A 57-year-old man is brought to the emergency department by his son for odd behavior. The patient and his son had planned to go on a hike today. On the drive up to the mountain, the patient began acting strangely which prompted the patient's son to bring him in. The patient has a past medical history of constipation, seasonal allergies, alcohol abuse, and IV drug abuse. His current medications include diphenhydramine, metoprolol, and disulfiram. The patient's son states he has been with the patient all morning and has only seen him take his over the counter medications and eat breakfast. His temperature is 102.0°F (38.9°C), blood pressure is 147/102 mmHg, pulse is 110/min, and oxygen saturation is 98% on room air. The patient appears uncomfortable. Physical exam is notable for tachycardia. The patient's skin appears dry, red, and flushed, and he is confused and not responding to questions appropriately. Which of the following is the best treatment for this patient's condition?
Q22
A 7-year-old boy is rushed to the emergency room after developing severe abdominal pain with nausea and vomiting for a day at a summer camp. He also has a bad cough and generalized muscle weakness. He was doing fine until these symptoms started on day 3 of his camp. Past medical history obtained from his parents on the phone was significant for recurrent nephrotic syndrome controlled by prolonged corticosteroid therapy. His blood pressure is 110/75 mm Hg, axillary temperature is 38.9°C (102.0°F) and random blood sugar is 49 mg/dL. On examination, he appears somnolent. His heart has a regular rate and rhythm and his lungs have rhonchi and focal wheezing, bilaterally. Results of other lab investigations are:
Sodium 131 mEq/L
Potassium 5.1 mEq/L
Chloride 94 mEq/L
Bicarbonate 16 mEq/L
Urea 44 mg/dL
Creatinine 1.4 mg/dL
A respiratory culture is positive for type A influenza. Which of the following is most likely to be the predisposing cause of the patient’s symptoms?
Q23
A previously healthy 13-year-old boy is brought to the emergency department by his parents for the evaluation of several episodes of vomiting since this morning. He reports nausea and severe headache. Over the past four days, he has had fever, a runny nose, and a sore throat. His mother gave him an analgesic drug that she uses for rheumatoid arthritis. He has not had any trauma. Last month, the patient traveled to Mexico with his family. He is at the 85th percentile for height and 25th percentile for weight. He appears weak. His temperature is 38°C (100°F), pulse is 90/min, respirations are 18/min, and blood pressure is 100/60 mm Hg. Mental status examination shows psychomotor agitation alternating with lethargy. Examination shows bilateral optic disc swelling. Serum studies show:
Urea nitrogen 30 mg/dL
Glucose 70 mg/dL
Aspartate aminotransferase (AST, GOT) 60 U/L
Alanine aminotransferase (ALT, GPT) 60 U/L
Arterial blood gas analysis on room air shows a pH of 7.30. Which of the following is the most likely cause of this patient's symptoms?
Q24
A 59-year-old man comes to your clinic accompanied by his wife complaining of nausea and dizziness. He reports that he is unsure when his symptoms started, but they have been affecting him for “a while.” It began as episodes of “unsteadiness” and progressed to a feeling of “spinning.” He cannot tell if his symptoms change with position, but reports that if he does not lie down he will become nauseous. When asked about other symptoms, his wife reports that she has also noticed the patient has worsening hearing loss. She complains that she is constantly repeating herself, especially if she speaks on his right side. The patient denies this and says that she just speaks too softly. The patient’s past medical history is significant for hypertension, alcoholism, and chronic obstructive pulmonary disease. His medications include aspirin, amlodipine, and fluticasone-salmeterol. He reports he drinks a glass of red wine every night with dinner and smokes a cigar on the weekends. Examination shows delayed horizontal nystagmus. Which of the following is the first-line treatment?
Q25
A 9-year-old boy is brought to the clinic by his dad for an annual well-child exam. The boy was diagnosed with ADHD at an outside clinic and has been on methylphenidate for symptom management for the past year. The father reports that the patient is more energetic but that his teacher still complains of him "spacing out" during class. The patient reports that it is difficult to follow in class sometimes because the teacher would just "skip ahead suddenly." He denies any headaches, vision changes, fever, or abdominal pain, but endorses decreased appetite since starting methylphenidate. What is the mechanism of action of the drug that would be most appropriate to continue for this patient's ADHD management?
Q26
Two weeks after hospitalization for acute psychosis, a 27-year-old woman with a history of paranoid schizophrenia comes to the physician because of difficulty walking and shaking movements of her hands. Current medications include fluphenazine, which was started during her recent hospitalization. Examination shows a shuffling gait, rigidity in the upper extremities, and a low-amplitude tremor of her hands that improves with activity. Mental status examination shows no abnormalities. Treatment with a drug with which of the following mechanisms of action is most likely to provide relief for this patient's current symptoms?
Q27
A 26-year-old man is brought to the emergency department because of abdominal pain, dizziness, shortness of breath, and swelling and pruritus of the lips, tongue, and throat for 1 hour. The symptoms began minutes after he started eating a lobster dinner. It is determined that his symptoms are due to surface crosslinking of IgE. This immunologic event most likely caused the release of which of the following?
Q28
A 28-year-old female presents to her primary care doctor complaining of new onset blurry vision. She first noticed her vision getting blurry toward the end of the day several days ago. Since then, she reports that her vision has been fine when she wakes up but gets worse throughout the day. She has also noticed that her eyelids have started to droop before she goes to bed. On exam, she has bilateral ptosis that is worse on the right. Administering edrophonium to this patient leads to an immediate improvement in her symptoms. Which of the following is most likely true about this patient’s condition?
Q29
A 62-year-old woman comes to the physician for a follow-up examination after a recent change in her medication regimen. She reports that she feels well. She has type 2 diabetes mellitus, hyperlipidemia, hypertension, essential tremor, and chronic back pain. Current medications are metformin, glyburide, propranolol, simvastatin, ramipril, amitriptyline, and ibuprofen. Fingerstick blood glucose concentration is 47 mg/dL. Serum studies confirm this value. Which of the following pharmacologic mechanisms is most likely responsible for the absence of symptoms in this patient?
Q30
A 29-year-old man comes to the physician for worsening restlessness over the past several days. Three weeks ago, he was started on trifluoperazine for the treatment of schizophrenia. He reports that, since then, he has often felt compelled to pace around his house and is unable to sit or stand still. He is switched to an alternative antipsychotic medication. Four weeks later, the patient reports improvement of his symptoms but says that he has developed increased drowsiness, blurred vision, and dry mouth. The patient was most likely switched to which of the following drugs?
Cholinergic/Adrenergic drugs US Medical PG Practice Questions and MCQs
Question 21: A 57-year-old man is brought to the emergency department by his son for odd behavior. The patient and his son had planned to go on a hike today. On the drive up to the mountain, the patient began acting strangely which prompted the patient's son to bring him in. The patient has a past medical history of constipation, seasonal allergies, alcohol abuse, and IV drug abuse. His current medications include diphenhydramine, metoprolol, and disulfiram. The patient's son states he has been with the patient all morning and has only seen him take his over the counter medications and eat breakfast. His temperature is 102.0°F (38.9°C), blood pressure is 147/102 mmHg, pulse is 110/min, and oxygen saturation is 98% on room air. The patient appears uncomfortable. Physical exam is notable for tachycardia. The patient's skin appears dry, red, and flushed, and he is confused and not responding to questions appropriately. Which of the following is the best treatment for this patient's condition?
A. Naloxone
B. IV fluids, thiamine, and dextrose
C. Physostigmine (Correct Answer)
D. Atropine
E. Neostigmine
Explanation: ***Physostigmine***
- The patient's symptoms (fever, tachycardia, hypertension, dry flushed skin, confusion, and agitation) are classic for **anticholinergic toxicity**, likely caused by **diphenhydramine**.
- **Physostigmine** is a reversible **acetylcholinesterase inhibitor** that crosses the blood-brain barrier, effectively counteracting both peripheral and central anticholinergic effects.
*Naloxone*
- **Naloxone** is used to reverse **opioid overdose**, which typically presents with **respiratory depression** and miosis, not seen here.
- While the patient has a history of IV drug abuse, the clinical picture does not align with opioid intoxication.
*IV fluids, thiamine, and dextrose*
- This combination is standard empirical treatment for altered mental status in patients with suspected **alcohol abuse** or **nutritional deficiencies**.
- While the patient has a history of alcohol abuse, his primary presentation points more specifically to anticholinergic toxicity.
*Atropine*
- **Atropine** is an **anticholinergic agent**; administering it would worsen the patient's already present anticholinergic toxicity.
- It is used to treat cholinergic crises, such as organophosphate poisoning, by blocking acetylcholine receptors.
*Neostigmine*
- **Neostigmine** is an **acetylcholinesterase inhibitor** but does **not cross the blood-brain barrier**, meaning it would only address peripheral cholinergic effects and not the patient's central nervous system symptoms like confusion.
- It is often used for myasthenia gravis or reversal of neuromuscular blockade.
Question 22: A 7-year-old boy is rushed to the emergency room after developing severe abdominal pain with nausea and vomiting for a day at a summer camp. He also has a bad cough and generalized muscle weakness. He was doing fine until these symptoms started on day 3 of his camp. Past medical history obtained from his parents on the phone was significant for recurrent nephrotic syndrome controlled by prolonged corticosteroid therapy. His blood pressure is 110/75 mm Hg, axillary temperature is 38.9°C (102.0°F) and random blood sugar is 49 mg/dL. On examination, he appears somnolent. His heart has a regular rate and rhythm and his lungs have rhonchi and focal wheezing, bilaterally. Results of other lab investigations are:
Sodium 131 mEq/L
Potassium 5.1 mEq/L
Chloride 94 mEq/L
Bicarbonate 16 mEq/L
Urea 44 mg/dL
Creatinine 1.4 mg/dL
A respiratory culture is positive for type A influenza. Which of the following is most likely to be the predisposing cause of the patient’s symptoms?
A. Iatrogenic suppression of a trophic effect on the adrenal glands (Correct Answer)
B. An extremely virulent form of Influenza
C. Bilateral hemorrhagic necrosis of the adrenal glands
D. Primary adrenal insufficiency
E. Immunosuppression
Explanation: **Iatrogenic suppression of a trophic effect on the adrenal glands**
- The patient's history of **prolonged corticosteroid therapy** for recurrent nephrotic syndrome likely led to **iatrogenic adrenal suppression**. This means the adrenal glands, specifically the cortex, became atrophic due to the exogenous corticosteroids, which inhibit **ACTH** (adrenocorticotropic hormone) release from the pituitary.
- The stress of influenza infection, coupled with suppressed adrenal function, can precipitate an **adrenal crisis**, characterized by **hypotension**, **hypoglycemia**, **hyponatremia**, **hyperkalemia**, and gastrointestinal symptoms, which are all present in this patient.
*An extremely virulent form of Influenza*
- While the patient has influenza, the constellation of symptoms, particularly **hypoglycemia**, **electrolyte abnormalities** (low sodium, high potassium), and a history of prolonged corticosteroid use, points beyond typical influenza severity.
- Influenza alone would not typically cause such profound metabolic disturbances and adrenal crisis in an otherwise healthy child.
*Bilateral hemorrhagic necrosis of the adrenal glands*
- This condition, known as **Waterhouse-Friderichsen syndrome**, is typically associated with **fulminant meningococcemia** or other severe bacterial sepsis, not primarily with influenza.
- While it can cause adrenal crisis, the clinical picture here is more consistent with chronic adrenal insufficiency unmasked by acute stress, given the corticosteroid history.
*Primary adrenal insufficiency*
- **Primary adrenal insufficiency** (e.g., Addison's disease) involves direct damage to the adrenal glands and would typically present with **hyperpigmentation** due to elevated ACTH, which is not mentioned.
- While the symptoms mimic adrenal crisis, the underlying cause in this case is likely **secondary adrenal insufficiency** due to exogenous steroid use, rather than primary destruction of the adrenal cortex.
*Immunosuppression*
- While prolonged corticosteroid therapy does cause **immunosuppression**, making the child more susceptible to infections like influenza, immunosuppression itself is not the direct predisposing cause of the acute **adrenal crisis** symptoms (abdominal pain, hypoglycemia, electrolyte imbalances).
- The critical link between the corticosteroid history and the current symptoms is the suppression of adrenal function, not merely the increased risk of infection.
Question 23: A previously healthy 13-year-old boy is brought to the emergency department by his parents for the evaluation of several episodes of vomiting since this morning. He reports nausea and severe headache. Over the past four days, he has had fever, a runny nose, and a sore throat. His mother gave him an analgesic drug that she uses for rheumatoid arthritis. He has not had any trauma. Last month, the patient traveled to Mexico with his family. He is at the 85th percentile for height and 25th percentile for weight. He appears weak. His temperature is 38°C (100°F), pulse is 90/min, respirations are 18/min, and blood pressure is 100/60 mm Hg. Mental status examination shows psychomotor agitation alternating with lethargy. Examination shows bilateral optic disc swelling. Serum studies show:
Urea nitrogen 30 mg/dL
Glucose 70 mg/dL
Aspartate aminotransferase (AST, GOT) 60 U/L
Alanine aminotransferase (ALT, GPT) 60 U/L
Arterial blood gas analysis on room air shows a pH of 7.30. Which of the following is the most likely cause of this patient's symptoms?
A. Infection with hepatitis A virus
B. Reye syndrome (Correct Answer)
C. Autoimmune destruction of pancreatic beta cells
D. Ruptured aneurysm in the circle of Willis
E. Antifreeze ingestion
Explanation: ***Reye syndrome***
- The combination of a recent **viral illness** (fever, runny nose, sore throat) treated with an **analgesic used for rheumatoid arthritis** (likely aspirin), followed by **encephalopathy** (psychomotor agitation, lethargy, severe headache, vomiting, optic disc swelling) and **liver dysfunction** (elevated AST/ALT, elevated urea nitrogen, acidosis), is highly characteristic of Reye syndrome.
- This syndrome is particularly associated with **aspirin use in children** recovering from viral infections, leading to mitochondrial damage in the liver and brain.
*Infection with hepatitis A virus*
- While hepatitis A can cause **nausea, vomiting**, and **elevated liver enzymes**, it is less likely to cause the severe neurological symptoms and metabolic derangements seen here, such as **optic disc swelling** and **acidosis**.
- The history of aspirin use after a viral illness points more strongly towards Reye syndrome over hepatitis A, despite a travel history to Mexico.
*Autoimmune destruction of pancreatic beta cells*
- This describes **Type 1 diabetes mellitus**, which would present with symptoms like **polyuria, polydipsia, weight loss**, and sometimes diabetic ketoacidosis.
- The patient's presentation with acute encephalopathy, liver dysfunction, and a normal blood glucose level makes this diagnosis unlikely.
*Ruptured aneurysm in the circle of Willis*
- A ruptured aneurysm would cause a **sudden, severe headache** and neurological deficits, but it would not explain the preceding viral illness, the **liver enzyme elevations**, or the **metabolic acidosis**.
- While optic disc swelling can occur with increased intracranial pressure, the overall clinical picture does not align.
*Antifreeze ingestion*
- Antifreeze (ethylene glycol) ingestion causes **severe metabolic acidosis** with a high anion gap, **renal failure**, and neurological symptoms.
- While it can explain the acidosis and altered mental status, there is **no history of exposure** and it would not account for the preceding viral illness or the specific pattern of liver enzyme elevation associated with Reye syndrome.
Question 24: A 59-year-old man comes to your clinic accompanied by his wife complaining of nausea and dizziness. He reports that he is unsure when his symptoms started, but they have been affecting him for “a while.” It began as episodes of “unsteadiness” and progressed to a feeling of “spinning.” He cannot tell if his symptoms change with position, but reports that if he does not lie down he will become nauseous. When asked about other symptoms, his wife reports that she has also noticed the patient has worsening hearing loss. She complains that she is constantly repeating herself, especially if she speaks on his right side. The patient denies this and says that she just speaks too softly. The patient’s past medical history is significant for hypertension, alcoholism, and chronic obstructive pulmonary disease. His medications include aspirin, amlodipine, and fluticasone-salmeterol. He reports he drinks a glass of red wine every night with dinner and smokes a cigar on the weekends. Examination shows delayed horizontal nystagmus. Which of the following is the first-line treatment?
A. CN VIII ablation
B. Epley maneuver
C. Thiamine
D. Low-salt diet
E. Meclizine (Correct Answer)
Explanation: ***Meclizine***
- The patient exhibits classic symptoms of **Meniere's disease**, including **vertigo**, **nausea**, and **unilateral hearing loss**, often accompanied by nystagmus. Meclizine is a first-line **antihistamine** commonly used for symptomatic relief of vertigo.
- Meclizine works by decreasing excitability of the inner ear labyrinth and blocking chemoreceptor trigger zone, thus alleviating **dizziness** and **nausea**.
*CN VIII ablation*
- **CN VIII ablation** (vestibular nerve section) is a **surgical procedure** considered only in severe, debilitating cases of **Meniere's disease** that are unresponsive to all other medical treatments.
- It is a **destructive procedure** that carries risks such as further hearing loss or facial nerve injury and is not a first-line treatment.
*Epley maneuver*
- The **Epley maneuver** is a repositioning technique used specifically to treat **benign paroxysmal positional vertigo (BPPV)**, which is caused by dislodged otoconia.
- While the patient has vertigo, the presence of **hearing loss** and progressive symptoms points away from BPPV, and the nystagmus is described as delayed horizontal, not typically characteristic of BPPV.
*Thiamine*
- **Thiamine** (vitamin B1) supplementation is primarily indicated for patients with **Wernicke-Korsakoff syndrome** due to chronic alcohol abuse, presenting with ataxia, confusion, and ophthalmoplegia.
- While the patient has a history of **alcoholism**, his dominant symptoms of **vertigo** and **hearing loss** are not directly addressed by thiamine, and there's no indication of acute Wernicke's encephalopathy.
*Low-salt diet*
- A **low-salt diet** is a common **lifestyle modification** recommended for patients with **Meniere's disease** to help reduce fluid retention in the inner ear.
- While it can be part of the long-term management, it is a **preventative/symptomatic control measure** rather than an immediate first-line pharmacological treatment for acute symptoms like severe nausea and dizziness.
Question 25: A 9-year-old boy is brought to the clinic by his dad for an annual well-child exam. The boy was diagnosed with ADHD at an outside clinic and has been on methylphenidate for symptom management for the past year. The father reports that the patient is more energetic but that his teacher still complains of him "spacing out" during class. The patient reports that it is difficult to follow in class sometimes because the teacher would just "skip ahead suddenly." He denies any headaches, vision changes, fever, or abdominal pain, but endorses decreased appetite since starting methylphenidate. What is the mechanism of action of the drug that would be most appropriate to continue for this patient's ADHD management?
A. Increase in the frequency of chloride channel opening
B. Increase in duration of chloride channel opening
C. Blockage of voltage-gated sodium channels and inhibition of glutamate release
D. Blockage of thalamic T-type calcium channels
E. Blockage of dopamine and norepinephrine reuptake (Correct Answer)
Explanation: ***Blockage of dopamine and norepinephrine reuptake***
- **Methylphenidate** (Ritalin) is a central nervous system stimulant that primarily works by **blocking the reuptake of dopamine and norepinephrine** into the presynaptic neuron, increasing their concentration in the synaptic cleft.
- This mechanism enhances **neurotransmission** in brain regions associated with attention and executive function, which are often impaired in ADHD.
*Increase in the frequency of chloride channel opening*
- This mechanism of action is characteristic of **benzodiazepines**, which are positive allosteric modulators of **GABA-A receptors**.
- Benzodiazepines are typically used for anxiety or seizure disorders, not for the treatment of ADHD.
*Increase in duration of chloride channel opening*
- This mechanism is characteristic of **barbiturates**, which also act on **GABA-A receptors** but increase the **duration** of chloride channel opening.
- Barbiturates have sedative effects and are used for conditions like seizure control and anesthesia, not ADHD.
*Blockage of voltage-gated sodium channels and inhibition of glutamate release*
- This mechanism is typical of some **antiepileptic drugs** like **lamotrigine** or **valproic acid**.
- These drugs are used to treat seizures and certain mood disorders, and are not the primary mechanism for first-line ADHD medications like methylphenidate.
*Blockage of thalamic T-type calcium channels*
- This mechanism is characteristic of **ethosuximide**, an anti-epileptic drug specifically used to treat **absence seizures**.
- This is not the mechanism of action for drugs used to manage ADHD.
Question 26: Two weeks after hospitalization for acute psychosis, a 27-year-old woman with a history of paranoid schizophrenia comes to the physician because of difficulty walking and shaking movements of her hands. Current medications include fluphenazine, which was started during her recent hospitalization. Examination shows a shuffling gait, rigidity in the upper extremities, and a low-amplitude tremor of her hands that improves with activity. Mental status examination shows no abnormalities. Treatment with a drug with which of the following mechanisms of action is most likely to provide relief for this patient's current symptoms?
A. GABA agonist
B. β-adrenergic antagonist
C. Dopamine antagonist
D. Histamine antagonist
E. Muscarinic antagonist (Correct Answer)
Explanation: ***Muscarinic antagonist***
- The patient exhibits classic symptoms of **drug-induced parkinsonism** (shuffling gait, rigidity, tremor) due to the antipsychotic **fluphenazine**.
- **Muscarinic antagonists** (e.g., benztropine, trihexyphenidyl) are effective in treating these **extrapyramidal symptoms (EPS)** by restoring the dopamine-acetylcholine balance in the basal ganglia.
*GABA agonist*
- **GABA agonists** (e.g., benzodiazepines) are primarily used for anxiety, seizures, and insomnia, and are not indicated for drug-induced parkinsonism.
- While they can have muscle relaxant properties, they do not specifically target the underlying neurochemical imbalance responsible for the patient's symptoms.
*β-adrenergic antagonist*
- **β-adrenergic antagonists** (e.g., propranolol) are typically used to treat **akathisia** (motor restlessness), another form of EPS, or essential tremor, not the parkinsonian symptoms described.
- They work by blocking peripheral β-receptors, which can reduce anxiety and tremor, but not the rigidity or bradykinesia of parkinsonism.
*Dopamine antagonist*
- **Dopamine antagonists** are the **cause** of the patient's symptoms as fluphenazine is a dopamine D2 receptor antagonist.
- Further antagonism of dopamine would **exacerbate** rather than alleviate the extrapyramidal symptoms.
*Histamine antagonist*
- **Histamine antagonists** (e.g., diphenhydramine) can have anticholinergic properties and might provide some relief, but they are not the primary or most effective treatment for drug-induced parkinsonism compared to direct muscarinic antagonists.
- Their primary role is in allergic reactions and sedation, and their anticholinergic effect is often a side effect rather than a targeted therapeutic action for EPS.
Question 27: A 26-year-old man is brought to the emergency department because of abdominal pain, dizziness, shortness of breath, and swelling and pruritus of the lips, tongue, and throat for 1 hour. The symptoms began minutes after he started eating a lobster dinner. It is determined that his symptoms are due to surface crosslinking of IgE. This immunologic event most likely caused the release of which of the following?
A. Cathepsin
B. Tryptase (Correct Answer)
C. Bradykinin
D. Interferon gamma
E. Serotonin
Explanation: ***Tryptase***
- The patient's symptoms (abdominal pain, dizziness, shortness of breath, lip/tongue/throat swelling, pruritus) after eating lobster are classic for an **IgE-mediated allergic reaction**, specifically **anaphylaxis**.
- **Tryptase** is a serine protease predominantly stored in and released from the **granules of mast cells** during allergic reactions, making it an excellent biomarker for mast cell activation.
*Cathepsin*
- Cathepsins are a group of proteases found in lysosomes and play a role in protein degradation. They are not primary mediators of immediate hypersensitivity reactions.
- While involved in some immune processes, cathepsins are not typically released in significant amounts during IgE-mediated anaphylaxis.
*Bradykinin*
- Bradykinin is a potent vasodilator and pain-producing peptide, but it is primarily involved in pathways like the **kallikrein-kinin system** and hereditary angioedema, not directly released by IgE crosslinking on mast cells.
- While it contributes to symptoms like angioedema, it is not a direct mediator released upon mast cell degranulation in anaphylaxis.
*Interferon gamma*
- **Interferon gamma (IFN-γ)** is a cytokine primarily produced by T lymphocytes and NK cells, essential for antiviral and antitumor immunity, and macrophage activation.
- It is a key mediator of **Th1-type immune responses** and is not involved in the immediate degranulation of mast cells in an IgE-mediated allergic reaction.
*Serotonin*
- Serotonin (5-hydroxytryptamine) is a neurotransmitter and vasoconstrictor found in platelets and the gastrointestinal tract, and also released by mast cells in some species.
- While human mast cells contain some serotonin, its contribution to systemic anaphylaxis in humans is generally considered less significant compared to histamine and other potent mediators.
Question 28: A 28-year-old female presents to her primary care doctor complaining of new onset blurry vision. She first noticed her vision getting blurry toward the end of the day several days ago. Since then, she reports that her vision has been fine when she wakes up but gets worse throughout the day. She has also noticed that her eyelids have started to droop before she goes to bed. On exam, she has bilateral ptosis that is worse on the right. Administering edrophonium to this patient leads to an immediate improvement in her symptoms. Which of the following is most likely true about this patient’s condition?
A. It is caused by a type III hypersensitivity reaction
B. It is associated with a neoplasm of lung neuroendocrine cells
C. It is caused by antibodies directed against presynaptic P/Q calcium channels
D. An increasing response will be seen on repeated nerve stimulation
E. It is associated with a benign proliferation of epithelial cells of the thymus (Correct Answer)
Explanation: ***It is associated with a benign proliferation of epithelial cells of the thymus***
- The patient's symptoms of progressive weakness throughout the day, ptosis, and improvement with edrophonium (an acetylcholinesterase inhibitor) are highly suggestive of **myasthenia gravis**.
- Approximately 75% of patients with myasthenia gravis have **thymic abnormalities**, with about 65% having **thymic hyperplasia** (a benign proliferation of epithelial cells) and 10% having a **thymoma**.
*It is caused by a type III hypersensitivity reaction*
- **Type III hypersensitivity reactions** involve immune complex deposition, as seen in diseases like Systemic Lupus Erythematosus or post-streptococcal glomerulonephritis.
- Myasthenia gravis is a **Type II hypersensitivity reaction**, where antibodies directly target specific cell surface antigens, in this case, acetylcholine receptors at the neuromuscular junction.
*It is associated with a neoplasm of lung neuroendocrine cells*
- A neoplasm of **lung neuroendocrine cells**, specifically **small cell lung carcinoma**, is associated with **Lambert-Eaton Myasthenic Syndrome (LEMS)**.
- LEMS presents with proximal muscle weakness that *improves* with activity, unlike the fatiguable weakness seen in myasthenia gravis.
*It is caused by antibodies directed against presynaptic P/Q calcium channels*
- Antibodies directed against **presynaptic P/Q calcium channels** are characteristic of **Lambert-Eaton Myasthenic Syndrome (LEMS)**.
- In LEMS, these antibodies reduce the release of acetylcholine into the synaptic cleft, leading to muscle weakness.
*An increasing response will be seen on repeated nerve stimulation*
- An **increasing (incremental) response** on repeated nerve stimulation is a characteristic finding in **Lambert-Eaton Myasthenic Syndrome (LEMS)**.
- In myasthenia gravis, repeated nerve stimulation typically shows a **decreasing (decremental) response** due to the depletion of functionally available acetylcholine receptors.
Question 29: A 62-year-old woman comes to the physician for a follow-up examination after a recent change in her medication regimen. She reports that she feels well. She has type 2 diabetes mellitus, hyperlipidemia, hypertension, essential tremor, and chronic back pain. Current medications are metformin, glyburide, propranolol, simvastatin, ramipril, amitriptyline, and ibuprofen. Fingerstick blood glucose concentration is 47 mg/dL. Serum studies confirm this value. Which of the following pharmacologic mechanisms is most likely responsible for the absence of symptoms in this patient?
A. Antagonism at β2-adrenergic receptors (Correct Answer)
B. Blockade of potassium channels in pancreatic β-cells
C. Inhibition of HMG-CoA reductase
D. Inhibition of angiotensin-converting enzyme
E. Inhibition of norepinephrine and serotonin reuptake
Explanation: ***Antagonism at β2-adrenergic receptors***
- The patient is taking **propranolol**, a **non-selective beta-blocker**, for essential tremor. Propranolol blocks both β1 and β2-adrenergic receptors.
- The typical **adrenergic warning symptoms of hypoglycemia** are mediated by β-adrenergic activation: tremor and anxiety (β2-mediated), and palpitations/tachycardia (β1-mediated).
- By blocking **β2 receptors** (and β1), propranolol **masks these hypoglycemia symptoms**, preventing the patient from recognizing dangerously low blood sugar (47 mg/dL).
- This is a clinically important drug interaction: **non-selective beta-blockers can mask hypoglycemia** in diabetic patients, particularly those on sulfonylureas like glyburide.
*Blockade of potassium channels in pancreatic β-cells*
- This mechanism describes the action of **sulfonylureas** like **glyburide**, which close ATP-sensitive potassium channels on pancreatic beta cells, causing depolarization and insulin release.
- Glyburide is the **likely cause** of this patient's hypoglycemia by increasing insulin secretion.
- However, this mechanism *causes* the hypoglycemia; it does not mask or prevent the symptoms of hypoglycemia.
*Inhibition of HMG-CoA reductase*
- This is the mechanism of action for **statins** like **simvastatin**, used to treat hyperlipidemia.
- Statins inhibit the rate-limiting enzyme in cholesterol synthesis and have **no direct effect** on blood glucose levels or the symptoms of hypoglycemia.
*Inhibition of angiotensin-converting enzyme*
- This describes the action of **ACE inhibitors** like **ramipril**, used to treat hypertension.
- ACE inhibitors primarily affect the **renin-angiotensin-aldosterone system** and blood pressure regulation.
- They do not mask hypoglycemia symptoms, though they may rarely potentiate hypoglycemia through improved insulin sensitivity.
*Inhibition of norepinephrine and serotonin reuptake*
- This is the mechanism of action for **tricyclic antidepressants (TCAs)** like **amitriptyline**, used for chronic pain in this patient.
- While TCAs have anticholinergic effects and can affect the autonomic nervous system, they do **not mask adrenergic hypoglycemia symptoms**.
- Amitriptyline does not significantly affect glucose metabolism or the sympathetic response to hypoglycemia.
Question 30: A 29-year-old man comes to the physician for worsening restlessness over the past several days. Three weeks ago, he was started on trifluoperazine for the treatment of schizophrenia. He reports that, since then, he has often felt compelled to pace around his house and is unable to sit or stand still. He is switched to an alternative antipsychotic medication. Four weeks later, the patient reports improvement of his symptoms but says that he has developed increased drowsiness, blurred vision, and dry mouth. The patient was most likely switched to which of the following drugs?
A. Fluphenazine
B. Metoclopramide
C. Haloperidol
D. Chlorpromazine (Correct Answer)
E. Trimipramine
Explanation: ***Chlorpromazine***
- **Chlorpromazine** is a **first-generation antipsychotic** that belongs to the **low-potency** class, meaning it has a lower risk of extrapyramidal symptoms (EPS) but a higher risk of anticholinergic side effects.
- The patient's initial symptoms of restlessness (akathisia) after starting **trifluoperazine** (a high-potency FGA) strongly suggest EPS. Switching to chlorpromazine would alleviate EPS but would likely cause the reported **drowsiness, blurred vision, and dry mouth** due to its significant **antihistaminic**, **anticholinergic**, and **alpha-1 adrenergic blocking effects**.
*Fluphenazine*
- **Fluphenazine** is a **high-potency first-generation antipsychotic**, similar to trifluoperazine.
- Switching to fluphenazine from trifluoperazine would likely **exacerbate or maintain** the patient's extrapyramidal symptoms, not alleviate them.
*Metoclopramide*
- **Metoclopramide** is a **dopamine receptor antagonist** primarily used as an antiemetic and prokinetic agent.
- While it can cause side effects similar to antipsychotics, it is **not an antipsychotic** medication used for schizophrenia and would not be an appropriate switch for symptom control.
*Haloperidol*
- **Haloperidol** is another **high-potency first-generation antipsychotic**, known for a high incidence of extrapyramidal symptoms.
- Switching to haloperidol would likely **worsen** the patient's akathisia and other EPS rather than improve them.
*Trimipramine*
- **Trimipramine** is a **tricyclic antidepressant**, not an antipsychotic, and is typically used for depression and anxiety.
- It would not treat schizophrenia and while it has anticholinergic effects, it would not explain the improvement in akathisia in an antipsychotic context.
