🧠 Mind Games (Psych)
A 24-year-old man is brought to the emergency department by his roommate because he has become increasingly withdrawn over the past year. He frequently mumbles to himself and has stopped attending medical school because he believes his classmates can "insert thoughts into his brain." Mental status examination reveals blunted affect, poverty of speech, hallucinations, and thought broadcasting. MRI demonstrates enlarged lateral ventricles.
The dysfunction responsible for this patient's positive symptoms is most likely due to increased dopaminergic activity in which pathway?
HY Pearl: Positive = mesolimbic ↑ dopamine; negative/cognitive = mesocortical ↓ dopamine. This distinction is tested constantly.
What is mesolimbic pathway
1. Dx = schizophrenia
2. Positive vs. negative sx:
Positive = "ADDING" something
Negative = "LOSS"
3. Positive & negative sx and pathways:
A 37-year-old man with schizophrenia is treated with haloperidol. Several weeks later, he develops bradykinesia, cogwheel rigidity, and resting tremor. What should be given to the patient to treat these SE?
What is benztropine OR diphenhydramine
Psychiatric emergencies:
1. Serotonin syndrome: benzodiazepine, cyproheptadine
2. Hypertensive crisis: phentolamine
3. NMS: dantrolene, dopaminergics, benzo
4. Acute dystonia: benzo, benztropine
5. Lithium toxicity: aggressive hydration w/ isotonic NaCl (+/- hemodialysis)
A previously healthy 3-year-old girl is brought to the emergency department with fever, vomiting, neck stiffness, hypotension, and a petechial rash. Blood cultures later grow gram-negative diplococci.
Which virulence factor is primarily responsible for this patient's hypotension and shock?
What is LOS endotoxin
1. organism = neisseria meningitidis
• gram-negative diplococci
• 3-year-old w/ fever + neck stiffness + petechial rash
2. nesseria meningitidis virulence factor: it sheds LOS (endotoxin).
LOS --> macrophage activation (TLR4) --> increased TNF-a, IL1, IL6 --> massive inflammation --> vasodilation + capillary leak --> hypotension
A patient with suspected bacterial meningitis is empirically started on ceftriaxone and vancomycin.
Why is vancomycin included in the empiric regimen?
What is coverage for penicillin-/cephalosporin-resistant Streptococcus pneumoniae
A 42-year-old woman with treatment-resistant schizophrenia is admitted for fever, headache, and altered mental status. She has been taking clozapine for the past 6 months. Physical examination reveals oral ulcers, and CBC demonstrates profound neutropenia. CSF Gram stain shows budding yeast.
Which organism is the most likely cause of this patient's meningitis?
What is Cryptococcus neoformans
Clozapine -> AGN -> opportunistic fungal infection -> cryptococcus.
A 33-year-old woman presents because she has been sleeping only 2 hours nightly for the past week. She has started three businesses, maxed out multiple credit cards, and insists she has been chosen to "revolutionize modern medicine." She required hospitalization after attempting to purchase an airplane despite having no pilot's license. Six months earlier she experienced several weeks of depressed mood.
The neurotransmitter most responsible for the patient's manic symptoms exerts its effects through which intracellular signaling mechanism?
What is a GPCR that inhibits adenylyl cyclase (D2 receptor) [Gi]
Mania → increased DP activity → D2 (Gi), resulting in decreased AC and decreased cAMP → most antipsychotics improve mania by blocking D2 receptors and increasing cAMP signaling.
A 55 y.o. M presents with fever and increasing confusion for the past 2 days. He has paranoid schizophrenia treated with chlorpromazine. He appears diaphoretic. His temperature is 40°C (104°F), pulse is 115/min, respirations are 31/min, and blood pressure is 158/105 mm Hg. Neurologic examination shows psychomotor agitation and incoherent speech. There is generalized muscle rigidity. His deep tendon reflexes are decreased bilaterally. Serum laboratory analysis shows a leukocyte count of 11,300/mm3 and serum creatine kinase concentration of 945 U/L.
What is the dx and appropriate tx?
What is neuroleptic malignant syndrome — dantrolene
This schizophrenic patient's presentation of fever, altered mental status, muscle rigidity, decreased DTRs, lutonomic instability (hypertension, tachycardia, diaphoresis), and elevated serum creatine kinase is indicative of neuroleptic malignant syndrome (NMS). Initial treatment of NMS should target the patient's rigidity and hyperthermia to prevent progression into rhabdomyolysis.
A 60-year-old woman with fever, altered mental status, and nuchal rigidity undergoes lumbar puncture. Gram stain demonstrates lancet-shaped gram-positive diplococci. Despite appropriate antibiotic therapy, she develops permanent hearing loss. Which adjunctive medication would've prevented this complication if given before or w/ the first abx dose?
What is dexmethasone
1. Agent = Streptococcus penumoniae (gram +, diplococci)
2. Abx: first-line, immediate = vancomycin + ceftriaxone
• vancomycin = convers penicillin/cephalosporin resistant pneumococcus
• ceftriaxone =corsses BBB and offers broad coverage
A patient develops severe diarrhea after receiving clindamycin for aspiration pneumonia. Stool testing is positive for Clostridioides difficile toxin.
Which bacterial ribosomal subunit is inhibited by the medication that most likely predisposed this patient to infection?
What is 50S ribosomal subunit
A 34-year-old man with bipolar I disorder has been stable on lithium for the past 5 years. He presents with fever, headache, neck stiffness, and photophobia. Lumbar puncture demonstrates neutrophilic pleocytosis, elevated protein, and decreased glucose. Empiric therapy with vancomycin, ceftriaxone, and ampicillin is initiated.
Three days later, he develops worsening tremor, ataxia, and confusion despite improvement in his meningitis symptoms.
Which medication is most likely responsible for his new neurologic findings?
What is lithium
Bacterial meningitis -> given vancomycin -> AKI -> lithium accumulates -> lithium toxicity
A 29-year-old graduate student presents because she is convinced that her coworkers are secretly poisoning her coffee. She otherwise functions well at work and has maintained employment for years. She denies hallucinations, disorganized speech, negative symptoms, mood episodes, and substance use. Symptoms have persisted for approximately 18 months.
Which diagnosis best explains this patient's illness?
What is delusional disorder
Delusional disorder:
A 28-year-old woman with treatment-resistant schizophrenia is started on a new antipsychotic after failing adequate trials of risperidone and olanzapine. Four weeks later, she presents with fever, malaise, odynophagia, and painful oral ulcers. Physical examination is notable for pharyngeal erythema without exudates.
Which laboratory study should have been monitored routinely while she was receiving this medication?
What is ANC/WBC
1. Treatment-resistant schizophrenia --> Clozapine
• Clozapine is used for treatment-resistant psychotic disorders or those with persistent suicidality
2. Infectious sx: fever, malaise, odynophagia, oral ulcers
• Clozapine toxicity (agranulocytosis) causes recurrent infections
3. So, check ANC (absolute neutrophil count) or WBC
A 68-year-old man presents with fever, headache, photophobia, and altered mental status. Lumbar puncture demonstrates elevated opening pressure, elevated protein, decreased glucose, and neutrophilic pleocytosis. Empiric therapy with vancomycin, ceftriaxone, and ampicillin is initiated.
CSF culture later grows a gram-positive rod demonstrating tumbling motility.
Which component of the empiric regimen specifically targeted this organism?
What is ampicillin
1. elevated ICP & protein, decreased glucose, neutrophil = bacterial meningitis
2. gram + rod & tumbling motility = listeria (actin polymerization to spread directly from cell to cell)
3. Note: age > 50+ meningitis --> think LISTERIA
4. Why not others?
• vancomycin: covers MRSA, penicillin-resistant s. pneumoniae
• ceftriaxone: great for n. meningitidis, s. pneumoniae, h. influenzae
A patient with cryptococcal meningitis is started on amphotericin B and flucytosine.
Why is flucytosine not recommended as monotherapy and what is its MOA?
What is rapid development of resistance + fungal cyp 450 enzyme, 14-a-demethylase, inhibition
Blocks conversion of lanosterol to ergosterol --> decreased ergosterol = unstable cell membrane and inhibited fungal growth.
A 35-year-old woman with treatment-resistant depression is switched from sertraline to selegiline after an appropriate washout period. Two weeks later, she develops bacterial pneumonia and is started on linezolid. Within 24 hours she becomes confused, febrile, diaphoretic, and develops hyperreflexia with inducible clonus.
Which medication should be discontinued immediately?
What is linezolid
1. Depression & given MAOi
2. However, linezolid = also a reversible MAOi
3. Combination = serotonin syndrome
4. Stop the offending drug (reversible MAOi, linezolid)
A 21-year-old college student is brought to the emergency department after being found wandering outside in freezing weather while wearing only shorts. During the interview he rapidly shifts between unrelated topics and repeatedly invents new words. Physical examination is otherwise normal. Functional imaging would most likely demonstrate decreased activity in which brain region responsible for these findings?
What is (dorsolateral) PFC
Cognitive dysfunction & disorganized speech correlate with hypodopamingergic activity in PFC.
Dopaminergic Pathway:
1. Mesocortical:
• VTA --> PFC
• decreased activity --> negative sx
• antipsychotics have limited benefit
2. Mesolimbic:
• VTA --> nucleus accumbens
• increased activity --> positive sx
• primary therapeutic target of antipsychotics.
3. Nigostriatal:
• SN --> striatum
• motor control
• decreased activity --> EPS
• Affected by antipsychotics + in Parkinson's
4. Tuberoinfundibular
• HT --> pituitary
• Regulation of prolactin secretion
• Decreased activity --> increased prolactin
• Significantly affected by antipsychotics
A 43-year-old man with bipolar I disorder is started on maintenance therapy. Three months later, he reports polyuria and excessive thirst. Laboratory testing demonstrates hypernatremia. Administration of desmopressin produces no significant increase in urine osmolality.
The medication responsible for this patient's symptoms inhibits which intracellular enzyme?
What is inositol monophosphatase
BPD maintenance = likely lithium → polyuria + polydipsia + ineffective ADH = nephrogenic DI → lithium is inhibiting inositol monophosphatase (downregulate secondary msg cascades and downregulate AQP2 in the CD).
A 20-year-old college freshman presents with fever, headache, nuchal rigidity, and a petechial rash. Blood cultures grow gram-negative diplococci.
Which additional intervention should be recommended for his asymptomatic roommate?
What is rifampin prophylaxis
• 3Rs (rash, roommate, rifampin).
• Menigococcal disease -> close contact exposed -> may carry bacteria in nasopharynx -> eradicate carriage via rifampin.
A 63-year-old man with diabetes presents with fever, facial pain, and black necrotic tissue involving the nasal turbinates. Biopsy demonstrates broad, nonseptate hyphae with right-angle branching. Liposomal amphotericin B is initiated.
Several days later, serum creatinine increases from 0.8 mg/dL to 2.1 mg/dL.
Which adverse effect is most likely to accompany this patient's acute kidney injury?
What is hypokalemia (and/or hypomagnesia)
1. Black necrotic nasal tissue + broad, nonseptae hyphae = mucormyoosis (mucor/rhizopus)
2. Creatinine 0.8 --> 2.1 indicates renal damage, specifically renal tubules
3. Damaged renal tubules waste electrolyte (loss of Mg/K)
A 47-year-old man with bipolar I disorder presents with acute mania. His medical history is significant for cirrhosis secondary to chronic hepatitis C. Laboratory studies demonstrate an INR of 2.3 and albumin of 2.5 g/dL.
Which mood stabilizer should be avoided because of this patient's underlying disease?
What is valproic acid
Valproate has a higher risk of hepatotoxicity compared to other mood stabilizers (i.e., lithium, carbamazepine, lamotrigine) through mitochondrial poisoning & energy failure (inhibition of beta-oxidation, depletion of CoA and carnitine)A 42-year-old woman with major depressive disorder is started on phenelzine after multiple failed trials of SSRIs. Two weeks later, she develops agitation, diaphoresis, diarrhea, hyperthermia, tremor, and bilateral lower-extremity hyperreflexia shortly after taking an over-the-counter cough suppressant. Creatine kinase is mildly elevated.
Question: What is the most likely diagnosis?
What is serotonin syndrome
1. Phenylzine = MAOi (prevent breakdown of serotonin)
Note: think tyramine crisis OR serotonin syndrome with MAOI
2. OTC cough suppresant = dextromethorpan (weak serotonin reuptake inhibitor)
3. Combined = serotonin syndrome.
4. Separate from NMS (dopamine-related): Malignant FEVER
• myoglobinuria
• fever
• encephalopathy
• vitals, unstable
• enzymes (CK significantly elevated)
• rigidity of the muscle ("lead pipe")
A 54-year-old woman with major depressive disorder is switched from fluoxetine to phenelzine after an appropriate washout period. Several weeks later, she develops severe hypertension, occipital headache, diaphoresis, and palpitations shortly after eating a meal containing aged cheese and cured meats.
Accumulation of which neurotransmitter within sympathetic nerve terminals most directly explains this patient's symptoms?
What is NE
1. Phenelzine = MAOI
2. Aged cheese, cured meats = increased level of tyramine
3. Tyramine displaces NE in the synaptic cleft, cause a huge amt of NE to flood into the synapse; however, with MAO blocked, body cannot quickly clear 5-HT, DP, NE.
4. Hypertensive crisis: severe HTN, occipital HA, diaphoresis, palpitations.
A patient with cryptococcal meningitis completes induction therapy with amphotericin B and flucytosine and improves clinically.
Which medication should be used next as consolidation therapy?
What is fluconazole
3 phases of cryptococcal meningitis:
1. Induction: amphotericin B + flucytosine
• amphotericin attacks ergosterol & punctures holes in the fungal membrane
• flucytosine inhibits fungal DNA/RNA synthesis
• need to stop amphotericin once induction phase is done d/t its toxicity (i.e., nephrotoxicity, hypo K+ & Mg+, anemia)
2. Consolidation: fluconazole
• gets into CSF well, can be taken orally, much safer weeks to months
• MOA: Inhibits fungal cytochrome P450 enzyme 14-α-demethylase (lanosterol demethylase)
3. Maintenance: low-dose fluconazole
A 46-year-old man with AIDS presents with odynophagia. Endoscopy demonstrates white plaques throughout the esophagus. He is started on fluconazole but fails therapy and is switched to caspofungin.
Why is the second medication effective despite failure of the first?
What is inhibition of β-(1,3)-D-glucan synthesis (inhibition of fungal cell wall synthesis)
1. Fluconazole: targets ergosterol
2. Caspofungin: targets cell wall
A 29-year-old woman presents with depressed mood, anhedonia, insomnia, and decreased concentration for the past 2 months. She has a history of bulimia nervosa and generalized tonic-clonic seizures following childhood meningitis. She smokes one pack of cigarettes daily and would like assistance with smoking cessation.
Which antidepressant would be contraindicated despite its potential benefit?
What is bupropion
Bupropion helps with smoking cessation and is an antidepressant that is unlikely to cause weight gain; however, it increases the lowers the threshold of seizures and is not appropriate for this patient who has generalized tonic-clonic seizures and is bulimic (risk factor for seizures).