Drug interactions and adverse effects Practice Questions

Q: A 62-year-old man with a history of atrial fibrillation is admitted for elective cardioversion. He has been on amiodarone for rate control for the past 8 months. Laboratory results show TSH < 0.01 mIU/L, free T4 elevated, and free T3 elevated. He denies palpitations or heat intolerance. A thyroid ultrasound with color Doppler is performed and demonstrates absent vascularity within a heterogeneous gland. Which of the following best describes the underlying pathophysiology of his thyroid abnormality?

Direct cytotoxic destruction of thyroid follicular cells by amiodarone causing release of stored hormone. ***Direct cytotoxic destruction of thyroid follicular cells by amiodarone causing release of stored hormone*** - This describes **Amiodarone-Induced Thyrotoxicosis (AIT) Type 2**, a destructive thyroiditis where preformed hormone is released into the circulation. - The absence of **vascularity** on color Doppler ultrasound is the pathognomonic finding that distinguishes this from **Type 1 AIT**. *Iodine overload from amiodarone causing excess thyroid hormone synthesis via the Jod-Basedow effect* - This refers to **AIT Type 1**, which typically occurs in patients with underlying latent thyroid disease like **multinodular goiter**. - It would show **increased vascularity** on Doppler ultrasound due to active synthesis, rather than the absent flow seen in this patient. *Amiodarone-induced autoimmune thyroiditis mediated by anti-TSH receptor antibodies* - **Anti-TSH receptor antibodies** (TRAb) are the hallmark of **Graves' disease**, which is an autoimmune hyperthyroidism. - While amiodarone contains high iodine, it does not typically cause Graves' disease, and Graves' would show **increased global vascularity**. *Competitive inhibition of thyroid peroxidase by amiodarone reducing organification of iodine* - This mechanism describes the **Wolff-Chaikoff effect**, which results in temporary **hypothyroidism**, not thyrotoxicosis. - In this case, the patient is thyrotoxic with **suppressed TSH** and **elevated T3/T4**, which is opposite to an organification block. *Amiodarone blocking peripheral conversion of T4 to T3 causing compensatory TSH suppression* - Amiodarone does inhibit **5'-deiodinase**, leading to decreased **T3** and increased **T4**, often with a transiently elevated TSH. - This does not explain the overt **hyperthyroidism** or the characteristic **lack of vascularity** seen on ultrasound in AIT Type 2.

Q: A 58-year-old man with type 2 diabetes on metformin and a recent kidney transplant on tacrolimus presents with persistent hyperglycemia. His nephrologist wants to optimize diabetic control while maintaining stable immunosuppression. His tacrolimus trough level has been stable at 8 ng/mL. Evaluate the safest approach to intensify diabetes management.

Switch to insulin therapy while monitoring tacrolimus levels closely. ***Switch to insulin therapy while monitoring tacrolimus levels closely*** - **Insulin** is the gold standard for managing **post-transplantation diabetes mellitus (PTDM)** because it lacks metabolic interactions with **calcineurin inhibitors** like tacrolimus. - It provides precise glycemic control and avoids the potential nephrotoxicity or **CYP3A4** metabolic interference associated with various oral hypoglycemic agents. *Add glipizide as it has no interaction with tacrolimus* - While **glipizide** is primarily metabolized by CYP2C9, most **sulfonylureas** are less preferred in transplant patients due to the risk of **hypoglycemia** and variable pharmacokinetics. - Sulfonylureas do not address the **insulin resistance** or beta-cell dysfunction often exacerbated by tacrolimus therapy as effectively as insulin. *Add pioglitazone which improves insulin sensitivity* - **Pioglitazone** can cause **fluid retention** and weight gain, which complicates the management of patients with a **kidney transplant** and potential cardiovascular risk. - It is metabolized by **CYP3A4** and **CYP2C8**, which can lead to unpredictable drug-drug interactions with the tacrolimus metabolic pathway. *Increase metformin dose and add sitagliptin* - Increasing **metformin** in a recent transplant recipient is risky due to potential fluctuations in **Glomerular Filtration Rate (GFR)**, increasing the risk of **lactic acidosis**. - While **DPP-4 inhibitors** like sitagliptin are generally safe, they are often insufficient for significant hyperglycemia and require renal dose adjustments. *Add glyburide for better glycemic control* - **Glyburide** is contraindicated if there is any degree of **renal impairment** (common post-transplant) due to the risk of prolonged, severe **hypoglycemia**. - It has active metabolites that are **renally excreted**, making it a dangerous choice compared to alternative agents or insulin.

Q: A 42-year-old woman with major depression has failed multiple SSRI trials. Her psychiatrist initiates phenelzine (MAOI). Two weeks later, she develops severe headache, diaphoresis, and hypertension (BP 210/120 mmHg) after eating at a restaurant. Which food item most likely precipitated this hypertensive crisis?

Aged cheddar cheese. ***Aged cheddar cheese*** - **Phenelzine** is a **Monoamine Oxidase Inhibitor (MAOI)** that blocks the breakdown of **tyramine**, an indirect sympathomimetic found in aged foods. - Ingestion of tyramine-rich foods like **aged cheddar** leads to massive **norepinephrine** release, resulting in a **hypertensive crisis**, headache, and diaphoresis. *Fresh mozzarella cheese* - Unlike aged varieties, **fresh cheeses** (e.g., mozzarella, ricotta, cottage cheese) contain negligible amounts of **tyramine**. - These are generally considered safe for patients on MAOIs and would not typically trigger a severe **sympathetic surge**. *Grilled chicken breast* - **Freshly prepared meats** are safe to consume; high tyramine levels only develop in meats that are **aged**, **fermented**, or **cured**. - There is no clinical association between fresh poultry and the precipitation of **adrenergic crisis** in the context of MAOI therapy. *Steamed vegetables* - Most vegetables are safe; only specific items like **fava beans** or **overripe/fermented** plant products contain significant tyramine. - **Steamed vegetables** lack the fermentation or aging process required to produce the toxic levels of amines that interact with **MAOIs**. *White rice* - **Grains** such as white rice are consistently low in tyramine and are not associated with **dietary drug interactions**. - This side dish would not cause the **severe hypertension (210/120 mmHg)** observed in this clinical scenario.

Question 1

A 62-year-old man with a history of atrial fibrillation is admitted for elective cardioversion. He has been on amiodarone for rate control for the past 8 months. Laboratory results show TSH < 0.01 mIU/L, free T4 elevated, and free T3 elevated. He denies palpitations or heat intolerance. A thyroid ultrasound with color Doppler is performed and demonstrates absent vascularity within a heterogeneous gland. Which of the following best describes the underlying pathophysiology of his thyroid abnormality?

Accepted Answer

Direct cytotoxic destruction of thyroid follicular cells by amiodarone causing release of stored hormone

Answer

Iodine overload from amiodarone causing excess thyroid hormone synthesis via the Jod-Basedow effect

Answer

Amiodarone-induced autoimmune thyroiditis mediated by anti-TSH receptor antibodies

Answer

Competitive inhibition of thyroid peroxidase by amiodarone reducing organification of iodine

Answer

Amiodarone blocking peripheral conversion of T4 to T3 causing compensatory TSH suppression

Question 2

A 70-year-old man with Parkinson disease controlled on levodopa/carbidopa for 5 years develops psychotic symptoms. His neurologist considers adding an antipsychotic but is concerned about worsening parkinsonism. His family reports he has good motor control currently but the hallucinations are distressing. Evaluate the most appropriate antipsychotic choice considering the drug interaction profile.

Accepted Answer

Quetiapine or clozapine, as they have minimal dopamine D2 receptor blockade in the nigrostriatal pathway

Answer

Haloperidol, as first-generation antipsychotics are most effective for psychosis

Answer

Risperidone, using the lowest effective dose to minimize motor effects

Answer

Olanzapine, which has moderate D2 blockade balancing efficacy and side effects

Answer

Aripiprazole, as a partial dopamine agonist will not worsen parkinsonism

Question 3

A 35-year-old woman taking combined oral contraceptives for 2 years develops a breakthrough seizure. She is started on carbamazepine for newly diagnosed epilepsy. Four weeks later, she presents with irregular vaginal bleeding and is concerned about contraceptive failure. Apply pharmacological principles to explain the most appropriate management.

Accepted Answer

Switch to higher-dose oral contraceptives or alternative contraception due to enzyme induction

Answer

Reassure that breakthrough bleeding is normal with carbamazepine and continue current contraception

Answer

Discontinue carbamazepine and choose a non-enzyme-inducing antiepileptic

Answer

Add supplemental estrogen to the current contraceptive regimen

Answer

Perform pregnancy test and continue current medications if negative

Question 4

A 58-year-old man with type 2 diabetes on metformin and a recent kidney transplant on tacrolimus presents with persistent hyperglycemia. His nephrologist wants to optimize diabetic control while maintaining stable immunosuppression. His tacrolimus trough level has been stable at 8 ng/mL. Evaluate the safest approach to intensify diabetes management.

Accepted Answer

Switch to insulin therapy while monitoring tacrolimus levels closely

Answer

Add glipizide as it has no interaction with tacrolimus

Answer

Add pioglitazone which improves insulin sensitivity

Answer

Increase metformin dose and add sitagliptin

Answer

Add glyburide for better glycemic control

Question 5

A 42-year-old woman with major depression has failed multiple SSRI trials. Her psychiatrist initiates phenelzine (MAOI). Two weeks later, she develops severe headache, diaphoresis, and hypertension (BP 210/120 mmHg) after eating at a restaurant. Which food item most likely precipitated this hypertensive crisis?

Accepted Answer

Aged cheddar cheese

Answer

Fresh mozzarella cheese

Answer

Grilled chicken breast

Answer

Steamed vegetables

Answer

White rice

Drug interactions and adverse effects — MCQs

Drug interactions and adverse effects — MCQs

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