weight loss ADA now recommends Metformin as the initial antidiabetic drug for newly dxed T2DM Typical dosing is 850 to1000mg BID Can de used in pediatric patients |
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Metformin AE
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Primarily affects GI tract: abdominal bloating, nausea, cramping, diarrhea, feeling of fullness
May also cause metallic taste, reduced vitamin B12 levels Lactic acidosis is rare but lethal if it occurs Does not cause hypoglycemia |
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Sulfonylureas
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First oral medications that were available.
First generation of drugs seldom used for therapy today. Second generation 100x more potent than first generation, & have fewer side effects than first generation. Cause an increase in insulin production by the pancreas, probably reduces glucose output by the liver, & increases peripheral sensitivity to insulin. |
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Sulfonylureas AE
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Side effects: hypoglycemia, GI effects-nausea, vomiting, diarrhea, heartburn.
Weight gain. |
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Sulfonylureas
Mech of action |
Causes insulin output of the pancreas to be increased.
Constant stimulation of pancreatic islet cells thought to lead to eventual burnout & loss of efficacy (10yrs) Effects on insulin secretion achieved through inhibition of K+ channels on beta cells preventing K+ influx, lowering membrane potential leading to depolarization Opens voltage dependent CA+2 channels stimulating secretion of insulin Onset of Action: ½ - 1 hour, best taken in morning 1/2 hr before breakfast Duration of Action: up to 24hr |
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Sulfonylureas Interactions
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Hypoglycemic effect increases when taken with alcohol, anabolic steroids, many other drugs
Adrenergics, corticosteroids, thiazides, others may reduce hypoglycemic effects Allergic cross-sensitivity may occur with loop diuretics and sulfonamide antibiotics May interact with alcohol, causing a disulfiram-type reaction A/Es include hematologic effects, nausea, epigastric fullness, heartburn, many others |
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Glinides
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Similar to sulfonylureas in mechanism of action but not structure
Increase insulin secretion from pancreas but have a much shorter duration of action & must be given with each meal Repaglinide (Prandin) & Nateglinide are only 2 drugs in this class Particularly useful with high postprandial blood sugars Can be used with metformin & thiasolidinediones but not sulfonylureas |
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Glinides AE
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Most common A/Es are hypoglycemia (especially if food is not taken with a dose) & weight gain
Usual dosage range is 0.5 to 4 mg three times a day; best taken 15 minutes before a meal Headache, hypoglycemic effects, dizziness, weight gain, joint pain, upper respiratory infection or flulike symptoms |
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Thiazolidinediones
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AKA the glitazones
Regulates genes involved in glucose & lipid metabolism so slower onset of action Decrease insulin resistance “Insulin sensitizing drugs” Increase glucose uptake and use in skeletal muscle Inhibit glucose & triglyceride production in the liver |
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Thiazolidinediones AE
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Moderate weight gain, edema, mild anemia
Hepatic toxicity—monitor ALT levels |
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Alpha Glucosidase Inhibitors
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Less commonly used & includes precose (acarbose) & glyset (miglitol).
Delay digestion of carbohydrate absorption of sucrose from intestinal system by inhibiting enzyme. Results in a lowering of the postprandial blood glucose, & helps to cause a lower Hgb a1c . Does not enhance insulin production so does not cause hypoglycemia, hyperinsulemia or weight gain. |
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Alpha-glucosidase inhibitors Mechanism of Action
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Reversibly inhibits enzyme alpha-glucosidase in small intestine
Result in delayed absorption of glucose Must be taken with meals to prevent excessive postprandial blood glucose elevations (with the “first bite” of a meal) Not recommended with inflammatory bowel disease, malabsorption syndromes, or intestinal obstruction A/Es: flatulence, diarrhea, abdominal pain |
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Amylin
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Amylin is a hormone secreted by beta cells along with insulin in response to food. It decreases postprandial blood sugars in 3 ways:
1.Slows gastric emptying 2.Suppresses glycagon secretion & hepatic glucose production 3.Increases satiety |
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Amylin Mimetic Mechanism of Action
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Mimics the natural hormone amylin
Slows gastric emptying Suppresses glucagon secretion, reducing hepatic glucose output Centrally modulates appetite and satiety Used when other drugs have not achieved adequate glucose control Subcutaneous injection only before meals Used with type 1 or 2 diabetes mellitus |
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Pramlintide (Symlin)
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First drug approved for use in type 1 DM since insulin
Contraindicated in patients with gastroparesis or those taking drugs that alter gastric motility Pre-meal insulin doses are often cut by 50% Can delay absorption of any other drugs so should be given at least 1 hr before others Doses: 15 to 60 mcg for type 1 & 60 to 120 mcg for type 2 given before major meals |
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Incretin
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Incretins are hormones released by gastrointestinal tract in response to food. Incretions do the following:
Stimulate insulin secretion Reduce postprandial glucagon production Slow gastric emptying Increase satiety |
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Incretin Mimetic Mechanism of Action
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Mimics the incretin hormones
Enhances glucose-driven insulin secretion from beta cells of the pancreas Only used for Type 2 diabetes when patients have been unable to achieve blood glucose control with metformin, a sulfonylurea, and/or a glitazone |
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Exenatide (Byetta):
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Sc Injection (pen) 60 min before meal
NOT used with insulin Delays absorption of other drugs Starting dose 5 mcg W/I 1 hr of am & pm meals; up to 10 mcg after 1 month Weekly formulation under development A/Es include: N & V, diarrhea, rare hemorrhagic or necrotizing pancreatitis Weight loss of 5-10 lbs may occur |
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Sitagliptin (Januvia)
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Different mode of action than exenatide as it affects a different incretin hormone
Used for T2DM as monotherapy or with metformin, a sulfonylurea, or a glitazone but not with insulin Given once daily Hypoglycemia may occur when combined with a sulfonylurea Patients should be watched for signs of pancreatitis |
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Incretin
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Incretins are hormones released by gastrointestinal tract in response to food. Incretions do the following:
Stimulate insulin secretion Reduce postprandial glucagon production Slow gastric emptying Increase satiety |
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Incretin Mimetic Mechanism of Action
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Mimics the incretin hormones
Enhances glucose-driven insulin secretion from beta cells of the pancreas Only used for Type 2 diabetes when patients have been unable to achieve blood glucose control with metformin, a sulfonylurea, and/or a glitazone |
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Exenatide (Byetta):
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Sc Injection (pen) 60 min before meal
NOT used with insulin Delays absorption of other drugs Starting dose 5 mcg W/I 1 hr of am & pm meals; up to 10 mcg after 1 month Weekly formulation under development A/Es include: N & V, diarrhea, rare hemorrhagic or necrotizing pancreatitis Weight loss of 5-10 lbs may occur |
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Sitagliptin (Januvia)
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Different mode of action than exenatide as it affects a different incretin hormone
Used for T2DM as monotherapy or with metformin, a sulfonylurea, or a glitazone but not with insulin Given once daily Hypoglycemia may occur when combined with a sulfonylurea Patients should be watched for signs of pancreatitis |
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The Action of Hormones on Body Functions
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Secretory and motor activities of the digestive tract
Energy production Composition and volume of extracellular fluid Adaptation, such as acclimatization and immunity Growth and development Reproduction and lactation |
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Endocrine System
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Main goal is maintenance of physiologic stability despite constant changes in internal & external environments
Every cell is influenced by endocrine system |
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Anterior lobe
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Growth Hormone
Thyroid-stimulating hormone (TSH) Adrenocorticotropic (ACTH) Prolactin Gonadotripic hormones (FSH and LH) |
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Posterior lobe
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Vasopressin
Oxytocin |
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Anterior pituitary drugs
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Cosyntropin
Somatotropin & Somatrem Octreotide |
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Posterior pituitary drugs
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Vasopressin & Desmopressin
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Cosyntropin
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ACTH replacement/travels to adrenal cortex & stimulates secretion of cortisol, an anti-inflammatory (the drug form is hydrocortisone, Solu-Cortef). Cortisol has many inflammatory effects including reduction of inflammatory leukocyte functions & scar tissue formation, also promotes renal retention of sodium which can result in edema & hypertension. Used to diagnose adrenocortical insufficiency.
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Somatotropin & Somatrem
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growth hormone (GH) replacements used with inadequate GH secretion & wasting associated with HIV. Stimulate anabolic (tissue building) processes: liver glycogenolysis, lipid mobilization & retention of sodium, potassium & phosphorus.
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Octreotide
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antagonizes GH by inhibiting GH release.
replaces somastatin/GH inhibiting factor |
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Vasopressin & Desmopressin
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mimic antidiuretic hormone (ADH) increase water resorption reducing water excretion by 90%
Potent vasoconstrictor in large doses which is used in hypotensive emergencies like shock & pulseless cardiac arrest Stops bleeding of esophageal varices Certain Factor VIII clotting disorders |
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Hypothyroidism causes
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Primary: abnormality in the thyroid gland itself
Secondary: results when the pituitary gland is dysfunctional & does not secrete TSH Tertiary: results when the hypothalamus gland does not secrete TRH, which stimulates the release of TSH |
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Cretinism
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Hyposecretion of thyroid hormone during youth
Low metabolic rate, retarded growth & sexual development, possible mental retardation |
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Myxedema
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Hyposecretion of thyroid hormone during adulthood
Decreased metabolic rate, loss of mental & physical stamina, weight gain, loss of hair, firm edema, yellow dullness of the skin |
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Goiter
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Enlargement of the thyroid gland
Results from overstimulation by elevated levels of TSH TSH is elevated because there is little or no thyroid hormone in circulation Common symptoms Thickened skin Hair loss Constipation Lethargy Anorexia |
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levothyroxine (Synthroid, Levothyroid)
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Synthetic thyroid hormone T4
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liothyronine (Cytomel)
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Synthetic thyroid hormone T3
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liotrix (Thyrolar)
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Synthetic thyroid hormone T3 & T4 combined
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Hyperthyroidism effects
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Diarrhea
Flushing Increased appetite Muscle weakness Sleep disorders Altered menstrual flow Fatigue Palpitations Nervousness Heat intolerance Irritability |
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Hyperthyroidism diseases
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Graves’ disease
Multinodular disease Plummer’s disease (rare) Also called toxic nodular disease Thyroid storm (induced by stress or infection) Severe & potentially life-threatening |
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Treatment of Hyperthyroidism
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Radioactive iodine
surgery Antithyroid drugs: thioamide derivatives -methimazole (Tapazole) -propylthiouracil (PTU) |
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Adrenal medulla secretes
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catecholamines
-Epinephrine -Norepinephrine |
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Adrenal cortex secretes corticosteroids
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Glucocorticoids
Mineralocorticoids (primarily aldosterone which is responsible for maintenance of normal sodium) All adrenal cortex hormones are steroid hormones |
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Glucocorticoids
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beclomethasone (several formulations)
fluticasone propionate hydrocortisone (several formulations) cortisone methylprednisolone prednisone Many others |
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Mineralocorticoid
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fludrocortisone acetate
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Adrenal steroid inhibitor
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aminoglutethimide
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Adrenocortical steroid
Mechanism of Action |
Most exert their effects by modifying enzyme activity
Different drugs differ in their potency, duration of action, & the extent to which they cause salt & fluid retention Glucocorticoids inhibit or help control inflammatory & immune responses |
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Adrenocortical steroid
Indications |
Adrenocortical deficiency
Cerebral edema Collagen diseases Dermatologic diseases GI diseases Exacerbations of chronic respiratory illnesses, such as asthma & COPD Organ transplant (decrease immune response) Palliative management of leukemias & lymphomas Spinal cord injury Many other indications |
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Glucocorticoids administration
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By inhalation for control of steroid-responsive bronchospastic states
Nasally for rhinitis & to prevent the recurrence of polyps after surgical removal Topically for inflammations of the eye, ear, & skin |
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aminoglutethimide
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Used in the treatment of Cushing’s syndrome, metastatic breast cancer, & adrenal cancer
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Estrogens: Indications
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Atrophic vaginitis
Hypogonadism Oral contraception (given with a progestin) Dysmenorrhea “Hot flashes” of menopause Uterine bleeding Palliative treatment of advanced breast & prostate cancer Osteoporosis treatment & prophylaxis Many other indications |
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Estrogens: Contraindications
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Any estrogen-dependent cancer
Undiagnosed abnormal vaginal bleeding Pregnancy Active thromboembolic disorder or history |
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Estrogens: Adverse Effects
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Thrombolytic events—most serious
Nausea—most common Hypertension, thrombophlebitis, edema Vomiting, diarrhea, constipation, abdominal pain May cause photosensitivity, chloasma Amenorrhea, breakthrough uterine bleeding Tender breasts, fluid retention, headaches Others |
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Progestins
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Synthetic derivatives of progesterone
hydroxyprogesterone (Hylutin) medroxyprogesterone (Provera) megestrol (Megace) etonogestrel implant (Implanon) Many others |
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Progestins: Indications
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Treatment of functional uterine bleeding caused by:
Hormonal imbalance, fibroids, or uterine cancer Treatment of primary & secondary amenorrhea Palliative treatment of some cancers & endometriosis Prevention of threatened miscarriage Alleviation of PMS symptoms |
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megestrol (Megace)
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Adjunct therapy for treatment of breast & endometrial cancers
Management of anorexia, cachexia, or unexplained weight loss in AIDS patients To stimulate appetite & promote weight gain in cancer patients |
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Progestins: Adverse Effects
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Liver dysfunction—cholestatic jaundice
Thrombophlebitis, thromboembolic disorders, such as PE Nausea, vomiting Amenorrhea, breakthrough uterine bleeding, spotting Edema, weight gain or loss Others |
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Contraceptive Drugs
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Oral medications
Monophasic, biphasic, & triphasic forms Triphasic form most closely duplicates the normal hormonal levels of the female cycle Newer extended cycle products Most contain estrogen-progestin combinations Other contraceptive forms available Long-acting injectable form of medroxyprogesterone (Depo-Provera) Transdermal contraceptive patch Intravaginal contraceptive ring |
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Contraceptive Drugs: Adverse Effects
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Drawbacks to the use of these drugs include:
Hypertension Thromboembolism, possible PE, MI, stroke Alterations in lipid & carbohydrate metabolism Increases in serum hormone concentrations These effects are caused by the estrogen component May also cause: Edema, dizziness, headache, depression, nausea, vomiting, diarrhea, increased appetite, increased weight, breast changes, many others |
