USMLE session 4
● 12.10.2013
● 8 Qs with discussion and review
Q1
A 52-year-old overweight male steamroller operator presents to his
primary care physician complaining of itchy, watery eyes and runny nose
in the springtime. He says that he has had this problem for as long as he
can remember but does not like going to doctors. His wife finally
convinced him to come today to see what his physician might be able to
do for him.
What is the most appropriate treatment for this patient?
(A) Albuterol
(B) Diphenhydramine
(C) Epinephrine
(D) Hydroxyzine
(E) Loratadine
Q - hints
A 52-year-old overweight male steamroller operator presents to his
primary care physician complaining of itchy, watery eyes and runny nose
in the springtime. He says that he has had this problem for as long as he
can remember but does not like going to doctors. His wife finally
convinced him to come today to see what his physician might be able to
do for him.
What is the most appropriate treatment for this patient?
(A) Albuterol - short-acting beta-agonist
(B) Diphenhydramine - H1-antagonist (1st gen.)
(C) Epinephrine - alpha- and beta- adrenergic agonist
(D) Hydroxyzine - H1-antagonist (1st gen.)
(E) Loratadine - H1-antagonist
A
Itchy, watery eyes with runny nose in spring is likely allergic rhinitis, commonly
called hay fever.
These symptoms are caused primarily by histamine acting on H1 receptors.
Histamine is released from mast cells when they encounter the antigen to which
they have been sensitized. Interrupting histamine release (i.e., cromolyn
sodium), blocking H1 receptors (diphenhydramine, loratadine, and hydroxyzine),
and physiologically antagonizing the effects of histamine (epinephrine) are all
methods employed to reduce symptoms of allergic rhinitis.
Epinephrine may be useful for a severe acute attack but not the best choice for
chronic symptom management.
The H1 antagonists are divided into first-generation (diphenhydramine,
hydroxyzine) and second-generation (loratadine) drugs. The secondgeneration
drugs are more specific for the H1 receptor and do not cross the
blood–brain barrier as readily so they have fewer anticholinergic and
antihistaminic side effects (such as drowsiness). This is important for the
patient because he operates heavy equipment.
subQ
What drugs have anticholinergic (antimuscarinic) properties?
● decreased secretions (salivation, bronchial, sweat..)
● mydriasis
● hyperthermia => vasodil.
● tachycardia
● sedation
● urinary retention, constipation
● behaviour excitatition and halucinations
subA
What drugs have anticholinergic (antimuscarinic) properties?
● decreased secretions (salivation, bronchial, sweat..)
● mydriasis
● hyperthermia => vasodil.
● tachycardia
● sedation
● urinary retention, constipation
● behaviour excitatition and halucinations
OLD Drugs:
● antihistamines (1st gen.): Diphenhydramine, Hydroxyzine, ...
● tricyclic antidepresants: amitriptylin, imipramin, ...
● antipsychotics (typical, low potency): thioridazine
● meperidin (=opioid)
● ...
● /many others/
subQ
What type of hypersensitivity reaction (according to Coombs) is allergic rhinitis?
Review
Review
Mast cells release:
● 1/ immediate (degranulation of preformed vesicles):
● histamine,
● serotonin;
● 2/ late (new synthesis&release):
● Leukotriens,
● cytokines (Eosinophil chemotactic factor)
Related
patfyz:
●aspirin
induced
asthma
●aspirin as an
antithrombotic
Q2
A 5-year-old boy is brought to his primary care physician by his parents
who say that he often has trouble catching his breath when he has been
playing hard outside. He is allergic to peanuts. At the moment, he is
breathing fine. Which of the following drugs is commonly used to
diagnose suspected asthma?
(A) Albuterol
(B) Methacholine
(C) Neostigmine
(D) Nicotine
(E) Pilocarpine
Q - hints
A 5-year-old boy is brought to his primary care physician by his parents
who say that he often has trouble catching his breath when he has been
playing hard outside. He is allergic to peanuts. At the moment, he is
breathing fine. Which of the following drugs is commonly used to
diagnose suspected asthma?
(A) Albuterol - short-acting beta2 agonist
(B) Methacholine - M-agonist
(C) Neostigmine - AchE inhibitor
(D) Nicotine - N-agonst
(E) Pilocarpine - M-agonist
A
A
In asthma, constriction of terminal bronchioles is episodic (in response
to irritants), not persistent.
Patients with airway hyperreactivity will react to lower doses of an
inhaled cholinergic agent. Methacholine is commonly used to diagnose
asthma in this way. It binds to muscarinic receptors on bronchiolar
smooth muscle, causing bronchoconstriction. Methacholine is a synthetic
choline ester that is degraded by cholinesterase more slowly than
acetylcholine.
(A) Albuterol is used in the treatment of asthma. It is an adrenergic b2-agonist and causes relaxation
of bronchial smooth muscle.
(C) Neostigmine is an acetylcholinesterase inhibitor. It is used in the treatment of myasthenia gravis
and neuromuscular blockade reversal. Neostigmine’s halflife is too long to be useful in diagnosing
asthma.
(D) Nicotine binds to nicotinic receptors, not the muscarinicreceptors found on bronchiolar smooth
muscle. It would not be useful in causing bronchoconstriction
(E) Pilocarpine is used in the treatment of glaucoma. Its half-life is too long to be useful in diagnosing
asthma.
● Asthma treatment is another story
Q3
A 22-year-old woman ingests an entire bottle of acetaminophen in an
attempted suicide. She unexpectedly feels well for the next 24 h, at
which time her boyfriend discovers what she has done and takes her to
the ER. The toxic metabolite of acetaminophen exerts its deleterious
effect by what mechanism?
(A) Depletion of endogenous antioxidant
(B) Hapten formation leading to autoantibody production
(C) Inhibition of cytochrome C oxidase
(D) Ischemia from decreased hepatic blood flow
(E) Paralysis of gall bladder causing bile stasis
A
A
Acetaminophen metabolism follows one of two pathways in the liver. Most (more
than 90%) undergoes phase II metabolism (=conjugation to glucuronide) directly
and is excreted via the kidney. The remainder undergoes phase I metabolism by
CYP1A2 or CYP2E1 to produce NAPQI (N-acetyl-p-benzoquinone imine), the
toxic metabolite of acetaminophen. NAPQI requires glutathione for its next
step of metabolism.
Excess acetaminophen in the body produces so much NAPQI that liver
glutathione (a natural, endogenous antioxidant) is depleted. Oxidative damage
then occurs.
(B) Penicillin in high doses can induce immune mediated hemolysis via the
hapten mechanism in which antibodies are targeted against the combination of
penicillin in association with red blood cells. Complement is activated by the
attached antibody leading to the removal of red blood cells by the spleen.
(C) Cyanide inhibits cytochrome C oxidase. This leads to blockage of the
electron transport chain in the mitochondria.
(D) (Rare) thrombosis of portal or hepatic vein may cause hepatic ishemia
(E) Neither acetaminophen nor its metabolites cause paralysis of the gall
bladder.
Q4
A 63-year-old woman with history of CAD, MI 2 years ago, years begins
to have lower extremity swelling. Heart sounds are regular and S3 is
present, on lung auscultation there are bibasilar crackles. She starts
taking a diuretic and the swelling improves significantly. Over the next
few days, however, she develops ringing in her ears. Which of the
following diuretics is she taking?
(A) Acetazolamide
(B) Furosemide
(C) Hydrochlorothiazide
(D) Mannitol
(E) Spironolactone
Q4 - hints
A 63-year-old woman with history of CAD, MI 2 years ago, years begins
to have lower extremity swelling. Heart sounds are regular and S3 is
present, on lung auscultation there are bibasilar crackles. She starts
taking a diuretic and the swelling improves significantly. Over the next
few days, however, she develops ringing in her ears. Which of the
following diuretics is she taking?
(A) Acetazolamide - carbonic anhydrase inhibitor
(B) Furosemide - Na/K/2Cl cotransporter inhibitor
(C) Hydrochlorothiazide - inhibits Na/Cl cotransport in early dist. tubule
(D) Mannitol - osmotic diuretic
(E) Spironolactone - competitive aldosterone antagonist
A4: side effects overview
(A) Acetazolamide - carbonic anhydrase inhibitor
● H ?
(B) Furosemide - Na/K/2Cl cotransporter inhibitor (subQ: barter sy. ?)
● Ca++, Mg++ ?
● K ?
● gout?
(C) Hydrochlorothiazide - inhibits Na/Cl cotransport in early dist. tubule
● Ca++ ?
● K+, H+ ?
● glycemia, lipidemia?
● gout exacerbation
(D) Mannitol - osmotic diuretic
(E) Spironolactone - competitive aldosterone antagonist
● K+ ?
● endocrine?
A4: side effects overview
(A) Acetazolamide - carbonic anhydrase inhibitor
● acidosis
(B) Furosemide - Na/K/2Cl cotransporter inhibitor (subQ: barter sy. ?)
● increased Ca++, Mg++ excretion
● hypoKalemia
● allergy (sulfa)
● interstitial nephritis
● gout exacerbation
(C) Hydrochlorothiazide - inhibits Na/Cl cotransport in early dist. tubule
● increased Ca++ excretion
● hypoKalemia, alkalosis (hypoH+)
● hyperglycemia, hyperlipidemia
● gout exacerbation
● allergy (sulfa)
(D) Mannitol - osmotic diuretic
(E) Spironolactone - competitive aldosterone antagonist
● hyperKalemia
● antiandrogen (gynecomastia)
Q5
A 17-year-old man is brought to the emergency department with severe
right lower quadrant pain that he first felt around his umbilicus. His white
blood cell count is 12,000/mL of blood. He is taken to the operating room
for emergent laparoscopic appendectomy. About an hour into the
surgery, his body temperature spikes and CO2 production rises
uncontrollably.
What is the next step in the treatment of this patient?
(A) Acetaminophen
(B) Bromocriptine
(C) Dantrolene
(D) Diazepam
(E) Naproxen
Q5
A 17-year-old man is brought to the emergency department with severe
right lower quadrant pain that he first felt around his umbilicus. His white
blood cell count is 12,000/mL of blood. He is taken to the operating room
for emergent laparoscopic appendectomy. About an hour into the
surgery, his body temperature spikes and CO2 production rises
uncontrollably.
What is going on?
(A) Acetaminophen
(B) Bromocriptine
(C) Dantrolene
(D) Diazepam
(E) Naproxen
A5
This scenario describes a case of malignant hyperthermia. Malignant
hyperthermia can be caused by any one of several genetic defects, most
of which are autosomal dominant. Most cases involve a mutated
ryanodine receptor and are triggered by anesthetic or succinylcholine
use during surgery. The signs and symptoms appear to arise from a
sudden increase in cellular metabolism. Dantrolene is the drug used to
treat malignant hyperthermia. It is believed to inhibit calcium release from
the sarcoplasmic reticulum. By paralyzing the muscle in this way, muscle
cell metabolism is drastically decreased.
(A) Acetaminophen has antipyretic and analgesic effects. It can
be used for mild pain and fevers but is not useful in malignant
hyperthermia.
(B) Bromocriptine is a dopamine agonist that can be used to
treat neuroleptic malignant syndrome. Neuroleptic malignant
syndrome in some ways resembles malignant hyperthermia, but
their pathophysiologies are very different. Bromocriptine is not
useful for treating malignant hyperthermia.
(D) Diazepam is a benzodiazepine that can be used to treat
serotonin syndrome. Serotonin syndrome in some ways
resembles malignant hyperthermia, but their pathophysiologies
are very different. Diazepam is not useful for treating malignant
hyperthermia.
(E) Naproxen is a nonsteroidal antiinflammatory drug (NSAID).
It can be used to decrease pain, inflammation, and fever, but
these are not hallmarks of malignant hyperthermia.
Q6
A 59-year-old man with hypertension, gastroesophageal reflux disorder,
AIDS, seizure disorder, tuberculosis and depression is currently
maintained on multiple medications, including propranolol. He does not
have his medication list at his current office visit with his primary care
physician. His blood pressure is 180/100 mm Hg. The patient states that
he is taking all of his medications as scheduled. Which of the following
drugs is the most likely explanation of this finding?
(A) Cimetidine
(B) Fluoxetine
(C) Paroxetine
(D) Rifampin
(E) Ritonavir
Q - hints
A 59-year-old man with hypertension, gastroesophageal reflux disorder,
AIDS, seizure disorder, tuberculosis and depression is currently
maintained on multiple medications, including propranolol. He does not
have his medication list at his current office visit with his primary care
physician. His blood pressure is 180/100 mm Hg. The patient states that
he is taking all of his medications as scheduled. Which of the following
drugs is the most likely explanation of this finding?
(A) Cimetidine - H2 antagonist
(B) Fluoxetine - SSRI
(C) Paroxetine - SSRI
(D) Rifampin - RNA polymerase inhibitor
(E) Ritonavir - HIV protease inhibitor
A
Drugs that interfere with, or inhibit, the metabolism of propranolol, such
as cimetidine, fluoxetine, paroxetine, and ritonavir, may potentiate its
antihypertensive effects.
Conversely, those that stimulate or induce its metabolism, such as
barbiturates, phenytoin, and rifampin, can decrease its effects. In this
case, the patient is taking rifampin; and it is affecting the metabolism of
propranolol and inducing rapid metabolism, which is minimizing its
antihypertensive effects.
Cimetidine, Fluoxetine, Paroxetine, Ritonavir inhibit P450 enzymes and
thus potentiates the antihypertensive effects of propranolol.
Review
Drugs metabolized by P450: many
most important: warfarin
Q7
A 63-year-old woman with history of atrial fibrilation treated with
amiodarone presents to her primary care physician complaining of
headache, productive cough, diarhoea. HR: 80/min, BP 110/70. Labs are
significant for increased CRP, and hyponatremia. Sputum culture grew
Legionella pneumophila. She is admitted and gives azithromycin. Which
of the following sequelae could be problematic for this patient?
(A) Asystole
(B) Myocardial infarction
(C) Pulmonary edema
(D) Pulmonary embolism
(E) QT interval prolongation
Q7
A 63-year-old woman with history of atrial fibrilation treated with
amiodarone presents to her primary care physician complaining of
headache, productive cough, diarhoea. HR: 80/min, BP 110/70. Labs are
significant for increased CRP, and hyponatremia. Sputum culture grew
Legionella pneumophila. She is admitted and gives azithromycin. Which
of the following sequelae could be problematic for this patient?
(A) Asystole
(B) Myocardial infarction
(C) Tendon rupture
(D) Pulmonary embolism
(E) QT interval prolongation
Q7
How does amiodarone work?
A7
A7
QT interval prolongation. Caution should be exerted when combining
several drugs with effects on the QT interval (e.g., quinidine with
azitrhomycin) or when giving these drugs combined with drugs known to
inhibit drug metabolism, leading to large increases in plasma drug
concentrations( -azole antifungals: fluconazole and itraconazole).
Macrolides may prolong QT via both mechanisms.
(A) Asystole is unlikely in this patient.
(B) The QT prolongation is more common than myocardial infarction
in this setting.
(C) Tendon rupture in adults is asociated with fluoroqiunolone use, not
macrolide.
(D) Pulmonary embolism would not be expected in this patient.
Review
Drugs metabolized by P450: many
most important: warfarin
Q8
A 44-year-old, previously healthy man has experienced worsening exercise
tolerance accompanied by marked shortness of breath for the past 6 months.
On physical examination, he is afebrile. His pulse is 78/min, respirations are
22/min, and blood pressure is 110/70 mm Hg. He has diffuse rales in all lung
fields and pitting edema to the knees. Laboratory studies show serum sodium,
130 mmol/L; potassium, 4 mmol/L; chloride, 102 mmol/L; CO2, 25 mmol/L;
creatinine, 2 mg/dL; and glucose, 120 mg/dL (6,7mmol). A 100-mL urine sample
is collected. There is 1.3 mmol of sodium and 40 mg of creatinine in the urine
sample. A chest radiograph shows cardiomegaly and pulmonary edema with
pleural effusions. An echocardiogram shows four-chamber cardiac dilation and
mitral and tricuspid valvular regurgitation, with an ejection fraction of 30%. A
coronary angiogram shows less than 10% narrowing of the major coronary
arteries. Which of the following is the most likely diagnosis?
(A) Rheumatic heart disease
(B) Hereditary hemochromatosis
(C) Chagas disease
(D) Diabetes mellitus
(E) Idiopathic dilated cardiomyopathy
Q8
A 44-year-old, previously healthy man has experienced worsening exercise
tolerance accompanied by marked shortness of breath for the past 6 months.
On physical examination, he is afebrile. His pulse is 78/min, respirations are
22/min, and blood pressure is 110/70 mm Hg. He has diffuse rales in all lung
fields and pitting edema to the knees. Laboratory studies show serum sodium,
130 mmol/L; potassium, 4 mmol/L; chloride, 102 mmol/L; CO2, 25 mmol/L;
creatinine, 2 mg/dL; and glucose, 120 mg/dL (6,7mmol). A 100-mL urine sample
is collected. There is 1.3 mmol of sodium and 40 mg of creatinine in the urine
sample. A chest radiograph shows cardiomegaly and pulmonary edema with
pleural effusions. An echocardiogram shows four-chamber cardiac dilation and
mitral and tricuspid valvular regurgitation, with an ejection fraction of 30%. A
coronary angiogram shows less than 10% narrowing of the major coronary
arteries. Which of the following is the most likely diagnosis?
(A) Rheumatic heart disease
(B) Hereditary hemochromatosis
(C) Chagas disease
(D) Diabetes mellitus
(E) Idiopathic dilated cardiomyopathy
Q8
Q8
A8
Congestive heart failure with four-chamber dilation is suggestive of dilated
cardiomyopathy; implicated in causation are myocarditis, alcohol abuse, and
genetic factors (in 20% to 50% of cases). Many cases of dilated
cardiomyopathy have no known cause. Dilation is more prominent than
hypertrophy, although both are present, and all chambers are involved.
A/ Rheumatic heart disease would most often produce some degree of valvular
stenosis, often with some regurgitation, and the course usually is more
prolonged.
B/ Hemochromatosis produces restrictive cardiomyopathy.
C/ Chagas disease affects the right ventricle more often than the left
D/ Coronary artery narrowing would be worse in diabetes mellitus and
accelerated atherosclerosis. Also, in DM, diastolic heart failure (a restrictive
pattern) eould be expected, rather tham dilatation.
subQ8
A 44-year-old, previously healthy man has experienced worsening exercise
tolerance accompanied by marked shortness of breath for the past 6 months.
On physical examination, he is afebrile. His pulse is 78/min, respirations are
22/min, and blood pressure is 110/70 mm Hg. He has diffuse rales in all lung
fields and pitting edema to the knees. Laboratory studies show serum sodium,
130 mmol/L; potassium, 4 mmol/L; chloride, 102 mmol/L; CO2, 25 mmol/L;
creatinine, 2 mg/dL (= 177 umol/l); and glucose, 120 mg/dL (6,7mmol). A 100mL
urine sample is collected. There is 1.3 mmol of sodium and 40 mg of
creatinine in the urine sample. A chest radiograph shows cardiomegaly and
pulmonary edema with pleural effusions. An echocardiogram shows fourchamber
cardiac dilation and mitral and tricuspid valvular regurgitation, with an
ejection fraction of 30%. A coronary angiogram shows less than 10% narrowing
of the major coronary arteries.
Why is the creatinine increased?
(ref. range: 0,6-1,2 mg/dL; 53-106 umol/l)
subQ8
Reason for azotemia?
●prerenal
●renal
●postrenal
subQ8: review of Renal failure
sub-subQ8: What is Fractional Excretion of Na+ and when to use it?
You may calculate Fractional excretion of sodium (FE-Na) used in oliguric
(<500ml/24h) patients to guide you in differentiating prerenal vs. renal failure.
sub-subQ8: What is Fractional Excretion of Na+ and when to use it?
You may calculate Fractional excretion of sodium (FE-Na) used in oliguric
(<500ml/24h) patients to guide you in differentiating prerenal vs. renal failure.
The FE-Na represents the amount of sodium excreted in the urine divided by the
amount of sodium that is filtered by the kidneys.
The calculation is as follows:
FE-Na- = [(UNa / PNa) / (UCr / PCr)] x 100
where
UNa- is a random urine sodium concentration,
PNa- is serum sodium,
UCr is random urine creatinine, and
PCr is plasma creatinine.
Creatinine is used in the formula, because the amount of sodium filtered is dependent on the glomerular
filtration rate (CFR), which closely approximates the creatinine clearance (CCr).
An FE-Na < 1% indicates ... ?
.
An FE-Na > 2% indicates ... ?
sub-subQ8: What is Fractional Excretion of Na+ and when to use it?
You may calculate Fractional excretion of sodium (FE-Na) used in oliguric
(<500ml/24h) patients to guide you in differentiating prerenal vs. renal failure.
The FE-Na represents the amount of sodium excreted in the urine divided by the
amount of sodium that is filtered by the kidneys.
The calculation is as follows:
FE-Na- = [(UNa / PNa) / (UCr / PCr)] x 100
where
UNa- is a random urine sodium concentration,
PNa- is serum sodium,
UCr is random urine creatinine, and
PCr is plasma creatinine.
Creatinine is used in the formula, because the amount of sodium filtered is dependent on the glomerular
filtration rate (CFR), which closely approximates the creatinine clearance (CCr).
An FENa < 1% indicates good tubular function and excludes acute tubular
necrosis (ATN) as a cause of oliguria.
An FENa > 2% indicates tubular dysfunction and is highly predictive of ATN as
the cause of oliguria.
sub-subQ8: What is Fractional Excretion of Na+ and when to use it?
A 44-year-old, previously healthy man has experienced worsening exercise
tolerance accompanied by marked shortness of breath for the past 6 months. On
physical examination, he is afebrile. His pulse is 78/min, respirations are 22/min,
and blood pressure is 110/70 mm Hg. He has diffuse rales in all lung fields and
pitting edema to the knees. Laboratory studies show serum sodium, 130 mmol/L;
potassium, 4 mmol/L; chloride, 102 mmol/L; CO2, 25 mmol/L; creatinine, 2
mg/dL (= 177 umol/l); and glucose, 120 mg/dL (6,7mmol). A 100-mL urine
sample is collected. There is 1.3 mmol of sodium and 40 mg of creatinine in the
urine sample. A chest radiograph shows cardiomegaly and pulmonary edema
with pleural effusions. An echocardiogram shows four-chamber cardiac dilation
and mitral and tricuspid valvular regurgitation, with an ejection fraction of 30%. A
coronary angiogram shows less than 10% narrowing of the major coronary
arteries.
Are you sure it's prerenal azotemia? Could FE-Na help you?
(ref. range: 0,6-1,2 mg/dL; 53-106 umol/l)
sub-subQ8: What is Fractional Excretion of Na+ and when to use it?
Are you sure it's prerenal azotemia?
Calculation of FE-Na:
Serum: sodium 130 mmol/L; creatinine 2 mg/dL (= 177 umol/l);
A 100-mL urine sample: 1.3 mmol of sodium and 40 mg of creatinine.
FE-Na = [(UNa / PNa) / (UCr / PCr)] x 100
sub-subQ8: What is Fractional Excretion of Na+ and when to use it?
Are you sure it's prerenal azotemia?
Calculation of FE-Na:
Serum: sodium 130 mmol/L; creatinine 2 mg/dL (= 177 umol/l);
A 100-mL urine sample: 1.3 mmol of sodium and 40 mg of creatinine.
FE-Na = [(UNa / PNa) / (UCr / PCr)] x 100 %
FE-Na = [(1,3 / 130) / (40 / 20)] x 100 %
FE-Na = [(0,01) / (2)] x 100 %
FE-Na = [(0,005)] x 100 %
FE-Na = 0,5%
So, is it prerenal azotemia?
subQ8: so, Does it make sense?
Thank you
Sources
● Lippincot's Q A pharm
(http://www.amazon.co.uk/Lippincotts-
Illustrated-Review-Pharmacology-
Stanley/dp/1451182864/)
● First Aid for Step 1, 2012
● https://www.mja.com.au/journal/2007/186/7/acci
dental-paracetamol-poisoning
● Goljan: Rapid review pathology, 3rd
● Kumar: Robbins and Cotran Review of
Pathology 3rd Edition
Q8
What precisely happens with BUN and Creatinine in acute renal failure?