The first drug approved for Rett syndrome is?
Which of the following is true about clinical therapeutic index?
What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
Which nomogram scale is used for aminoglycoside dosage?
Osimertinib is used in NSCLC with which mutation?
Match the following: Column A: a. Beta 1 b. Beta 2 c. Beta 3 Column B: 1. Mirabegron 2. Betaxolol 3. Salbutamol
A 35-year-old male patient presents to surgery emergency with painful erection for past 7 hours. He has a history of mood disorder and was recently prescribed a medication by treating psychiatrist. Which is the likely offending drug?
INI-CET 2023 - Pharmacology INI-CET Practice Questions and MCQs
Question 11: The first drug approved for Rett syndrome is?
- A. L-carnitine
- B. Naltrexone
- C. Trofinetide (Correct Answer)
- D. Folinic acid
Explanation: ***Trofinetide*** - **Trofinetide** (marketed as Daybue) is the first drug specifically approved by the FDA for the treatment of Rett syndrome, receiving approval in March 2023. - It is an analog of the **N-terminal tripeptide of insulin-like growth factor-1 (IGF-1)** and is thought to reduce neuroinflammation and support synaptic function in the brain, improving core symptoms of Rett syndrome. *L-carnitine* - **L-carnitine** is a nutritional supplement that has been studied in Rett syndrome for potential mitochondrial dysfunction, but it is not a primary treatment or an FDA-approved drug for the condition. - While sometimes used adjunctively, there is limited evidence for its efficacy as a standalone therapy in Rett syndrome. *Naltrexone* - **Naltrexone** is an opioid antagonist typically used to treat opioid and alcohol dependence. - It has been explored in some neurodevelopmental disorders, but it is not approved for or considered a primary treatment for Rett syndrome. *Folinic acid* - **Folinic acid** is a form of folic acid that can bypass metabolic blocks in folate pathways, sometimes used in conditions with cerebral folate deficiency. - While metabolic abnormalities can occur in Rett syndrome, folinic acid is not an FDA-approved drug for Rett syndrome.
Question 12: Which of the following is true about clinical therapeutic index?
- A. Dose in which efficacy and toxicity can be balanced in an individual (Correct Answer)
- B. Therapeutic index is LD50/ED50
- C. It is only used for a specific individual
- D. It measures therapeutic index in populations rather than individuals
Explanation: ***Dose in which efficacy and toxicity can be balanced in an individual*** - The **clinical therapeutic index** refers to the optimal range of drug dosage that produces the maximum desired therapeutic effect with minimal adverse side effects **in a specific patient**. - It involves a personalized approach to find the **balance between efficacy and toxicity** for individual patient care. *It is only used for specific individual* - While it is applied to specific individuals, the concept of a **clinical therapeutic index** is derived from a broader understanding of drug pharmacokinetics and pharmacodynamics established in clinical trials. - This statement is too restrictive, as population data informs the individual application. *Measures therapeutic index in a population vs individual* - The traditional **therapeutic index (TI)** is typically a population-based measure (LD50/ED50 or TD50/ED50), whereas the **clinical therapeutic index** focuses on the individual patient. - This option incorrectly suggests that the clinical TI measures population rather than focusing on the individual’s treatment optimization. *Therapeutic index is ED50/LD50* - The classic definition of the **therapeutic index (TI)** is **LD50/ED50** (Lethal Dose 50% / Effective Dose 50%), which is a ratio for preclinical animal studies. - For humans, the more relevant measure is the **therapeutic window** or the ratio of **TD50/ED50** (Toxic Dose 50% / Effective Dose 50%), but this is still a population measure, not the clinical therapeutic index for an individual.
Question 13: What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
- A. Sorafenib
- B. Lapatinib (Correct Answer)
- C. Vemurafenib
- D. Erlotinib
Explanation: ***Lapatinib*** - Lapatinib is a **dual tyrosine kinase inhibitor** that targets both **HER-2** and **epidermal growth factor receptor (EGFR)**, acting as a **small molecule inhibitor** that binds to the intracellular domain of these receptors. - Unlike trastuzumab (a monoclonal antibody targeting the extracellular domain), Lapatinib's **intracellular mechanism of action** allows it to overcome common mechanisms of trastuzumab resistance, such as receptor truncation or masking of the extracellular epitope. - It is specifically approved for the treatment of **HER-2 positive metastatic breast cancer** in combination with capecitabine after progression on trastuzumab-containing regimens. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** primarily targeting RAF, VEGFR, and PDGFR, and is used in renal cell carcinoma and hepatocellular carcinoma. - It does not specifically target HER-2 and is **not indicated** for HER-2 positive trastuzumab-resistant breast cancer. *Vemurafenib* - Vemurafenib is a **BRAF inhibitor** used for treating BRAF V600E mutation-positive melanoma. - This drug has no direct indications or demonstrated efficacy for **HER-2 positive breast cancer** and does not address trastuzumab resistance mechanisms. *Erlotinib* - Erlotinib is an **EGFR tyrosine kinase inhibitor** primarily used for non-small cell lung cancer with activating EGFR mutations. - While it targets EGFR, it does **not effectively target HER-2** and lacks the dual inhibition necessary to overcome trastuzumab resistance in HER-2 positive breast cancer.
Question 14: Which nomogram scale is used for aminoglycoside dosage?
- A. Hartford nomogram (Correct Answer)
- B. Hallstead scale
- C. Salazar scale
- D. Rumack Matthew nomogram
Explanation: ***Hartford nomogram*** - The **Hartford nomogram** is the standard tool for determining **once-daily (extended-interval) aminoglycoside dosing** based on **creatinine clearance**. - It helps clinicians optimize aminoglycoside therapy by allowing for less frequent dosing while maintaining therapeutic drug levels and minimizing **nephrotoxicity** and **ototoxicity**. - Developed at Hartford Hospital, this nomogram guides dosing intervals (24, 36, or 48 hours) based on a single serum level drawn 6-14 hours post-dose. *Hallstead scale* - The **Hallstead scale** is not a standard nomogram used in clinical practice for drug dosing. - This term does not correspond to a recognized clinical tool for medication management or aminoglycoside therapy. *Salazar scale* - The **Salazar-Corcoran equation** is used for estimating **creatinine clearance in obese patients**, not as a nomogram for aminoglycoside dosing. - While it may be used in the pharmacokinetic assessment before aminoglycoside dosing, it is not a dosing nomogram itself. *Rumack Matthew nomogram* - The **Rumack-Matthew nomogram** is used for assessing the risk of **hepatotoxicity** after an **acetaminophen overdose** by plotting plasma acetaminophen levels against time. - It is not used for aminoglycoside dosage or therapeutic drug monitoring.
Question 15: Osimertinib is used in NSCLC with which mutation?
- A. L858R mutation
- B. M790T mutation
- C. T890M mutation
- D. T790M mutation (Correct Answer)
Explanation: ***T790M mutation*** - **Osimertinib** is a third-generation **EGFR tyrosine kinase inhibitor (TKI)** specifically designed to overcome resistance to earlier generation EGFR TKIs. - The **T790M mutation** in the EGFR gene is the most common mechanism of acquired resistance to first and second-generation EGFR TKIs in non-small cell lung cancer (NSCLC). *L858R mutation* - The **L858R mutation** is an activating **EGFR mutation** typically sensitive to first and second-generation EGFR TKIs. - While patients with **L858R** may eventually develop resistance, **osimertinib** is primarily used in the setting of acquired resistance, often mediated by **T790M**. *M790T mutation* - This is not a recognized common or clinically significant activating or resistance mutation in the **EGFR gene** for NSCLC. - The correct resistance mutation that **osimertinib** targets is **T790M**, not **M790T**. *T890M mutation* - This is a typographical error for the clinically relevant **T790M mutation**. - The number sequence is critical for identifying specific amino acid substitutions in gene mutations.
Question 16: Match the following: Column A: a. Beta 1 b. Beta 2 c. Beta 3 Column B: 1. Mirabegron 2. Betaxolol 3. Salbutamol
- A. a-2, b-3 ,c-1 (Correct Answer)
- B. a-2, b-1, c-3
- C. a-3, b-2, c-1
- D. a-3, b-1, c-2
Explanation: ***a-2, b-3, c-1*** - This pairing correctly matches **Betaxolol** with **Beta 1 selective** antagonism, **Salbutamol** with **Beta 2 selective** agonism, and **Mirabegron** with **Beta 3 selective** agonism. - **Betaxolol** is a beta-1 selective adrenergic receptor antagonist, primarily used in ophthalmology to reduce intraocular pressure and as an antihypertensive. **Salbutamol** is a selective beta-2 adrenergic agonist used as a bronchodilator in asthma and COPD, causing relaxation of bronchial smooth muscle. **Mirabegron** is a selective beta-3 adrenergic agonist used to treat overactive bladder by relaxing the detrusor muscle. *a-2, b-1, c-3* - This option incorrectly assigns **Mirabegron** to Beta 2. Mirabegron is a **Beta 3 selective agonist**. - It also incorrectly assigns **Salbutamol** to Beta 3. Salbutamol is a **Beta 2 selective agonist**. *a-3, b-2, c-1* - This option incorrectly assigns **Salbutamol** to Beta 1. Salbutamol is a **Beta 2 selective agonist**. - It also incorrectly assigns **Betaxolol** to Beta 2. Betaxolol is a **Beta 1 selective antagonist**. *a-3, b-1, c-2* - This option incorrectly assigns **Salbutamol** to Beta 1 and **Betaxolol** to Beta 3. - **Salbutamol** is a Beta 2 selective agonist, and **Betaxolol** is a Beta 1 selective antagonist.
Question 17: A 35-year-old male patient presents to surgery emergency with painful erection for past 7 hours. He has a history of mood disorder and was recently prescribed a medication by treating psychiatrist. Which is the likely offending drug?
- A. Venlafaxine
- B. Tianeptine
- C. Trazodone (Correct Answer)
- D. Mirtazapine
Explanation: ***Trazodone*** - **Trazodone** is a commonly known antidepressant that can cause **priapism** as a side effect, especially at higher doses, due to its alpha-adrenergic blocking activity. [1] - The patient's presentation of a **painful erection lasting 7 hours** after starting a new psychiatric medication strongly points towards a drug-induced cause, for which trazodone is a well-established culprit. [1] *Venlafaxine* - **Venlafaxine** is an SNRI antidepressant that generally does not cause priapism as a recognized side effect. - Its adverse effect profile primarily includes nausea, insomnia, and sexual dysfunction (e.g., erectile dysfunction, anorgasmia), rather than prolonged erections. *Tianeptine* - **Tianeptine** is an atypical antidepressant that is not known to cause priapism. - It works by enhancing serotonin reuptake and is more commonly associated with side effects such as nausea, constipation, and dizziness. *Mirtazapine* - **Mirtazapine** is a tetracyclic antidepressant that works by blocking alpha-2 adrenergic receptors and certain serotonin receptors. - While it can cause sedation and weight gain, priapism is not a typical or recognized side effect of mirtazapine.