INI-CET 2026 Practice Questions

Q: What is the primary molecular mechanism by which UV light induces carcinogenesis?

Thymine dimers. ***Thymine dimers*** - UV radiation, particularly **UVB**, causes structural damage to **DNA** by inducing the formation of **pyrimidine dimers** (specifically cyclobutane pyrimidine dimers involving thymine residues) between adjacent bases. - If these lesions are not effectively repaired by the **nucleotide excision repair (NER)** pathway, they lead to **mutations** (commonly C to T transitions) in critical genes like **TP53** during DNA replication, driving carcinogenesis. *Inhibition of TP53* - While UV damage often leads to mutations in the **TP53 gene**, this is a downstream consequence of DNA damage, not the primary molecular mechanism of UV-induced injury itself. - **TP53** is typically inactivated via **mutations** caused by failed repair of DNA photoproducts, rather than direct inhibition of the protein by UV light. *Activation of NF-kappa beta signaling pathway* - The **NF-kappaB pathway** is primarily involved in **inflammatory and immune responses** rather than being the direct mechanism of DNA damage-induced carcinogenesis. - While UV exposure does activate inflammatory pathways, this is a secondary response to tissue stress and not the foundational cause of **mutagenesis** and cancer initiation. *Upregulation of cyclin proteins* - Uncontrolled cell cycle progression due to **cyclin** dysregulation is a hallmark of cancer, but it is a result of accumulated **genetic mutations**. - This represents a cellular outcome of cancer development rather than the direct photochemical event initiated by UV radiation interacting with genomic DNA.

Q: On histopathological examination of liver from a chronic alcoholic, the following image is observed. Which special stain is the best choice to confirm the diagnosis?

Masson Trichrome. ***Masson Trichrome*** - This stain is the gold standard for visualizing **fibrosis** and connective tissue, which appear blue or green against a red background of hepatocytes. - In a patient with chronic alcoholism, it effectively highlights the **pericellular fibrosis** and **bridging fibrosis** characteristic of cirrhotic liver progression. *Gomori Methenamine Silver (GMS)* - Primarily utilized to identify **fungal organisms**, such as *Pneumocystis jirovecii* or *Candida* species. - It has no role in assessing hepatic fibrosis or the structural architecture of the liver in chronic alcohol abuse. *Periodic Acid Schiff (PAS)* - Frequently used to detect **glycogen** or **mucins** in tissues; it is particularly useful for identifying diastase-resistant globules in **Alpha-1 Antitrypsin Deficiency**. - While it can stain some basement membranes, it is not the standard choice for quantifying or visualizing fibrous septa in cirrhosis. *Gram stain* - Specifically designed to classify bacteria into **Gram-positive** and **Gram-negative** groups based on their cell wall composition. - It provides no utility in evaluating chronic liver parenchymal damage or the extent of fibrotic deposition in alcoholic liver disease.

Q: Calculate the Therapeutic Index of the given drug from the dose-response curve below:

4. ***4*** - The **Therapeutic Index (TI)** is calculated as the ratio of the **Lethal Dose (LD50)** to the **Effective Dose (ED50)**, represented by the formula **TI = LD50 / ED50**. - Given the typical interpretation of such graphs in pharmacology exams, if the ED50 is at 25mg and the LD50 is at 100mg, the calculation 100/25 yields a **Therapeutic Index of 4**. *0.25* - This value represents the **reciprocal** of the correct answer (ED50/LD50), which is incorrect terminology. - A value less than 1 would imply that the **effective dose** is higher than the **lethal dose**, which would make the drug impossible to use safely. *0.75* - This value is not derived from the standard ratio of **LD50** over **ED50** in typical dose-response curve assessments. - It does not correctly reflect the **margin of safety** associated with the drug's therapeutic window. *2* - This result would be obtained if the ratio between the **lethal** and **effective doses** was 2:1. - This likely reflects a misreading of the **x-axis intercepts** for potency or toxicity on the provided graph.

Q: What is the mechanism of action of Resmetirom?

Stimulation of Thyroid Hormone Receptor-beta. ***Stimulation of Thyroid Hormone Receptor-beta*** - Resmetirom is a first-in-class, oral, liver-directed **selective thyroid hormone receptor-beta (THR-β) agonist**. - By stimulating this receptor specifically in the liver, it helps reduce **hepatic lipotoxicity**, downregulate **fibrogenesis**, and improve lipid metabolism, making it indicated for **non-alcoholic steatohepatitis (NASH)** with liver fibrosis. *Blockage at NPC1L1 transporter* - This mechanism describes **Ezetimibe**, a drug used to treat **hypercholesterolemia** by inhibiting cholesterol absorption in the small intestine. - It does not target liver fibrosis or NASH directly through thyroid hormone pathways. *Activation of PPAR-γ* - This is the mechanism of **Thiazolidinediones** (e.g., Pioglitazone), which are insulin-sensitizing agents. - While used in diabetes and sometimes studied in NASH, they work by enhancing insulin sensitivity rather than selectively agonizing hepatic THR-β. *Blockage of Acetyl Co-A carboxylase* - Inhibitors of acetyl-CoA carboxylase (ACC), such as Firsocostat, were investigated for NASH to reduce **de novo lipogenesis**. - They function by inhibiting the rate-limiting step in fatty acid synthesis, distinct from thyroid receptor modulation.

Q: What is the mechanism of action of Pretomanid under the BPaLM regimen?

Inhibition of mycolic acid synthesis. ***Inhibition of mycolic acid synthesis*** - Pretomanid is a **nitroimidazooxazine** that acts as a prodrug, which is activated by the mycobacterial deazaflavin-dependent nitroreductase enzyme (Ddn). - Once activated, it interferes with **mycolic acid synthesis** and also generates reactive nitrogen species that lead to the inhibition of cellular respiration and ATP depletion in both actively replicating and dormant **Mycobacterium tuberculosis**. *Inhibition of ATP synthase* - This mechanism is specific to **bedaquiline**, another component of the BPaLM regimen, which targets the proton pump of the mycobacterial ATP synthase. - Inhibition of this enzyme leads to the rapid depletion of intracellular ATP, resulting in bacteriostasis and eventual cell death. *Inhibition of RNA polymerase* - This is the primary mechanism of action for **rifamycins** (such as Rifampicin), which bind to the beta unit of RNA polymerase. - By preventing transcription, Rifampicin effectively halts bacterial protein synthesis. *Inhibition of arabinoglycan synthesis* - This mechanism is characteristic of **ethambutol**, which inhibits the arabinosyl transferase enzymes involved in cell wall synthesis. - Disruption of arabinoglycan synthesis weakens the mycobacterial cell wall, making the organism more susceptible to other antibiotics.

Q: Identify the type of elimination kinetics represented in the given graph:

First-order kinetics. ***First-order kinetics*** - This process is characterized by the elimination of a **constant fraction** of the drug per unit time, resulting in an **exponential decay** curve on a linear plot. - The rate of elimination is directly **proportional to the plasma concentration** of the drug, meaning faster elimination occurs when drug levels are higher. *Zero-order kinetics* - This involves the elimination of a **constant amount** of drug per unit time, regardless of the plasma concentration. - It typically results in a **linear decline** in plasma concentration over time, often seen when elimination pathways are **saturated**. *Nonlinear kinetics* - This term usually refers to situations where the rate of elimination does not change proportionally with dose, often because the metabolic enzyme systems are **saturated**. - While both zero-order and Michaelis-Menten kinetics are forms of nonlinear elimination, the term is too broad to describe a standard decay curve specifically. *Saturation kinetics* - This describes a state where the capacity of an enzyme or transport system is fully utilized and the system reaches its **maximum velocity (Vmax)**. - When a system becomes saturated at therapeutic levels, it shifts from first-order to **zero-order elimination**.

Q: Lamotrigine is most effective in which of the following seizure types?

Tonic-clonic seizures. ***Tonic-clonic seizures*** - Lamotrigine is a **broad-spectrum** anticonvulsant that is highly effective for the management of **generalized tonic-clonic seizures**. - It works by blocking **voltage-gated sodium channels** and inhibiting the release of excitatory neurotransmitters like **glutamate**. *Absence seizures* - **Ethosuximide** is the first-line treatment for uncomplicated absence seizures, not lamotrigine. - While lamotrigine has some activity against absence seizures, it is not the primary drug of choice for this specific type. *Atonic seizures* - Atonic seizures (drop attacks) are typically refractory and often treated with **valproate** or as part of Lennox-Gastaut syndrome management. - While lamotrigine is used in generalized epilepsy syndromes, it is not the defining or most specific indication compared to tonic-clonic seizures. *Myoclonic seizures* - **Valproate** is widely considered the most effective agent for myoclonic seizures, particularly in the context of juvenile myoclonic epilepsy. - Lamotrigine is often used as an adjunct or alternative, but it is not the classic first-line choice for pure myoclonic epilepsy.

Q: Unlike other calcium channel blockers, Cilnidipine does not cause reflex tachycardia. What is the reason for this?

It additionally blocks N-type calcium channels. ***It additionally blocks N-type calcium channels*** - Cilnidipine is a unique **dihydropyridine calcium channel blocker** that inhibits both **L-type** and **N-type** calcium channels. - The blockade of **N-type calcium channels** inhibits the release of **norepinephrine** from sympathetic nerve terminals, which prevents the reflex sympathetic activation (tachycardia) typically seen with other vasodilators. *It additionally blocks T-type calcium channels* - While **T-type calcium channel blockers** (like efonidipine) can also reduce heart rate, this is not the primary mechanism of action for cilnidipine. - Cilnidipine's unique profile specifically relates to the inhibition of neurotransmitter release from the sympathetic nervous system via **N-type channel blockade**. *It additionally blocks C-type calcium channels* - There is no clinically relevant drug class of **C-type calcium channel blockers** commonly referred to in cardiovascular pharmacology. - This is a distracter option, as cilnidipine is specifically categorized by its dual action on **L-type** and **N-type** channels. *It additionally blocks sodium channels* - Sodium channel blockade is a characteristic of **Class I antiarrhythmic drugs** (like lidocaine or procainamide), not calcium channel blockers. - Cilnidipine does not exert its cardioprotective effects through the blockade of sodium channels.

Q: A patient is diagnosed with invasive mucormycosis following COVID-19 infection. Which of the following antifungal agents has NO activity against Mucor species and should be avoided?

Voriconazole. ***Voriconazole*** - Voriconazole is a triazole antifungal that lacks significant activity against the **Mucorales** order, which causes mucormycosis. - Clinical guidelines state it should be avoided, as it may even promote the development of **breakthrough fungal infections** by eradicating competing fungal flora like *Aspergillus*. *Isavuconazole* - This agent is a second-line, extended-spectrum triazole that demonstrates efficacy in treating **invasive mucormycosis**. - It is often used for patients who cannot tolerate polyenes or as step-down therapy after initial stabilization. *Posaconazole* - Posaconazole is an azole with demonstrated activity against **Mucorales** species and is approved for use in the treatment of mucormycosis. - It is frequently utilized as **salvage therapy** or for long-term step-down treatment following initial induction therapy. *Liposomal Amphotericin B* - This is the **first-line treatment** of choice for invasive mucormycosis due to its potent fungicidal activity against these pathogens. - It is preferred because it achieves high concentrations in affected tissues with a relative reduction in **nephrotoxicity** compared to non-liposomal formulations.

Question 1

What is the primary molecular mechanism by which UV light induces carcinogenesis?

Accepted Answer

Thymine dimers

Answer

Inhibition of TP53

Answer

Activation of NF-kappa beta signaling pathway

Answer

Upregulation of cyclin proteins

Question 2

On histopathological examination of liver from a chronic alcoholic, the following image is
observed. Which special stain is the best choice to confirm the
diagnosis?

Accepted Answer

Masson Trichrome

Answer

Gomori Methenamine Silver (GMS)

Answer

Periodic Acid Schiff (PAS)

Answer

Gram stain

Question 3

Calculate the Therapeutic Index of the given drug
from the dose-response curve below:

Accepted Answer

4

Answer

0.25

Answer

0.75

Answer

2

Question 4

What is the mechanism of action of Resmetirom?

Accepted Answer

Stimulation of Thyroid Hormone Receptor-beta

Answer

Blockage at NPC1L1 transporter

Answer

Activation of PPAR-γ

Answer

Blockage of Acetyl Co-A carboxylase

Question 5

What is the mechanism of action of Pretomanid under the BPaLM regimen?

Accepted Answer

Inhibition of mycolic acid synthesis

Answer

Inhibition of ATP synthase

Answer

Inhibition of RNA polymerase

Answer

Inhibition of arabinoglycan synthesis

Question 6

Identify the type of elimination kinetics represented in the given
graph:

Accepted Answer

First-order kinetics

Answer

Zero-order kinetics

Answer

Nonlinear kinetics

Answer

Saturation kinetics

Question 7

A 45-year-old chronic smoker is being counselled for smoking cessation therapy. Which of the
following statements regarding nicotine replacement and pharmacotherapy is correct?

Accepted Answer

Acidic beverages should be avoided 15 minutes before using nicotine gum to maximize absorption

Answer

Nicotine patch provides superior efficacy compared to nicotine gum

Answer

Bupropion is associated with more adverse effects than Varenicline

Answer

Varenicline carries a black box warning for cardiovascular toxicity

Question 8

Lamotrigine is most effective in which of the following seizure types?

Accepted Answer

Tonic-clonic seizures

Answer

Absence seizures

Answer

Atonic seizures

Answer

Myoclonic seizures

Question 9

Unlike other calcium channel blockers, Cilnidipine does not cause reflex tachycardia. What is
the reason for this?

Accepted Answer

It additionally blocks N-type calcium channels

Answer

It additionally blocks T-type calcium channels

Answer

It additionally blocks C-type calcium channels

Answer

It additionally blocks sodium channels

Question 10

A patient is diagnosed with invasive mucormycosis following COVID-19 infection. Which of the
following antifungal agents has NO activity against Mucor species and should be avoided?

Accepted Answer

Voriconazole

Answer

Isavuconazole

Answer

Posaconazole

Answer

Liposomal Amphotericin B

INI-CET 2026

Pathology

Pharmacology