CYP450 inhibition and induction US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for CYP450 inhibition and induction. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
CYP450 inhibition and induction US Medical PG Question 1: A 72-year-old man presents to the emergency department with a 1 hour history of bruising and bleeding. He says that he fell and scraped his knee on the ground. Since then, he has been unable to stop the bleeding and has developed extensive bruising around the area. He has a history of gastroesophageal reflux disease, hypertension, and atrial fibrillation for which he is taking an oral medication. He says that he recently started taking omeprazole for reflux. Which of the following processes is most likely inhibited in this patient?
- A. Sulfation
- B. Oxidation (Correct Answer)
- C. Filtration
- D. Acetylation
- E. Glucuronidation
CYP450 inhibition and induction Explanation: ***Oxidation***
- The patient is taking **omeprazole**, a proton pump inhibitor, which is a known **CYP450 inhibitor**.
- Since the patient is also on an **oral anticoagulant** for atrial fibrillation, inhibition of CYP450 enzymes can reduce the metabolism of the anticoagulant, leading to **increased anticoagulant effect** and subsequent bleeding and bruising.
*Sulfation*
- **Sulfation** is a phase II metabolic reaction that converts compounds into more polar and excretable forms, but omeprazole primarily affects phase I metabolism involving CYP450 enzymes.
- While sulfation can be important for the metabolism of some drugs, it is not the primary process inhibited by omeprazole to cause increased bleeding with oral anticoagulants.
*Filtration*
- **Filtration** is a renal process and not a metabolic enzyme pathway affected by omeprazole.
- Omeprazole's interaction with anticoagulants mainly occurs through hepatic metabolism, not renal filtration.
*Acetylation*
- **Acetylation** is a phase II metabolic reaction, primarily carried out by **N-acetyltransferases**.
- Omeprazole is primarily known to interact with **CYP450 enzymes** (phase I metabolism) rather than N-acetyltransferases.
*Glucuronidation*
- **Glucuronidation** is a phase II metabolic reaction involving **UGT enzymes** that typically inactivates and increases the excretion of drugs.
- While important for drug metabolism, omeprazole's primary drug interactions leading to increased anticoagulant effects are via **CYP450 inhibition** (phase I metabolism), not directly through glucuronidation.
CYP450 inhibition and induction US Medical PG Question 2: You are seeing a patient in clinic who recently started treatment for active tuberculosis. The patient is currently being treated with rifampin, isoniazid, pyrazinamide, and ethambutol. The patient is not used to taking medicines and is very concerned about side effects. Specifically regarding the carbohydrate polymerization inhibiting medication, which of the following is a known side effect?
- A. Vision loss (Correct Answer)
- B. Paresthesias of the hands and feet
- C. Cutaneous flushing
- D. Arthralgias
- E. Elevated liver enzymes
CYP450 inhibition and induction Explanation: ***Vision loss***
- The "carbohydrate polymerization inhibiting medication" refers to **ethambutol**, which inhibits **arabinosyl transferase** (involved in mycobacterial cell wall arabinogalactan synthesis)
- **Ethambutol** causes **optic neuritis**, leading to **decreased visual acuity**, **red-green color blindness**, and potentially **irreversible vision loss**
- **Regular ophthalmologic monitoring** is essential during ethambutol therapy
*Paresthesias of the hands and feet*
- This describes **peripheral neuropathy** caused by **isoniazid**
- Isoniazid interferes with **pyridoxine (vitamin B6) metabolism**, leading to neurotoxicity
- Risk factors include malnutrition, diabetes, alcoholism, and pregnancy
- Prevented by **pyridoxine supplementation**
*Cutaneous flushing*
- Not a characteristic side effect of first-line anti-tuberculosis medications
- More commonly associated with niacin or certain allergic/vasodilatory reactions
*Arthralgias*
- Classic side effect of **pyrazinamide**, often affecting small joints
- Caused by **pyrazinamide-induced hyperuricemia** (inhibits renal uric acid excretion)
- May require dose adjustment or discontinuation if severe
*Elevated liver enzymes*
- **Hepatotoxicity** can occur with **rifampin**, **isoniazid**, and **pyrazinamide**
- Requires regular monitoring of liver function tests during TB treatment
- Most common serious adverse effect of combination TB therapy
CYP450 inhibition and induction US Medical PG Question 3: A drug discovery team is conducting research to observe the characteristics of a novel drug under different experimental conditions. The drug is converted into the inactive metabolites by an action of an enzyme E. After multiple experiments, the team concludes that as compared to physiologic pH, the affinity of the enzyme E for the drug decreases markedly in acidic pH. Co-administration of an antioxidant A increases the value of Michaelis-Menten constant (Km) for the enzyme reaction, while co-administration of a drug B decreases the value of Km. Assume the metabolism of the novel drug follows Michaelis-Menten kinetics at the therapeutic dose, and that the effects of different factors on the metabolism of the drug are first-order linear. For which of the following conditions will the metabolism of the drug be the slowest?
- A. Acidic pH, co-administration of antioxidant A and of drug B
- B. Acidic pH, co-administration of antioxidant A, no administration of drug B (Correct Answer)
- C. Physiologic pH, co-administration of antioxidant A, no administration of drug B
- D. Acidic pH, co-administration of drug B, no administration of antioxidant A
- E. Acidic pH, without administration of antioxidant A or drug B
CYP450 inhibition and induction Explanation: ***Acidic pH, co-administration of antioxidant A, no administration of drug B***
- **Decreased affinity** at acidic pH reduces the enzyme's ability to bind the drug, slowing metabolism.
- Co-administration of **antioxidant A increases Km**, indicating a further reduction in enzyme affinity and thus slower metabolism.
*Acidic pH, co-administration of antioxidant A and of drug B*
- While acidic pH and antioxidant A slow metabolism, co-administration of **drug B decreases Km**, which would increase enzyme affinity and counteract the slowing effect to some extent.
- The combination would result in a slower metabolism than baseline, but likely not the slowest possible due to the partially opposing effects of A and B.
*Physiologic pH, co-administration of antioxidant A, no administration of drug B*
- At **physiologic pH**, the enzyme's affinity for the drug is higher than at acidic pH, promoting faster metabolism.
- Although antioxidant A increases Km, the favorable pH for enzyme activity means metabolism will not be as slow as under acidic conditions.
*Acidic pH, co-administration of drug B, no administration of antioxidant A*
- **Acidic pH** reduces enzyme affinity, slowing metabolism.
- However, the co-administration of **drug B decreases Km**, which increases enzyme affinity and would partially offset the reduced affinity caused by the acidic pH, leading to a faster metabolism compared to when antioxidant A is present.
*Acidic pH, without administration of antioxidant A or drug B*
- At **acidic pH**, the enzyme's affinity for the drug decreases, which slows metabolism.
- However, in this condition, there are no additional factors (like antioxidant A) further increasing Km, nor factors (like drug B) decreasing Km, so the metabolic rate would be slower than physiologic pH but not as slow as when antioxidant A is also present.
CYP450 inhibition and induction US Medical PG Question 4: A 76-year-old man comes to the physician for a follow-up examination. One week ago, he was prescribed azithromycin for acute bacterial sinusitis. He has a history of atrial fibrillation treated with warfarin and metoprolol. Physical examination shows no abnormalities. Compared to one month ago, laboratory studies show a mild increase in INR. Which of the following best explains this patient's laboratory finding?
- A. Drug-induced hepatotoxicity
- B. Depletion of intestinal flora
- C. Inhibition of cytochrome p450 (Correct Answer)
- D. Increased gastrointestinal absorption of warfarin
- E. Increased non-protein bound warfarin fraction
CYP450 inhibition and induction Explanation: ***Inhibition of cytochrome p450***
- **Azithromycin**, while a weaker inhibitor compared to erythromycin and clarithromycin, **does inhibit CYP3A4 and other cytochrome P450 enzymes** to a clinically significant degree.
- This inhibition **reduces warfarin metabolism**, leading to increased warfarin levels and **enhanced anticoagulant effect**, manifesting as an **increased INR**.
- This pharmacokinetic interaction is well-documented and is the **primary mechanism** for azithromycin-warfarin interaction.
*Depletion of intestinal flora*
- The theory that antibiotics deplete **vitamin K-producing gut bacteria** leading to increased warfarin effect is a **common misconception**.
- Humans obtain vitamin K primarily from **dietary sources** (leafy greens, vegetable oils), not from gut bacterial synthesis; intestinal bacteria contribute minimally to vitamin K stores.
- This mechanism has been **debunked** in modern pharmacology literature and does not explain antibiotic-warfarin interactions.
*Drug-induced hepatotoxicity*
- While hepatotoxicity can impair **clotting factor synthesis** and increase INR, **azithromycin** rarely causes significant liver injury.
- The presentation shows only a **mild INR increase** one week after starting therapy, without other signs of liver dysfunction.
- This acute, mild change is more consistent with a **pharmacokinetic drug interaction** than hepatotoxicity.
*Increased gastrointestinal absorption of warfarin*
- **Warfarin** has high oral bioavailability (~100%) under normal conditions.
- **Azithromycin** does not enhance the **gastrointestinal absorption** of warfarin.
- This mechanism is not supported by pharmacological evidence for this drug interaction.
*Increased non-protein bound warfarin fraction*
- Displacement of warfarin from **plasma protein binding sites** can transiently increase free drug.
- However, **azithromycin** does not significantly displace warfarin from **albumin**.
- This mechanism does not explain the sustained INR elevation seen with azithromycin therapy.
CYP450 inhibition and induction US Medical PG Question 5: A 46-year-old male with a history of recurrent deep venous thromboses on warfarin presents to his hematologist for a follow-up visit. He reports that he feels well and has no complaints. His INR at his last visit was 2.5 while his current INR is 4.0. His past medical history is also notable for recent diagnoses of hypertension, hyperlipidemia, and gastroesophageal reflux disease. He also has severe seasonal allergies. He reports that since his last visit, he started multiple new medications at the recommendation of his primary care physician. Which of the following medications was this patient likely started on?
- A. Cetirizine
- B. Hydrochlorothiazide
- C. Omeprazole (Correct Answer)
- D. Lisinopril
- E. Atorvastatin
CYP450 inhibition and induction Explanation: ***Omeprazole***
- **Omeprazole** is a **proton pump inhibitor (PPI)** commonly prescribed for gastroesophageal reflux disease (GERD).
- PPIs like omeprazole are known to **inhibit CYP2C19**, an enzyme responsible for metabolizing **warfarin**, leading to increased warfarin levels and a higher **INR**.
*Cetirizine*
- **Cetirizine** is an antihistamine used for allergies, and it generally has a **negligible interaction** with warfarin.
- While it can cause some sedation, it does not significantly alter **warfarin metabolism** or INR.
*Hydrochlorothiazide*
- **Hydrochlorothiazide** is a diuretic used for hypertension, and its interaction with warfarin is typically **minimal** or can sometimes *decrease* INR due to fluid loss concentrating clotting factors.
- It would not explain the observed **increase in INR** from 2.5 to 4.0.
*Lisinopril*
- **Lisinopril** is an ACE inhibitor used for hypertension and generally has **no significant interaction** with warfarin.
- It does not inhibit or induce the **cytochrome P450 enzymes** involved in warfarin metabolism.
*Atorvastatin*
- **Atorvastatin** is a statin used for hyperlipidemia, and while some statins can slightly affect INR, **atorvastatin's effect is generally minor** and unpredictable, not typically causing such a significant jump.
- Its metabolic pathway does not strongly inhibit the **CYP enzymes** critical for warfarin breakdown.
CYP450 inhibition and induction US Medical PG Question 6: A 72-year-old woman with a history of atrial fibrillation on warfarin, diabetes, seizure disorder and recent MRSA infection is admitted to the hospital. She subsequently begins therapy with another drug and is found to have a supratherapeutic International Normalized Ratio (INR). Which of the following drugs is likely contributing to this patient's elevated INR?
- A. Carbamazepine
- B. Phenobarbital
- C. Glipizide
- D. Rifampin
- E. Valproic acid (Correct Answer)
CYP450 inhibition and induction Explanation: ***Valproic acid***
- **Valproic acid** inhibits the **CYP2C9** enzyme and can displace **warfarin** from **plasma protein binding sites**, increasing free warfarin levels and leading to a **supratherapeutic INR**.
- This interaction is particularly relevant in patients on warfarin, as it directly potentiates its anticoagulant effect.
*Carbamazepine*
- **Carbamazepine** is a potent **CYP450 enzyme inducer**, which would typically **decrease** warfarin levels and **lower** the INR.
- It would counteract the anticoagulant effect of warfarin, not enhance it.
*Phenobarbital*
- **Phenobarbital** is another strong **CYP450 enzyme inducer**, similar to carbamazepine.
- Its use would likely **reduce** the plasma concentration of warfarin, resulting in a **subtherapeutic INR**.
*Glipizide*
- **Glipizide** is an **oral hypoglycemic agent** and does not have a significant direct interaction with warfarin that would elevate the INR.
- While some sulfonylureas can have minor anticoagulant effects, they are not a primary cause of **supratherapeutic INR** in this context.
*Rifampin*
- **Rifampin** is a powerful **CYP450 enzyme inducer**, known to significantly **reduce** the effectiveness of many drugs, including warfarin.
- It would lead to a **lower** INR, increasing the risk of thrombotic events.
CYP450 inhibition and induction US Medical PG Question 7: A 66-year-old man was referred for endoscopic evaluation due to iron deficiency anemia. He has had anorexia and weight loss for two months. Three years ago, the patient had coronary artery bypass grafting and aortic mechanical valve replacement. He has a 12-year history of diabetes mellitus and hypertension. He takes warfarin, lisinopril, amlodipine, metformin, aspirin, and carvedilol. His blood pressure is 115/65 mm Hg, pulse is 68/min, respirations are 14/min, temperature is 36.8°C (98.2°F), and blood glucose is 220 mg/dL. Conjunctivae are pale. Heart examination reveals a metallic click just before the carotid pulse. Which of the following is the most appropriate switch in this patient’s drug therapy before the endoscopy?
- A. Metformin to empagliflozin
- B. Aspirin to clopidogrel
- C. Lisinopril to losartan
- D. Warfarin to heparin (Correct Answer)
- E. Amlodipine to diltiazem
CYP450 inhibition and induction Explanation: ***Warfarin to heparin***
- The patient is on **warfarin** due to his **mechanical aortic valve**, which increases his risk of bleeding during endoscopy.
- Switching to **heparin (bridging therapy)** allows for a shorter half-life and easier reversal if bleeding occurs, making it safer for the procedure.
*Metformin to empagliflozin*
- This change in **antidiabetic medication** does not address the immediate concern of bleeding risk for endoscopy.
- **Empagliflozin** can cause **euglycemic diabetic ketoacidosis** and its benefits related to cardiovascular outcomes are long term, not relevant to peri-procedural management.
*Aspirin to clopidogrel*
- Both **aspirin** and **clopidogrel** are **antiplatelet agents** that increase bleeding risk.
- Switching from one to the other does not mitigate the bleeding risk for endoscopy; often, one or both are held before such procedures if possible.
*Lisinopril to losartan*
- Both **lisinopril** and **losartan** are **antihypertensive medications** (ACE inhibitor and ARB, respectively) with similar effects on blood pressure.
- This change would not impact the **bleeding risk** or the need for peri-procedural anticoagulation management.
*Amlodipine to diltiazem*
- Both **amlodipine** and **diltiazem** are **calcium channel blockers** used for hypertension and angina.
- While they have different mechanisms, switching between them does not address the immediate safety concern of **bleeding risk** during endoscopy.
CYP450 inhibition and induction US Medical PG Question 8: A 39-year-old female presents to the clinic with the complaints of dry skin for a few months. She adds that she also has constipation for which she started eating vegetables and fruits but with no improvement. She lives with her husband and children who often complain when she turns the air conditioning to high as she cannot tolerate low temperatures. She has gained 5 kgs (11.2 lb) since her last visit 2 months back although her diet has not changed much. Her past medical history is relevant for cardiac arrhythmias and diabetes. She is on several medications currently. Her temperature is 98.6° F (37° C), respirations are 15/min, pulse is 57/min and blood pressure is 132/98 mm Hg. A physical examination is within normal limits. Thyroid function test results are given below:
Serum
TSH: 13.0 μU/mL
Thyroxine (T4): 3.0 μg/dL
Triiodothyronine (T3): 100 ng/dL
Which of the following medications is most likely to be responsible for her symptoms?
- A. Amiodarone (Correct Answer)
- B. Digoxin
- C. Metformin
- D. Theophylline
- E. Warfarin
CYP450 inhibition and induction Explanation: ***Amiodarone***
- Amiodarone is a known cause of both **hypothyroidism** and **hyperthyroidism** due to its iodine content and direct toxic effects on the thyroid gland. The patient's symptoms (dry skin, constipation, **cold intolerance**, **weight gain**, bradycardia) and thyroid function tests (high TSH, low T4, low T3) are highly consistent with drug-induced hypothyroidism.
- The patient's history of **cardiac arrhythmias** makes amiodarone a plausible medication she would be taking, as it is a common antiarrhythmic drug.
*Digoxin*
- Digoxin is primarily used to treat **heart failure** and certain arrhythmias, but it does not typically cause thyroid dysfunction.
- Its common side effects include gastrointestinal upset, visual disturbances, and various arrhythmias, which do not align with the patient's predominant symptoms of hypothyroidism.
*Metformin*
- Metformin is an oral hypoglycemic agent used to treat **Type 2 diabetes**, a condition the patient also has.
- It does not have substantial effects on thyroid hormone synthesis or metabolism and is not associated with hypothyroidism or hyperthyroidism.
*Theophylline*
- Theophylline is a bronchodilator used in the treatment of **asthma** and **COPD**.
- It is not known to cause thyroid dysfunction, and its side effects mainly involve the central nervous system, gastrointestinal tract, and cardiovascular system.
*Warfarin*
- Warfarin is an **anticoagulant** prescribed to prevent blood clots.
- It has no direct known interaction with thyroid hormone synthesis or metabolism and is not associated with thyroid dysfunction.
CYP450 inhibition and induction US Medical PG Question 9: A 30-year-old woman presents to her primary care provider with blood in her urine and pain in her left flank. She has a 5-year history of polycystic ovarian syndrome managed with oral contraceptives and metformin. She is single and is not sexually active and denies a history of kidney stones or abdominal trauma. She has a 15-pack-year smoking history but denies the use of other substances. Her family history is significant for fatal lung cancer in her father at age 50, who also smoked, and recently diagnosed bladder cancer in her 45-year-old brother, who never smoked. On review of systems, she denies weight loss, fever, fatigue, paresthesia, increased pain with urination, or excessive bleeding or easy bruising. She is admitted to the hospital for a workup and observation. Her vital signs and physical exam are within normal limits. A urine pregnancy test is negative. PT is 14 sec and PTT is 20 sec. The rest of the laboratory results including von Willebrand factor activity and lupus anticoagulant panel are pending. A CT angiogram is ordered and is shown in the picture. What is indicated at this time to prevent a potential sequela of this patient’s condition?
- A. Surgery
- B. Administer heparin (Correct Answer)
- C. Administer warfarin
- D. Administer streptokinase
- E. Thrombectomy
CYP450 inhibition and induction Explanation: ***Administer heparin***
- The CT angiogram shows a **renal vein thrombosis**, indicated by the filling defect within the left renal vein and enlargement of the left kidney with nephrogram striations. Heparin is an anticoagulant used to prevent further clot formation and propagation.
- Anticoagulation with **heparin** is the immediate treatment for acute renal vein thrombosis, preventing pulmonary embolism and preserving renal function.
*Surgery*
- **Surgical thrombectomy** or embolectomy is typically reserved for cases where medical management fails, or there is rapid deterioration of renal function or impending renal infarction.
- Given that the patient's vital signs are stable and no acute renal failure is indicated, conservative management with anticoagulation is the first-line approach.
*Warfarin*
- **Warfarin** is an oral anticoagulant used for long-term management of thrombosis but has a delayed onset of action.
- It is not suitable for **acute management** where immediate anticoagulation is required. Heparin would be initiated first, followed by a transition to warfarin for chronic therapy.
*Streptokinase*
- **Streptokinase** is a thrombolytic agent used to dissolve existing clots. Thrombolysis carries a high risk of bleeding and is generally reserved for severe cases with significant renal dysfunction or bilateral thrombosis.
- Given the patient's stable condition, the risks associated with thrombolytic therapy likely outweigh the benefits compared to anticoagulation.
*Thrombectomy*
- **Thrombectomy**, either surgical or catheter-directed, is an invasive procedure to remove the thrombus.
- It is usually considered if there's no improvement with anticoagulation, or in cases of complete renal vein occlusion leading to acute kidney injury or severe renal infarction.
CYP450 inhibition and induction US Medical PG Question 10: A 65-year-old man with a history of myocardial infarction is admitted to the hospital for treatment of atrial fibrillation with rapid ventricular response. He is 180 cm (5 ft 11 in) tall and weighs 80 kg (173 lb). He is given an intravenous bolus of 150 mg of amiodarone. After 20 minutes, the amiodarone plasma concentration is 2.5 mcg/mL. Amiodarone distributes in the body within minutes, and its elimination half-life after intravenous administration is 30 days. Which of the following values is closest to the volume of distribution of the administered drug?
- A. 60 L (Correct Answer)
- B. 80 L
- C. 150 L
- D. 17 L
- E. 10 L
CYP450 inhibition and induction Explanation: ***60 L***
- The **volume of distribution (Vd)** is calculated using the formula: **Vd = Dose / Plasma Concentration**.
- Given: Dose = 150 mg (150,000 mcg), Plasma concentration = 2.5 mcg/mL
- Calculation: Vd = 150,000 mcg / 2.5 mcg/mL = 60,000 mL = **60 L**
- Note: This calculation represents a simplified scenario. In clinical practice, amiodarone has an extremely large volume of distribution (60-100 L/kg or ~4,800-8,000 L in this patient) due to extensive tissue distribution, but the question tests the ability to apply the basic pharmacokinetic formula.
*80 L*
- This value would result if the plasma concentration were 1.875 mcg/mL (150,000 mcg / 80,000 mL), not the given 2.5 mcg/mL.
- This represents a common calculation error when working with pharmacokinetic parameters.
*150 L*
- This value would require a plasma concentration of 1 mcg/mL (150,000 mcg / 150,000 mL), which is lower than the measured 2.5 mcg/mL.
- This error might occur if the dose value were confused with the volume of distribution.
*17 L*
- This value would be obtained with a plasma concentration of approximately 8.8 mcg/mL (150,000 mcg / 17,000 mL), significantly higher than the measured 2.5 mcg/mL.
- This represents a significant underestimation of Vd and would suggest limited drug distribution.
*10 L*
- This value would require a plasma concentration of 15 mcg/mL (150,000 mcg / 10,000 mL), which is 6-fold higher than the given 2.5 mcg/mL.
- Such a small Vd would suggest drug confined primarily to plasma, which is inappropriate for lipophilic drugs with extensive tissue distribution.
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