5/16/21

HyGuru USMLE Step 1

Rapid Review Pharmacology

Rahul Damania, MD, FAAP

Cardiology

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Rapid Review Pharmacology

Cardiology
• Anti-Ar'hy*hmics
• Hear* Failure Phar6acolog9
• Anti-Lipid Agents

Anti-Arrhythmics

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• 50 yo presents with palpitations. He

recently returned from a Christmas Party.
The patient is noted to have an irregularly
irregular heart rate. Pulse is 120/min.
Which of the following EKG findings
NBME Style
confirms this patient’s diagnosis?
Question
• A. Prolonged QT interval.
• B. Delta-wave QRS morphology.
• C. Absent P waves.
• D. ST Segment depression.

Question Take-Home Message

Organ System Question Type Content Specification

Cardiology EKG Atrial Fibrillation

Paraphrase: Step Beyond:

• Alcoholism trigger + palpitations + • A patient with atrial fibrillation may have a
irregularly irregular (afib) = absent P foci most likely in which area?
waves. • Cavo-atrial junction (near SA node!)

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Cardiology
Test Taking
Strategy for
the USMLE

Virchow’s Triad
Stasis
Patient Presentation USMLE Significance

• Focal neurological • Thromboembolic

deficit stroke

• Acute mesenteric
• Abdominal pain ischemia
• Thromboembolic LE
Hypercoagulable Endothelial Cell • Cool pale occlusion
extremity
State Injury • Watch for cholesterol
• Cardiogenic shock
+ afib
• Loss of preload

• Ablation • Cavotricuspid isthmus

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§ A patient with unstable

vital signs + arrhythmia
gets synchronized
cardioversion.

Rhythm
Rate control
Control

Calcium Channel
Beta-Blockers Anti-arrHythmics
Blockers (non-DHP)

treating arrythmias

Rhythm
Control

Anti-
arrHythmics

class 1 class 2 class 3 class 4

β- K channel
a b c CCB
blockers blockers
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Anti-arrhythmic drugs

Class Drug Name Mnemonic

• 1A • Procainamide, Quinidine, Disopyramide • I Proclaim Queen Disopyramid

• 1B • Lidocaine, Mexiletine • I’d Buy Lydia’s Mexican Tacos

• 1C • Propofenone, Flecainide • Profane Flec of Poop

USMLE Questions rarely will

ask you which medication
goes with which arrythmia à
more mechanisms and ADE.

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Anti-arrhythmic drugs

Class Drug Name Mnemonic Sotalol is a β-blocker like

medication so watch for low
• III • Amiodarone • A heart rate.
It also can cause prolonged
QT à TdP (just like 1a)
• III • Ibutilide • I

• III • Dofetilide • D

• III • Sotalol

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Systemic Manifestations of Amiodarone for the USMLE

Ocular
• Optic neuropathy
Cardiac
Pulmonary • Heart Block
• Chronic interstitial • QT Prolongation à TdP
pneumonitis

Dermatologic
• Blue-gray skin Endocrine
discoloration • Hypo/Hyperthyroidism

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Cardiac Physiology
Integration

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Compare & Contrast Two Action Potentials

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physiology review
▸ In ventricular muscle, what ion determines the phase 4 of the
cardiac action potential?
▹ Potassium permeability
■ K equilibrium potential is -84 mV
▸ What ion determines phase 0 of the ventricular action potential?
▹ Na influx.

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physiology review
▸ What phase of the ventricular action potential defines the
difference between nodal action potential vs. ventricular action
potential?
▹ Phase 2 à Cardiac action potential has a plateau phase which is due to Ca influx
and K efflux.
■ Ventricular muscle has Ca induced Ca release, and gap-junctions.

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Compare & Contrast Two Action Potentials

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treating arrythmias

Rhythm
Control

Anti-
arrHythmics

class 1

C A B

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treating arrythmias

• Flecainide
• A patient who presents after
• Propafenone
Rhythm MI à which one would
• Loves partially depolarized tissues
worsen arrythmia?
Control à can bind for long à toxicity.
• Mexilitine
• A patient who presents after • Lidocaine
MI à which one would be • Binds to inactivated Na channels à
Anti- best for any arrhythmia and comes off quickly [ischemic
arrHythmics prevention? tissue has higher RMP and
inactivated Na channels]

• Ear ringing? • Quinchonism à Quinidine

class 1 • SLE like syndrome • Procainamide

C A B

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DRUG INDUCED LUPUS

USMLE High-Yield What are the HY

Presentation Clue: medications are
related to drug
• A patient with • Anti-Histone induced SLE?
fever and joint antibody
pain with malar • Procainamide
rash after being
positive • Na channel blocker
treated for • Slow acetylators • Hydralazine
arrythmia, htn, an are predisposed • Increases cGMP and
vasodilates
inflammatory to developing
• INH
disease, or this à remember
• Mycolic acid inhibitor
tuberculosis acetylation (give with B6)
causes DNA to be • TNF alpha inhibitors
ACTIVE (etanercept, infliximab,
etc.)

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• A 60 yo M presents with chest pain on exertion.

He has a history of COPD. He is started on a
medication which decreases HR and O2
consumption of heart. Within 48 hrs he is noted
to have SOB & wheezing. What is the likely
medication which may have contributed to his
NBME Style
Question acute symptoms?
• A. Ibutilide
• B. Sotalol
• C. Propranolol
• D. Verapamil

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Cardiology β-blocker
Side Effect

Paraphrase: Step Beyond:

• Pt with underlying bronchospasm + β- • What medication combats β2 mediated
blocker = bronchoconstriction bronchoconstriction?
• Terbutaline, Albuterol, Salmeterol,
Formetorol.

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treating arrythmias

Rhythm
Control

Anti-arrHythmics

β-blockers

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non-selective β-blockade

▹ Lungs:
■ Bronchoconstriction
▹ Liver:
■ Decreases gluconeogenesis &
glycogenolysis.
Beta-blockers can
mask symptoms of
hypoglycemia in
diabetics.

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Calcium Channel Blockers

DHP—CCB non-DHP—CCB
• -dipine •Verapamil
• Blockage of L-type •Diltiazem
calcium channels à • ⬆ AV nodal delay
⬇ Ca-calmodulin • ⬇ contractility & HR
complex à ⬇ ML
Kinase à ⬆ smooth
muscle relaxation
• ADE: gum, edema

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Calcium channel blockers on the usmle

Goal is to vasodilate
Calcium Channel
USMLE Vignette
Blocker
• Nicardipine
• Patient with BP >180/120 + end organ damage
• Clevidipine

• Subarachnoid hemorrhage to prevent

• Nimodipine vasospasm

• Vasospasm with Raynaud’s

• Amlodipine • Angina
• Arterial hypertension

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• A 50 yo M presents with refractory hypertension. He

has tried ACE inhibitors with no change in his blood
pressure. He is started on a new medication. Ten
days later, he is noted to have dizziness and swelling
in his legs. He has orthostatic vital signs at his follow
up visit. Which of the following medications likely
NBME Style contributed to this effect?
Question
• A. Amlodipine
• B. Lisinopril
• C. Verapamil
• D. Metoprolol

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Cardiology Amlodipine
Side Effect

Paraphrase: Step Beyond:

• BP med + swelling + reflex tachycardia • A patient’s increase in HR after vasodilation
= amlodipine. is most likely due to which physiologic
mechanism?
• Baroreceptor reflex (dec carotid stretch)

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treating arrythmias

Key Concepts:
Rhythm ▹ CàAàB:
Control ■ Use dependence
▹ Procainamide
Summary of Anti-arrhythmics ▹ Side effects of β-blockade
Anti- ▹ Amiodarone
arrHythmics ▹ non-DHP vs. DHP

class 1 class 2 class 3 class 4

β- K channel
a b c CCB
blockers blockers
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Heart Failure
Pharmacology

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Cardiology
Test Taking
Strategy for
the USMLE

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• A patient presents with exertional dyspnea. He

has a history of atherosclerosis. He is unable to
lay flat. He has an elevated BP and crackles on
exam. Levels of which substance will be high in
the pulmonary vasculature?

NBME Style • A. Prostaglandin E1

Question • B. Angiotensinogen
• C. Renin
• D. Angiotensin II

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Question Take-Home Message

Organ System Question Type Content Specification

Cardiology Pathophysiology Renin-Angiotensin-Aldosterone System

Paraphrase: Step Beyond:

• Patient with SOB + crackles + HF à • High Angio II has preferential effect on
what is high in pulmonary circuit = which arteriole in the kidney: afferent or
angio II. efferent?
• Efferent à maintains glomerular perf.

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Renin Angiotensin Aldosterone System

Angiotensinogen

Aldosterone
Low perfusion to kidney Renin

Angio 1 Angio II

ADH

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Shock CO SVR PCWP/LVEDV SVO 2

Cardiogenic
‘pump failure’ Low High High Low

Understand atherosclerotic
stigmata in exam questions:
• Diabetes Mellitus
• Hypertension
Heart
• Dyslipidemia Failure
USMLE Test • Obesity

Taking Strategy:
Congestive
Heart Failure
Acute Chronic

Stroke Volume: Modulate

Optimize Preload, Reduce RAAS to
Cardiac Output Afterload, arrythmia decrease
Contractility mortality

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sacubitril is a Neprilysin inhibitor

§ Increased fluid à
increased preload à
higher MVO2

Impairs ⬆ Natiuresis
Neprilysin breakdown of
⬆ Diuresis
inhibition Angiotensin II
⬇ Mortality
ANP

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Acute heart failure pharmacology for the usmle step 1

Heart Failure

Acute

Nitroprusside:
• Inhibits complex IV in ETC
Furosemide ⬆ cGMP Ionotropy
• Use hydroxocobalamin,
CN toxicity nitrites, sodium thiosulfate
• “Skin discoloration, confusion,
lactic acidosis, AV O2 is
narrow.”
Epinephrine Dobutamine Isoproterenol Milrinone

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chronic heart failure pharmacology for the usmle step 1

Patient Patient
USMLE Significance Heart Failure USMLE Significance
Presentation Presentation

• Reduce renin • Spironolactone • AR antagonist

• β-blockers • Eplerenone • Ascites
• Decrease MVO2
• Amiloride/Triam • Gynecomastia
• -pril
• Cough Chronic • Neprilysin inhibitor
• Sacubitril
• ACE inhibitors • Face swelling = • Increases bradykinin
angioedema
• ⬆cGMP à arteriolar
• Teratogen
dilation
• Hydralazine
• -sartan Modulate RAAS to
• Reflex tachycardia
• ARB • Drug induced SLE
• Teratogen decrease mortality

Sacubitril
Beta-Blockers ACE inhibitors ARBs Spironolactone Hydralazine
(neprilysin)

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• A patient presents with nausea, vomiting and

confusion. She was noted to recently have
started on a medication for heart failure. Her
vitals are notable for bradycardia, and pre-mature
ventricular contractions. A side effect of which of
NBME Style the following medications may likely explain her
Question symptomatology?
• A. Aspirin
• B. Digoxin
• C. Spironolactone
• D. Metoprolol

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Key USMLE points:

Cardiac muscle has

Ca2+ induced Ca2+
release

Contractility is
proportional to how
much intracellular
Ca2+ is present

Increases
parasympathetic tone
of AV node à
bradycardia (rate
control).

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Anti Lipid Agents

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Anti-Lipid Agents for the USMLE

Pathology / Pathophysiology Class Effect or Big Picture

Decrease lipids à
decreases
atherosclerosis
Vignette USMLE Significance
• 70% of lumen Reduce synthesis
• Angina occluded Mechanism of Action Reduce reuptake & absorb
Alter gene transcription
• Leg pain • Claudication
• Chronic mesenteric
• Abd pain ischemia
Specific Names Statin, Cholestyramine,
Ezetimibe, Gemfibrozil,
• Bruit Alirocumab, Niacin

• Abd mass
• Cardiac procedure SE Hepatotoxicity, Myopathy,
Flushing
+ foot net-like rash

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Lipid Agents
LDL lowered by increased
Pharmacological Agent USMLE High Yields LDL-R ⬆ on hepatocyte:
• -statin
• Clathrin coated pits
• HMG CoA Reductase • vs. HMG CoA Synthase
inhibitors • ⬆ AST, ALT, CPK (fibrate) • PCSK9 inhibitors prevent
• Upregulation of LDL-R LDL receptor breakdown
(Alirocumab, Evolocumab)
• Cholestyramine
• Bile acid resins • Decreased reabsorption of
bile acids Less bile acid absorption
• Ezetimibe ➡ brush border ➡ liver upregulates LDL-R
inhibition choles & uses up its own
• NPCL1 receptor inhibitors cholesterol
• Acarbose in DM ➡ brush
border inhibition of glu
• Fibrɑtes
• ⬆ HDL (via transcriptxn)
• PPAR ɑ • Activation LPL
• Cholesterol gallstones
(inhibits 7ɑhydroxylase)

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Lipid Agents

Main Target Drug

• Statins
• Cholestyramine
⬇ LDL • Ezetimibe
• Niacin
• PCSK9 inhibitors

⬇ TAG • Fibrates

⬆ HDL • Niacin

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• A patient presents with acute pancreatitis. She

has a history of familial dyslipidemia. Her
triglycerides are ≥500 mg/dL and she has failed
fibrates. She was recently started on a
medication however was noted to have skin
NBME Style flushing and warmth after taking this pill. An
Question increase in which of the following substances
may be causing these symptoms?
• A. Prostaglandin
• B. Substance P
• C. Histamine
• D. Serotonin
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Question Take-Home Message

Organ System Question Type Content Specification

Cardiology Vitamin Side Effect Niacin

Paraphrase: Step Beyond:

• High lipid + pharmacological agent + • What medication may mitigate the flushing
flushing = high prostaglandin and skin warmth caused by niacin?
• Aspirin

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Fat soluble vitamins review

Vitamin Deficiency Excess

• Difficulty driving at night • Headache + Papilledema after

• Vitamin A
• Lack of epithelial cell turnover Acne treatment

• An immigrant child with bowed legs & ribcage • Increased osteoblast activity à
• Vitamin D abnormality (rickets) osteoclasts à decreases bony
• Kidney failure (⬇ 1 ɑ-hydroxylas) matrix

• Patient with hemolytic anemia + high LDH

• Vitamin E
• Neuropathy
• Fat soluble vitamins
deficiencies should be
• Baby born at home or exclusively breast fed à brain related to pancreas and SI
bleed pathologies (i.e. CF)
• Vitamin K
• Immature gut + liver
• Liver failure (⬆ PT / PTT)

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endocrinology

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Rapid Review Pharmacology

Endocrinology
• Diabetes Phar6acolog9

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Polyuria,
polydipsia,
weight loss

Na abnl,
Glucose abnl
Approach to urine osm

Diabetes for
the USMLE
Diabetes Diabetes
Insipidus Mellitus

Nephrogenic Central Type 2

(no response (response to Type 1 (DKA) (Metabolic
to DDAVP) DDAVP) Syndrome)

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• 27-year-old patient with insulin-dependent diabetes

mellitus has difficulty with compliance. He is found
unresponsive deep labored breathing. Which of the
following arterial blood gases taken in the Emergency
Department would be expected in this patient?

pH pCO2 HCO3 AG

NBME Style A ⬇ ⬆ ↔ ⬆
Question
B ⬇ ⬇ ⬇ ⬆

C ⬇ ⬆ ↔ ⬆

D ⬆ ↔ ⬇ ⬇
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Hyperosmolar
Diabetic Ketoacidosis
Hyperglycemic State
Type 1 Diabetics; younger Type 2 Diabetics; older
Insulin resistance à
Lymphocytic Infiltration
amyloid

Glucose ~300
HHS vs. DKA Hyperventilation Glucose >600-900
USMLE Step 1 Abdominal pain/nausea

Elevated AG Normal AG
Ketones +/-
Serum Ketones +
Less acidosis (HCO3 ~18-20)
Profound acidosis
Profound dehydration

IV Insulin + fluid resuscitation

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GLUT Receptor Review • Mutations in glucokinase as

a glucose sensor are
implicated in maturity onset
GLUT Agent Location diabetes of the young.

• GLUT-1 • RBC & BBB

Hexokinase Glucokinase
• GLUT-2 • Liver & β-pancreatic cell • Most tissues • Liver & β-cells
• Low Km • High Km
• GLUT-3 • Placenta • High affinity • Low affinity
• Maintaining • Conversion to
• Skeletal Muscle & intracellular glycogen;
• GLUT-4 Adipocyte glucose release of
• Responsive to insulin concentration insulin

• GLUT-5 • Fructose in sperm.

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Insulin HyGuru High-Yield

Secretagogues
• ⬆ Closure of KATP in β-cell
• Sulfonylureas • Hypoglycemia

Biguanides • Stimulates AMPK à ⬇ insulin resistance

• Metformin • Lactic acidosis (renal insufficiency)

Thiazolidinediones • ✅ PPAR ɣ à ⬇ insulin resistance

• -glitazone • Worsens CHF
Diabetes
Pharmacology GLP-1 agonists
• ⬆ insulin secretion, ⬇ gastric emptying
for the USMLE • Exenatide

DPP4 inhibitors
• ⬆ [GLP-1]
• Sitagliptin

ɑ glucosidase ➖ • % brush-border glu reabsorption

• Acarbose • Diarrhea

SGLT2 inhibitors • % PCT glu reabsorption

• -flozin • UTIs

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Increased GLP-1 activity increases endogenous insulin

More insulin
DDP-4 Inhibition ⬆ GLP-1 activity effect

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• A patient has uncontrolled diabetes. He is noted to have

HgbA1c of 10.1% & 10.5% at his prior two visits. He is controlled
on metformin and insulin. The patient realizes that the
diabetes is out of control, however states that he forgets to
take his medications as he overall feels well. What is the best
next response to address insulin compliance?

• A. You need to take your medications or you may suffer

NBME Style irreversible consequences.
Question
• B. Let’s discuss what you do not understand – remember
diabetes is a silent killer.

• C. I’m sorry it has been challenging to take your medications,

especially on days you feel well.

• D. Let’s refer you to our diabetes educator – she may have

some good tricks to help you lower your HgbA1c.

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Insulin
Rapid Acting
• Lispro 3
• Aspart
• Glulisine

Exogenous insulin:
Short Acting
• Regular Insulin ⬆ Insulin ⬇ C-peptide
• Use for DKA 6

NPH
• 12 hr duration 12
• BID

Long Acting
• Glargine 24
• Detemir
• Mimics pancreas

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hematology

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Rapid Review Pharmacology

Hematology
• Anti-Coagulants

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Hypercoagulable States

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“White woman with recurrent

clots”

Factor V Leiden
Hypercoaguable States

Mech: Point mutation (arg à glu)

that causes a factor 5 that cannot
be inactivated (i.e. resistant to
Protein C degradation)

“Lupus pt with recurrent

spontaneous abortions”

Anti-Cardiolipin
Mech: Ab to beta-2 glycoprotein,
high-yield: increased PTT but
hypercoagulable

Prothrombin G20210A Mutation that causes increased

mutation prothrombin production

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Factor V Leiden Pathophysiology

No inactivation of
Factor 5 & 8 are No Factor 5 clotting cascade
procoagulants Leiden à ⬆ thrombosis

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“Pt with clots that is

treated with Heparin
Hypercoaguable States

and has no PTT increase”

Antithrombin deficiency
Antithrombin normally
potentiated by Heparin
thus increasing PTT.

“Pt with necrotic skin

after Warfarin”
Protein C + S deficiency
Protein C and S are
natural anti-coag with
short half life

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Anti-Coagulation for the

USMLE

Direct factor Thrombolytic

Anti-platelet Heparin Warfarin
inhibitors Agents

Primary
Hemostasis Secondary
Hemostasis

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Primary hemostasis

Adhesion Activation Aggregation

Weak Platelet Plug

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Primary hemostasis

Aggregation
Aggregation

ASA
• Acetylation of
COX àinhibits
TXA2
Activation
Aspirin uncouples
ox-phos which can
Adhesion cause lactic
acidosis

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• A patient presents with a focal neurological deficit that

subsides within 40 minutes. Her head CT shows no acute
abnormalities. A TIA is diagnosed. She is started on a
medication which modulates the Arachidonic Acid
Pathway. Which of the following adverse effects is most
likely to occur?
NBME Style
Question • A. Gastrointestinal bleeding.

• B. Sexual dysfunction.

• C. Respiratory depression.

• D. Tinnitus and metabolic alkalosis.

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Question Take-Home Message

Organ System Question Type Content Specification

Pharmacological
Hematology Aspirin
Side Effect

Paraphrase: Step Beyond:

• Patient with TIA + ASA + side effect = GI • Aspirin overdose causes toxicity to which
bleeding. cranial nerve?
• Cranial never VIII à tinnitus

69

Primary hemostasis

Aggregation
Aggregation

ASA
• Acetylation of
COX àinhibits
TXA2
Activation

P2Y12 inhibitors
Adhesion • ADP receptor blockers
• Clopidogrel, Prasugrel,
Ticagrelor

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Clopidogrel is a non-competitive antagonist of ADP receptor

71

Primary hemostasis

Aggregation
Aggregation

ASA
• Acetylation of
COX àinhibits
TXA2
Activation

P2Y12 inhibitors
Adhesion • ADP receptor blockers
• Clopidogrel, Prasugrel,
Ticagrelor, Ticlodipine**

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Primary hemostasis

Aggregation
Aggregation

Cilostazol, Dipyridamole
Activation • PDE-3 Inhibitor
• ⬆ cAMP
• Decrease ADP action

Adhesion

Used in claudication;
ASA+DPY à TIA

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Primary hemostasis

Aggregation
Aggregation

Abciximab,
Eptifibatide, Tirofiban

Activation
Glanzmann
thrombasthenia mimics
this medication
Adhesion

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Anti-Coagulation for the

USMLE

Direct factor Thrombolytic

Anti-platelet Heparin Warfarin
inhibitors Agents

Primary
Hemostasis Secondary
Hemostasis

75

Treat & Prevent:

• ACS, Stroke, Anti-platelet
Claudication

• Bleeding
Activation • GI upset Aggregation
• Petechiae

Aspirin Clopidogrel Cilostazol Abciximab

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Anti-Coagulation for the

USMLE

Direct factor Thrombolytic

Anti-platelet Heparin Warfarin
inhibitors Agents

Primary
Hemostasis Secondary
Hemostasis

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USMLE Pharmacology
Heparin Warfarin
• Inhibits Vit K epoxide reductase à no gamma-
• Increases activity of anti-thrombin 3 à blocks
carboxylation of 2, 7, 9, 10, C, S à less active
thrombin à inhibits fibrin plug à blood thinning
clotting factors à blood thinning

• UFH: follow PTT

• LMWH: -parin, more Xa specific • Warfarin: follow PT/INR
• Fondaparinux: more Xa specific
• Acute bleeding: FFP (contains clotting factors) or
• Use Protamine for reversal
prothrombin complex concentrates
• Can also use prothrombin complex precipitate
• Long term: Vitamin K supplements

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• A 23 yo F recently started on an oral contraceptive pill. She is

noted to have leg swelling and is diagnosed with a deep vein
thrombosis four weeks after OCP initiation. Platelet count at
admission was normal. After initiating anti-coagulation
therapy, she is noted to have a decreased platelet count. Her
other cell lines are unaffected. Which of the following
NBME Style pathophysiologic mechanisms best explains this patient’s
Question thrombocytopenia?

• A. Decreased ADAMSTS13.

• B. Impaired vWF release from endothelial cells.

• C. Antibodies to gp 2b/3a.

• D. Anti-platelet factor 4/heparin antibodies.

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Heparin Induced thrombocytopenia

Thrombosis
Heparin + PF4 + OR
IgG Combine Activate Platelet Splenic M Φ eat
and cause
bleeding

Watch for trigger +

low Plt in labs

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Anti-Coagulation for the

USMLE

Direct factor Thrombolytic

Anti-platelet Heparin Warfarin
inhibitors Agents

Non-valvular
atrial-fibrillation + Direct
Factor Xa ➖
anti-coag Thrombin ➖

81

Factor Xa inhibitors
Direct
• Rivaroxaban
• Apixaban

Direct Thrombin Indirect

Inhibitors • Fondaparinux

Argatroban
Bivalirudin
Dabigatran

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Secondary Hemostasis Agents

Direct Xa inhibitors
Direct thrombin inhibitors
• Selective inhibition • Factor II antagonist
of Factor Xa

• Ease of
monitoring
• Idarucimab; aPCC
for reversal

83

Chemotherapeutics
immunologic Agents

84

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Rapid Review Pharmacology

Chemotherapeutics and immunologics

• Cell Cycle Agents
• Chemotherapeutic Agents & Toxicities
• Monoclonal Ab

85

Cell Cycle Agents

86

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Cells over-proliferate

USMLE Test • Increased cellular

Taking Strategy: burden on the
USMLE:
Mechanisms of • ⬆ K, ⬆ UA, ⬆
Cancer Phos, ⬇ Ca

Cells fail to undergo

apoptosis

87

Cell Cycle physiology

M Phase inhibitors
• Vinchristine, Vinblastine
• Paclitaxel

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M – phase inhibitors

Vincristine
• Prevent microtubule Paclitaxel
assembly.
• Prevent microtubule
• Prevent mitotic disassembly.
spindle formation.
• Spindle cannot
• Inhibits
break down in
metaphase phase anaphase.
• Neurotoxic à • Myelosupression.
peripheral neuritis,
areflexia.

89

Microtubule Medication High Yield USMLE points

Mebendazole • Anti-helminthic • Watch for

eosinophilia à
helminth infection
Griseofulvin • Anti-fungal

Colchicine • Used for gout and pericarditis

Chemotherapeutic: Bind Tubulin and inhibit

Vincristine
•
its polymerization into microtubules,
Vinblastine •
preventing mitotic spindle formation
(M-phase arrest)

• Chemotherapeutic: Hyper-stabilizes
polymerized microtubules in M phase so that
Paclitaxel mitotic spindle cannot breakdown
• (A-phase arrest)

90

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Cell Cycle physiology

G1 Inhibitors
• Cisplatin, Busulfan,
Cyclophosphamide,
Carmustine

M Phase inhibitors
• Vinchristine, Vinblastine
• Paclitaxel

91

g1 inhibitors cross link dna

Cisplatin

Busulfan
Cross Link DNA
• Cyclophosphamide:
Cyclophosphamide
• N7-guanine

Carmustine

92

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• A 59 yo F was diagnosed with breast cancer one month

ago. She was started on systemic chemotherapy. She
presents with dysuria, and gross hematuria. Exam is
notable for suprapubic tenderness. CPK is normal.
Patient is found to be anemic. There is no UTI. Which of

NBME Style the following pre-treatments may have benefitted this

Question patient?

• A. Oxybutynin

• B. Aspirin

• C. Mesna

• D. Folinic Acid

93

hemorrhagic cystitis
Give hydration &
mesna – sulfahydryl
group donor

Cyclophosphamide Toxic metabolite Hemorrhagic

Ifosphamide Acrolein cystitis

94

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Review of G1 inhibitors

Cisplatin Busulfan Cyclophosphamide Carmustine

• Cross link DNA • Cross link DNA • Cross link DNA • Cross link DNA

• Grossly bloody
• Abnormal Rinne
• ⬇ TLC – fibrosis urine • CNS Toxicity
• ⬆ Cr
• SIADH

95

Cell Cycle physiology

G1 Inhibitors
• Cisplatin, Busulfan,
Cyclophosphamide, Carmustine

S Phase • Cytarabine
Inhibitors • 6-MP
• AZT • 5-FU
• MTX • HU
• Cladribine

M Phase inhibitors
• Vinchristine, Vinblastine
• Paclitaxel

96

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Azathioprine is converted to 6-mp

AZT
Decreased IMP, a
6-MP purine analog

XO decreases levels of
6-MP; Allopurinol
inhibits XO à ⬆ 6-MP

97

• AZT is used in:

• ALL
• CML

• Causes Bone Marrow Suppression

USMLE Test à Immunosuppressed State
Taking Strategy • Reactivation of HSV & Hep B
• MRSA & Pseudomonas

• Fever + Neutropenia = badness

• Use broad-spectrum abx!

98

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Cell Cycle physiology

G1 Inhibitors
• Cisplatin, Busulfan,
Cyclophosphamide, Carmustine

S Phase • Cytarabine
Inhibitors • MTX
• AZT • 5-FU
• 6-MP • HU
• Cladribine

M Phase inhibitors
• Vinchristine, Vinblastine
• Paclitaxel

99

Hairy Cell Leukemia

• Cladribine

• Purine Analog
• Use for Hairy Cell
Leukemia

100

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Cladribine is to Purines as cytarabine is to pyrimidines

• Cytarabine

Anytime you inhibit

DNA synthesis, B12,
• Bone marrow folate à think BM
suppression
suppression

101

Cell Cycle physiology

G1 Inhibitors
• Cisplatin, Busulfan,
Cyclophosphamide, Carmustine

S Phase • Cytarabine
Inhibitors • MTX
• AZT • 5-FU
• 6-MP • HU
• Cladribine

M Phase inhibitors
• Vinchristine, Vinblastine
• Paclitaxel

102

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• Two (X and Y) chemo drugs decrease thymidylate

formation. Drug X inhibits DHFR and the toxicity can be
overcome by N5-formyl THF supplementation. Drug Y has
increased BM suppression with N5-formyl THF
NBME Style supplementation. What are the likely agents?
Question Drug X Drug Y
QID: 1892
MTX and 5 A • Cladribine • Cytarabine
FU
B • 5-FU • MTX

C • MTX • 5-FU

103

Methotrexate & 5-fu has different effects with LEUKOVORIN

Toxicity of both agents

is BM suppression

DHFR & More folate N5

Thymidylate • MTX # DHFR THF improves
Synthase • 5-FU # MTX toxicity
Thymidylate but increases 5-
use folate ➡ Synthase
PURINES FU toxicity

104

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Question Take-Home Message

Organ System Question Type Content Specification

Hematology Experimental MTX vs. 5-FU Purine Synthesis

Paraphrase: Step Beyond:

Drug X = amendable to folic acid What is another DHFR inhibitor?
rescue + Drug Y = increased toxicity • TMP-SMX
with folic acid. Drugs?

105

Nucleoside Synthesis
HMP Shunt Pathway

Ribose-5-PO4 becomes Carbamoyl Phosphate

PRPP

PRPP

IMP becomes OMPà UMP

AMP & GMP
IMP OMP àUDPàCTP

UDP to dUDP à
inhibited by RNR

Purines Pyrimidine

Purine you start with Sugar & add Base – Pyrimidine you start with Base & add Sugar

106

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Monoclonal Ab

107

HER 2 neu
umab Trastuzumab Breast CA
Get echo prior

Cetuximab EGFR ➡ K-ras inhib

ximab
mAb CD 20 &
Rituximab Complement ✅
ADCC ✅; PML

VEG-F
Bevacizumab
Macular degen

zumab

CD52 &➡
Alemtuzumab
lymphocytes die

108

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Renal

109

Rapid Review Pharmacology

Renal
• Diuretics

110

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• A kidney embryologist is examining renal development.

He notes a gene, GDNF, when mutated inhibits the
metanephric blastema from forming. Which of the
following renal structures will most likely be affected with
this mutation?

NBME Style • A. Major calyces

Question
• B. Collecting Duct

• C. Ureteric bud

• D. Glomerulus

111

Kidney Metanephros Ureteric Bud

Embryology
• Glomeruli & Bowman’s Space • Collecting Duct

Interaction of
• Proximal convoluted Tubule • Major & minor renal
metanephric
diverticulum (ureteric & LoH calyces
bud) + metanephric
blastema à mature
kidney • Distal Convoluted Tubule • Renal pelvis ureters

112

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Key Features of the Nephron for the USMLE

Proximal Convoluted Tubule:

• Reabsorbs majority of water no matter hydration
status
• Highly metabolically active (trigger + ⬆ Cr)
• Reabsorbs majority of Na, K and solutes
• PCT dysfunction is Fanconi (think FTT)
• Glutamine à releases NH3

Descending Loop of Henle

• Permeable to Water

113

Key Features of the Nephron for the USMLE

Ascending Loop of Henle

• Impermeable to water à Corticomedullary
gradient determined by Na/K/2Cl transporter

Distal Convoluted Tubule

• PTH controls Ca2+ from the DCT
• Lowest osmolarity of entire nephron

114

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• A patient is noted to be found in the desert. She notes

that she has been deprived of water for the whole day.
Assuming normal physiology, which of the following
areas of the nephron would have the highest osmolarity
in this patient?

NBME Style A C

Question

D
B

115

Question Take-Home Message

Organ System Question Type Content Specification

Renal Normal Physiology Dehydration

Paraphrase: Step Beyond:

Dehydration + which area will be The collecting duct is acted on by ADH.
most concentrated = collecting What is the GPCR by which ADH acts?
duct • V2 à Gz

116

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Key Features of the Nephron for the USMLE

Collecting Duct
• Aldosterone effect
• ADH effect

117

renal pharmacology
Medication MOA USMLE Points
• Carbonic Anhydrase • Decreases CSF and
• Acetazolamide Inhibition à HCO3 Aq humor
peed out • Alk urine ; acid blood
• Furosemide, • Na-K-2Cl à • Increases PGE à
Torsemide, diminishes afferent arteriole
Bumetanide, hypertonic • Loops lose Ca
Ethacrynic acid medullary gradient • Decreases preload
• Causes:
• HCTZ, Metolazone • Na/Cl co transporter
• Hyper G L U C
• Spironolactone
• Aldosterone • Hyper K
• Eplerenone
antagonist • Hyper H
• Amiloride

118

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⬆ K+

Inhibits RAAS

§ Aldosterone:
§ Brings in Na
§ Makes you pee
out K & H+

119

Pharmacology Compare and Contrast

Loop Diuretics
• Furosemide, Thiazide Diureitcs
torsemide, • HCTZ, chlorthalidone,
bumetanide. § Contraction metozalone.
Alkalosis
• Loops lose Ca • Hypercalcemia
(hypocalcemia) (hypocalcuric)
• Interstitial nephritis • Worsens Gout
• Worsens Gout

120

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• A student has just completed Rahul’s USMLE Step 1

Pharmacology course. The student really is tired of all of
these NBME questions and has to pee. To dull the pain of
these questions the student takes NSAIDs. Assuming
normal kidney function, which of the following changes is

NBME Style most likely going to be seen with NSAID use?

Question Afferent [PG] GFR FeNa

⬇ ⬆ ⬇
⬆ ⬆ ⬆

⬇ ⬇ ⬇
121

You are also a…

Prepared student!

122

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