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.
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Airsupra (Albuterol/budesonide) Pharmacology
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.
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Daptomycin Pharmacology
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.
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Cefepime Pharmacology
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.
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Midodrine Pharmacology Podcast
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.
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