A 69-year-old man comes to the physician because of a 3-month history of urinary urgency, nocturia, and progressive pain in his lower back. The pain is worse at night and does not respond to ibuprofen. Rectal examination shows an enlarged, asymmetric prostate with a nodular surface. Prostate-specific antigen concentration is 11 ng/ml (N < 4). A biopsy of the prostate shows a high-grade adenocarcinoma. A CT scan of the pelvis shows multiple osteoblastic lesions of the lumbar spine. The patient is started on a drug that competes with androgens for interaction with the testosterone receptors. Treatment with which of the following drugs was most likely initiated in this patient?
Q202
A 16-year-old boy presents with shortness of breath after prolonged exposure to cold air during a recent hike with his friends. Past medical history is significant for asthma, untreated because he doesn't like using medications. The patient says he is a non-smoker and occasionally drinks alcohol. On physical examination, his temperature is 37.0°C (98.6°F), pulse rate is 120/min, blood pressure is 114/76 mm Hg, and respiratory rate is 32/min. Auscultation of the chest reveals bilateral wheezing. Nebulized ipratropium bromide results in significant clinical improvement. Which of the following second messenger systems is affected by this drug?
Q203
A 23-year-old man presents to the physician with nausea, vomiting, constipation, and abdominal pain for the past 24 hours. He has also developed difficulty in swallowing and blurring of vision. He also complains of significant dryness of his mouth and throat. When asked about his diet, he reports that he has been saving money by eating dented and old canned goods. On physical examination, his vital signs are stable. His neurologic examination reveals bilateral fixed dilated pupils, weakness of extraocular muscles, and weak gag reflex, while sensations and gait are normal. Laboratory evaluation of his stool isolates a toxin produced by gram-positive, anaerobic, spore-forming bacilli. Which of the following mechanisms best explains the action of the toxin?
Q204
A 65-year-old woman returns to the outpatient oncology clinic to follow up on her recently diagnosed breast cancer. A few months ago, she noticed a lump during a breast self-exam that was shown to be breast cancer. A lumpectomy revealed invasive ductal carcinoma that was estrogen- and progesterone receptor-positive with nodal metastases. She is following up to discuss treatment options. She had her last menstrual period 10 years ago and has not had any spotting since that time. Her mother had breast cancer and she remembered her taking chemotherapy and had a poor quality of life, thus she asks not to be treated similarly. Which of the following is the mechanism of action of the best treatment option for this patient?
Q205
A 30-year-old man presents to his primary care doctor for a 2 month follow-up appointment. He had recently separated from his male partner of 10 years and has been struggling to maintain his weight and the rigors of work in a new start-up company. At his initial visit, he was prescribed escitalopram. 2 weeks later, the patient was instructed to continue taking the medication despite feeling more depressed. After expressing increased desire to carry out suicidal thoughts, he was hospitalized for a brief course. During this visit, he reports that he is feeling much better, but he has an elective inguinal hernia repair scheduled for the end of the week. "The surgeon said to not take anything before the surgery. Besides, I'm feeling better and don't feel like taking escitalopram everyday." What is the most appropriate response?
Q206
A medical examiner was called to investigate the death of a 75-year-old type 1 diabetic Caucasian male who was a retired physician. His caretaker discovered his body in the bedroom with an empty syringe and a small bottle of lispro lying on the nightstand. She explains that his wife of 50 years passed away six months ago and that he had no children or family. He had become extremely depressed and did not want to live anymore. Which of the following would be most consistent with his blood chemistry if a blood sample were taken?
Q207
A 53-year-old woman with type 2 diabetes mellitus is admitted for evaluation of recurrent episodes of nausea, tremors, and excessive sweating. She works as a nurse and reports self-measured blood glucose levels below 50 mg/dL on several occasions. Her family history is positive for borderline personality disorder. The only medication listed in her history is metformin. Which of the following is the most appropriate next step in management?
Q208
A 22-year-old man presents to the emergency department with a 2-day history of fever and altered mentation. He reports fever without chills and rigors and denies sore throat, abdominal pain, headache, loose stool, burning micturition, or seizures. He has a history of tics and is currently on a low dose of haloperidol. At the hospital, his temperature is 39.6°C (103.2°F); the blood pressure is 126/66 mm Hg, and the pulse is 116/min. He is profusely sweating and generalized rigidity is present. He is confused and disoriented. He is able to move all his limbs. Normal deep tendon reflexes are present with bilateral downgoing plantar responses. A brain MRI is unremarkable. Urine toxicology is negative. The white blood cell count is 14,700/mm3. Creatine kinase is 5600 U/L. Lumbar puncture is performed and cerebrospinal fluid (CSF) studies show:
CSF opening pressure 22 cm H20
CSF white blood cells 4 cells/mm3
CSF red blood cells 0 cells/mm3
CSF glucose 64 mg/dL
CSF protein 48 mg/dL
Serum glucose 96 mg/dL
What is the most likely diagnosis?
Q209
A 64-year-old man presents to his primary care physician because of a tremor that he has developed over the last several months. He says that the tremor is worst when he is resting but becomes better when he engages in movements such as picking up the remote for his TV. His wife also says that his movements have become slower over the last few months. Physical exam reveals increased resistance to passive motion of his extremities. Gait exam also shows trouble with starting movement and short, shuffling steps. The most likely cause of this patient's symptoms involve the degeneration of a certain subset of neurons. When the substance released by these neurons interact with a G-alpha-s coupled receptor, which of the following effects occurs?
Q210
A 28-year-old female is brought to the emergency department after being found unconscious outside of a local night club by her friends. On arrival the patient is stuporous. Her temperature is 35°C (95°F), blood pressure is 105/75 mm Hg, pulse is 55/min, and respirations are 10/min. Examination shows dry mucous membranes. The pupils are small and react sluggishly to light. She does not respond to any commands, and painful stimuli cause her to withdraw all extremities. No injection marks can be found on her extremities. The remainder of the examination shows no abnormalities. Which of the following is the most likely cause of her symptoms?
Cholinergic/Adrenergic drugs US Medical PG Practice Questions and MCQs
Question 201: A 69-year-old man comes to the physician because of a 3-month history of urinary urgency, nocturia, and progressive pain in his lower back. The pain is worse at night and does not respond to ibuprofen. Rectal examination shows an enlarged, asymmetric prostate with a nodular surface. Prostate-specific antigen concentration is 11 ng/ml (N < 4). A biopsy of the prostate shows a high-grade adenocarcinoma. A CT scan of the pelvis shows multiple osteoblastic lesions of the lumbar spine. The patient is started on a drug that competes with androgens for interaction with the testosterone receptors. Treatment with which of the following drugs was most likely initiated in this patient?
A. Docetaxel
B. Flutamide (Correct Answer)
C. Finasteride
D. Degarelix
E. Leuprolide
Explanation: ***Flutamide***
- The patient has **metastatic prostate cancer** with osteoblastic lesions, indicating a need for **androgen-deprivation therapy**. Flutamide is an **androgen receptor antagonist** that competes with androgens for binding to testosterone receptors.
- It is often used in combination with **GnRH agonists** (like leuprolide) to prevent **tumor flare** caused by the initial surge in testosterone, or as monotherapy in some cases.
*Docetaxel*
- **Docetaxel** is a **chemotherapeutic agent** (a taxane) used primarily for patients with **castration-resistant prostate cancer** or when hormonal therapies are no longer effective.
- It works by stabilizing microtubules, preventing cell division, and does not compete with androgens for testosterone receptors.
*Finasteride*
- **Finasteride** is a **5-alpha reductase inhibitor** that blocks the conversion of testosterone to **dihydrotestosterone (DHT)**, which is the more potent androgen in the prostate.
- It is used for **benign prostatic hyperplasia (BPH)** and **androgenic alopecia**, but not typically for metastatic prostate cancer as the primary treatment mechanism described.
*Degarelix*
- **Degarelix** is a **GnRH receptor antagonist** that directly suppresses the release of LH and FSH, leading to a rapid and sustained reduction in testosterone levels without an initial flare.
- While it causes androgen deprivation, it does not directly compete with androgens for binding to the testosterone receptors on cancer cells; its action is upstream.
*Leuprolide*
- **Leuprolide** is a **GnRH agonist** that initially causes a surge in LH and FSH, followed by downregulation and desensitization of the GnRH receptors, leading to reduced testosterone production.
- Like degarelix, it causes androgen deprivation, but it does not directly compete with androgens at the receptor level; its action is also upstream.
Question 202: A 16-year-old boy presents with shortness of breath after prolonged exposure to cold air during a recent hike with his friends. Past medical history is significant for asthma, untreated because he doesn't like using medications. The patient says he is a non-smoker and occasionally drinks alcohol. On physical examination, his temperature is 37.0°C (98.6°F), pulse rate is 120/min, blood pressure is 114/76 mm Hg, and respiratory rate is 32/min. Auscultation of the chest reveals bilateral wheezing. Nebulized ipratropium bromide results in significant clinical improvement. Which of the following second messenger systems is affected by this drug?
A. Tyrosine kinase system
B. Phosphoinositol system (Correct Answer)
C. Arachidonic acid system
D. Cyclic guanosine monophosphate (cGMP) system
E. Cyclic adenosine monophosphate (cAMP) system
Explanation: ***Phosphoinositol system***
- **Ipratropium bromide** is an **anticholinergic drug** that blocks **muscarinic M3 receptors** on bronchial smooth muscle.
- M3 receptors are **Gq protein-coupled receptors** that activate the **phosphoinositol (PIP2) pathway**.
- When activated, Gq proteins stimulate **phospholipase C (PLC)**, which cleaves **PIP2** into **IP3** (inositol trisphosphate) and **DAG** (diacylglycerol).
- IP3 increases **intracellular calcium**, causing **bronchoconstriction**; ipratropium **blocks this pathway**, resulting in **bronchodilation**.
- This is the primary second messenger system affected by ipratropium.
*Cyclic adenosine monophosphate (cAMP) system*
- The **cAMP system** is associated with **β2-adrenergic receptors** (Gs-coupled), not muscarinic M3 receptors.
- **Beta-agonists** like albuterol work through cAMP to cause bronchodilation, but ipratropium does not directly affect this pathway.
- While there may be indirect effects, M3 receptors primarily signal through the phosphoinositol system, not cAMP.
*Tyrosine kinase system*
- The **tyrosine kinase system** is activated by **growth factors** (e.g., insulin, EGF, PDGF) through receptor tyrosine kinases.
- This pathway involves autophosphorylation and activation of downstream signaling cascades like **MAPK** and **PI3K/Akt**.
- Muscarinic receptors are **G protein-coupled receptors (GPCRs)**, not tyrosine kinase receptors.
*Arachidonic acid system*
- The **arachidonic acid pathway** produces **prostaglandins, leukotrienes**, and **thromboxanes** via **cyclooxygenase** and **lipoxygenase** enzymes.
- This system is targeted by **NSAIDs** (block COX) and **leukotriene modifiers** (e.g., montelukast), not by anticholinergics.
- While inflammation plays a role in asthma, ipratropium's mechanism does not primarily involve this pathway.
*Cyclic guanosine monophosphate (cGMP) system*
- The **cGMP system** is primarily associated with **nitric oxide (NO) signaling** and **atrial natriuretic peptide (ANP)**.
- NO activates **guanylyl cyclase**, increasing cGMP levels and causing **smooth muscle relaxation** and **vasodilation**.
- M3 muscarinic receptors do not primarily signal through the cGMP pathway.
Question 203: A 23-year-old man presents to the physician with nausea, vomiting, constipation, and abdominal pain for the past 24 hours. He has also developed difficulty in swallowing and blurring of vision. He also complains of significant dryness of his mouth and throat. When asked about his diet, he reports that he has been saving money by eating dented and old canned goods. On physical examination, his vital signs are stable. His neurologic examination reveals bilateral fixed dilated pupils, weakness of extraocular muscles, and weak gag reflex, while sensations and gait are normal. Laboratory evaluation of his stool isolates a toxin produced by gram-positive, anaerobic, spore-forming bacilli. Which of the following mechanisms best explains the action of the toxin?
A. Prolonged depolarization of NM receptors
B. Blockade of release of acetylcholine at neuromuscular junctions (Correct Answer)
C. Competitive antagonism of acetylcholine at postsynaptic receptors
D. Blockade of voltage-gated fast sodium channels in motor neurons
E. Inactivation of acetylcholinesterase at neuromuscular junctions
Explanation: ***Blockade of release of acetylcholine at neuromuscular junctions***
- The clinical presentation, including the consumption of **dented canned goods**, **fixed dilated pupils**, **extraocular muscle weakness**, and **weak gag reflex**, is classic for **botulism**.
- The botulinum toxin, produced by *Clostridium botulinum*, acts by **preventing the release of acetylcholine** from presynaptic terminals at neuromuscular junctions, leading to **flaccid paralysis**.
*Prolonged depolarization of NM receptors*
- This mechanism is associated with **depolarizing neuromuscular blockers** (e.g., succinylcholine) which initially cause fasciculations followed by paralysis due to persistent receptor activation, not seen in botulism.
- Such agents lead to initial muscle contraction before paralysis, unlike the direct weakness caused by botulinum toxin.
*Competitive antagonism of acetylcholine at postsynaptic receptors*
- This mechanism is characteristic of **nondepolarizing neuromuscular blockers** (e.g., rocuronium), which compete with acetylcholine for binding sites on the postsynaptic membrane.
- While this also causes muscle weakness, it is not the action of botulinum toxin, which acts presynaptically.
*Blockade of voltage-gated fast sodium channels in motor neurons*
- Toxins that block **voltage-gated sodium channels** (e.g., tetrodotoxin, saxitoxin) prevent nerve impulse generation, leading to paralysis by inhibiting action potential propagation.
- This mechanism would affect nerve conduction upstream of neurotransmitter release, which is distinct from botulinum toxin's action.
*Inactivation of acetylcholinesterase at neuromuscular junctions*
- Inactivation of **acetylcholinesterase** (e.g., by organophosphates) leads to an accumulation of acetylcholine in the synaptic cleft, causing **cholinergic crisis** with symptoms like excessive salivation, lacrimation, urination, and defecation, which are the opposite of the dry mouth and constipation seen here.
- This mechanism would cause overstimulation rather than paralysis from neurotransmitter deficiency at the synapse.
Question 204: A 65-year-old woman returns to the outpatient oncology clinic to follow up on her recently diagnosed breast cancer. A few months ago, she noticed a lump during a breast self-exam that was shown to be breast cancer. A lumpectomy revealed invasive ductal carcinoma that was estrogen- and progesterone receptor-positive with nodal metastases. She is following up to discuss treatment options. She had her last menstrual period 10 years ago and has not had any spotting since that time. Her mother had breast cancer and she remembered her taking chemotherapy and had a poor quality of life, thus she asks not to be treated similarly. Which of the following is the mechanism of action of the best treatment option for this patient?
A. Cell cycle arrest
B. Estrogen receptors downregulation in the breast
C. Inhibit peripheral conversion of androgens to estrogen (Correct Answer)
D. Antagonist for estrogen receptors in the breast
E. Antagonist for estrogen receptors in the hypothalamus
Explanation: ***Inhibit peripheral conversion of androgens to estrogen***
- The patient has **estrogen and progesterone receptor-positive breast cancer** and is **postmenopausal**. Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) are the best treatment option for postmenopausal women with hormone-sensitive breast cancer.
- Aromatase inhibitors work by blocking the **aromatase enzyme**, which is responsible for the peripheral conversion of androgens to estrogens, thereby reducing estrogen levels in postmenopausal women and inhibiting cancer growth.
*Cell cycle arrest*
- While many chemotherapeutic agents induce cell cycle arrest, this patient's preference for avoiding chemotherapy and the **hormone-sensitive nature of her cancer** suggest a less aggressive, targeted hormonal therapy is more appropriate.
- Cell cycle arrest is a general mechanism for many cancer treatments, but it's not the primary, specific mechanism for the best treatment for this particular patient given her clinicopathological features and preferences.
*Estrogen receptors downregulation in the breast*
- This mechanism is characteristic of **selective estrogen receptor degraders (SERDs)** like fluvestrant, which destroy estrogen receptors.
- While an effective treatment for hormone-sensitive breast cancer, especially in later lines, aromatase inhibitors are generally preferred as initial adjuvant therapy in postmenopausal women with positive nodal disease.
*Antagonist for estrogen receptors in the breast*
- This describes the mechanism of **selective estrogen receptor modulators (SERMs)** such as tamoxifen, which act as antagonists in breast tissue and agonists in other tissues like bone.
- Tamoxifen is primarily used in premenopausal women or in high-risk postmenopausal women who cannot tolerate aromatase inhibitors or for other specific indications; aromatase inhibitors are generally preferred for postmenopausal women with nodal involvement.
*Antagonist for estrogen receptors in the hypothalamus*
- Antagonism of estrogen receptors in the hypothalamus could theoretically impact the **hypothalamic-pituitary-gonadal axis**, but this is not the direct or primary therapeutic mechanism for treating hormone-sensitive breast cancer.
- Drugs like **clomiphene citrate**, which induce ovulation, act at the hypothalamus but are not used for breast cancer treatment.
Question 205: A 30-year-old man presents to his primary care doctor for a 2 month follow-up appointment. He had recently separated from his male partner of 10 years and has been struggling to maintain his weight and the rigors of work in a new start-up company. At his initial visit, he was prescribed escitalopram. 2 weeks later, the patient was instructed to continue taking the medication despite feeling more depressed. After expressing increased desire to carry out suicidal thoughts, he was hospitalized for a brief course. During this visit, he reports that he is feeling much better, but he has an elective inguinal hernia repair scheduled for the end of the week. "The surgeon said to not take anything before the surgery. Besides, I'm feeling better and don't feel like taking escitalopram everyday." What is the most appropriate response?
A. Continue escitalopram on day of surgery and continue afterwards for 4 more months (Correct Answer)
B. Hold escitalopram the day of surgery and continue afterwards for 4 more months
C. Continue escitalopram until surgery and discontinue afterwards
D. Discontinue escitalopram
E. Hold escitalopram the day before surgery and continue afterwards for 4 more months
Explanation: ***Continue escitalopram on day of surgery and continue afterwards for 4 more months***
- For patients on **antidepressants** prior to surgery, it is generally recommended to continue the medication throughout the perioperative period to avoid **withdrawal symptoms** and potential relapse of depressive symptoms.
- Continuing escitalopram for at least **4-9 months** after symptom resolution is recommended to reduce the risk of relapse for a first episode of depression.
*Hold escitalopram the day of surgery and continue afterwards for 4 more months*
- Holding escitalopram on the day of surgery increases the risk of **serotonin withdrawal syndrome**, which can manifest as dizziness, nausea, headaches, and flu-like symptoms.
- There is generally **no medical reason** to discontinue SSRIs like escitalopram perioperatively as they do not significantly increase the risk of bleeding or anesthesia complications.
*Continue escitalopram until surgery and discontinue afterwards*
- Discontinuing escitalopram immediately after surgery, especially given the patient's recent hospitalization for suicidal ideation, poses a high risk of **relapse of depression** and potential re-emergence of suicidal thoughts.
- The patient's statement "feeling better" should be interpreted cautiously; it might reflect a **partial response** to treatment rather than full remission, and abrupt discontinuation can destabilize his mental health.
*Discontinue escitalopram*
- Abrupt discontinuation of escitalopram, particularly given the patient's past history of **severe depression** and recent suicidal ideation, is highly inadvisable and significantly increases the risk of **relapse** and withdrawal symptoms.
- This approach fails to address the underlying depression and the need for continued treatment to maintain mental stability.
*Hold escitalopram the day before surgery and continue afterwards for 4 more months*
- Similar to holding on the day of surgery, holding escitalopram the day before can initiate **withdrawal symptoms** and destabilize the patient's mood, potentially complicating the perioperative period.
- There is no clinical indication for a pre-operative hold of escitalopram, as its continuation is generally considered safe and beneficial.
Question 206: A medical examiner was called to investigate the death of a 75-year-old type 1 diabetic Caucasian male who was a retired physician. His caretaker discovered his body in the bedroom with an empty syringe and a small bottle of lispro lying on the nightstand. She explains that his wife of 50 years passed away six months ago and that he had no children or family. He had become extremely depressed and did not want to live anymore. Which of the following would be most consistent with his blood chemistry if a blood sample were taken?
A. Glucose: 95 mg/dL, high insulin and C-peptide levels
B. Glucose: 25 mg/dL, high insulin and absent C-peptide levels (Correct Answer)
C. Glucose: 95 mg/dL, low insulin and low C-peptide levels
D. Glucose: 25 mg/dL, high insulin and high C-peptide levels
E. Glucose: 25 mg/dL, high insulin and normal C-peptide levels
Explanation: **Glucose: 25 mg/dL, high insulin and absent C-peptide levels**
- The presence of an empty syringe and a bottle of **lispro**, a **rapid-acting insulin**, indicates a likely insulin overdose. This would lead to profound **hypoglycemia** (glucose: 25 mg/dL) and **high insulin levels**.
- As the patient has **Type 1 diabetes**, his pancreas does not produce insulin, resulting in **absent C-peptide levels**. Administered exogenous insulin (lispro) does not contain C-peptide, so C-peptide levels would remain absent even with high exogenous insulin.
*Glucose: 95 mg/dL, high insulin and C-peptide levels*
- A glucose level of 95 mg/dL is within the normal range and inconsistent with a fatal insulin overdose scenario, which typically causes severe **hypoglycemia**.
- High insulin with high C-peptide levels would typically suggest conditions like an **insulinoma** or an overdose of a sulfonylurea, which stimulates endogenous insulin production, not an overdose of exogenous insulin in a Type 1 diabetic.
*Glucose: 95 mg/dL, low insulin and low C-peptide levels*
- Glucose at 95 mg/dL is normal to low-normal, which would not typically be seen in a fatal insulin overdose.
- Low insulin and low C-peptide levels are characteristic of controlled or untreated **Type 1 diabetes** or other forms of insulin deficiency, not an acute insulin overdose.
*Glucose: 25 mg/dL, high insulin and high C-peptide levels*
- While a glucose level of 25 mg/dL and high insulin are consistent with an insulin overdose, **high C-peptide levels** in a Type 1 diabetic are contradictory. Type 1 diabetics produce little to no C-peptide.
- High C-peptide levels would suggest endogenous insulin production, which is absent in Type 1 diabetes and not introduced by exogenous lispro.
*Glucose: 25 mg/dL, high insulin and normal C-peptide levels*
- Although **hypoglycemia** and **high insulin** are consistent with an overdose, "normal" C-peptide levels are unlikely in a Type 1 diabetic who has received exogenous insulin.
- In Type 1 diabetes, C-peptide is typically very low or undetectable, reflecting minimal to no endogenous insulin production.
Question 207: A 53-year-old woman with type 2 diabetes mellitus is admitted for evaluation of recurrent episodes of nausea, tremors, and excessive sweating. She works as a nurse and reports self-measured blood glucose levels below 50 mg/dL on several occasions. Her family history is positive for borderline personality disorder. The only medication listed in her history is metformin. Which of the following is the most appropriate next step in management?
A. Measure serum C-peptide concentration
B. Ask the patient if she is taking any medications other than metformin (Correct Answer)
C. Search the patient's belongings for insulin
D. Measure glycated hemoglobin concentration
E. Report the patient to her employer
Explanation: ***Ask the patient if she is taking any medications other than metformin***
- The patient's presentation with recurrent **hypoglycemic symptoms** (nausea, tremors, sweating) and documented low blood glucose, while only being prescribed metformin (which does not cause hypoglycemia), strongly suggests **exogenous insulin or sulfonylurea use**.
- A direct question about other medications is a crucial initial step to ascertain the cause of her hypoglycemia and to rule out **factitious hypoglycemia**, especially given her profession as a nurse and a family history that might suggest psychological vulnerabilities, although not a direct diagnosis for the patient.
*Measure serum C-peptide concentration*
- While **low C-peptide** in the presence of hypoglycemia would suggest exogenous insulin administration, and high C-peptide might point to an insulinoma, this test should be done *after* ruling out common causes like the undisclosed use of other medications.
- This is a more invasive and less direct initial step compared to simply asking the patient about medication use, especially when a readily reversible cause (undisclosed medication) is possible.
*Search the patient's belongings for insulin*
- Searching a patient's belongings without their consent is a serious ethical breach and a violation of privacy.
- This action should only be considered as a last resort in extreme circumstances and with appropriate legal and ethical oversight, not as an initial diagnostic step.
*Measure glycated hemoglobin concentration*
- **Glycated hemoglobin (HbA1c)** reflects average blood glucose levels over the past 2-3 months and is used to monitor long-term glycemic control in diabetic patients.
- While useful for diabetes management, it will not directly identify the acute cause of recurrent hypoglycemic episodes or distinguish between endogenous and exogenous insulin sources.
*Report the patient to her employer*
- Reporting the patient to her employer prematurely, without a definitive diagnosis or understanding the full context of her condition, is unethical and unprofessional.
- The immediate priority is to diagnose and manage the patient's medical condition, ensuring her safety and well-being, before considering professional implications.
Question 208: A 22-year-old man presents to the emergency department with a 2-day history of fever and altered mentation. He reports fever without chills and rigors and denies sore throat, abdominal pain, headache, loose stool, burning micturition, or seizures. He has a history of tics and is currently on a low dose of haloperidol. At the hospital, his temperature is 39.6°C (103.2°F); the blood pressure is 126/66 mm Hg, and the pulse is 116/min. He is profusely sweating and generalized rigidity is present. He is confused and disoriented. He is able to move all his limbs. Normal deep tendon reflexes are present with bilateral downgoing plantar responses. A brain MRI is unremarkable. Urine toxicology is negative. The white blood cell count is 14,700/mm3. Creatine kinase is 5600 U/L. Lumbar puncture is performed and cerebrospinal fluid (CSF) studies show:
CSF opening pressure 22 cm H20
CSF white blood cells 4 cells/mm3
CSF red blood cells 0 cells/mm3
CSF glucose 64 mg/dL
CSF protein 48 mg/dL
Serum glucose 96 mg/dL
What is the most likely diagnosis?
A. Cerebral venous sinus thrombosis
B. Acute disseminated encephalomyelitis
C. Encephalitis
D. Neuroleptic malignant syndrome (Correct Answer)
E. Meningitis
Explanation: ***Neuroleptic malignant syndrome***
- The patient's presentation with **fever, altered mentation, muscle rigidity, profuse sweating, elevated creatine kinase**, and a history of **haloperidol** use is highly consistent with Neuroleptic Malignant Syndrome (NMS).
- **Haloperidol** is a dopamine antagonist, and its use is a well-known risk factor for NMS, which is characterized by a severe idiosyncratic reaction to neuroleptic medications.
*Cerebral venous sinus thrombosis*
- This condition typically presents with **severe headaches, focal neurological deficits, and seizures**, often seen on MRI or CT venography.
- The patient's normal MRI and generalized symptoms without focal deficits make this diagnosis less likely.
*Acute disseminated encephalomyelitis*
- ADEM is an **autoimmune demyelinating disease** often following an infection or vaccination, typically presenting with multifocal neurological deficits.
- The patient's presentation, particularly the muscle rigidity and elevated CK, is not typical for ADEM, and the MRI is unremarkable.
*Encephalitis*
- Encephalitis involves **brain inflammation**, manifesting as fever, altered mental status, and seizures, with CSF usually showing **lymphocytic pleocytosis**.
- The CSF in this patient is largely normal (minimal pleocytosis), and the prominent **muscle rigidity and very high CK** point away from uncomplicated encephalitis.
*Meningitis*
- Meningitis primarily involves **inflammation of the meninges**, characterized by fever, headache, nuchal rigidity, and photophobia, with CSF showing pleocytosis and abnormal protein/glucose.
- While the patient has fever and altered mentation, **nuchal rigidity is absent**, and the CSF findings (especially the normal cell count and glucose) do not support a diagnosis of meningitis.
Question 209: A 64-year-old man presents to his primary care physician because of a tremor that he has developed over the last several months. He says that the tremor is worst when he is resting but becomes better when he engages in movements such as picking up the remote for his TV. His wife also says that his movements have become slower over the last few months. Physical exam reveals increased resistance to passive motion of his extremities. Gait exam also shows trouble with starting movement and short, shuffling steps. The most likely cause of this patient's symptoms involve the degeneration of a certain subset of neurons. When the substance released by these neurons interact with a G-alpha-s coupled receptor, which of the following effects occurs?
A. Stimulation of the subthalamic nucleus
B. Inhibition of the globus pallidus internus (Correct Answer)
C. Inhibition of the globus pallidus externus
D. Stimulation of the globus pallidus externus
E. Stimulation of the globus pallidus internus
Explanation: ***Inhibition of the globus pallidus internus***
- This patient's symptoms are highly suggestive of **Parkinson's disease**, characterized by **resting tremor**, **bradykinesia** (slow movements), **rigidity** (increased resistance to passive motion), and **gait abnormalities**.
- Parkinson's disease results from the degeneration of **dopaminergic neurons** in the **substantia nigra pars compacta**. Dopamine released by these neurons acts on **D1 receptors (Gαs-coupled)** in the striatum, which are part of the **direct pathway** of the basal ganglia.
- D1 receptor activation **excites striatal neurons** in the direct pathway, which then send **GABAergic (inhibitory) projections** to the **globus pallidus internus (GPi)**, resulting in **inhibition of the GPi** and ultimately **facilitating movement**.
*Stimulation of the subthalamic nucleus*
- The subthalamic nucleus (STN) is **stimulated by the indirect pathway**, which is relatively overactive in Parkinson's disease due to dopamine deficiency.
- Stimulation of the STN leads to **increased excitation of the GPi**, thus suppressing movement.
- D1 (Gαs-coupled) receptors do **not** directly stimulate the STN; they act on the direct pathway through the striatum.
*Inhibition of the globus pallidus externus*
- In the indirect pathway, dopamine acts through **D2 (Gαi-coupled) receptors**, not D1 (Gαs-coupled) receptors.
- D2 activation **inhibits striatal neurons** in the indirect pathway, reducing their inhibitory output to the **globus pallidus externus (GPe)**, which leads to disinhibition of the GPe.
- This is **not** the effect of D1 (Gαs-coupled) receptor activation.
*Stimulation of the globus pallidus externus*
- The **GPe is not stimulated by D1 receptor activation**.
- D1 receptors act primarily on the **direct pathway** (striatum → GPi), not the indirect pathway involving the GPe.
- The GPe is influenced by D2 receptor activity in the indirect pathway, not D1 receptors.
*Stimulation of the globus pallidus internus*
- D1 receptor activation in the direct pathway leads to **inhibition, not stimulation**, of the GPi.
- The GPi is **excited by the subthalamic nucleus** in the indirect pathway, but this is not mediated by D1 (Gαs-coupled) receptors.
- **Inhibition of the GPi** (via excited striatal neurons) is the correct effect of D1 receptor activation, facilitating movement.
Question 210: A 28-year-old female is brought to the emergency department after being found unconscious outside of a local night club by her friends. On arrival the patient is stuporous. Her temperature is 35°C (95°F), blood pressure is 105/75 mm Hg, pulse is 55/min, and respirations are 10/min. Examination shows dry mucous membranes. The pupils are small and react sluggishly to light. She does not respond to any commands, and painful stimuli cause her to withdraw all extremities. No injection marks can be found on her extremities. The remainder of the examination shows no abnormalities. Which of the following is the most likely cause of her symptoms?
A. Heroin (Correct Answer)
B. Cannabis
C. Phencyclidine
D. MDMA
E. Amitriptyline
Explanation: ***Heroin***
- The patient's **depressed mental status** (**stupor**, **unconscious**), **miotic (small) pupils**, **bradycardia**, **bradypnea**, and **hypothermia** are all classic signs of **opioid overdose**.
- Although no injection marks were found, heroin can be **snorted** or **smoked**, and the combination of symptoms strongly points towards opioid toxicity.
- The **dry mucous membranes** are somewhat atypical for pure opioid toxicity (more consistent with anticholinergic effects) but may be secondary to **dehydration** or environmental exposure; the overwhelming clinical presentation of **opioid toxidrome** (miosis, respiratory depression, CNS depression) takes precedence.
*Cannabis*
- While cannabis can cause **somnolence** and **impaired coordination**, it typically does not lead to severe **respiratory depression**, **pinpoint pupils**, or **unconsciousness** to this degree.
- The vital signs are not consistent with typical cannabis intoxication, which might include **tachycardia** and **conjunctival injection**.
*Phencyclidine*
- **Phencyclidine (PCP)** intoxication is usually characterized by **agitation**, **hallucinations**, **nystagmus**, and sometimes **hypertension** and **tachycardia**, which contradict this patient's presentation.
- While it can cause altered mental status, the **miosis**, **bradycardia**, and **respiratory depression** are not typical.
*MDMA*
- **MDMA (Ecstasy)** typically causes **sympathomimetic effects** such as **tachycardia**, **hypertension**, **hyperthermia**, **mydriasis (dilated pupils)**, and **agitation**, which are all opposite to the patient's symptoms.
- It does not induce significant **respiratory depression** or **miosis**.
*Amitriptyline*
- **Amitriptyline**, a tricyclic antidepressant (TCA), overdose can cause significant central nervous system depression, but it is typically associated with **anticholinergic effects** such as **mydriasis (dilated pupils)**, **tachycardia**, **dry mucous membranes**, **urinary retention**, and potentially **seizures** or **arrhythmias**.
- The **pinpoint pupils** and **bradycardia** are inconsistent with TCA overdose, making this diagnosis unlikely despite the presence of dry mucous membranes.