Fludrocortisone (Florinef) Pharmacology

On this podcast episode, I cover fludrocortisone. Fludrocortisone is a synthetic corticosteroid with potent mineralocorticoid activity and minimal glucocorticoid effects. It works primarily by promoting sodium reabsorption and potassium excretion in the distal renal tubules, leading to increased water retention and expansion of extracellular fluid volume. This pharmacologic action helps maintain blood pressure and electrolyte balance. Fludrocortisone is most commonly indicated for the treatment of adrenocortical insufficiency, such as Addison’s disease, and for managing orthostatic hypotension by enhancing vascular tone and volume status. Adverse effects are typically related to its mineralocorticoid potency and may include hypertension, edema, hypokalemia, and weight gain. Long-term use can also lead to complications such as heart failure exacerbation, osteoporosis, and mood changes. Because of its sodium-retaining effects, careful monitoring of blood pressure, electrolytes, and signs of fluid overload is recommended during therapy.

One of the most important yet often overlooked concepts in pharmacology is the prescribing cascade. It occurs when a new medication is prescribed to treat a side effect caused by another drug, without realizing that the first medication is the root cause. This leads to a chain reaction of additional prescriptions, unnecessary complexity, and often, new adverse effects. Prescribing cascades can sneak up on even the most careful clinicians. A patient develops a new symptom after starting a medication—perhaps swelling, dizziness, or urinary changes—and instead of identifying the drug as the culprit, another medication is added to manage the symptom. Over time, this cycle contributes to polypharmacy, drug interactions, and reduced quality of life. These cascades are particularly concerning in older adults, where multiple comorbidities and high medication counts make it easy for adverse effects to be misinterpreted as new conditions. But they can occur at any age and in any clinical setting. The key to preventing prescribing cascades is maintaining a critical mindset: Assume any new symptoms could be an adverse effect. Review the timing of medication changes relative to the onset of symptoms. Consider deprescribing or adjusting doses before adding new drugs. Encourage thorough medication reconciliation and communication across providers. Recognizing and interrupting the prescribing cascade is one of the simplest and most impactful ways we can improve medication safety. In this podcast, I share some of my favorite real-world examples that illustrate just how easily these cascades can happen.

Airsupra is a combination inhaler that contains albuterol and budesonide, approved for as-needed use in adults with asthma. It represents the first rescue inhaler to combine a short-acting beta-2 agonist (SABA) with an inhaled corticosteroid (ICS) in a single device. The albuterol component provides rapid bronchodilation by relaxing airway smooth muscle, while budesonide works to reduce airway inflammation and mucus production. This dual mechanism allows Airsupra to not only relieve acute bronchoconstriction but also address the underlying inflammatory process that contributes to asthma exacerbations. Clinically, Airsupra is indicated for as-needed treatment or prevention of bronchoconstriction in adults with asthma, but it is not approved for COPD. The typical dosing is two inhalations as needed, with a maximum of six doses (12 inhalations) in a 24-hour period. The rationale for its use aligns with recent asthma guideline updates, which emphasize minimizing SABA-only use because it fails to address inflammation and may contribute to worse outcomes over time. Common adverse effects include tremor, nervousness, tachycardia, and hypokalemia from albuterol, as well as oral thrush and hoarseness from budesonide. Patients should rinse and spit after each use to reduce the risk of oral candidiasis. Drug interactions can occur with non-selective beta-blockers, which may blunt albuterol’s effects. CYP3A4 also plays a role in budesonide metabolism. Systemic absorption typically isn't too much of an issue with infrequent use.

In this episode of Real Life Pharmacology, we take a deep dive into daptomycin, a lipopeptide antibiotic primarily used for serious Gram-positive infections, including MRSA and VRE. Daptomycin works by binding to bacterial cell membranes in a calcium-dependent manner, causing rapid depolarization and cell death. One key limitation is that daptomycin should never be used for pneumonia because pulmonary surfactant inactivates the drug. Clinically, it’s often reserved for bacteremia, endocarditis, or complicated skin and soft tissue infections. From a pharmacokinetic standpoint, daptomycin is given intravenously and primarily eliminated unchanged by the kidneys, so dose adjustments are necessary in renal impairment. Monitoring creatine kinase (CK) levels is crucial, as one of the major adverse effects is myopathy and, rarely, rhabdomyolysis. Patients on statins have a higher risk of muscle toxicity, and clinicians should consider holding or monitoring statin therapy closely. Eosinophilic pneumonia is another rare but serious adverse reaction that can develop after prolonged therapy. Daptomycin has minimal drug interactions, making it an appealing option when other agents pose risks. Overall, it’s a powerful antibiotic when used appropriately, but requires careful monitoring for muscle and respiratory-related side effects.

Cefepime is a fourth-generation cephalosporin antibiotic with broad-spectrum activity against both gram-positive and gram-negative organisms, including Pseudomonas aeruginosa. It works by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins, leading to cell lysis and death. Clinically, cefepime is commonly used in hospital settings for serious infections such as pneumonia, febrile neutropenia, urinary tract infections, skin infections, and intra-abdominal infections. It’s typically administered intravenously, with doses often ranging from 1 to 2 grams every 8 to 12 hours depending on the indication and renal function. From a pharmacokinetic standpoint, cefepime is primarily renally eliminated, so dose adjustments are required in patients with impaired kidney function. Failure to reduce the dose appropriately can lead to neurotoxicity — one of the key adverse effects associated with cefepime — manifesting as encephalopathy, confusion, myoclonus, or seizures, particularly in elderly or renally impaired patients. Common side effects include gastrointestinal upset and rash. Cefepime has relatively limited drug interactions, though concurrent nephrotoxic agents can increase the risk of renal injury.

Midodrine is an oral alpha-1 agonist most commonly used for the treatment of symptomatic orthostatic hypotension. Its mechanism of action is through peripheral vasoconstriction, which helps increase blood pressure. Because of its short duration of action, it is typically dosed three times daily, with the last dose recommended in the late afternoon to reduce the risk of hypertension at night. Clinically, midodrine is often considered when non-pharmacologic strategies for orthostatic hypotension (such as increased salt/fluid intake, compression stockings, or physical counter-maneuvers) are not enough. Pharmacists should also be aware of prescribing cascades—such as urinary retention leading to tamsulosin initiation—that can arise when midodrine is used. Midodrine is generally not metabolized through cytochrome P450 pathways, so significant drug–drug interactions are less common. However, caution should be exercised with other agents that can raise blood pressure (like decongestants) or slow the heart rate (such as beta-blockers). Monitoring parameters include blood pressure, pulse, symptoms of urinary retention, and the patient’s overall response to therapy.

Zosyn (piperacillin/tazobactam) is a broad-spectrum β-lactam/β-lactamase inhibitor combination used widely in hospitals. Piperacillin covers gram-positive, gram-negative, and anaerobic bacteria, while tazobactam helps protect against β-lactamase breakdown. It is commonly used for pneumonia, intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. An important pharmacology pearl for exams is understanding that Pseudomonas, but it doesn't cover MRSA. The drug is renally eliminated, so dosing adjustments are needed in kidney impairment. Many institutions use extended or prolonged infusions to maximize time above the MIC, which can improve efficacy. Standard dosing is 3.375 g to 4.5 g every 6–8 hours, with modifications for dialysis patients. Adverse effects include hypersensitivity, gastrointestinal upset, electrolyte imbalances like hypokalemia, and blood count changes with prolonged therapy. A key clinical concern is nephrotoxicity risk, especially when used with vancomycin. Monitoring renal function and electrolytes are important. Methotrexate and probenecid are two medications that can interact with Zosyn. Concentrations of Zosyn can be increased when these medications are used in combination.

Senna is a stimulant laxative. Its pharmacological activity comes from natural compounds called sennosides. Metabolites act locally in the colon to stimulate peristalsis, thereby accelerating bowel movements. While osmotic laxatives are generally considered first-line laxative agents, this makes senna a useful alternative for the short-term treatment of constipation. The pharmacokinetics of senna are unique in that its onset of action typically takes 6 to 12 hours after oral administration, reflecting the time required for colonic bacteria to metabolize sennosides into active compounds. This delayed onset makes senna better suited for bedtime dosing when overnight relief is desired. Although senna is effective, its use carries potential adverse effects. Common side effects include abdominal cramping, diarrhea, and, rarely, electrolyte disturbances such as hypokalemia. Chronic or excessive use can lead to dependency and possibly melanosis coli, a benign but visible pigmentation of the colon lining. Drug interactions may occur, particularly with medications affected by potassium levels, such as digoxin or diuretics. For these reasons, senna is generally recommended for short-term use, with emphasis on evaluating underlying causes of constipation before long-term therapy is considered.

Revefenacin (brand name Yupelri) is a long-acting muscarinic antagonist (LAMA) used for the maintenance treatment of chronic obstructive pulmonary disease (COPD). It works by blocking muscarinic receptors, particularly the M3 subtype, in airway smooth muscle. This antagonism reduces cholinergic bronchoconstriction and leads to sustained bronchodilation. Unlike short-acting anticholinergics such as ipratropium, revefenacin provides 24-hour bronchodilation with once-daily dosing. One of the distinguishing features of revefenacin is that it is the first nebulized LAMA approved for COPD maintenance therapy. Many patients with advanced COPD, physical limitations, or difficulty using handheld inhalers benefit from a nebulized formulation, as it allows medication delivery without requiring hand-breath coordination or a forceful inhalation. This makes it a useful option for patients with poor inhaler technique or those transitioning from hospital care. Pharmacokinetically, revefenacin is delivered via nebulization, with peak effects typically observed within a couple of hours. Importantly, systemic absorption is relatively low, but elderly patients or those with hepatic impairment may be more susceptible to anticholinergic side effects. Clinically, revefenacin improves lung function, reduces COPD symptoms, and can decrease exacerbation frequency. Common adverse effects include cough, dry mouth, constipation, and urinary retention. Caution is advised in patients with narrow-angle glaucoma or prostatic hyperplasia due to its antimuscarinic properties. Revefenacin is not intended for acute bronchospasm or rescue therapy—it is strictly for long-term, once-daily maintenance.

Desmopressin is a synthetic analog of vasopressin, also known as antidiuretic hormone (ADH). It works by mimicking the action of natural ADH on the kidneys, primarily increasing water reabsorption in the collecting ducts. This effect reduces urine production and helps concentrate the urine. Because of this mechanism, desmopressin is commonly used in conditions like diabetes insipidus, nocturnal enuresis (bedwetting), and sometimes for nocturia in adults. It also has a role in certain bleeding disorders, such as mild hemophilia A and von Willebrand disease, since it can increase plasma levels of factor VIII and von Willebrand factor. In this podcast, we will explore desmopressin pharmacology and much more. Desmopressin is available in several dosage forms, including oral tablets, intranasal spray, and injectable formulations. The choice depends on the indication and patient-specific factors such as age, convenience, or the need for rapid effect. Adverse effects of desmopressin are largely related to water balance. Because it reduces urine output, patients are at risk for water retention and hyponatremia, which can lead to headaches, confusion, seizures, or in severe cases, coma. Monitoring sodium levels is especially important in elderly patients and those taking other medications that can affect fluid or electrolyte balance. Clinicians also need to be mindful of drug interactions. Medications that increase the risk of hyponatremia, such as SSRIs, carbamazepine, or certain diuretics, may enhance desmopressin’s adverse effects. Conversely, drugs that blunt its activity can reduce effectiveness. Careful monitoring and patient education are key parts of safe use.