Pantoprazole Pharmacology

On this episode, I cover pantoprazole pharmacology, adverse effects, and drug interactions.

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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.

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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.

Codeine Pharmacology

On this episode, I discuss codeine pharmacology and practical clinical practice pearls.

Codeine is metabolized by CYP2D6 to the active metabolite morphine. I discuss how this can be affected by genetics as well as other medications.

Constipation is a problem with codeine and all opioids in general. Education and making a plan with patients to combat this side effect is important.

Codeine is less potent than other opioids such as fentanyl, hydromorphone, and hydrocodone.

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!