NURS 251 Module 4

Module 4 4.1: Introduction to Endocrinology The endocrine system, also referred to as the hormone system, is a series of glands located throughout the body that functions to maintain homeostasis. By modulating the release of chemical messengers (hormones), the endocrine system is able to send signals to regulate organ functions. The endocrine system is unique in that it works through hormones that generally have a longer and slower onset and duration of action. There are actually eight endocrine glands throughout the body including: the pineal, pituitary, thyroid, thymus, adrenal, pancreas, ovary and testis. Each of these glands releases a hormone into the body that is responsible for regulating growth, metabolism, or reproduction. This module will focus on select glands such as the pituitary gland, thyroid gland, and adrenal cortex and the pharmacologic options available when they fail to work properly. Physiology Overview The pituitary gland is sometimes called the “master gland” because it controls many of the other glands within the endocrine system. The pituitary gland is located in the region of the forebrain near the hypothalamus. Hormones released from the pituitary gland work by a negative feedback loop. This means the pituitary gland releases a hormone that signals an endocrine gland to release a subsequent hormone. The presence of this subsequent hormone then signals back to the pituitary gland to stop releasing the original hormone. The pituitary gland has two lobes, the anterior pituitary gland and the posterior pituitary gland. As outlined in Table 4.1, each lobe secretes its own distinct hormones. Table 4.1 Hormones of the Pituitary Gland Anterior Pituitary Gland Posterior Pituitary Gland Adrenocorticotropic Hormone (ACTH) Follicle Stimulating Hormone (FSH) Growth Hormone (GH) Luteinizing Hormone (LH) Prolactin (PH) Thyroid Stimulating Hormone (TSH) Antidiuretic Hormone (ADH) Oxytocin Pathophysiology and Related Drug Therapy Pituitary Generally, medications that affect the pituitary gland are being used as replacements for a hormone deficiency within the body. Examples of medications used to treat a pituitary hormone deficiency include (1) Somatropin (2) Octreotide, (3) Vasopressin and (4) Desmopressin. Somatropin- mimics the effects of growth hormone (GH) by promoting growth within the body. Typically, somatropin is used in children to promote linear growth when they do not produce a sufficient amount of endogenous hormone on their own. Octreotide- inhibits GH release and is structurally similar to the body’s GH release-inhibiting factor or somatostatin. It is useful in the treatment of severe watery diarrhea resulting from slow growing tumors because it reduces the concentration of the protein that causes the diarrhea. Vasopressin- is a potent vasoconstrictor and mimics the actions of the body’s antidiuretic hormone (ADH). It works by increasing water reabsorption in the distal tubule and collecting duct of the nephron (see Module 3). This can reduce water excretion up to 90%. It is also an especially effective vasoconstrictor in higher doses and can be used in emergency situations when blood pressure is dropping dangerously low. Desmopressin- is a synthetic vasopressin. As such, it also mimics ADH and works to increase water reabsorption in the nephron. Additionally, desmopressin shows dose-dependent activity on clotting factors, making it useful in treating certain blood disorders. Thyroid The thyroid gland is located in the neck and is responsible for the regulation of the body’s metabolism through the release of three hormones: Thyroxine (T4), triiodothyronine (T3), and calcitonin. Thyroid Stimulating Hormone (TSH) is the endogenous substance that the pituitary gland secretes to control the release of these thyroid gland hormones. There are two main problems that can occur the thyroid gland: (1) Hypothyroidism and (2) Hyperthyroidism. Hypothyroidism- A common condition characterized by diminished production of the thyroid hormones. Symptoms of this condition include cold intolerance, unintentional weight gain, depression, dry brittle hair and nails, and fatigue. Overall, think of the symptoms as a decrease in the body’s metabolism resulting in an overall slowing. Drug Therapy- The treatment for hypothyroidism is relatively straight forward. It is to provide thyroid hormone replacement to the patient. While there are natural and synthetic options available, the synthetic levothyroxine (synthetic T4) is used in the majority of patients. Essentially, levothyroxine works in the same manner as the endogenous hormones. By taking levothyroxine, the deficiency is corrected. Levothyroxine is the drug of choice in most cases due to its predictable effects and long enough half-life to allow for once daily dosing. However, it can be impacted by food or drugs, so it is recommended to take on an empty stomach 30-60 minutes prior to breakfast. Hyperthyroidism- A condition characterized by excessive production of the thyroid hormones. In contrast to hypothyroidism, hyperthyroidism causes an overall increase in the body’s metabolism. Symptoms of this condition include diarrhea, flushing, increased appetite, muscle weakness, fatigue, palpitations, irritability, nervousness, heat intolerance, and altered menstrual flow. Drug Therapy- Propylthiouracil (PTU) and Methimazole are two anti-thyroid drugs available that work by inhibiting the formation of the thyroid hormones. Two weeks of PTU therapy may be needed prior to symptom improvement. On the other hand, Methimazole, is rarely used clinically. It is also important to note that is some cases where drug therapy is ineffective, or the patient is unable to tolerate treatment, surgical resection of the thyroid gland is often performed. Such a patient would be then considered to have hypothyroidism and would need thyroid hormone replacement for the rest of their life. Adrenal Glands The adrenal glands are located on the upper surface of each kidney. Although there are two parts of the adrenal glands, the adrenal medulla (the inner part) and the adrenal cortex (the outer part), the focus will be on the adrenal cortex in this section. The hormones released by the adrenal cortex are generally referred to as corticosteroids or just steroids. Importantly, there are two distinct types of corticosteroids: (1) glucocorticoids and (2) mineralocorticoids, Glucocorticoids are critical to the body’s overall function and work to stimulate the production of glucose (gluconeogenesis) and the breakdown of proteins (catabolism). When the body undergoes any type of stress including trauma or surgery, the need for glucose increases. For tissues to be able to repair glucose is a necessary component. Two specific glucocorticoid hormones exist and can be released in the form of either cortisol or cortisone. When there is a deficiency in glucocorticoids, a person is said to have Addison’s disease. Conversely, when a person is producing excess glucocorticoids, the patient is said to have Cushing’s disease. Mineralocorticoids, such as the hormone aldosterone, are also released by the adrenal cortex. Aldosterone is critical to the regulation of sodium and potassium as well as water in the extracellular fluid. The regulatory effects of aldosterone, therefore, plays a role in blood pressure. The renin angiotensin system (Module 3) is a major regulator of aldosterone secretion as is the adrenocorticotropic hormone (ACTH), although to a lesser degree. Corticosteroids as Drug Therapy Glucocorticoids and Mineralocorticoids are both endogenous hormones that work within the body. There are also several synthetic versions of these hormones given through medications. The primary uses of these medications are both as replacement therapy (as in Addison’s disease), but also in the treatment of inflammatory or allergic conditions. Glucocorticoids are used more frequently clinically. Common examples of clinically useful steroids include the naturally occurring steroids and synthetic preparations. Synthetic steroids have been altered in some way to produce greater antiinflammatory effect. The synthetic steroids also produce fewer undesirable mineralocorticoid side effects. Examples include: Natural Occurring Short Acting Steroids: Cortisone and Hydrocortisone Synthetic Intermediate Acting Steroids: Methylprednisolone, Prednisolone, Prednisone, and Triamcinolone Synthetic Long Acting Steroids: Betamethasone and Dexamethasone Clinical Uses Anti-inflammatory effects- The glucocorticoids work at the cellular level to bind to receptors that either activate the production of anti-inflammatory proteins or prevent pro-inflammatory protein production. As virtually every cell in the human body has glucocorticoid receptors, the effects of these drugs can be far reaching. Although this can be a good thing, it also means that there are often many unwanted effects because the drugs are not limited to one site of action. Synthetic glucocorticoids have many clinical uses. In high doses, they may be used to interrupt flares of inflammation until another medication that is more targeted can take effect. In lower doses, they are often used to prevent flares and protect the body from the damages of inflammation. Some of the more common glucocorticoids available and their clinical uses, are shown in Table 4.2. Table 4.2 Corticosteroids and corresponding indications Adrenal Steroid Indication(s) Fludrocortisone (Mineralocorticoid) Addison’s disease Glucocorticoids Budesonide nasal spray (Rhinocort) Allergic Rhinitis Dexamethasone Allergic Disorders Multiple Sclerosis Fluticasone (Flonase) Allergic Rhinitis Methylprednisolone (Medrol) Anti-inflammatory Prednisone Anti-inflammatory and Immunosuppressive Adverse Events- The adverse events profile of corticosteroid drugs is very dependent on the dose and duration of treatment. Typical adverse events include increased appetite, weight gain, indigestion, and restlessness. Less common adverse events include changes in skin color, dizziness, increased sweating, flushing, and skin rash. Adverse events associated with long term use- In patients that have to be on corticosteroids for extended periods of time, they can manifest symptoms similar to Cushing’s disease such as abnormal fat deposits which cause a rounded “moon face” or “buffalo hump” on their shoulders. Steroid psychosis is a sign of steroid addiction and is associated with long term use, typically at higher doses. Symptoms would include mood and personality changes and insomnia. When patients are on corticosteroids long-term, there is a psychological dependency that develops, so they need to be discontinued gradually with medical supervision. Abrupt withdrawal can cause a severe mental depression. Generally, long-term use of glucocorticoids is not safe and patients can experience many serious adverse events. Prolonged use will result in increased gluconeogenesis which can lead to obesity or diabetes. It will also lead to increased protein catabolism which will show up as muscle weakness and wasting, thinning of skin, osteoporosis, decreased growth in children, decreased wound healing, and increased infections. Ovaries The Reproductive cycle The ovaries are part of the endocrine system and as such, the reproductive cycle actually begins with the hypothalamus. In basic terms, the hypothalamus releases Gonadotropin releasing hormone (GnRH) which signals the anterior pituitary gland to secrete Follicle stimulating hormone (FSH) and Luteinizing hormone (LH). All of the above events signal more changes within the body, such as the release of estrogen and progestin. This, in turn, causes the body to both prepare the endometrium for the implantation of a possibly fertilized egg and for the body to release an egg into the ovary or ovulate. As we have seen in other parts of the endocrine system, there is a negative feedback mechanism. Specifically, when there are high levels of estrogen and progesterone, this inhibits the release of FSH and LH. Oral Contraception One of the most common methods of contraception among women is oral contraception. As mentioned above, high hormone levels in the body of estrogen and progesterone inhibit the release of FSH and LH. Therefore, by taking an oral contraceptive, the woman is introducing exogenous estrogen and progesterone into their body that would not normally be there. This is enough of a change to signal the inhibition of FSH and LH resulting in no ovulation as well as changes to the endometrium that prevent implantation. The effectiveness of oral contraceptives is directly related to the patient’s compliance to taking the pill every day. Generally, the dosing schedule is to take one pill daily for 3 weeks and then to take a placebo pill for the last week of the cycle, allowing the body to go through the process of menstruation. Different oral contraceptives may vary in the amount of estrogen and progesterone present or the number of active pills vs. placebo pills, but the mechanism of action is the same for all of them. Adverse effects- nausea, vomiting, headache, dizziness, irritability, depression, fluid retention, breast tenderness, and weight gain. Typically, these can be managed by selecting an alternative oral contraceptive that may have a slightly different dose combination that the patient may tolerate better. Estrogen increases the risk of a patient having a blood clot, stroke, and heart attack. The likelihood of one of these occurring is related to risk factors such as smoking, hypertension, obesity, diabetes, and high cholesterol. Pancreas The pancreas is located behind the stomach and is involved in the secretion of insulin and glucagon, both of which play a critical role in regulating glucose levels within the body. Insulin is the hormone secreted by the beta cells of the pancreas in response to a rise in glucose levels in the blood. Glucagon is the hormone secreted by the alpha cells responsible for converting glycogen (how glucose is stored in the liver) to glucose in response to a drop in glucose levels in the blood. Without sufficient insulin, glucose remains in the bloodstream and is unable to enter the cells where it can be used. This lack of insulin is called diabetes. 4.2: Diabetes Diabetes- There are 23.6 million people in the United States that have diabetes. Diabetes is when the pancreas no longer produces insulin or the cells in the body stop responding to insulin or some combination of the two. There are two types of diabetes: type 1 and type 2. Type 1 is far less common making up about 10% of all people with diabetes. Pathophysiology of Diabetes Type 1 diabetes is an autoimmune disorder in which autoantibodies are produced against the beta cells in the pancreas. As beta cells secrete insulin, their targeted destruction by the antibodies results in a complete or nearly complete lack of insulin. Although type 1 diabetes is more commonly diagnosed in children or adolescents, the reason for this occurrence is unknown. Symptoms do not appear in these patients until ~90% of their beta cells have been destroyed. Without insulin, glucose levels rise. Type 1 diabetes necessitates long term insulin replacement therapy. Type 2 diabetes more commonly presents in adults and can be controlled by lifestyle modifications, oral drug therapy and/or insulin; however, insulin is not always necessary as it is in type 1 diabetes. Type 2 diabetes is far more common than type 1, accounting for at least 90% of all patients with diabetes. The cause of type 2 is different than type 1 and is caused by both an insulin resistance and an insulin deficiency. This means that there is overall less insulin, and the insulin that is present is not working efficiently. Insulin deficiency results from a loss of the normal responsiveness of the beta cells. In addition, there is not only a reduction in the number of insulin receptors on the cells, but the receptors that are present are less sensitive. Notably, obesity is a contributing factor in type 2 diabetes. Upwards of 80% of patients diagnosed with diabetes are obese. The excess adipose (fat) tissue actually worsens the insulin resistance. Symptoms and Complications Symptoms of diabetes include a rise in blood glucose levels called hyperglycemia. Hyperglycemia is defined as higher than normal glucose levels in the blood, fasting blood glucose greater than 126 mg/dL. Some of this excess glucose gets eliminated in the urine causing glycosuria which means an increase in urine glucose. Polyuria (increased urination) is also a common symptom that patients complain of. This can cause patients to become dehydrated and experience polydipsia (excessive thirst). Patients may also complain of excessive hunger, also known as polyphagia. The disproportionate feelings of hunger occur because, despite high levels of glucose being in the blood, the glucose is unable to enter the cells. Due to the inability of the body to process glucose for energy, it turns to proteins and fats. This can lead to a process called ketosis, meaning there is an increased production of ketone bodies as a result of fat metabolism, during which Diabetic Ketoacidosis (DKA) can result. DKA is a complex multisystem complication of uncontrolled diabetes that without treatment can lead to coma and death. Symptoms include extreme hyperglycemia, ketones in the serum, and electrolyte imbalances. Approximately 25% of the time, the presentation of DKA is how type 1 diabetes is diagnosed. Complications are mostly a result of the high amount of glucose in the blood over time. Think of the presence of glucose making the consistency of the blood more like syrup than water. This thick sugary fluid is much harder to pump throughout the body and the sugar is causing damage everywhere it goes. As shown in Table 4.3, there are both microvascular and macrovascular complications. Macrovascular are primarily diseases of the coronary arteries. Microvascular are long term complications that affect the small blood vessels. Table 4.3 Complications of Diabetes Macrovascular Microvascular Increased risk of stroke Diabetic nephropathy (numbness in hand and feet) High blood pressure Retinopathy (damage to eyes) Increased risk of coronary artery disease Nephropathy (Kidney damage) Peripheral vascular disease (lack of blood flow to legsleading to slow wound healing) Blood Glucose Management According to the American Diabetes Association, the criteria for diagnosing diabetes is a repeated blood glucose of 126 mg/dL or more after fasting or 200 mg/dL or higher 2 hours after eating. Each patient may have individual goals from their provider that take into account their specific needs. Table 4.4 outlines some general recommendations regarding blood glucose values. Table 4.4 Blood Glucose Goals for People with Diabetes Value Goal Fasting Blood Glucose 70-140mg/dL Preprandial (before a meal) 80-130 mg/dL Postprandial (2 hours after a meal) < 180 mg/dL HbA1C < 7% In addition to blood glucose values, another assessment can be done via the Hemoglobin A1C (HbA1c). HbA1c is a form of hemoglobin that has glucose attached to it. By measuring HbA1c levels, the average glucose plasma concentration over the last 3 months can be identified. Therefore, monitoring HbA1C is very helpful when a provider is trying to assess how well the patient is managing their blood sugar over time. Hypoglycemia is defined as a blood glucose level less than 70 mg/dL with signs and symptoms of hypoglycemia. These signs and symptoms include confusion, irritability, tremors, and sweating. If left untreated, the patient will have a seizure, followed by coma and death. Patients should be educated on these signs and know how to treat them should they occur. There are glucose tablets and gels available that provide a quick convenient form of a simple sugar that will raise blood sugar quickly. However, a patient could just as easily drink something like orange juice or a regular soda that has simple sugars and achieve similar effects. Drug therapy General treatment recommendations for Type 2 diabetes include lifestyle modifications for everyone at the time of diagnosis in combination with an oral medication called metformin, as long as there is no contraindication. If after 3-6 months of the maximum tolerated metformin dose (typically 2500 mg per day), the patient has not reached their goal blood sugar values; then it is recommended to add a second oral agent, a GLP-1 agonist (non-insulin injection), or insulin. There are many factors to consider when selecting which to add next including: efficacy, cost, side effects, other conditions the patient may have, effects on weight, risk of low blood sugar and patient choice. Table 4.5 provided a summary of some of the more commonly used oral antidiabetic options available. Table 4.5 Oral Antidiabetic Drugs Drug Class (example) Mechanism Adverse Effects Special Considerations Biguanide (metformin) Decreases glucose production in the liver GI adverse effects can be expected. This typically occurs at the initiation and is self-limiting. Recommended to titrate the dose up slowly to target dose and to take with food. *First line Not associated with weight gain or low blood sugar. Sulfonylureas (Glipizide) Bind to receptors on the beta cells in the pancreas to stimulate the release of insulin Hypoglycemia is the most common. The amount can depend on the person’s eating habits and if they They are the oldest class of antidiabetic medications. Can be used in combination with metformin and TZDs. have any kidney or liver disease. Other adverse effects include weight gain, rash, nausea, heartburn. Thiazolidinediones- TZDs (Pioglitazone) Decrease insulin resistance by enhancing the sensitivity of insulin receptors TZDs have a warning that they can cause or worsen heart failure and are not recommended in patients with symptomatic heart failure. They also cause peripheral edema and weight gain. Referred to as insulin sensitizing drugs. May be used in combination with sulfonylureas and metformin. Dipeptidyl Peptidase IV- (DPP IV) Inhibitors (Sitagliptin) Inhibit the enzyme that is responsible for the breakdown of incretin hormones. This reduces fasting and postprandial glucose Most commonly include upper respiratory tract infection, headache, and diarrhea. Hypoglycemia is possible but more likely if being used in combination with a sulfonylurea May increase digoxin levels. Injectable Antidiabetic Drugs There are two main classes of injectable antidiabetic drugs (1) Amylin agonists and (2) Incretin Mimetics. Amylin Agonists- Amylin is a hormone released by beta cells specifically in response to food. It functions to decrease postprandial glucose levels. This happens in three ways: slows gastric emptying, slows glucagon secretion and glucose production in the liver, and increases the sense of feeling full. Amylin agonists work by mimicking the body’s amylin. Uses- Pramlintide (Symlin) is the only drug in this class. It is indicated for both type 1 and type 2 diabetes for patients on insulin that are not achieving their goal postprandial glucose ranges. This is the first drug approved for type 1 diabetes besides insulin. Adverse Events- nausea, vomiting, anorexia, and headache. Special Considerations- It should not be used in patients with gastroparesis of in patients on medications that can alter GI motility. Amylin agonists are given as a subcutaneous injection prior to a major meal. Incretin Mimetics- incretins are hormones released by the GI tracts in response to food. They stimulate insulin secretion, lower postprandial glucagon, slow gastric emptying and increase the feeling of fullness. Incretin mimetics similarly enhance all of these effects. Uses- Exenatide (Byetta) was the first incretin mimetic approved. Another is dulaglutide (Trulicity). All of these medications are indicated for type 2 diabetes only when oral medications were not enough. Adverse Events- They all share the risk of developing thyroid C-cell tumors. More common adverse events include nausea, vomiting, and diarrhea. Special considerations- Weight loss of 5-10 pounds can be expected. These drugs are also given either on a daily (exenatide) or weekly (dulaglutide) basis by subcutaneous injection. 4.3: Insulin Insulin is the required therapy for all patients with type 1 diabetes. It often is a necessary part of the drug regimen for a patient with type 2 diabetes as well. Insulin production has evolved significantly since it was first introduced. Rather than being isolated from animals, all insulin is now synthesized in labs. Synthetic insulin works by acting as a substitute for the natural insulin that the patient fails to produce. Although all insulins can be used to treat either type 1 or type 2 diabetes, each patient will require an individualized dosing schedule dependent on their needs. As shown in Table 4.6, there are several different varieties of insulin available that vary in their onset of action and duration of action. Insulins are commonly classified based on how quickly they take effect and how long they last. We will look at the four most commonly used insulin types. Table 4.6 Insulin Overview Insulin Product Example Pharmacologic Class Clinical Use Insulin lispro, aspart, glulisine (Humalog, Novolog, Apidra) Human recombinant rapid-acting insulin analogue Given at meal times (15 minutes prior) to cover the glucose a patient ingests during the meal Regular insulin (Humulin R, Novolin R) Human recombinant short-acting insulin Same as rapid acting except that it needs to be given about 30 minutes prior to meal due to slower onset Insulin isophane suspension (NPH) Intermediate acting insulin Often combines with regular insulin to reduce the number of injections to twice daily dosing (i.e. Humulin 70/30 and Humulin 50/50) Insulin glargine, detimer (Lantus, Levemir) Human recombinant long-acting insulin analogue Give once daily (usually at bedtime) to provide 24-hour coverage. Used to get fasting glucose at goal. (in some cases, can be doses twice daily) There are two main sources of glucose that diabetic patients need coverage for. The first is the glucose produced by the liver that is present all day long at fairly stable levels. The second is the glucose that is introduced to the body at meal times, which clearly has high peaks right after a meal. Figure 4.1 below maps out the pharmacokinetic profiles of the different insulin types to see how they provide coverage for the different sources of glucose. Figure 4.1 Insulin Pharmacokinetics. The expected onset of action and duration of action of the different types of insulin available is shown. For example, the rapid acting insulins (lispro, aspart, and glulisine) have the quickest onset and shortest duration. Whereas the long acting insulins like detemir and glargine have a slower onset and much longer overall duration without much of a peak. The most physiologic insulin regimen, meaning that it is most similar to the way the body functions in a person without diabetes, is the combination of a long-acting insulin given once daily and a rapid-acting insulin given at meal times. An example of a dosing regimen might be that a person gives themselves Lantus at bedtime to cover their baseline insulin needs and then Humalog with each meal. This would require 4 injects per day and most likely testing their blood sugar four times a day as well. Given this is a lot to ask of a patient, so often times even though this is the most physiologic regimen, providers choose a different approach. Examples of different approaches include: 1. Dosing an NPH insulin twice a day. 2. Using a long acting in combination with oral medications. Notably, type 1 diabetes does not really allow for less injections since these patients are not making any insulin. However, often times in type 2 diabetes patients can reach their goals with fewer injections. Problem Set Question 1 Where in the body is the pituitary gland located and what is the primary substance released? The pituitary gland is located in the brain near the hypothalamus. Its primary role is to release hormones into the body that control other glands within the endocrine system. Question 2 What are the two lobes of the pituitary gland called and list the hormones associated with both lobes. Anterior Pituitary Gland Posterior Pituitary Gland Adrenocorticotropic Hormone (ACTH) Follicle Stimulating Hormone (FSH) Growth Hormone (GH) Luteinizing Hormone (LH) Prolactin (PH) Thyroid Stimulating Hormone (TSH) Antidiuretic Hormone (ADH) Oxytocin Question 3 Name the uses of the following drugs: somatropin, octreotide, vasopressin and desmopressin. Somatropin- used in children who are deficient in Growth Hormone to promote linear growth. Octreotide- Used in the treatment of severe watery diarrhea caused by a slow growing tumor. Vasopressin- used in emergency situations when blood pressure is dropping too low Desmopressin- used to treat certain blood disorders. Question 4 List the two common disorders associated with the thyroid gland and three symptoms the patient may experience if they have that condition. Hypothyroidism: cold intolerance, unintentional weight gain, depression, dry brittle hair and nails, and fatigue Hyperthyroidism: diarrhea, flushing, increased appetite, muscle weakness, fatigue, palpitations, irritability, nervousness, heat intolerance and altered menstrual flow Question 5 Summarize how levothyroxine works to treat hypothyroidism and include any special instructions for use. Essentially levothyroxine works in the same manner as the endogenous hormone, Thyroxine or T4. By taking levothyroxine, the deficiency is corrected. However, it can be impacted by food or drugs and so it is recommended to take on an empty stomach 30-60 minutes prior to breakfast. Question 6 List the two drugs available for hyperthyroidism and briefly describe how they work. methimazole and propylthiouracil (PTU) are two antithyroid drugs available that work by inhibiting the formation of the thyroid hormones. Question 7 List the two conditions that can occur when there is a deficiency or excess of glucocorticoids released from the adrenal cortex. Specify which is an excess of hormone and which is a deficiency. Addison’s disease- deficiency, Cushing’s syndrome- excess Question 8 Describe how glucocorticoids exert their anti-inflammatory effect. The glucocorticoids work at the cellular level to bind to receptors that either activate the production of anti-inflammatory proteins or prevent proinflammatory protein production. Question 9 Describe the risks associated with long term use of glucocorticoids. Symptoms similar to Cushing’s disease such as, abnormal fat deposits causing a rounded “moon face” or “buffalo hump” on their shoulders. Steroid psychosis is associated with long term use. Prolonged use will result in increased gluconeogenesis which can lead to obesity or diabetes. It will also lead to increased protein catabolism which will show up as muscle weakness and wasting, thinning of skin, osteoporosis, decreased growth in children, decreased wound healing, increased infections. Question 10 Explain the basic mechanism of action around contraceptive medications. By taking an oral contraceptive, the women is introducing exogenous estrogen and progesterone into their body that would not normally be there. This is enough of a change to signal the inhibition of FSH and LH resulting in no ovulation as well as changes to the endometrium that prevent implantation. Question 11 Describe the basic pathophysiology of diabetes, specifically in the pancreas. Diabetes is when the pancreas no longer produces insulin or the cells in the body stop responding to insulin or some combination of the two. Question 12 Define the following terms: hyperglycemia, hypoglycemia, insulin. hyperglycemia- higher than normal glucose level in the blood; fasting blood glucose greater than 126mg/dl Hypoglycemia- lower than normal range of glucose levels in the blood. Typically defines as less than 70mg/dl accompanied with symptoms in patients with diabetes. Insulin- Insulin is the hormone secreted by the beta cells of the pancreas in response to a rise in glucose levels in the blood Question 13 Differentiate between type 1 diabetes and type 2 diabetes. Type 1 diabetes is an autoimmune disorder in which autoantibodies are produced against the beta cells in the pancreas that secrete insulin. Type 2 diabetes is far more common accounting for at least 90% of all patients with diabetes. Type 2 is caused by both an insulin resistance and an insulin deficiency. Meaning there is overall less insulin and that the insulin that is there is not working efficiently. This insulin deficiency results from a loss of the normal responsiveness of the beta cells. In addition, there is a reduction in the number of insulin receptors on the cells and the receptors present are less sensitive. Obesity is a contributing factor in type 2 diabetes. Question 14 List long term consequences of diabetes, both micro and macro vascular. Macrovascular Microvascular Increased risk of stroke Diabetic nephropathy (numbness in hand and feet) High blood pressure Retinopathy (damage to eyes) Increased risk of coronary artery disease Nephropathy (Kidney damage) Peripheral vascular disease (lack of blood flow to legsleading to slow wound healing) Question 15 Cover typical blood glucose goals including fasting blood glucose, pre and post prandial blood glucose and HbA1c. The typical blood glucose goals are Value Goal Fasting Blood Glucose 70-140mg/dl Preprandial (before a meal) 80-130 mg/dl Postprandial (2 hours after a meal) <180 mg/dl HbA1C <7% Question 16 Briefly describe the mechanism of action for the following oral antidiabetic medications: biguanides, sulfonylureas, TZDs, and DPP IV inhibitors. Biguanides- Decreases glucose production in the liver Sulfonylureas- Bind to receptors on the beta cells in the pancreas to stimulate the release of insulin TZDs- Decrease insulin resistance by enhancing the sensitivity of insulin receptors DPP IV inhibitors- Inhibit the enzyme that is responsible for the breakdown of incretin hormones. This reduces fasting and postprandial glucose Question 17 Describe how the two non-insulin injectable drug classes work to lower blood glucose. Amylin Agonists- amylin is a hormone released by the beta cells specifically in response to food. It functions to decrease postprandial glucose levels. This happens in three ways: slows gastric emptying, slows glucagon secretion and glucose production in the lover, increases the sense of feeling full. Amylin agonists work by mimicking the body’s amylin. Incretin Mimetics- incretins are hormones released by the GI tracts in response to food. They stimulate insulin secretion, lower postprandial glucagon, slow gastric emptying and increase the feeling of fullness. Incretin mimetics similarly enhance all of these effects. Question 18 List the four main categories of insulin and put them in order based on quickest onset of action. Insulin lispro, aspart, or glulisine (Humalog, Novolog, Apidra), Regular insulin (Humulin R, Novolin R), Insulin isophane suspension (NPH), Insulin glargine or detimer (lantus or Levemir