Question

The role of P450s in drug-drug interactions axiore gactive drug 1. Your patient is a 64-year old male who is currently taking tacrine* for treatment of early stage Alzheimer's disease and lovastatin for high cholesterol. Predict and explain how the drug concentration may change for each drug if the patient makes the following changes in his habits. Each change is independent, don't carry over answers. Your explanation must include a brief explanation of what type of enzyme regulation is being mimicked in each scenario in Substrates (partial list) Inhibitors (partial list) Inducers (partial list) T iede CYP1A2 Caffeine, melatonin, Cimetidine, ciproflaxin, Tobacco tacrine, tizanidine CYP3A4/3A5 Dasatinib, indinavir, Atazanavir, saquinavir, Rifampin, St. John's lovastatin, simvastatin telithromycin need a) He begins taking St. John's Wort, an herbal supplement said to aid in memory, in an effort to retain mental acuity. b) He develops gastroesophageal reflux disease (GERD) and is prescribed cimetidine to help reduce the formation of excess gastric acid. c) After developing a chronic cough, which can be an early warning sign of lung cancer, he quits smoking. *Tacrine has been taken off the market. As has ended up being true for most drugs designed to improve cognition or delay symptom onset in Alzheimer's patients, the impact of the drug was small and its clinical relevance doubtful. This, combined with concerns about safety, means it is no longer prescribed in the USA

Answer 1

a)St. John's wort extract (SJW) (Hypericum perforatum L.) is among the most commonly used herbal medications in the United States. The predominance of clinical reports indicates that SJW increases the activity of cytochrome P450 3A4 (CYP3A4) enzyme and reduces plasma concentrations of certain drugs. Although the inductive effect of SJW on CYP3A4 is clear, other reports indicate that SJW constituents may have, to a small degree, some enzyme inhibitory effects.

b) Drug interactions with many antihypertensive agents that are metabolized by the cytochrome P450 system have been reported. For example, cimetidine hydrochloride can decrease metabolism and increase steady-state plasma concentrations of several concomitantly administered drugs, including calcium channel blockers .  

c)      

• A cough that does not go away or gets worse
• Coughing up blood or rust-colored sputum (spit or phlegm)
• Chest pain that is often worse with deep breathing, coughing, or laughing
• Hoarseness
• Loss of appetite
• Unexplained weight loss
• Shortness of breath
• Feeling tired or weak
• Infections such as bronchitis and pneumonia that don’t go away or keep coming back
• New onset of wheezing