Glipizide Pharmacology

Glipizide, or Glucotrol, is a sulfonylurea used for the treatment of Type 2 Diabetes. Pharmacologically, glipizide acts by stimulating beta-cells in the pancreas to release insulin. Specifically, glipizide will block the opening of ATP-sensitive potassium channels on the plasma membrane of beta-cells on the pancreas. The result of that is depolarization, which then causes stimulation of voltage-sensitive calcium channels, eventually causing the exocytosis of insulin. The increased insulin will then promote the storage of glucose, decreasing the amount of glucose in the blood. 

Due to the pharmacology of glipizide, the concerning adverse drug reactions are hypoglycemia and weight gain. Other adverse drug reactions include diaphoresis, dizziness, syncope, nervousness, anxiety, tremors, and diarrhea. The contraindications include hypersensitivity, Type 1 Diabetes, and DKA. Glipizide is not used as often due to the risk of hypoglycemia and weight gain. Glipizide is usually dosed once daily, but it can be split up if the dose is escalated. There are differences in administration depending on the formulation. For immediate release formulations, glipizide should be taken 30 minutes before meals to ensure that absorption is stable. For extended formulations, it can be given with breakfast or any other meal. 

Of all the sulfonylureas, glipizide is preferred in CKD. Other sulfonylureas, like glyburide, are not preferred due to a decrease in elimination that can result in dose accumulation. In geriatric populations, dosing is less aggressive to lessen the risk of any adverse drug reactions and more specifically hypoglycemia. There’s a risk of cross-reactivity with sulfonamide allergies, but the risk will vary and is low risk. If SJS occurs due to a sulfonamide-containing drug, glipizide likely wouldn’t be recommended.

The drug-drug interactions of glipizide include medications that can increase the risk of hypoglycemia, for example, medications like quinolone antibiotics and B-blockers can mask the symptoms of hypoglycemia. Other interactions include the type where it can counteract the effect of glipizide, for example, medications that can increase blood glucose levels like corticosteroids, antipsychotics such as olanzapine and clozapine, stimulants, and transplant medications like cyclosporine and tacrolimus. There are also CYP interactions that can impact glipizide since it’s metabolized by CYP2C9. More monitoring is warranted when medications that can inhibit CYP2C9, like fluconazole, and medications that can induce CYP2C9, like rifampin, are also given. In cases of overdose, hypoglycemia is most likely to occur. Correction of decreased glucose levels is necessary.

Show notes provided by Chong Yol G Kim, PharmD Student.

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Insulin Glargine Pharmacology

On this episode, I discuss insulin glargine pharmacology. Insulin glargine is a long-acting insulin that has the common brand names Lantus, Basaglar, and Toujeo. Due to the pharmacology of insulin glargine, it provides a baseline coverage of insulin. It cannot manage acute elevations in blood glucose like target-specific meals. Instead, insulin glargine is used to decrease blood sugar throughout the day. 

It is normally dosed once a day, and sometimes a patient will have another type of insulin that’s rapid-acting, like Humalog. The daily insulin dose will vary, but it’s frequently a 50/50 split between long-acting, and rapid-acting. Dosing of insulin glargine in Type 2 diabetes is usually started at 10 units, but that can vary based on the patient or pertinent clinical data. Whenever doses need to be changed, it’s typically done in the range of 3-7 day intervals. Generally, when dose increases are desired, and the risk for hypoglycemia is low, a 10-20% increase is mostly what’s done. When converting between different types of insulin, the majority are 80% to 1:1 equivalent. Clinical monitoring is vital with any conversion.

Insulin glargine is best suited in long-acting situations due to its formulation. Its solubility varies at different levels of acidity. The pH of the injected solution is 4, where insulin glargine is completely soluble. When the solution is at physiological pH, around 7.4, micro-precipitations can form causing small amounts of insulin glargine to be released over 24 hours. The onset of action of insulin glargine is roughly 3-4 hours, and hypoglycemia is not an immediate concern because of this. If a medication error occurs with insulin glargine, it likely wouldn’t be noticed immediately due to its kinetics. For rapid-acting insulin like Humalog, it would be noticed more quickly.

Monitoring for insulin glargine is individualized, but it’s generally done through measuring A1c levels. Serum potassium levels can also be monitored, but with longer-acting insulins, it is less of a concern. The most common adverse reactions of insulin glargine are hypoglycemia, weight gain, peripheral edema, and immunological reactions. Drug-drug interactions aren’t a large concern with insulins, due to the amount of monitoring of patients on them. There are risks of potentiation of hypoglycemia or masking of the signs and symptoms of hypoglycemia. With diabetic patients, the compounded risk of hypoglycemia might be greater if they’re taking other medications like metformin, GLP-1 agonists, sulfonylureas, SGLT2 inhibitors, etc. Some other drugs that can increase the risk of hypoglycemia are quinolone antibiotics, B-blockers, or thiazide diuretics. The efficacy of insulin glargine can also be decreased by corticosteroids, stimulants, antipsychotics, or transplant medications.

In cases of overdose, because of the pharmacology of insulin glargine, hypoglycemia is common. The milder cases of hypoglycemia can be treated with oral carbohydrates, and simply adjusting the dose, meal patterns, or exercise may suffice. In severe cases of hypoglycemia, coma, seizure, or neurologic impairment may occur. Symptoms of severe hypoglycemia can be treated with glucagon or glucose and these patients typically need to be hospitalized. Once an overdosed patient recovers from hypoglycemia, clinical observation, and carbohydrate intake may be necessary to avoid recurrence.

Show notes provided by Chong Yol G Kim, PharmD Student.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

Study Materials For Pharmacists and Students

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Resources

Paragraph 1: taken from podcast

Paragraph 2: taken from podcast

Paragraph 3: pH solubility (https://go.drugbank.com/drugs/DB00047#mechanism-of-action), medication error taken from podcast

Paragraph 4: taken from podcast, ADRs taken from Lexicomp

Paragraph 5: overdose information (“FDA Approved Drug Products: Lantus (Insulin glargine) for subcutaneous injection”)

Empagliflozin Pharmacology

On this episode I discuss empagliflozin pharmacology and how this medication lowers blood sugar.

In this episode, I talk about empagliflozin pharmacology. Empagliflozin is more commonly known by the brand name Jardiance and is in the class of sodium-glucose co-transporter-2 inhibitors or SGLT2 inhibitors. Jardiance use has definitely escalated over the last few years in the management of type 2 diabetes, but this has been changing a little bit as well due to recent evidence for the cardiovascular benefits from this medication.

The sodium-glucose co-transporter-2 is found in the kidney and is responsible for helping the body reabsorb glucose back into the bloodstream. The way empagliflozin works is by inhibiting this transporter, more glucose is excreted into the urine and ultimately lowering the blood sugar since it is not being reabsorbed. Empagliflozin has additional benefits outside of blood sugar reductions. Studies found that patients with or without diabetes receive cardiovascular protective effects from this medication, including a reduction in heart failure hospitalizations and reducing the risk of death in patients with ASCVD. Additionally, empagliflozin has shown some benefits in protecting renal function over time in patients with and without chronic kidney disease (CKD).

Dosing is pretty straightforward for this medication. Empagliflozin is taken once daily and is an oral medication, which is nice for patients who do not want injectable therapy. Dosing starts at 10 mg once daily and may be increased up to 25 mg daily if tolerated. This increase is typically done after about 4 weeks to see if it is needed. In patients with renal dysfunction and an eGFR less than 45 mL/min, FDA labeling states that empagliflozin should not be initiated, although there is a gray area in the 30-45 mL/min range that needs further study.

When thinking about the side effects of empagliflozin, it is helpful to keep the mechanism of action in mind, where we are increasing the urinary glucose. This can also lead to more fluid being excreted with the glucose, causing a decrease in blood pressure and dehydration risks. This is important to keep in mind for patients who are more prone to hypotension, including elderly patients. Empagliflozin also causes increased genitourinary fungal infections and UTIs due to the increase in sugar in the urine. Other rare adverse effects include ketoacidosis, necrotizing fasciitis risk, bone fracture, and lower limb amputation, however, this one has more controversial evidence.

For monitoring parameters, assessing A1c reduction and blood sugars is definitely important in our patients with diabetes. Patients on empagliflozin should also have their renal function monitored, as well as any blood pressure lowering. It is also important to keep an eye on any prescribing of antifungals, the incidence of UTIs, and assessing for signs of ketoacidosis.

The most important and common drug interactions are typically associated with additive effects with empagliflozin. Diuretic use can increase the risk for dehydration and hypotension. Additive blood sugar-lowering effects when empagliflozin is used with other agents such as insulin and sulfonylureas and can increase the patient’s risk for hypoglycemic episodes. Finally, blood pressure medication dosages may need to be reduced if empagliflozin is causing hypotension. Since empagliflozin is not hepatically metabolized, CYP450 drug interactions are not a problem.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

Resources: 

Empagliflozin. Micromedex DrugDex. IBM Micromedex. Accessed July 29, 2021.Yusuf T, Raji YR, Lasisi TJ, et al. Predictors of taste dysfunction and its severity among patients with chronic kidney disease. Ear Nose Throat J. Published online July 19, 2021. doi:10.1177/01455613211019708.

Glucagon Pharmacology

On this episode of the RLP podcast, I discuss glucagon pharmacology.

It is important to remember with glucagon that patients will still require glucose following administration to improve their blood sugar numbers.

Glucagon is typically reserved for moderate to severe episodes of hypoglycemia when patients have altered consciousness.

The major adverse effect with glucagon is nausea and vomiting which often may prevent oral intake of glucose for some time after administration.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

Dulaglutide Pharmacology

Dulaglutide is a GLP-1 agonist used in the management of diabetes.

Dulaglutide has 4 different dosages that can be used to help lower A1C. As the dose goes up, so does the potential for adverse effects however.

Like most of the GLP-1 agonists, dulaglutide is only available as an injection. Semaglutide is an exception to this.

Nausea is the primary adverse effect of dulaglutide which some patients may get used to over time.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

Dapagliflozin Pharmacology

Dapagliflozin is an SGLT-2 Inhibitor that reduces blood sugar by increasing the excretion of sugar through the urine.

Genital and urinary infections is a potential risk with the use of SGLT2 Inhibitors like dapagliflozin.

Dapagliflozin has received FDA approval for use in heart failure (in patients even without diabetes).

Be aware of agents that may enhance the risk for hypoglycemia such an insulin and sulfonylureas.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

Oral Semaglutide Pharmacology

On this episode, I discuss the pharmacology of oral semaglutide. It is a GLP-1 agonist that is the first one in the class to have an oral formulation.

There is a recommended dose titration with oral semaglutide that can take a month or two to get therapeutic doses. I disucss this further in this episode.

The most common adverse effect of oral semaglutide is nausea.

Oral semaglutide is dosed once daily which is nice to try to maximize patient adherence.

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Pioglitazone Pharmacology

pioglitazone pharmacology

On this episode, I cover pioglitazone pharmacology. The primary mechanism of action with pioglitazone is that it is an agonist at Peroxisome Proliferator Activated Receptor Gamma receptor. This improves insulin sensitivty in the periphery.

Two common side effects exist with pioglitazone. This drug can cause weight gain and also contribute to edema.

Pioglitazone has a boxed warning and is contraindicated in patients who have symptomatic heart failure.

There are a few potential interactions with pioglitazone. Trimethoprim and gemfibrozil can inhibit the breakdown of pioglitazone.

A couple of advantages of pioglitazone include that it is generic (inexpensive) and that it is dosed once daily.

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GLP-1 Agonist Pharmacology

The GLP-1’s are a relatively newer class of medications used to lower blood sugars in diabetes.

GLP-1’s work by simulating the effects of incretin hormones in the body. They can help promote fullness, lower weight, and stimulate insulin release following a meal.

GLP-1’s can cause significant GI side effects. Nausea is by far the most common adverse effect. It can even lead to diarrhea and vomiting in some cases.

There is boxed warning on the GLP-1 agonists. Be aware of patients who have had a history of thyroid cancer as this may be a contraindication.

GLP-1 agonists can help lower A1C and stimulate weight loss which is a huge benefit for most patients with Type 2 diabetes.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!