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HyGuru USMLE Step 1

Rapid Review Pharmacology

R ah ul D am an ia, M D , FA A P

Thank You for Attending!

introduction to the course

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Notes On Course Introduction

Neurology

Rapid Review Pharmacology

Neurology
• Anesthesia
• Parkinson’s Dr0gs
• Alzheimer's Dr0gs

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Anesthesia

Understand vocabulary:
• Potency ↔ Lipid Solubility
USMLE Test Taking
Strategy: • Potency ↔ Minimum Alveolar
Anesthesiology
Questions Concentration (MAC)
• Blood Solubility ↔ Induction

A new anesthetic is being developed. It has

increased amounts of potency. Which
parameter best correlates to potency of
inhaled anesthetics?
NBME Style A. Arteriovenous concentration gradient
Question
B. Blood / gas coefficient
C. Minimum alveolar concentration
D. Hepatic metabolism

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Question Take-Home Message

Organ System Question Type Content Specification

Neurology Experimental Potency

Paraphrase: Step Beyond:

New gas + high potency = low MAC • What is the ED50 in a potent gas?
• Low

10

Lipid solubility is directly related to potency

Lipid Solubility Potency

11

Potency is inversely related to Minimum alveolar concentration

M inim um Alveolar
Potency
Concentration

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Understand vocabulary:
• Potency ↔ Lipid Solubility
USMLE Test Taking
Strategy: • Potency ↔ Minimum Alveolar
Anesthesiology
Questions Concentration (MAC)

• Blood Solubility ↔ Induction

13

blood solubility is inversely related to onset time

Blood Solubility Onset Tim e (Induction)

14

Effect N20 halothane

§ N 2O
§ It fills air filled
spaces quickly à do
not use it in
pneum othorax.

15

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Anesthestic Agents

Class Effect or Big Picture Causes dcc in pain

and amnesia

Pathology / Pathophysiology Mechanism of Action Mechanism unknown

Malignant
Hyperthermia

Anesthesia
Principles
Specific Names -ane (halothane,
sevoflurane, etc.)

Slows things down

SE Malignant Hyperthermia

16

A 28 yo M is going to the operating room for gall

bladder resection. The patient has increased
muscle tone intra-operatively. There is a climbing
ETCO2. Which of the following mechanisms will
improve this patient’s situation?
NBME Style • A. Ach degradation in nAch synapses
Question
• B. GABA mediated depolarization of membrane
• C. Increased ɑ2 stimulation
• D. Decreased sarcoplasmic calcium release

17

Question Take-Home Message

Organ System Question Type Content Specification

Neurology Mechanism Malignant Hyperthermia

Paraphrase: Step Beyond:

OR + high muscle tone = dantrolene • What other pathology can dantrolene
be used in?
• Neuroleptic Malignant Syndrome

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Malignant hyperthermia

Autonomic Instab
RyR mutation
Trigger with ⬆ CPK
anesthesia Increased intra-
⬆ ETCO2 +
cytosolic Ca2+
lactate

§ Tease out from :

§ Serotonin
§ Watch for triggers syndrom e:
in exam questions § m ore
§ “They went clonus
for surgery” § N euroleptic
M alignant:
§ lead pipe.

19

Rapid review of anesthetics

▸ A pt on coronary bypass surgery is getting induced with
sevoflurane. It is noted that the agent has a low MAC.
What effect would low MAC have on potency?
▸ High potency. What can we say about the lipid solubility of this
agent?
▸ High lipid solubility.

20

• An experimental anesthetic is administered to a

patient at a constant rate. Results of experiment
show large arteriovenous gradient after
inhalation. What is the likely property of this
agent?
NBME Style • A. Low tissue solubility
Question
• B. Low potency
• C. Slow onset in CNS
• D. Fast onset in CNS

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Question Take-Home Message

Organ System Question Type Content Specification

Neurology Experimental A-V difference

Paraphrase: Step Beyond:

high A-V gradient + anesthesia= • A high A-V gradient correlates with
slow onset of action higher or lower tissue extraction?
• Higher!

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High A-VO2 difference means more anesthesia in tissues à less in CNS

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Systems based side effects

▸ Neurology:
▸ Cardiology:
▹ Which inhaled anesthetic is most
▸ Myocardial depression. What effect
pro-epilepsy?
does this have on contractility?
■ Enflurane.
▸ Decreases
▸ Respiratory:
▸ Cerebral vasculature:
▸ Respiratory depression
▸ Vasodilation. What effect on cerebral perfusion?
▸ What acid base abnormality? ▸ Increases
▸ Respiratory Acidosis. ▸ Reduces cerebral metabolic demand.

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Cerebral
Autoregulation

25

Cerebral Blood Flow

Hypercapnea Hypocapnea
• High CO2 à cerebral • Low CO2 à cerebral
vasodilation. vasoconstriction.
• Increases cerebral • Decreases cerebral
blood flow. blood flow.

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• A patient is going to undergo surgery with

an inhaled anesthetic. The patient is noted
to have CNS depression. What parameter
will increase during anesthesia?
NBME Style • A. Cerebral Blood Flow
Question
• B. Respiratory Rate
• C. Glomerular Filtration Rate
• D. Hepatic Blood Flow

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Question Take-Home Message

Organ System Question Type Content Specification

Neurology Physiology Systemic Effects of Anesthesia

Paraphrase: Step Beyond:

• Anesthesia + physiologic • Increased cerebral blood flow has what

effect on cerebral perfusion pressure?
parameter which ⬆ = cerebral
blood flow • Increases (CPP = MAP – ICP)

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H yG u ru H ig h -Y ield

G A B A A g e n ts
• ⬆ High lipid solubility (i.e. goes into tissues)
• Thiopental • ⬆ High volume of distribution

G A B A A g e n ts
• ⬆ f requency of GABA channel opening
• M idazolam

G A B A A g e n ts
• ⬆ GABA à hypotension (dec SVR)
• Propofol • Lipophillic à rapidly goes into fat

G A B A A g e n ts
• ⬆ GABA à inhibits Ca 2+ channels
GABA Agents • Gabapentin • Neuropathic pain (tingling)

G A B A A g e n ts
• ⬆ GABA à Blocks Na 2+ channels
• Topiram ate • Sedation, Stones, Skinny

G A B A A g e n ts • ⬆ GABA by inhibiting GABA

transam inase
• VPA
• LFT + neural tube defects

G A B A A g e n ts
• ⬆ duration of GABA channel opening
• Barbiturates • Induces CYP

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• A patient has an outpatient procedure for his hip.

He is given intermittent doses of propofol. One
hour after the procedure he is awake and
discharged home. Which of the following
mechanisms most likely explains this rapid
recovery?
NBME Style
Question • A. Lung elimination of the drug
• B. Renal excretion of the drug
• C. Tissue redistribution of medication
• D. Spontaneous degradation of plasma

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Question Take-Home Message

Organ System Question Type Content Specification

Neurology Pharmacology Propofol (on-off effect)

Paraphrase: Step Beyond:

• Propofol + rapid offset = • A bolus of propofol will have what effect on

CNS peak concentrations?
increased tissue redistribution
• Increased à propofol goes to pulsatile
tissue first à then redistributes to fat.

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Parkinson’s Drugs

32

Parallel to keep in mind:

USMLE Test Taking
Strategy: • Parkinson’s is to dopamine whereas
Parkinson’s vs.
Alzeihmer’s Alzeihmer’s is to acetylcholine.

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Contrasting Pathologies

Alzheimer’s
Parkinson’s • ADL decline
• Tremor at rest, • Cortical atrophy
bradykinesia • Aβ amyloid (21) à
• Loss of pigment in amyloid hemorrhage
substantia nigra • Neurofib tangles à
• ɑ - synuclein (Lewy hyperPO4 tau
Body) § Lew y Body Dem entia (frontotemporal
§ C ortical ɑ
synuclein dementia)
inclusions.

34

decreased dopamine in pars compacta à more inhibition of movement

§ Initiate movement M otor Cortex

Thalam us
Striatum

Substantia Nigra
Pars Com pacta
Globus Pallidus Interna
§ Globus Pallidus at a basal level
Substantia Nigra Reticularis
inhibits the thalamus.

35

• 70 yo M has Parkinson’s. He has increased

bradykinesia despite levodopa/carbidopa.
The patient will likely need
neuroanatomical stimulation of which
NBME Style structure to improve his bradykinesia?
Question • A. Hippocampus
• B. Subthalamic nuclei
• C. Basal nucleus of Meynert
• D. Internal capsule

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decreased dopamine in pars compacta à more inhibition of movement

§ Initiate movement M otor Cortex

Thalam us
Striatum

Substantia Nigra
Pars Com pacta
Globus Pallidus Interna
§ Globus Pallidus at a basal level
Subthalam ic Nuclei Substantia Nigra Reticularis
inhibits the thalamus.

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Question Take-Home Message

Organ System Question Type Content Specification

Neurology Neuroanatomy Basal Ganglia Neurotransmission

Paraphrase: Step Beyond:

• Pt with Parkinsons with on-off • A lesion of subthalamic nucleus would
phenomena + bradykinesia + produce which clinical exam finding?
stimulation of brain = subthalamic • Hemiballismus
nuclei

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Parkinsonian Pharmacology

Class Effect or Big Picture Increase Dopamine

Pathology / Pathophysiology Mechanism of Action Increase Dopamine directly

Prevent Dopamine
breakdown
Increase Dopam ine w hich
w ill drive the D 1 pathway
Specific Names Carbidopa, Ropinirole,
Bromocriptine, Raselegiline,
Amantadine

On-off phenomena
SE

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• A 50 yo M patient with Parkinson’s disease

is currently on seligiline. He is now started
on L-dopa and carbidopa. Which of the
following side effects will be seen with this
NBME Style change?
Question • A. Hypotension
• B. Tachyarrythmias
• C. Psychosis and anxiety
• D. Infection

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Question Take-Home Message

Organ System Question Type Content Specification

Neurology Pharmacology SE Side Effect of L-Dopa and Carbidopa

Paraphrase: Step Beyond:

• Pt on dopamine medication + side • What is the MOA of selegiline?
effect = psychosis
• MAO-B inhibitors à decreases
Dopamine Breakdown

41

Parkinsonian pharmacology

Rasagiline

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• A patient at night has constant awakenings. He

wakes up his partner frequently throughout the
night due to an insensible urge to move his lower
extremities. An agent is prescribed which increases
dopaminergic effect. What is the likely medication?
• Ropinirole & Pramipexole

Pharmacology • A male presents with low libido. He states he has

Integration been having changing of his vision as he sees
frequently with tunnel vision. A head CT is
performed indicating “a lesion near the sella
turcica.” Prolactin levels are ≥200. An agent which
modulates which neurotransmitter will be likely
considered?
• Dopamine agonist à bromocriptine.

43

review of agents
▸ To decrease peripheral conversion of L-DOPA which
agent is likely prescribed?
▸ Carbidopa
▸ What two classes of medications prevent the breakdown of Dopa
or Dopamine?
▹ COM-T Inhibitors – Entacapone & Tolcapone
▹ MAO-B Inhibitors – Rasagiline & Seligiline

44

• A patient with Parkinson’s is noted to have a severe decline in

motor function. He has been intermittently taking his L-DOPA.
VS notable for hyperthermia. Exam shows inability to raise his
arm, and incomprehensible speech. A medication which
modulates NMDA is started. One day later he breaks out in a
rash. What is the likely dermatological finding?

Amantadine

• Livedo Reticularis
• Amantadine à
• NMDA Antagonist
• Increases Dopamine at synaptic cleft
• Can cause prolonged QT
• Flu virus à prevents uncoating.

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Alzheimer’s Drugs

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pathology review of Alzheimer's for the usmle

47

• A patient with Alzheimer's admitted to the

hospital with fever and cough. Patient has
drooling and mild L sided droop. X-ray shows
right lower lobe opacity. What is the most likely
mechanism behind this patient’s diagnosis?

NBME Style • A. Swallowing muscle dysfunction

Question • B. Immobility
• C. Impaired immune response
• D. Malnutrition

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Question Take-Home Message

Organ System Question Type Content Specification

Pathophysiology
Neurology Aspiration PNA
Mechanism

Paraphrase: Step Beyond:

• Pt with Alzeihmers + RLL X-ray + fever = • Which antibiotic would be ideal of aspiration
Aspiration PNA PNA?
• Clindamycin

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Alzheimer's Pharmacology

Class Effect or Big Picture Increase Ach

Pathology / Pathophysiology Mechanism of Action Prevent Ach Breakdown

D ecrease in A ch
G lob al C ereb ral A trop h y
Loss of A D Ls
Specific Names Donepezil
Rivastigmine
Galantamine

SE Wet

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Alzheimer pharmacology

51

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NMDA Integration for the usmle

⬆ book on anti-NM DA
encephalitis 🔥 🧠

52

• A child presents with profuse vomiting and

diarrhea. He is tachypneic and sweating with
constricted pupils. Upon history you note he was
playing in the back of the garage at the baby-
sitters house when these symptoms came upon.
What is the likely diagnosis?
Autonomic • Organophosphate poisoning
Pharmacology
Integration
• What is the likely agent which will reverse this
phenomena?
• Atropine (competitive muscarinic
antagonist)
• 2-PAM (regenerates AChE)

53

Contrasting ANS

Cholinomimetic Anti-Cholinergic
• Wet: diarrhea, • Dry: urinary
lacrimation, retention, abdominal
bronchorrhea pain, skin flushing
• Bronchoconstriction • Bronchodilation
• Bradycardia • Tachycardia
• Small Pupils • Large Pupils
§ U SM LE Test Taking:
§ Pupils & Vital Signs

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• A patient is found to have genetic testing

positive for Apolipoprotein E-4. In the future, this
patient is most likely to suffer from?
• A. T2 DM
• B. Parkinson’s Disease
NBME Style • C. HOCOM
Question • D. Alzheimers

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review of agents
▸ A patient who overdosed on rivastigmine is most likely to have which changes in heart rate?
▸ Bradycardia

▸ 32 yo woman complains of double vision. She says this occurs in the afternoon. Exam
shows weakness of her eyes when asked to actively keep them elevated. What is the
mechanism behind the likely pathology?
▹ Antibodies to nAchR à Myasthenia Gravis
■ Key USMLE question: progressive weakness + bulbar symptoms

▸ What is the role of chest imaging for this type 2 hypersensitivity pathology?
▹ Thymoma à generate the anti-bodies.

▸ In summary:
▹ Acetylcholinesterase inhibitors are used for Alzheim er’s & Myasthenia Gravis.

56

Psychiatry

57

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Rapid Review Pharmacology

Psychiatry
• Anti-Psychotics
• Anti-Depressants

58

Anti-Psychotics

59

• A patient is newly diagnosed with psychosis. She is

started on an anti-psychotic. The patient is at follow-up
three weeks later and states that it has been “challenging
to have sex…I just don’t feel interested.” Exam is notable
for increased glandular nodularity of breast with
intermittent bilateral expulsion of white discharge. What
NBME Style is the likely pathway which is affected?
Question
• A. Arcuate fasciculus

• B. Nigrostriatal
• C. Mesolimbic

• D. Tubuloinfundibular

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Psychiatry Dopamine Pathways
Side Effect

Paraphrase: Step Beyond:

• Pt on anti-psychotic + signs of • A patient with acute psychosis most likely
hyperprolactin state + neuroanatomy has upregulation of which dopamine
tie-in = tubuloinfundibular pathway?
• Mesolimbic

61

USMLE Neuroanatomy Integration

62

Psychosis Pharmacology

Class Effect or Big Picture Decrease

Dopamine

Pathology / Pathophysiology Mechanism of Action D2 antagonism

Hallucinations + Delusions
*Haloperidol
+ Disorganized thinking
Specific Names *Fluphenazine
Manic Episodes **Clozapine, **Olanzapine,
**Risperidone, **Quetiapine
Delirium
*EPS
SE **Metabolic Syndrome
NMS

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• Many of the 1st generation anti-

psychotics are very lipid soluble &
stored in fat. What is the Vd?
• High – amount of drug in body / plasma
concentration.
Gen Pharm
Integration

64

• A patient is found on the street confused and dis-

sheveled. He states he is “God’s best friend.” He has
history of a psychiatric disorder, however has
intermittent compliance with medications. His toxicology
screen is negative. He is prescribed acute treatment for
psychosis as he becomes violent. Subsequently he has
NBME Style diffuse rigidity, tachycardia, and hypertension. His CPK is
Question elevated. What is the likely diagnosis?
• A. Serotonin Syndrome
• B. Neuroleptic malignant syndrome
• C. Dystonic reaction
• D. Malignant hyperthermia

65

§ Treatment
Neuroleptic malignant syndrome
§ Dantrolene
§ Ergot
derivatives

Autonomic Instab
Trigger with anti- Dopamine ⬆ Muscle rigidity
psychotic (1st gen) Antagonism (CPK)
⬆ Hyperthermia

§ Tease out from :

§ Serotonin
syndrom e:
§ m ore clonus
+ diarrhea
§ M alignant
H ypertherm ia:
§ Anesthesia

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Psychiatry Neuroleptic Malignant Syndrome
Side Effect

Paraphrase: Step Beyond:

• Pt tx with anti-psychotic + lead pipe • Dantrolene is used in the treatment along
rigidity + fever + ANS instability = NMS with Dopamine Agonists. What is the MOA
of Dantrolene?
• Ryanodine receptor antagonist

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teasing pathologies out on the usmle

68

Antipsychotics

1st generation 2nd generation

Aripriprazole,
Clozapine, Olanzapine,
Low Potency High Potency Quetiapine,
Risperidone,
Ziprasidone

SE: non-neuro Trifluoperazine,

Pimozide, Thioridazine, (anticholinergic, Fluphenazine, SE: more neuro esp.
Chlorpromazine antihistamine, a1 ant) Haloperidol EPS

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• A patient has been treated on Olanzapine for 3 years. The

patient was lost to follow up. She now presents to the
primary care doctor for follow up. The patient’s BMI is 28
kg/m2. Which of the following studies most likely needs
to be obtained at this visit?
• A. Hemoglobin A1c
NBME Style
Question • B. Prolactin level
• C. Electrocardiogram

• D. Thyroid Panel
• E. BUN : Cr ratio

70

Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Psychiatry Metabolic Syndrome
Side Effect

Paraphrase: Step Beyond:

• Pt on second gen anti-psychotic + long • What is the criteria for metabolic syndrome?
term follow up = Hgb A 1c & lipid panel • H igh w aist circum ference

• H igh TAG , H igh fasting glucose, high TAG

§ Corticosteroids à
• H igh BP
can cause drug
induced metabolic
syndrome.

71

Anti-psychotic Side Effects

1st Generation Anti-Cholinergic

• Extrapyramidal Symptoms: • Dry: urinary
• Bradykinesia
retention, abdominal
• Dystonia (torticollis)
• Akathisia pain, skin flushing
• Tremors • Bronchodilation
• Prolonged QT syndrome
• Neuroleptic Malignant
• Tachycardia
Syndrome • Large Pupils

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review of agents
▸ Neck stiffness, and inability to relax in a schizophrenic
on a first-gen antipsychotic. What is the MOA of the
likely Rx?
▹ Benztropine à Acute dystonia

▸ Cannot sit still/restlessness in a schizophrenic on a

first-gen antipsychotic. What is the treatment?
▹ Beta-blocker à Akathesia.

73

review of agents
▸ Slow narrow gait, tremor at rest, flat affect, drooling in a
schizophrenic on a first gen-antipsychotic. What is the
diagnosis?
▹ Pseudo-parkinsonism

▸ Lip smacking and tongue movements in a patient on long term

treatment with first gen antipsychotic. What is the likely
diagnosis?
▹ Tardive Dyskinesia.

74

Antipsychotics

§ USMLE Point
§ 2nd generation
work on many
receptors à know
SE
1st generation 2nd generation

Aripriprazole,
Clozapine, Olanzapine,
Low Potency High Potency Quetiapine,
Risperidone,
Ziprasidone

SE: non-neuro Trifluoperazine,

Pimozide, Thioridazine, (anticholinergic, Fluphenazine, SE: more neuro esp.
Chlorpromazine antihistamine, a1 ant) Haloperidol EPS

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Second generation anti-psychotics

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• A patient presents to the psychiatrist for refractory

schizophrenia. She has tried 3 anti-psychotics, both
first and second generation and has failed. She has
hypertension and obesity. Clozapine treatment is
initiated. At her 2 week follow up visit, which of the
following labs should be monitored?
NBME Style • A. Electrocardiogram
Question
• B. Creatinine
• C. Hepatic Function Panel
• D. Absolute neutrophil count

77

Agranulocytosis
• Ganciclovir
• Colchicine § Watch for
Integrative recurrent
USMLE • PTU/Methimazole infections à
Pharmacology • Clozapine sore throat,
myocarditis
• Carbamazepine

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Anti-Depressants

79

SSRI Pharmacology

Class Effect or Big Picture Increase Serotonin

Pathology / Pathophysiology Mechanism of Action Inhibit Serotonin Re-Uptake

at the Synaptic Cleft
MDD
Fluoxetine
GAD Paroxetine
OCD Specific Names Sertraline
Citalopram
PTSD Escitalopram
Panic Disorder Sexual dysfunction
Insomina
SE Serotonin Syndrome

80

• A patient presents with anhedonia and depressed mood.

She is diagnosed with major depressive disorder. She is
started on first-line pharmacological treatment. Two days
later, the patient is found to be febrile, hypertensive, and
tachycardic. She has diarrhea, and hyperreflexia. Which
of the following amino acids is a precursor of the
NBME Style neurotransmitter responsible for this patient’s
Question symptoms?
• A. Glutamic Acid

• B. Histamine
• C. Tryptophan

• D. Methionine

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Psychiatry Serotonin Syndrome
Side Effect

Paraphrase: Step Beyond:

• Pt with MDD + pharmacotherapy + • What is the treatment of Serotonin
tremor + flushing + diarrhea = Serotonin Syndrome?
Syndrome • Stop SSRI; supportive care; cyproheptadine

82

Amino acid derivatives

Integrative
USMLE
Biochemistry

83

§ SSRIs take 4-6

weeks to reach
effect.

Serotonin Atypical
SSRI SNRI antagonists Antidepressants

Fluoxetine Mirtazapine (ɑ2

Paroxetine Venlafaxine antagonist)
Trazodone
Sertraline Duloxetine Buproprion (NDRI)
Citalopram Varenicline

84

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Selective serotonin reuptake inhibitors

▸ A patient who was recently on an SSRI which was
discontinued 2/2 sexual side effects. She is
immediately started on trancylopramine and
§ Atypical depression
develops increased BP, flushing, clonus. What à ↑ appetite and
sleep, leaden
may have prevented this? paralysis,
rejection
▸ Washout of SSRI for 2 weeks prior to starting sensitivity, and
m ood reactivity.
MAO-I
▸ What are the MAO-I?
▹ Transcylopramine, Phenelzine, Isocarboxid

85

SNRI • A patient presents with • Duloxetine is used for

generalized pain + muscle fibromyalgia & stress
soreness + depressive incontinence.
symptoms = fibromyalgia

Venlafaxine
Duloxetine

86

• Trazodone causes Serotonin

• A patient presents with priapism. antagonists
depression à started on a • Trazodone causes
medication à persistent sedation (H1
erection? blockade).

Trazodone

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• A nursing hom e patient. Low • Mirtazipine causes appetite

BMI. Insom nia + needs stim ulation + sedation.
Atypical nutritional support?

Antidepressants • A fem ale low BMI + m etabolic • Buproprion lowers the seizure
alkalosis + callous on knuckles? threshold.
• Pt who fails SSRI à switch to • Used for pt who has
m ed for MDD? im potence from SSRI.

• Varenicline m akes you very

Mirtazapine (ɑ2 • Stop sm oking
clean from Nicotine
antagonist)
Buproprion (NDRI)
Varenicline

88

A child presents with confusion and a

temperature of 103. He is found to have QT
prolongation on his EKG. He was found to be
at a friend’s home for a sleepover. In the ICU
he has twitching activity consistent with
seizures. An overdose is suspected.
Treatment is initiated to form an ionized
Tricyclic Anti- state of the medication. What is the likely
Depressants therapeutic intervention which may help
treat this scenario?
• NaHCO3 à

89

Tricyclic Antidepressant toxicity

§ Important Suffix:
§ -Ipramine

Coma EKG QTc

Convulsions prolongation
TCA overdose
Cardiotoxicity Urinary retention
Anticholinergic Confusion

§ TC A overdose:
§ Blocks fast N a
channels.
§ TC A:
§ Im ipram ine w e use
for nocturnal
enuresis.
§ C lom ipram ine can
cause high PRL.

90

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pulmonary

91

Rapid Review Pharmacology

Pulmonary
• Asthma Medications
• Pulmonary Hypertension Medications
• Anti-Allergic Agents

92

Asthma

93

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• A 50 yo woman presents with episodic

shortness of breath and cough. She is
otherwise healthy. CXR is normal.
Spirometry shows low FEV1 & sputum shows
eosinophilic predominance. The patient
NBME Style likely has her long-term cough triggered by
Question which of the following?
• A. House dust mite
• B. Barley, wheat, oats, and rye
• C. Shellfish
• D. Acetominophen

94

• Recognize atopy in USMLE questions:

• Eczema
• Asthma
• Allergic Rhinitis
• ⬆ IgE
USMLE Test
Taking Strategy

95

§ 2 signals à class switch:

§ CD40 (Th2)
§ CD40L (B-Cell)
• IgE
-4
IL
•
Immunology M epolizum ab
Integration
•

•
• Allergen • CD4+ IL-
5

• TH2

• Eosinophils

96

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§ ⬇ inflammation
§ ⬇ wet
parasympathetics

β2 agonists
Inhaled Anti-Leukotriene Muscarinic
Steroids Agents antagonists

Albuterol
Budesonide
Terbutaline Montelukast Tiotropium
Fluticasone
Salmeterol Zafirlukast Ipratropium
Mometasone
Formoterol

97

Asthma Pharmacology

Decrease B2
Class Effect or Big Picture hyperresponsiveness

Pathology / Pathophysiology Mechanism of Action Reduce inflammation &

muscarinic activity

• Bronchial SABA
hyperresponsiveness LABA
Specific Names ICS
• Mucus plugging Anti-Leukotriene
• Inflammation Anti-Cholinergic

SE Tachycardia + Tremor

98

• A 40 yo M recently immigrated from Azerbaijan.

The patient has had intermittent abdominal pain.
Patient undergoes abdominal ultrasound showing
a complex liver cyst. Labs are notable for high IgM
Echinococcus granulosis. Patient undergoes liver
surgery to remove the cyst, and subsequently
acute complications & passes away. What is the
NBME Style
Question likely etiology of death?
• A. Septic shock

• B. Live failure
• C. Anaphylaxis

• D. Interventricular hemorrhage

99

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Question Take-Home Message

Organ System Question Type Content Specification

Respiratory Multimedia Echinococcus (hyatid cyst)

Paraphrase: Step Beyond:

• Immigrant + liver cyst + cyst • What receptor is stimulated during the
manipulation + death = anaphylaxis treatment of anaphylactic shock?
• β-1 = β-2 > ɑ1 (Epinephrine)

100

• A child with asthm a

• Β 1 perm issive effect
exacerbation + albuterol +
trem or & palpitations?

• A child with asthm a • Increased cortisol state + β 2

β2 agonists exacerbation + hyperglycem ia? m ediated glycogenolysis

• A child with asthm a

exacerbation + m uscle • HypoK from Na/K ATPase.
weakness?

Albuterol
Terbutaline § LABA meds can cause
cardiotoxicity + tachyphylaxis
Salmeterol
Formoterol

101

Autonomic Receptors in the Lungs

• M3 receptors increase:
• β2 receptors increase:
• bronchial secretions
• bronchodilation
• smooth muscle airway
contraction

102

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• A 20 yo woman with history of eczema and

allergies presents to the intensive care unit for an
asthma exacerbation. She is intubated and despite
life saving measures she passes away. Autopsy is
notable for airway mucus plugging and cellular
infiltration on the bronchial wall. Which of the
NBME Style following medications may have prevented her
Question cellular reaction?
• A. Albuterol

• B. Ipratropium
• C. Montelukast

• D. Fluticasone

103

• Local thrush 2/2 Candida

• A patient with • Buds that do not separate

à pseudohyphae
white plaques Think im m unocom prom ised as
•
Inhaled easily scraped off.
well in USM LE vignettes.

Steroids
• Im pairm ent of fibroblast activity
• Skin atrophy for
à collagen synthesis ⬇
topical steroids

Budesonide
Fluticasone
Mometasone

104

Systemic Manifestations of steroid therapy for the USMLE

Gastrointestinal
Hypertension
• Peptic ulcers &
hemorrhage • Increased upregulation
of sympathomimetic
• Reduced AA receptors.
pathway à ⬇ PG

Metabolic Derangements
MSK • ⬆ lipolysis
• Avascular necrosis • ⬆ gluconeogenesis
• Proximal muscle weakness • ⬆ proteolysis
• Osteoporosis à • ⬆ insulin resistance
• RANK-L osteoclasts
• Growth plate ⬇

105

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• A patient is on long term steroids for Lupus. She is noted

to be going to the intensive care unit for a liver surgery.
The patient intra-operatively becomes hypotensive and
tachycardic. Hypovolemic shock is ruled out. What is the
likely diagnosis?
• Adrenal insufficiency 2/2 chronic HPA suppression
Complications • Remember chronic steroids:
of Chronic
• ⬇ CRH
Steroids
• ⬇ ACTH
• ⬇ Cortisol

• During stressful states (i.e. surgeries), patients need

to be started on stress-dose steroids (Hydrocortisone,
Methylprednisolone, Fludrocortisone) à or they can
have adrenal crisis.

106

Membrane
Phospholipids
Arachidonic Acid

LOX Prostaglandins

Anti-Leukotriene
Agents
Leukotrienes: TXA2, PGD2, PGI2 & PGE2
PGF2ɑ

LTB4: PMN ⬆
LTC4 & LTE4: Bronchoconstriction Bronchodilation Vasodilation
Montelukast bronchospasm +
permeability
Zafirlukast

107

ADJUNCTIVE TREATMENTS IN ASTHMA

• Prevents binding of IgE to FcεR1 à

Omalizumab decrease mast cell activity

• PDE inhibition à ⬆ cAMP à

Theophylline bronchodilation

• Prevents release of mediators in mast

Cromolyn cells

108

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Pulmonary Htn

109

Pathophysiology of pulmonary hypertension

§ Keeping preload
optimal is key!

Chronic hypoxic
pulmonary
vasoconstriction Right ventricular
Increased PVR afterload ⬆
Airway smooth
muscle
hypertrophy

§ U SM LE Point:
§ Increased R V pressures
§ Tricuspid regurgitation
§ Jugular venous
distension
§ H epatom egaly
§ Peripheral edem a

110

Key USMLE Step 1 Concepts

Right Heart Failure 2/2 Pulmonary
Hypertension

Left Heart Failure

Acute Respiratory Distress Syndrome

111

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Pulmonary Hypertension Pharmacology

Decrease PVR
Class Effect or Big Picture

Pathology / Pathophysiology Mechanism of Action Increase vasodilation

Modulate Endothelin, NO,
PGI2

• Increased Pulmonary Specific Names Bosentan, Sildenafil, iNO

Vascular Resistance -prost

SE Hypotension, Liver toxicity

(Bosentan)

112

USMLE Questions:
q Bosenten à
ü Endothelin antagonist
ü Liver toxicity
q Nitric Oxide à
ü ⬆ cGMP (iNO)
ü Sildenafil à PDE-5
ü ⬆ cGMP
q Prostacyclin à
ü Epoprostenol
ü Iloprost
ü Treprostinil

113

Anti-Allergy

114

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Contrasting receptor locations

H1: H2 :
• Anti-allergy o Anti-acid
o 1st generation o ECL cells à stimulate
o Cross BBB parietal à H/K ATPase
o Gq o Gs

115
H1 anti-histamines

Diphenhydramine
Promethazine
Sedation
1st generation
Anti-Allergy
Chlorpheniramine
Hydroxyzine
Cyproheptadine

Loratadine
2nd generation More Anti-Allergy Cetirizine
Fexofenadine

116

Reproductive

117

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Rapid Review Pharmacology

Reproductive
• Selective EstAogen Receptor Modulators
(SERMs)
• Testosterone Agents

118

Selective Estrogen Receptor

Modulators

119

SERMs

Decrease effects of
Class Effect or Big Picture Estrogen

Pathology / Pathophysiology Mechanism of Action Antagonize intracellular

estrogen receptor

• Estrogen à
endometrial or breast Specific Names Tamoxifen, Raloxifene,
hyperplasia à dysplasia Clomiphene

Increased risk for DVT and

SE vasomotor symptoms

120

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Characteristics of Steroid Receptors

• Steroid Hormones:
• Testosterone
• Progesterone
• Estrogen
• Glucocorticoids
• Mineralocorticoids

• T4 / T3
• (1,25) Vitamin D

121

• A 55 yo woman is diagnosed with breast

cancer. She undergoes biopsy noting ER+
and PR+. HER-2 neu is negative. She is
started on tamoxifen. The patient is most
NBME Style likely at risk to develop which long term
Question
581 complication?
• A. Increased endometrial hyperplasia.
• B. Decrease in HDL.
• C. Decrease in bone mass.
• D. Increase in breast cancer progression.

122

Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Reproductive Selective Estrogen Receptor Modulators
Mechanism

Paraphrase: Step Beyond:

• Breast cancer patient + tamoxifen + • If this patient developed leg-swelling and
long term complication? = endometrial SOB. What is the likely concern?
hyperplasia. • DVT à PE [OCP and SERMs cause
hypercoag]

123

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SERMs for the USMLE

Selective Estrogen Receptor

Modulators

Pay attention to agonism vs

antagonism in tissues

Tamoxifen Raloxifene Clomiphene

Antagonist at breast + Agonist at Antagonist at breast + endometria Blocks hypothalamic estrogen à
bone + endometria Agonist at bone (osteoprogerin) triggering LH and FSH surge

124

Two Cell Hypothesis

Reproductive physiology integration
§ Aromatase inhibitors à
§ 5-ɑ-reductase inhibitors à
anastrozole
finasteride
§ Decreases testosterone to
§ DHT blocker à flutamide
estrogen

125

• A patient is diagnosed with osteoporosis.

She is advised to increase weight-bearing
exercise. She would like to also start
hormonal therapy. Which of the following
medications will be beneficial in decreasing
NBME Style risk of both bone fractures and breast
Question cancer in this patient?
• A. Alendronate
• B. Raloxifene
• C. Leuprolide
• D. Estradiol therapy

126

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Reproductive Selective Estrogen Receptor Modulators
Mechanism

Paraphrase: Step Beyond:

• Antagonist at the breast + agonist on • Which of the SERMs increases the risk of
the bone = Raloxifene uterine sarcoma?
• Tamoxifen

127

Testosterone Agents

128

Testosterone Agents

Anti-Androgenic USMLE Significance

USMLE questions will have • Inhibits 5 ɑ reductase
gynecomastia, sexual • Finasteride • Elderly pt + hesitancy with stream + incom plete
dysfunction in questions à voiding
indicating testosterone ⬇
• Increased cortisol state + β 2 m ediated
• Flutam ide
glycogenolysis

• Inhibition of RAAS
• Spironolactone
• Polycystic ovarian syndrom e
• Decrease testosterone synthesis in adrenals.
• Ketoconazole
• Inhibits fungal sterol synthesis

• Cim etidine • H 2 blocker

129

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Gastroenterology

130

Acid Suppression

131

Rapid Review Pharmacology

Gastroenterology
• Acid Suppression

132

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Gastrointestinal physiology

Gastrin + ECL cells

133

134

• A 38-year-old male patient with a duodenal ulcer

is treated successfully cimetidine. Which of the
following mechanisms best describes the agent
started in this patient?
• (A) Blocks muscarinic receptors on parietal cells
NBME Style • (B) Blocks Gq receptors on parietal cells
Question
• (C) Decreases intracellular cAMP levels
• (D) Activation of primary-active transport
• (E) Enhances the action of acetylcholine (ACh) on
parietal cells

135

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Gastroenterology Cimetidine
Mechanism

Paraphrase: Step Beyond:

• Duodenal ulcer + cimetidine + which • A patient with recurrent distal duodenal
GPCR = H2 decreases Gs (i.e. cAMP) ulcers or jejunal ulcers brings up concern for
which pathology?
• Zollinger Ellison (MEN-1)

136

Studying Pharmacology for the USMLE

Class Effect or Big Picture Decrease acid

Pathology / Pathophysiology Mechanism of Action Block H2 receptor on parietal

cells decreasing Gs activity
Parietal Cell function

Specific Names Cimetidine, Ranitidine

-prazole

SE CYP inhibitor & Gynecomastia

137

• A patient is admitted to the hospital with a

hip fracture. She has a history of
osteoporosis. She has a history of
pharmacologically controlled hypertension,
seizures, GERD. Her medications are
reviewed. Which of the following may
NBME Style
Question increase the risk of bone fractures 2/2
osteoporosis?
• A. Atorvastatin
• B. Levetiracetam
• C. Nitroglycerin
• D. Omeprazole

138

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Anatomy of a c. Diff question on the usmle

§ Understand triggers in
USMLE Questions

Normal Flora
Recent Abx Use disruption Stool PCR
(Clindamycin)
Toxin A & B à Oral vancomycin
PPI cytoskeletal
damage IV Metronidazole
Hospitalization
Pseudomembrane

§ Presentation on the
U SM LE:
§ w atery diarrhea
§ leukocytosis
§ abdom inal pain

139

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