## Enzyme Induction: Rifampicin and Theophylline **Key Point:** Rifampicin is a potent inducer of multiple CYP450 enzymes, including CYP1A2, which is the primary enzyme metabolizing theophylline. Induction increases theophylline clearance, reducing its plasma concentration and therapeutic effect, necessitating dose escalation. ### Mechanism of Interaction 1. Rifampicin binds to pregnane X receptor (PXR) and constitutive androstane receptor (CAR) 2. Upregulation of CYP1A2 gene expression 3. Increased theophylline metabolism → reduced half-life 4. Lower steady-state theophylline concentration → loss of bronchodilator effect 5. **Clinical consequence:** Asthma control deteriorates; theophylline dose must increase by 50–100% **High-Yield:** Rifampicin is the most potent CYP450 inducer in clinical practice. It induces CYP3A4, CYP2C9, CYP2C19, CYP1A2, and glucuronidation pathways. ### Drugs Affected by Rifampicin Induction | Drug Class | Examples | Clinical Impact | | --- | --- | --- | | Theophyllines | Theophylline | Reduced bronchodilation | | Anticoagulants | Warfarin | Reduced anticoagulation → thrombosis risk | | Oral contraceptives | Ethinyl estradiol | Reduced contraceptive efficacy | | Antifungals | Ketoconazole, itraconazole | Reduced antifungal levels | | Protease inhibitors | Ritonavir, lopinavir | Reduced antiretroviral effect | | Corticosteroids | Prednisolone | Reduced anti-inflammatory effect | **Clinical Pearl:** Patients on warfarin or oral contraceptives starting rifampicin require close monitoring and dose adjustments to prevent treatment failure or unintended pregnancy. **Mnemonic:** **Rifampicin Induces = CRASH-PC** - **C**orticosteroids - **R**etrovirals (PIs, NNRTIs) - **A**ntiarrhythmics (quinidine) - **S**ulfonamides (sulfonylureas) - **H**ypoglycemics - **P**rotein synthesis inhibitors - **C**ontroceptives
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