Pharmacology- Endocrine: Diabetes Treatment

Sulfonylureas are a class of diabetic medication that is contraindicated if a person has an allergy to Sulfa drugs. This means that if someone is allergic to Sulfa drugs, they should not take Sulfonylureas as it could cause an allergic reaction. It is important for individuals with diabetes to be aware of any allergies they may have and to inform their healthcare provider so that appropriate medications can be prescribed.

The correct answer is to consume glucose-containing foods. This is because when a patient is conscious and alert, they are able to eat or drink something to raise their blood sugar levels quickly. Glucose-containing foods such as fruit juice, soft drink, crackers, milk, and glucose tablets can provide a rapid source of glucose to counteract the hypoglycemia. It is important to avoid foods containing fat in this situation because fat slows down the absorption of glucose and may delay the increase in blood sugar levels. Taking the patient to the hospital for evaluation and treatment may be necessary in severe cases or if the hypoglycemia does not improve with oral intake.

Biguanides, such as metformin, are considered the first-line agent for diabetes unless contraindicated. They work by reducing glucose production in the liver, increasing insulin sensitivity in the muscles, and decreasing glucose absorption in the intestines. Thiazolidinediones, DPP-4 inhibitors, and meglitinides are also used in the management of diabetes, but they are typically considered second-line agents. Thiazolidinediones improve insulin sensitivity, DPP-4 inhibitors increase insulin secretion, and meglitinides stimulate insulin release. However, due to their efficacy, safety profile, and cost-effectiveness, biguanides are generally preferred as the initial treatment option for diabetes.

Metformin is the correct answer because it is a commonly prescribed medication for diabetes that can cause side effects such as diarrhea, abdominal discomfort, and lactic acidosis. Glyburide, Prandin, and Januvia are other medications used to treat diabetes, but they do not typically cause these specific side effects.

Obese patients, individuals with sedentary lifestyles, and those going through puberty often require a higher total daily insulin (TDI) dosage. This is because obesity can lead to insulin resistance, sedentary lifestyles can decrease insulin sensitivity, and during puberty, hormonal changes can affect insulin requirements. Therefore, the statement "Higher total daily insulin (TDI) needed for obese patients, those with sedentary lifestyles, & during puberty" is true.

Thiazolidinediones (TZDs)- Considerations/ADEs
• Wt gain, edema
• Black box warning - Contraindicated in patients w/
CHF, NYHA III/IV

Bile acid sequestrants are known to decrease glucose levels, but the exact mechanism by which they do so is unknown. They act as bile acid binders, which suggests that they may bind to bile acids in the intestines and prevent their reabsorption. This may indirectly affect glucose metabolism, but the precise details are not yet fully understood.

Thiazolidinediones should be avoided in a patient with comorbidities that include coronary disease (HF) because these medications have been associated with an increased risk of heart failure. Thiazolidinediones work by increasing insulin sensitivity, but they can also cause fluid retention and worsen heart failure symptoms. Therefore, prescribing this medication to a patient with coronary disease and heart failure could potentially exacerbate their condition and lead to adverse outcomes.

SGLT2 inhibitors are a class of medication used to treat type 2 diabetes. They work by inhibiting the sodium-glucose cotransporter 2 in the kidneys, which leads to increased glucose excretion in urine. This mechanism of action can cause genitourinary (GU) infections, as glucose in the urine can promote bacterial growth. Weight loss can occur as a result of the increased glucose excretion. Polyuria, or increased urination, is a common side effect of SGLT2 inhibitors due to the increased glucose excretion. Lastly, SGLT2 inhibitors have been associated with an increase in LDL cholesterol levels.

With prandial insulin, each dose is determined by estimating the carbohydrate content of the meal. Prandial insulin is also known as mealtime insulin and is taken before or after meals to control blood sugar levels after eating. It helps to regulate the rise in blood sugar that occurs after consuming carbohydrates. Basal insulin, on the other hand, is taken to provide a steady level of insulin throughout the day and night, regardless of meals.

Basal insulin is the correct answer because it controls glucose production between meals and overnight. Basal insulin is a long-acting insulin that provides a steady release of insulin throughout the day and night, helping to maintain blood sugar levels in the absence of food intake. It helps to regulate glucose production by the liver and prevents excessive glucose release, ensuring stable blood sugar levels during fasting periods.

Amylin analogs bind to amylin receptors and slow gastric emptying. This means that they delay the emptying of the stomach, which in turn slows down the absorption of carbohydrates (sugar) ingested. By slowing down the absorption of carbohydrates, amylin analogs can help decrease postprandial (PP) hyperglycemia, which is high blood sugar levels after eating. This mechanism of action is important in managing blood sugar levels in individuals with diabetes.

Alpha-glucosidase inhibitors are contraindicated in patients with inflammatory bowel disease or cirrhosis. These medications work by slowing down the digestion and absorption of carbohydrates in the intestines. In patients with inflammatory bowel disease, this can exacerbate symptoms and lead to further inflammation. Similarly, in patients with cirrhosis, these medications can worsen the condition by causing bloating, gas, and diarrhea. Therefore, it is important to avoid the use of alpha-glucosidase inhibitors in these patient populations.

Sulfonylureas work by increasing endogenous insulin secretion. They bind to receptors on pancreatic beta cells, which triggers a series of reactions that ultimately leads to the production and release of more insulin. This helps to stimulate the pancreas to produce more insulin and regulate blood glucose levels.

Alpha-glucosidase inhibitors work by blocking enzymes that digest starches in the small intestine, which slows down the absorption of glucose. This leads to a decrease in postprandial (PP) hyperglycemia, as the rise in blood sugar levels after a meal is reduced. This explanation aligns with the given answer choice.

Biguanides are a class of diabetic medication that is contraindicated in patients with impaired renal function. This is because biguanides can increase the risk of lactic acidosis, a serious condition that can occur when there is a buildup of lactic acid in the body. Impaired renal function can decrease the body's ability to excrete lactic acid, leading to an increased risk of lactic acidosis. Additionally, biguanides need to be held 24 hours before and 48 hours after an IV dye load because the dye can further impair renal function and increase the risk of lactic acidosis. Therefore, biguanides should be avoided in patients with impaired renal function and during the peri-procedural period involving IV dye administration.

GLP-1 receptor agonists work by inhibiting the breakdown of glucagon-like peptide-1 that is secreted during meals. This leads to an increase in insulin release and synthesis, as well as a decrease in glucagon levels. This mechanism helps to regulate blood sugar levels by promoting insulin sensitivity and reducing the production of glucose by the liver.

Alpha-glucosidase inhibitors are contraindicated in patients with inflammatory bowel disease and cirrhosis because these medications work in the gut. Inflammatory bowel disease can cause inflammation and damage to the intestines, and cirrhosis affects the liver. Since alpha-glucosidase inhibitors work by slowing down the digestion of carbohydrates in the gut, they may worsen the symptoms and complications of these conditions. Therefore, it is recommended to avoid using alpha-glucosidase inhibitors in patients with inflammatory bowel disease and cirrhosis.

Amylin analogs are a type of medication that can be used in both Type 1 and insulin-dependent Type II DM. They are administered via subcutaneous injection, typically immediately prior to meals. These analogs mimic the effects of amylin, a hormone that is normally produced by the pancreas along with insulin. By using amylin analogs, blood sugar levels can be better controlled, as they help to slow down the rate at which food is absorbed from the stomach and reduce the amount of glucose released by the liver. This can be especially beneficial when taken before meals, as it can help to prevent post-meal spikes in blood sugar levels.

Meglitinides stimulate insulin secretion rapidly and for a short duration, making them most effective when glucose is present. They bind to receptors on pancreatic beta cells, triggering a series of reactions that lead to insulin secretion. This mechanism helps to control blood sugar levels by increasing the amount of insulin available in the body. Unlike other medications, meglitinides do not decrease hepatic glucose production or slow the absorption of carbohydrates.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors are a class of diabetic medication that suppresses glucagon secretion and delays gastric emptying. Glucagon is a hormone that increases blood sugar levels, so suppressing its secretion helps to control blood sugar levels in diabetic patients. Delaying gastric emptying promotes satiety, which can help in managing weight and controlling food intake. Therefore, DPP-4 inhibitors address both the hormonal imbalance and the feeling of hunger, making them an effective choice for diabetic patients.

- Biguanides: Reduce production of glucose by the liver and increase insulin sensitivity ‐ Sulfonylureas: Stimulate the pancreas to produce more insulin ‐ Meglitinides: Stimulate the pancreas to produce more insulin ‐ Thiazolidinediones: Increase insulin sensitivity of the body cells and reduce the production of glucose by the liver ‐ DPP‐4 inhibitors: Intensify the effect of intestinal hormones (incretins) involved in the control of blood sugar, increase insulin release/synthesis, decrease glucagon levels ‐ GLP‐1 receptor agonists: Mimic the effect of certain intestinal hormones (incretins) involved in the control of blood sugar, increase insulin release, decrease glucagon levels ‐ Alpha-glucosidase inhibitors: Slow the absorption of carbohydrates (sugar) ingested, decrease PP hyperglycemia ‐ Bile acid sequestrants: Bile acid binder, decrease glucose via unknown mechanisms ‐ Amylin mimetics: Binds to amylin receptors slows gastric emptying

Thiazolidinediones work by decreasing insulin resistance, which means they increase the sensitivity of muscle and adipose cells to insulin. This helps the cells take up glucose more effectively and lowers blood sugar levels. Additionally, thiazolidinediones also suppress hepatic glucose production, further reducing blood sugar levels.

For a patient who is severely confused or unconscious due to hypoglycemia, the appropriate treatment would be a glucagon injection. Glucagon is a hormone that helps raise blood sugar levels by stimulating the liver to release stored glucose. This is a fast-acting treatment that can quickly raise the patient's blood sugar levels and help alleviate their symptoms. However, it is also important for the patient to be taken to the hospital for further evaluation and treatment to determine the underlying cause of the hypoglycemia and prevent future episodes.

Dipeptidyl Peptidase-4 (DPP-4) inhibitors work by inhibiting the enzyme DPP-4, which is responsible for breaking down incretins such as glucagon-like peptide-1 (GLP-1). By inhibiting DPP-4, these inhibitors slow down the metabolism of incretins, leading to increased insulin synthesis and release. Additionally, they decrease glucagon levels, which helps to lower blood sugar levels. This overall effect of DPP-4 inhibitors helps to improve glycemic control in patients with diabetes.

Meglitinides
Similar to sulfonylureas, but more rapid onset- shorter acting
MOA: stimulate insulin secretion (rapidly and for a short duration) most effective in the presence of glucose.
Efficacy
• Decreases peak postprandial glucose
• Decreases plasma glucose 60-70 mg/dl
• Reduce A1C 0.5- 1.5%
• * Depends on glucose for activity

Glucagon-Like Peptide-1 Agonists have a lower risk of hypoglycemia compared to Thiazolidinediones and Meglitinides. They also cause weight loss, which is a beneficial effect for patients with diabetes. However, they can also cause GI symptoms and pancreatitis, so caution is advised in patients with these conditions. Additionally, they are cautioned in patients with renal dysfunction and gastroparesis, as their use may be associated with adverse effects in these populations.

NPH insulin has a greater risk of nocturnal hypoglycemia compared to Glargine. Nocturnal hypoglycemia refers to low blood sugar levels during the night while the person is asleep. NPH insulin has a shorter duration of action and peaks in its effect about 4-6 hours after administration, which can increase the risk of hypoglycemia during the night. On the other hand, Glargine insulin has a longer duration of action and provides a more stable and consistent blood sugar control, reducing the risk of nocturnal hypoglycemia.

The consequences of hypoglycemia include falls, angina, confusion, fatal arrhythmia, irritability, and dementia. Hypoglycemia is a condition characterized by low blood sugar levels, which can lead to a variety of symptoms and complications. Falls can occur due to dizziness or weakness caused by low blood sugar. Angina, or chest pain, may result from reduced blood flow to the heart. Confusion and irritability are common neurological symptoms associated with hypoglycemia. In severe cases, hypoglycemia can cause fatal arrhythmia, an abnormal heart rhythm, and long-term complications such as dementia may also occur.

Bile Acid Sequestrants are a drug class that can cause constipation, indigestion, flatulence, and possible dysphagia. They can also exacerbate hypertriglyceridemia, which is an increase in triglyceride levels in the blood. These drugs work by binding to bile acids in the intestines, preventing their reabsorption. This leads to increased excretion of bile acids and cholesterol, which can help lower cholesterol levels. However, the side effects mentioned are common with this class of drugs.

Amylin analogs are medications that can increase the risk of hypoglycemia, which is a condition characterized by low blood sugar levels. These medications can also cause side effects such as headaches, nausea, and cough. Additionally, caution should be exercised when using amylin analogs in patients with gastroparesis, a condition that affects the movement of food through the stomach. Therefore, amylin analogs have a higher risk of hypoglycemia and exhibit the mentioned side effects, making them the correct answer to the question.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors have a lower risk of hypoglycemia compared to other diabetic medications. However, they have been associated with side effects such as pancreatitis, nausea/vomiting (N/V), angioedema, and anaphylaxis. Additionally, caution should be exercised when prescribing DPP-4 inhibitors to patients with renal insufficiency.

Meglitinides and alpha-glucosidase inhibitors are medications that can decrease peak postprandial glucose levels. These medications work by different mechanisms to help control blood sugar levels after meals. Meglitinides stimulate the release of insulin from the pancreas, while alpha-glucosidase inhibitors slow down the digestion of carbohydrates and prevent a rapid increase in blood sugar levels. Thiazolidinediones and biguanides are other types of medications used to treat diabetes, but they do not specifically target postprandial glucose levels.

Alpha-Glucosidase Inhibitors are medications that work by slowing down the digestion of carbohydrates in the small intestine. They are not systemically absorbed, meaning they do not enter the bloodstream and have their effects localized in the gastrointestinal tract. This is why they do not cause hypoglycemia, as they do not directly affect blood sugar levels. Additionally, Alpha-Glucosidase Inhibitors are classified as Pregnancy Category B, which means that there is no evidence of risk to the fetus in animal studies, but there are no adequate studies in pregnant women.

Sulfonylureas are a class of medications used to treat type 2 diabetes. Adverse drug reactions associated with sulfonylureas include weight gain, rash, photosensitivity, hepatic impairment, and renal impairment. Weight gain can occur as a side effect of these medications. Rash and photosensitivity can occur as allergic reactions to sulfonylureas. Sulfonylureas can also affect the liver and kidneys, leading to hepatic and renal impairment. Therefore, individuals with hepatic or renal impairment should use caution when taking sulfonylureas.

Patient Characteristics
• Older age
• Female gender
• African American ethnicity
• Longer duration of diabetes
• Neuropathy
• Renal impairment
• Previous hypoglycemia