A 19-year-old South Asian male presents to the family physician concerned that he is beginning to go bald. He is especially troubled because his father and grandfather "went completely bald by the age of 25," and he is willing to try anything to prevent his hair loss. The family physician prescribes a medication that prevents the conversion of testosterone to dihydrotestosterone. Which of the following enzymes is inhibited by this medication?
Q902
A 72-year-old Caucasian woman presents with three months of progressive central vision loss accompanied by wavy distortions in her vision. She has hypertension controlled with metoprolol but has no other past medical history. Based on this clinical history she is treated with intravitreal injections of a medication. What is the mechanism of action of the treatment most likely used in this case?
Q903
A 51-year-old woman comes to the physician because of daytime sleepiness and dry mouth for one month. She says her sleepiness is due to getting up to urinate several times each night. She noticed increased thirst about a month ago and now drinks up to 20 cups of water daily. She does not feel a sudden urge prior to urinating and has not had dysuria. She has a history of multiple urinary tract infections and head trauma following a suicide attempt 3 months ago. She has bipolar I disorder and hypertension. She has smoked one pack of cigarettes daily for 25 years. Examination shows poor skin turgor. Mucous membranes are dry. Expiratory wheezes are heard over both lung fields. There is no suprapubic tenderness. She describes her mood as "good" and her affect is appropriate. Neurologic examination shows tremor in both hands. Laboratory studies show a serum sodium of 151 mEq/L. Urine osmolality is 124 mOsm/kg H2O. Which of the following is the most likely explanation for this patient's symptoms?
Q904
A scientist is studying mechanisms by which cancer drugs work to kill tumor cells. She is working to optimize the function of a drug class in order to reduce toxicity and increase potency for the target. After synthesizing a variety of analogs for the drug class, she tests these new pharmacologic compounds against a panel of potential targets. Assay results show that there is significant binding to a clustered group of proteins. Upon examining these proteins, she finds that the proteins add a phosphate group to an aromatic amino acid sidechain. Which of the following disorders would most likely be treated by this drug class?
Q905
Five days after undergoing an open colectomy and temporary colostomy for colon cancer, a 73-year-old man develops severe pain and swelling of the left calf. He was diagnosed with colon cancer 3 months ago. He has hypothyroidism and hypertension. His father died of colon cancer at the age of 68. He does not smoke. Prior to admission, his medications included levothyroxine, amlodipine, and carvedilol. Since the surgery, he has also been receiving unfractionated heparin, morphine, and piperacillin-tazobactam. He is 172 cm (5 ft 8 in) tall and weighs 101 kg (223 lb); BMI is 34.1 kg/m2. He appears uncomfortable. His temperature is 38.1°C (100.6°F), pulse is 103/min, and blood pressure is 128/92 mm Hg. Examination shows multiple necrotic lesions over bilateral thighs. The left calf is erythematous, tender, and swollen. Dorsiflexion of the left foot elicits pain behind the knee. The abdomen is soft and nontender. There is a healing midline incision and the colostomy is healthy and functioning. The remainder of the examination shows no abnormalities. Laboratory studies show:
Hemoglobin 13.6 g/dL
Leukocyte count 12,100/mm3
Platelet count 78,000/mm3
Prothrombin time 18 seconds (INR = 1.1)
Activated partial thromboplastin time 46 seconds
Serum
Na+ 138 mEq/L
Cl- 103 mEq/L
K+ 4.1 mEq/L
Urea nitrogen 18 mg/dL
Glucose 101 mg/dL
Creatinine 1.1 mg/dL
Which of the following is the most appropriate next step in management?
Q906
A 4-year-old boy is brought to the emergency department by his mother after cutting his buttock on a piece of broken glass. There is a 5-cm curvilinear laceration over the patient's right buttock. His vital signs are unremarkable. The decision to repair the laceration is made. Which of the following will offer the longest anesthesia for the laceration repair?
Q907
An 11-year-old boy is brought to a pediatrician by his parents with the complaint of progressive behavioral problems for the last 2 years. His parents report that he always looks restless at home and is never quiet. His school teachers frequently complain that he cannot remain seated for long during class, often leaving his seat to move around the classroom. A detailed history of his symptoms suggests a diagnosis of attention-deficit/hyperactivity disorder. The parents report that he has taken advantage of behavioral counseling several times without improvement. The pediatrician considers pharmacotherapy and plans to start methylphenidate at a low dose, followed by regular follow-up. Based on the side effect profile of the medication, which of the following components of the patient’s medical history should the pediatrician obtain before starting the drug?
Q908
A 67-year-old man comes to the physician because of numbness and burning sensation of his legs for the past week. He also complains that his stools have been larger and rougher than usual. He has non-Hodgkin lymphoma and is currently receiving chemotherapy with prednisone, vincristine, rituximab, cyclophosphamide, and doxorubicin. He has received 4 cycles of chemotherapy, and his last chemotherapy cycle was 2 weeks ago. His temperature is 37.1°C (98.8°F), pulse is 89/min, and blood pressure is 122/80 mm Hg. Examination shows decreased muscle strength in the distal muscles of the lower extremities. Ankle jerk is 1+ bilaterally and knee reflex is 2+ bilaterally. Sensation to pain, vibration, and position is decreased over the lower extremities. Serum concentrations of glucose, creatinine, electrolytes, and calcium are within the reference range. Which of the following is the most likely cause of this patient's symptoms?
Q909
A 58-year-old woman comes to the physician because of a 6-month history of difficulty walking, clumsiness of her arms and legs, and slurred speech. Physical examination shows masked facies and a slow, shuffling gait. When her ankles are passively flexed, there is involuntary, jerky resistance. Treatment is initiated with a combination of levodopa and carbidopa. The addition of carbidopa is most likely to decrease the risk of which of the following potential adverse drug effects?
Q910
A 12-year-old boy presents to the pediatrician with complaints of chronic cough for the past two years. The cough is present during the day, especially after returning from school. His school teacher says he does not cough at school. The cough is absent while he is asleep, although it increases during examinations or when he experiences boredom. His mother reports that there was a one-month period where he did not cough, but during that month, he used to shrug his shoulders frequently, especially when he was stressed or fatigued. There is no history of sneezing, nasal discharge, nasal congestion, headache, ear symptoms, or breathing difficulty. Detailed history does not suggest the presence of a mood disorder, obsessive-compulsive symptoms, or attention-deficit/hyperactivity disorder. There is no past history of a known neurological disorder, and there is no history of substance abuse. On physical examination, his vital signs are stable. Examination of his respiratory and cardiovascular systems is normal. However, the pediatrician notes repeated eye blinking; upon asking about eye blinking, the mother reports that he has had this habit since he was almost eight years old. Further inquiry suggests that eye blinking, coughing, and grunting disappear for a few weeks without explanation, only to reappear again. Which of the following drugs is likely to be most effective to control this patient’s symptoms?
Autonomic/CV Drugs US Medical PG Practice Questions and MCQs
Question 901: A 19-year-old South Asian male presents to the family physician concerned that he is beginning to go bald. He is especially troubled because his father and grandfather "went completely bald by the age of 25," and he is willing to try anything to prevent his hair loss. The family physician prescribes a medication that prevents the conversion of testosterone to dihydrotestosterone. Which of the following enzymes is inhibited by this medication?
A. Cyclooxygenase 2
B. Desmolase
C. Aromatase
D. cGMP phosphodiesterase
E. 5-alpha-reductase (Correct Answer)
Explanation: ***5-alpha-reductase***
- The medication described inhibits the conversion of **testosterone to dihydrotestosterone (DHT)**, which is catalyzed by the enzyme **5-alpha-reductase**.
- **Androgenetic alopecia** (male pattern baldness) is driven by DHT, and inhibiting this enzyme reduces DHT levels in the scalp, thereby slowing hair loss.
*Cyclooxygenase 2*
- **Cyclooxygenase 2 (COX-2)** is involved in the synthesis of **prostaglandins** from arachidonic acid, mediating inflammation and pain.
- COX-2 inhibitors are used as anti-inflammatory drugs (e.g., celecoxib), not for male pattern baldness.
*Desmolase*
- **Cholesterol desmolase** (CYP11A1) is an enzyme that catalyzes the first committed step in **steroidogenesis**, converting cholesterol to pregnenolone.
- Inhibition of desmolase would affect the synthesis of all steroid hormones, not specifically target the conversion of testosterone to DHT for hair loss treatment.
*Aromatase*
- **Aromatase** is an enzyme responsible for converting androgens (like testosterone) into **estrogens**.
- Aromatase inhibitors are used in the treatment of estrogen-receptor positive breast cancer, not male pattern baldness.
*cGMP phosphodiesterase*
- **cGMP phosphodiesterase (PDE5)** is an enzyme that breaks down cyclic GMP (cGMP), which is involved in smooth muscle relaxation.
- PDE5 inhibitors (e.g., sildenafil) are used to treat **erectile dysfunction** and **pulmonary hypertension**, not hair loss.
Question 902: A 72-year-old Caucasian woman presents with three months of progressive central vision loss accompanied by wavy distortions in her vision. She has hypertension controlled with metoprolol but has no other past medical history. Based on this clinical history she is treated with intravitreal injections of a medication. What is the mechanism of action of the treatment most likely used in this case?
A. Increase outflow of aqueous humor
B. Crosslink corneal collagen
C. Decrease ciliary body production of aqueous humor
D. Inhibit choroidal neovascularization (Correct Answer)
E. Inhibit carbonic anhydrase enzyme
Explanation: ***Inhibit choroidal neovascularization***
- This patient's symptoms of **progressive central vision loss** and **wavy distortions (metamorphopsia)** in a 72-year-old suggest **wet age-related macular degeneration (AMD)**.
- The treatment for wet AMD is typically **anti-VEGF (vascular endothelial growth factor) intravitreal injections**, which work by inhibiting **choroidal neovascularization**, preventing the growth of abnormal blood vessels that leak fluid and blood.
*Increase outflow of aqueous humor*
- This mechanism is characteristic of medications used to treat **open-angle glaucoma**, such as **prostaglandin analogs** (e.g., latanoprost).
- Glaucoma typically presents with **peripheral vision loss** and increased intraocular pressure, not central vision changes or metamorphopsia.
*Crosslink corneal collagen*
- **Corneal collagen cross-linking** is a procedure used to strengthen the cornea in conditions like **keratoconus**, which causes progressive corneal thinning and irregular astigmatism.
- It does not address central vision loss due to retinal pathology.
*Decrease ciliary body production of aqueous humor*
- This is the mechanism of action for medications like **beta-blockers** (e.g., timolol) and **alpha-2 agonists** (e.g., brimonidine) used in the treatment of **glaucoma**.
- These drugs reduce intraocular pressure, which is not the primary issue in wet AMD.
*Inhibit carbonic anhydrase enzyme*
- **Carbonic anhydrase inhibitors** (e.g., dorzolamide) reduce aqueous humor production by blocking the enzyme in the ciliary body.
- These are also used to lower intraocular pressure in **glaucoma**, a condition distinct from macular degeneration.
Question 903: A 51-year-old woman comes to the physician because of daytime sleepiness and dry mouth for one month. She says her sleepiness is due to getting up to urinate several times each night. She noticed increased thirst about a month ago and now drinks up to 20 cups of water daily. She does not feel a sudden urge prior to urinating and has not had dysuria. She has a history of multiple urinary tract infections and head trauma following a suicide attempt 3 months ago. She has bipolar I disorder and hypertension. She has smoked one pack of cigarettes daily for 25 years. Examination shows poor skin turgor. Mucous membranes are dry. Expiratory wheezes are heard over both lung fields. There is no suprapubic tenderness. She describes her mood as "good" and her affect is appropriate. Neurologic examination shows tremor in both hands. Laboratory studies show a serum sodium of 151 mEq/L. Urine osmolality is 124 mOsm/kg H2O. Which of the following is the most likely explanation for this patient's symptoms?
A. Mood stabilizer intake (Correct Answer)
B. Neuroleptic malignant syndrome
C. Primary hyperaldosteronism
D. Hypothalamic injury
E. Paraneoplastic syndrome
Explanation: ***Mood stabilizer intake***
- The patient's history of **bipolar I disorder** and symptoms of **polyuria, polydipsia, high serum sodium, low urine osmolality**, and **dry mucous membranes** strongly suggest **nephrogenic diabetes insipidus**.
- **Lithium**, a common mood stabilizer for bipolar disorder, can induce **nephrogenic diabetes insipidus** by interfering with the renal collecting duct's response to **ADH**, leading to excessive water loss and dehydration with compensatory polydipsia.
*Neuroleptic malignant syndrome*
- This condition is characterized by **fever, severe muscle rigidity, altered mental status, and autonomic dysfunction**.
- The patient's symptoms of chronic polyuria and polydipsia, without other features of NMS, do not align with this diagnosis.
*Primary hyperaldosteronism*
- Typically presents with **hypertension and hypokalemia**, often with metabolic alkalosis.
- It does not explain the pronounced polyuria, polydipsia, and hypernatremia seen in this patient, which are more indicative of a water balance disorder.
*Hypothalamic injury*
- Can cause **central diabetes insipidus** by affecting ADH production or release, leading to similar symptoms of polyuria and polydipsia.
- However, given her history of bipolar disorder, **lithium-induced nephrogenic diabetes insipidus** is a more probable and direct explanation compared to a less specific head trauma association without further evidence of central DI.
*Paraneoplastic syndrome*
- While it can manifest with various symptoms, **syndromes causing polyuria and polydipsia** are rare and usually associated with underlying malignancies that are not indicated here.
- Symptoms like **hypercalcemia from parathyroid hormone-related peptide (PTHrP)** could cause polyuria, but her **hypernatremia and low urine osmolality** are more consistent with diabetes insipidus.
Question 904: A scientist is studying mechanisms by which cancer drugs work to kill tumor cells. She is working to optimize the function of a drug class in order to reduce toxicity and increase potency for the target. After synthesizing a variety of analogs for the drug class, she tests these new pharmacologic compounds against a panel of potential targets. Assay results show that there is significant binding to a clustered group of proteins. Upon examining these proteins, she finds that the proteins add a phosphate group to an aromatic amino acid sidechain. Which of the following disorders would most likely be treated by this drug class?
A. HER2 negative breast cancer
B. Non-Hodgkin lymphoma
C. Testicular cancer
D. Chronic myeloid leukemia (Correct Answer)
E. Brain tumors
Explanation: ***Chronic myeloid leukemia***
- This drug class targets **proteins that add a phosphate group to an aromatic amino acid side chain**, which are **tyrosine kinases**. The **BCR-ABL fusion protein** in CML is a constitutively active tyrosine kinase.
- **Imatinib** and other **tyrosine kinase inhibitors (TKIs)** are highly effective treatments for CML by inhibiting the aberrant BCR-ABL signaling.
*HER2 negative breast cancer*
- This type of breast cancer does not overexpress the **HER2 receptor tyrosine kinase**, so drugs targeting tyrosine kinases would not be effective for this subtype.
- Treatment typically involves **hormone therapy** (if receptor-positive) or **chemotherapy**.
*Non-Hodgkin lymphoma*
- While some lymphomas can involve **kinase dysregulation**, the description of targeting proteins that specifically phosphorylate **aromatic amino acid side chains** (tyrosine kinases) isn't the primary, broadly effective mechanism for most non-Hodgkin lymphomas.
- Treatment often involves **chemotherapy regimens**, **monoclonal antibodies** (e.g., rituximab targeting CD20), and sometimes radiation.
*Testicular cancer*
- Testicular cancers are generally highly sensitive to **platinum-based chemotherapy** (e.g., cisplatin) and do not typically involve the **tyrosine kinase pathways** described as the primary druggable target.
- The main treatment involves surgery, chemotherapy, and sometimes radiation.
*Brain tumors*
- While some brain tumors (e.g., **glioblastoma**) can involve **receptor tyrosine kinase (RTK) upregulation**, drugs often have **difficulty crossing the blood-brain barrier** effectively, and the described mechanism isn't a universally effective primary treatment strategy for most brain tumors.
- Treatment varies widely by tumor type but often includes **surgery, radiation, and chemotherapy**.
Question 905: Five days after undergoing an open colectomy and temporary colostomy for colon cancer, a 73-year-old man develops severe pain and swelling of the left calf. He was diagnosed with colon cancer 3 months ago. He has hypothyroidism and hypertension. His father died of colon cancer at the age of 68. He does not smoke. Prior to admission, his medications included levothyroxine, amlodipine, and carvedilol. Since the surgery, he has also been receiving unfractionated heparin, morphine, and piperacillin-tazobactam. He is 172 cm (5 ft 8 in) tall and weighs 101 kg (223 lb); BMI is 34.1 kg/m2. He appears uncomfortable. His temperature is 38.1°C (100.6°F), pulse is 103/min, and blood pressure is 128/92 mm Hg. Examination shows multiple necrotic lesions over bilateral thighs. The left calf is erythematous, tender, and swollen. Dorsiflexion of the left foot elicits pain behind the knee. The abdomen is soft and nontender. There is a healing midline incision and the colostomy is healthy and functioning. The remainder of the examination shows no abnormalities. Laboratory studies show:
Hemoglobin 13.6 g/dL
Leukocyte count 12,100/mm3
Platelet count 78,000/mm3
Prothrombin time 18 seconds (INR = 1.1)
Activated partial thromboplastin time 46 seconds
Serum
Na+ 138 mEq/L
Cl- 103 mEq/L
K+ 4.1 mEq/L
Urea nitrogen 18 mg/dL
Glucose 101 mg/dL
Creatinine 1.1 mg/dL
Which of the following is the most appropriate next step in management?
A. Switch from unfractionated heparin to warfarin therapy
B. Transfuse platelet concentrate
C. Administer vitamin K
D. Switch from unfractionated heparin to argatroban therapy (Correct Answer)
E. Administer fresh frozen plasma
Explanation: ***Switch from unfractionated heparin to argatroban therapy***
- The patient's presentation with new **thrombosis (severe pain and swelling of the left calf)**, **thrombocytopenia (platelet count 78,000/mm3)**, and recent exposure to **unfractionated heparin (UFH)** is highly suggestive of **Heparin-Induced Thrombocytopenia (HIT) with thrombosis (HITT)**.
- In suspected or confirmed HIT, UFH must be immediately discontinued, and a **direct thrombin inhibitor (DTI)** like **argatroban** should be initiated to prevent further thrombosis.
*Switch from unfractionated heparin to warfarin therapy*
- While warfarin is used for long-term anticoagulation, it should **not be initiated as monotherapy in acute HIT** due to the risk of **venous limb gangrene** and further thrombosis during the initial phase of warfarin action (due to initial procoagulant effect).
- Warfarin can only be started **after platelet counts have recovered** and a non-heparin anticoagulant (like a DTI) has been administered for at least 5 days, given there is an overlap period.
*Transfuse platelet concentrate*
- Platelet transfusions are generally **contraindicated in HIT** because they can worsen the prothrombotic state by providing more substrate for platelet activation, potentially exacerbating thrombosis.
- Platelet transfusions are reserved for **life-threatening bleeding** in patients with HIT, which is not the case here.
*Administer vitamin K*
- Vitamin K is the antidote for **warfarin** overdose and has no role in the management of HIT. The patient's PT/INR is only mildly elevated, likely due to heparin and not warfarin, as he was not on warfarin.
- Administering vitamin K would not address the underlying pathology of HIT and would not be beneficial.
*Administer fresh frozen plasma*
- Fresh frozen plasma (FFP) contains clotting factors and is used to reverse coagulopathy in cases of **severe bleeding or factor deficiencies**, or for rapid reversal of warfarin.
- It is **not indicated for HIT**, as HIT is a prothrombotic condition involving platelet activation, not a deficiency in clotting factors that would be corrected by FFP.
Question 906: A 4-year-old boy is brought to the emergency department by his mother after cutting his buttock on a piece of broken glass. There is a 5-cm curvilinear laceration over the patient's right buttock. His vital signs are unremarkable. The decision to repair the laceration is made. Which of the following will offer the longest anesthesia for the laceration repair?
A. Lidocaine
B. Lidocaine mixed with bupivacaine
C. Bupivacaine with epinephrine (Correct Answer)
D. Lidocaine with epinephrine
E. Bupivacaine
Explanation: ***Bupivacaine with epinephrine***
- **Bupivacaine** is a long-acting local anesthetic, and adding **epinephrine** to it further prolongs its duration of action by causing vasoconstriction, which slows systemic absorption.
- This combination would provide the **longest duration of anesthesia** suitable for a laceration repair that requires extended pain control.
*Lidocaine*
- **Lidocaine** is an intermediate-acting local anesthetic with a relatively shorter duration of action compared to bupivacaine.
- While effective for initial anesthesia, its effect would likely wear off sooner than desired for a comprehensive repair.
*Lidocaine mixed with bupivacaine*
- Mixing lidocaine with bupivacaine can provide a **faster onset of action** (due to lidocaine) and a longer duration (due to bupivacaine) as compared to lidocaine alone.
- However, the overall duration would typically still be *shorter* than bupivacaine with epinephrine due to the lack of vasoconstriction from epinephrine, leading to faster systemic absorption.
*Lidocaine with epinephrine*
- Adding **epinephrine** to **lidocaine** prolongs its duration of action by inducing vasoconstriction.
- While this is a practical choice for many procedures, bupivacaine inherently has a longer duration than lidocaine, making *bupivacaine with epinephrine* the longest-acting option among those given.
*Bupivacaine*
- **Bupivacaine** alone provides longer anesthesia than lidocaine alone.
- However, without **epinephrine**, its duration is not as long as it could be, as epinephrine would delay its absorption and prolong its local effect.
Question 907: An 11-year-old boy is brought to a pediatrician by his parents with the complaint of progressive behavioral problems for the last 2 years. His parents report that he always looks restless at home and is never quiet. His school teachers frequently complain that he cannot remain seated for long during class, often leaving his seat to move around the classroom. A detailed history of his symptoms suggests a diagnosis of attention-deficit/hyperactivity disorder. The parents report that he has taken advantage of behavioral counseling several times without improvement. The pediatrician considers pharmacotherapy and plans to start methylphenidate at a low dose, followed by regular follow-up. Based on the side effect profile of the medication, which of the following components of the patient’s medical history should the pediatrician obtain before starting the drug?
A. Past history of recurrent wheezing
B. Past history of idiopathic thrombocytopenic purpura
C. Past history of recurrent fractures
D. Past history of Kawasaki disease (Correct Answer)
E. Past history of Guillain-Barré syndrome
Explanation: ***Past history of Kawasaki disease***
- Methylphenidate, a stimulant, can cause **cardiovascular side effects** such as increased heart rate and blood pressure.
- A history of Kawasaki disease, which can lead to **coronary artery aneurysms** and other cardiac complications, necessitates a thorough cardiac evaluation before initiating stimulant therapy to prevent potentially serious cardiovascular events.
*Past history of recurrent wheezing*
- **Recurrent wheezing** primarily involves the respiratory system and is not typically a contraindication or concern with methylphenidate use.
- While general health is important, there is no direct interaction or exacerbation of asthma/wheezing expected from methylphenidate.
*Past history of idiopathic thrombocytopenic purpura*
- **Idiopathic thrombocytopenic purpura (ITP)** is a hematological disorder affecting platelet count and clotting.
- There is no known direct interaction or significant risk of exacerbation of ITP with methylphenidate.
*Past history of recurrent fractures*
- **Recurrent fractures** may suggest underlying bone density issues or other musculoskeletal conditions.
- Methylphenidate does not directly impact bone health or fracture risk, making this history less relevant for its initiation.
*Past history of Guillain-Barré syndrome*
- **Guillain-Barré syndrome** is an autoimmune disorder affecting the peripheral nervous system, leading to muscle weakness and paralysis.
- While neurological history is generally important, there is no specific contraindication or heightened risk for patients with a history of Guillain-Barré syndrome taking methylphenidate.
Question 908: A 67-year-old man comes to the physician because of numbness and burning sensation of his legs for the past week. He also complains that his stools have been larger and rougher than usual. He has non-Hodgkin lymphoma and is currently receiving chemotherapy with prednisone, vincristine, rituximab, cyclophosphamide, and doxorubicin. He has received 4 cycles of chemotherapy, and his last chemotherapy cycle was 2 weeks ago. His temperature is 37.1°C (98.8°F), pulse is 89/min, and blood pressure is 122/80 mm Hg. Examination shows decreased muscle strength in the distal muscles of the lower extremities. Ankle jerk is 1+ bilaterally and knee reflex is 2+ bilaterally. Sensation to pain, vibration, and position is decreased over the lower extremities. Serum concentrations of glucose, creatinine, electrolytes, and calcium are within the reference range. Which of the following is the most likely cause of this patient's symptoms?
A. Paraneoplastic autoantibodies
B. Guillain-Barré syndrome
C. Adverse effect of vincristine (Correct Answer)
D. Charcot–Marie–Tooth disease
E. Spinal cord compression
Explanation: ***Adverse effect of vincristine***
- The patient's symptoms of **numbness, burning sensation, decreased distal muscle strength, and sensory deficits** (pain, vibration, position) are classic signs of **peripheral neuropathy**, a common and dose-limiting side effect of vincristine.
- **Vincristine** is known to disrupt **microtubule formation**, which is crucial for axonal transport in neurons, leading to nerve damage and constipation due to autonomic neuropathy (manifesting as larger, rougher stools).
*Paraneoplastic autoantibodies*
- While paraneoplastic syndromes can cause neuropathies, they typically develop **before or concurrently with cancer diagnosis** and tend to be progressive, rather than appearing after several cycles of chemotherapy in this pattern.
- The patient's symptoms are highly consistent with a known drug toxicity, making paraneoplastic antibodies a less likely primary cause.
*Guillain-Barré syndrome*
- **Guillain-Barré syndrome** typically presents as an **acute, ascending paralysis** often preceded by an infection, which is not described here.
- While it causes neuropathy, the temporal onset and the patient's ongoing chemotherapy make a drug-induced neuropathy more probable.
*Charcot–Marie–Tooth disease*
- **Charcot–Marie–Tooth disease** is a group of **hereditary neuropathies** that typically present in childhood or early adulthood with a *slowly progressive* course.
- The acute, subacute onset of symptoms within the past week, in an older patient receiving chemotherapy, makes this genetic condition highly unlikely.
*Spinal cord compression*
- **Spinal cord compression** would likely cause more prominent **motor weakness**, **spasticity**, and potentially a distinct sensory level or bowel/bladder dysfunction, which are not the primary features here.
- The diffuse sensory findings and distal predominance of weakness are more characteristic of a peripheral neuropathy rather than a myelopathy.
Question 909: A 58-year-old woman comes to the physician because of a 6-month history of difficulty walking, clumsiness of her arms and legs, and slurred speech. Physical examination shows masked facies and a slow, shuffling gait. When her ankles are passively flexed, there is involuntary, jerky resistance. Treatment is initiated with a combination of levodopa and carbidopa. The addition of carbidopa is most likely to decrease the risk of which of the following potential adverse drug effects?
A. Visual hallucinations
B. Dyskinesia
C. Urinary retention
D. Orthostatic hypotension (Correct Answer)
E. Resting tremor
Explanation: ***Orthostatic hypotension***
- Carbidopa inhibits **peripheral DOPA decarboxylase**, preventing the conversion of levodopa to dopamine in the systemic circulation.
- This reduces systemic dopamine levels, thereby decreasing adverse effects such as **nausea, vomiting**, and **orthostatic hypotension** caused by peripheral dopamine action.
*Visual hallucinations*
- **Visual hallucinations** are a central dopaminergic side effect of levodopa and are not directly prevented by carbidopa.
- Carbidopa increases the amount of levodopa reaching the brain, which can potentially worsen central side effects if not managed with dosage adjustments.
*Dyskinesia*
- **Dyskinesia** is a common long-term motor complication of levodopa therapy, resulting from pulsating dopamine stimulation in the brain.
- Carbidopa itself, by increasing the availability of levodopa to the brain, does not reduce the risk of dyskinesia and may even contribute to it.
*Urinary retention*
- **Urinary retention** is not a characteristic immediate side effect of levodopa-carbidopa therapy; instead, anticholinergic medications may cause this.
- Levodopa's primary effects are on the dopamine system, and its association with urinary retention is not prominent.
*Resting tremor*
- **Resting tremor** is a cardinal symptom of Parkinson's disease and is typically *improved* by levodopa, not caused or worsened by it.
- Carbidopa enhances the therapeutic effect of levodopa, thereby helping to reduce the tremor.
Question 910: A 12-year-old boy presents to the pediatrician with complaints of chronic cough for the past two years. The cough is present during the day, especially after returning from school. His school teacher says he does not cough at school. The cough is absent while he is asleep, although it increases during examinations or when he experiences boredom. His mother reports that there was a one-month period where he did not cough, but during that month, he used to shrug his shoulders frequently, especially when he was stressed or fatigued. There is no history of sneezing, nasal discharge, nasal congestion, headache, ear symptoms, or breathing difficulty. Detailed history does not suggest the presence of a mood disorder, obsessive-compulsive symptoms, or attention-deficit/hyperactivity disorder. There is no past history of a known neurological disorder, and there is no history of substance abuse. On physical examination, his vital signs are stable. Examination of his respiratory and cardiovascular systems is normal. However, the pediatrician notes repeated eye blinking; upon asking about eye blinking, the mother reports that he has had this habit since he was almost eight years old. Further inquiry suggests that eye blinking, coughing, and grunting disappear for a few weeks without explanation, only to reappear again. Which of the following drugs is likely to be most effective to control this patient’s symptoms?
A. Levetiracetam
B. Atomoxetine
C. Haloperidol
D. Fluoxetine
E. Clonidine (Correct Answer)
Explanation: **Clonidine**
- This patient's presentation with chronic cough, shoulder shrugs, eye blinking, and grunting, characterized by **waxing and waning symptoms** and **suggestibility (cough absent at school but present post-school, increasing with boredom/examinations)**, is highly suggestive of **Tourette's disorder** or a **chronic tic disorder**.
- **Clonidine**, an alpha-2 adrenergic agonist, is a first-line treatment for tic disorders, especially in children, due to its efficacy in reducing tic severity with a favorable side effect profile.
*Levetiracetam*
- **Levetiracetam** is an antiepileptic drug used to treat various seizure types, including focal and generalized seizures.
- It is **not indicated for tic disorders** and would not be effective in controlling the patient's symptoms.
*Atomoxetine*
- **Atomoxetine** is a selective norepinephrine reuptake inhibitor primarily used to treat **attention-deficit/hyperactivity disorder (ADHD)**.
- While tics can co-occur with ADHD, atomoxetine is **not a primary treatment for tic disorders** and may even exacerbate tics in some individuals.
*Haloperidol*
- **Haloperidol** is a first-generation antipsychotic with strong dopamine receptor-blocking activity, highly effective in severe tic disorders due to its potent antipsychotic effects.
- However, it has a significant side effect profile, including **extrapyramidal symptoms (dystonia, parkinsonism, akathisia, and tardive dyskinesia)**, making it a second or third-line option after alpha-2 agonists or atypical antipsychotics like risperidone, especially given the patient's age and milder symptom presentation.
*Fluoxetine*
- **Fluoxetine** is a selective serotonin reuptake inhibitor (SSRI) primarily used to treat **depression, anxiety disorders, and obsessive-compulsive disorder (OCD)**.
- While OCD can co-occur with tic disorders, fluoxetine directly targets mood and anxiety symptoms, **not the tics themselves**.