Amboss Cardiovascular USMLE Step 1 | Complete Practice Questions & Verified Answers
Decreased production of cyclic guanosine Cyclic guanosine monophosphate (cGMP) is a compound that mediates the
monophosphate vasodilatory effects of ACE inhibitor therapy by acting on myosin-light-chain
phosphatase to dephosphorylate myosin, which leads to vascular smooth muscle
cell relaxation. ACE inhibitor therapy increases, not decreases, the production of
cGMP.
Atorvastatin is a type of statin, or HMG-CoA reductase inhibitor, used to treat
hypercholesterolemia. It inhibits cholesterol synthesis in the liver. Although
atorvastatin would have interactions with other lipid-lowering agents and
CYP3A4 inhibitors, it has no significant interactions with antihypertensives like
lisinopril.
Procaine Procaine is an ester-type local anesthetic that can be used for minor surgical
procedures and spinal anesthesia. It has not been proven effective in managing
extravasation caused by vasopressor agents.
Phentolamine The ischemic tissue damage in this patient is caused by persistent
vasoconstriction due to activation of α1 receptors by the extravasated pressor
agent, which increases arteriolar smooth muscle IP3. As a short-acting,
nonselective α-antagonist, phentolamine counteracts the α1 receptor-mediated
vasoconstriction, improving blood flow to the damaged area and preventing
further tissue loss. Terbutaline and topical nitroglycerin ointment may also be
considered in cases of pressor extravasation.
Tamsulosin Tamsulosin is an α1-antagonist that is most commonly used for the treatment of
BPH. Tamsulosin acts selectively on α1A receptors in the prostate gland and has
only minimal effect on peripheral vasomotor tone.
Conivaptan Conivaptan acts as an ADH inhibitor and is used in the treatment of SIADH. It
has not been proven effective in managing extravasation caused by vasopressor
agents.
Heparin Heparin is most commonly used for the treatment of thrombosis or embolic
disease, which could also manifest with a cool, pale extremity. However, signs of
ischemia restricted to the antecubital fossa, as seen in this patient, are more
suggestive of ischemia due to vasopressor extravasation, in which case heparin
would not be effective.
Midodrine Midodrine is an α1 agonist that promotes vasoconstriction and is used for
autonomic insufficiency and orthostatic hypotension. It would only worsen the
symptoms of vasopressor extravasation in this patient.
Inhibition of funny channels Ivabradine is a drug that inhibits the funny current responsible for cardiac
pacemaker activity and thus reduces heart rate. While this medication is
prescribed as a second-line agent for symptomatic treatment of patients with
heart failure, ivabradine overdose would likely cause profound bradycardia
Inhibition of Na+-K+-2Cl--cotransporters Loop diuretics (e.g., furosemide) are drugs that inhibit Na+-K+-2Cl-
cotransporters in the thick ascending loop of Henle within nephrons. This leads to
increased production of urine and a subsequent reduction of blood volume and
cardiac preload. While this medication is commonly prescribed to patients with
heart failure, loop diuretic overdose would likely cause hypotension,
hyponatremia, hypokalemia, hypocalcemia, and metabolic alkalosis
Blockade of aldosterone receptors Aldosterone receptor antagonists (e.g., spironolactone, eplerenone)
competitively inhibit aldosterone receptors in the distal tubule and collecting duct
of nephrons. This leads to decreased Na+ reabsorption and K+ excretion,
subsequently causing diuresis. While potassium-sparing diuretics such as
aldosterone receptor antagonists are commonly prescribed to patients with heart
failure and can cause hyperkalemia, an overdose would likely cause
hypotension, hyponatremia, and metabolic acidosis
Inhibition of Na+/K+-ATPase Cardiac glycosides are drugs that inhibit Na+/K+-ATPases, and digoxin is the
only drug of this class commonly used clinically as a positive inotrope in heart
failure. Digoxin has a narrow therapeutic index, and this patient exhibits
symptoms and laboratory findings consistent with digoxin poisoning. Given his
recent life stressors (job loss, financial worries), the possibility that this patient
overdosed on his prescribed digoxin to attempt suicide should be considered.
,Amboss Cardiovascular USMLE Step 1 | Complete Practice Questions & Verified Answers
Blockade of beta-adrenergic receptors Beta blockers (e.g., metoprolol) are drugs that inhibit sympathetic activation of
beta-adrenergic receptors. They reduce blood pressure by decreasing heart rate,
reducing contractility, and causing peripheral vasoconstriction. While beta
blockers are commonly prescribed to patients with heart failure and can cause
hyperkalemia at high doses, overdose would likely cause hypotension,
bradycardia, bronchospasm, and hypoglycemia
Inhibition of angiotensin-converting enzyme ACE inhibitors (e.g., enalapril) reduce the conversion of angiotensin I to
angiotensin II and thereby reduce blood pressure as well as cardiac preload and
afterload. While this medication is commonly prescribed to patients with heart
failure, ACE inhibitor overdose would likely cause severe hypotension
Blockade of Na+ channels Epithelial sodium channel blockers (e.g., triamterene and amiloride) directly
inhibit epithelial Na+ channels in the distal tubule and collecting duct of
nephrons. This decreases Na+ reabsorption and K+ excretion, which causes
diuresis. Though potassium-sparing diuretics such as epithelial sodium channel
blockers are commonly prescribed to patients with heart failure and can cause
hyperkalemia, an overdose would likely cause hypotension, hyponatremia, and
metabolic acidosis
Inhibition of myocardial Na+/K+ ATPase The primary action of digoxin, inhibition of myocardial Na+/K+ ATPase, results in
a higher intracellular Na+ concentration and reduced efficacy of Na+/Ca2+
exchangers, which leads to higher intracellular Ca2+ concentration and,
subsequently, increased cardiac inotropy.
Inhibition of AV node L-type Ca2+ channels Calcium channel blockers act via the inhibition of AV nodal L-type Ca2+ channels
and can cause PR interval prolongation.
Increase in vagal tone Digoxin indirectly increases vagal tone via inhibition of neuronal Na+/K+ ATPase,
causing a negative chronotropic effect that leads to a PR interval prolongation as
seen in this patient's ECG. This indirect effect on vagal tone can lead to
bradyarrhythmia and increase the risk of AV block. Cardiac glycosides have a
narrow therapeutic index and require close monitoring of serum concentrations.
Hypokalemia increases the risk of digoxin toxicity by enhancing its affinity for
Na+/K+ ATPase. Other ECG findings seen with digoxin use include premature
ventricular beats, T-wave inversion or flattening, downsloping ST-segment
depression, and a decrease in the QT interval.
Activation of Na+/Ca2+ exchanger Digoxin inhibits Na+/K+ ATPase in cardiomyocytes, which then indirectly inhibit,
rather than activate, the activity of Na+/Ca2+ exchangers. This inhibitory effect
leads to higher intracellular Ca2+ concentrations and an increase in cardiac
contractility.
Decrease in intracellular cAMP Beta blockers inhibit the sympathetic activation of β-adrenergic receptors leading
to PR interval prolongation, bradycardia, and decreased cardiac contractility.
Inactivation of potassium channels Inactivation of potassium channels is the mechanism of action of class III
antiarrhythmic drugs such as amiodarone. Side effects of this drug class include
cardiovascular depression, including bradycardia, heart block, and hypotension.
Inactivation of sodium channels Local anesthetics (e.g., bupivacaine) bind to voltage-gated sodium channels of
the nerve fibers and block them, which leads to an inhibition of nerve excitation
and impulse conduction (pain signals). When absorbed systemically, bupivacaine
also acts as a class IB antiarrhythmic drug and can cause hypotension and
bradycardia, as seen in this patient. Ventricular arrhythmias and asystole may
also occur. Of the commonly used local anesthetics, bupivacaine is most likely to
result in cardiovascular toxicity, because of its high potency and long duration of
action.
Activation of acetylcholine receptors Activation of acetylcholine receptors is the mechanism of action of depolarizing
agents such as succinylcholine. Side effects include hypercalcemia,
hyperkalemia, and malignant hyperthermia, which may lead to hypotension and
bradycardia. However, succinylcholine is used for the induction of anesthesia,
not for a brachial plexus block.`
, Amboss Cardiovascular USMLE Step 1 | Complete Practice Questions & Verified Answers
Inactivation of ryanodine receptors Inactivation of ryanodine receptors is the mechanism of action of muscle
relaxants like dantrolene. Side effects of dantrolene include CNS depression, and
infrequently, AV block or tachycardia. However, dantrolene is not an anesthetic
drug used for brachial plexus block but rather can be used to treat toxicity
associated with inhaled anesthetics (e.g., malignant hyperthermia).
Activation of GABA receptors Activation of GABA receptors is the mechanism of action of benzodiazepines
(e.g., midazolam) and barbiturates (e.g., phenobarbital), some of which may be
used for general anesthesia or sedation. Side effects may include CNS and
cardiovascular depression, including bradycardia and hypotension. However,
GABA receptor activation cannot be used to achieve brachial plexus block.
Pulsating headaches Headaches are a common side effect of nitrates and affect approx. 10% of
patients. These headaches are either mild-to-moderate and occur immediately
after drug administration (due to nitric oxide-induced vasodilation) or migraine-
like, occurring several hours after drug intake (due to nitric oxide-mediated
release of neurotransmitters such as calcitonin gene-related peptide and
glutamate, and/or altered ion channel function). Nitrate-induced vasodilation
decreases both preload and afterload and improves myocardial perfusion, but
may also result in cutaneous flushing and hypotension.
Digital vasospasm Digital vasospasm (secondary Raynaud phenomenon) is a potential side effect of
beta blockers. This side effect is mediated by the blockade of beta blockers on
β2-receptors, which causes vasoconstriction.
Hypertensive urgency Nitrates can cause hypotension, rather than hypertensive urgency. Nitrates are
used to treat hypertensive crisis for short-term reduction of blood pressure and
are contraindicated in hypotensive patients.
Nonproductive cough Nonproductive cough is a side effect of ACE inhibitors. This side effect is due to
decreased breakdown of bradykinin, which increases production of arachidonic
acid metabolites (e.g., prostaglandins). The accumulation of prostaglandins in the
upper respiratory tract and the lungs results in nonproductive cough.
Lupus-like syndrome Lupus-like syndrome (drug-induced lupus erythematosus/DILE) is a side effect of
antihypertensives, such as hydralazine and methyldopa. Other drugs that can
lead to DILE include monoclonal TNF-α inhibitors, such as infliximab or
etanercept, procainamide, penicillamine, isoniazid, minocycline, and phenytoin.
Lower extremity edema Lower extremity edema is a common side effect of dihydropyridine calcium
channel blockers (CCBs), particularly amlodipine. CCBs cause vasodilation,
which increases the hydrostatic pressure within the blood vessels, causing
extravasation of plasma into the interstitial space. Although nitrates can rarely
cause lower extremity edema, it is not the most common side effect associated
with this drug class.
Erectile dysfunction Erectile dysfunction is a known side effect of beta blockers, which effect β2-
receptors in the vasculature. Patients taking PDE-5 inhibitors for erectile
dysfunction have an increased risk of life-threatening hypotension if nitrates are
taken within 24 hours of a PDE-5 inhibitor.
Coronary artery vasospasm Coronary artery vasospasm is the underlying mechanism of Prinzmetal angina.
Episodes of Prinzmetal angina typically occur at rest (in contrast to exertional
angina) and common triggers include stress, smoking, alcohol, drugs (e.g.,
cocaine), and triptan use. The transient appearance of anterior ST-segment
elevations (as opposed to depressions) and spontaneous resolution of symptoms
in the setting of recent alcohol use and stress support this diagnosis.
Pulmonary artery occlusion Patients with pulmonary artery occlusion due to pulmonary embolism typically
present with pleuritic chest pain, rather than the substernal pain reported here.
The absence of dyspnea and prominent risk factors for PE (e.g., recent surgery,
immobility, hypercoagulable state) in this patient also make pulmonary artery
occlusion an unlikely cause of his symptoms. Moreover, ECG findings are usually
normal or suggestive of right heart strain (e.g., right bundle branch block, right
axis deviation).
Decreased production of cyclic guanosine Cyclic guanosine monophosphate (cGMP) is a compound that mediates the
monophosphate vasodilatory effects of ACE inhibitor therapy by acting on myosin-light-chain
phosphatase to dephosphorylate myosin, which leads to vascular smooth muscle
cell relaxation. ACE inhibitor therapy increases, not decreases, the production of
cGMP.
Atorvastatin is a type of statin, or HMG-CoA reductase inhibitor, used to treat
hypercholesterolemia. It inhibits cholesterol synthesis in the liver. Although
atorvastatin would have interactions with other lipid-lowering agents and
CYP3A4 inhibitors, it has no significant interactions with antihypertensives like
lisinopril.
Procaine Procaine is an ester-type local anesthetic that can be used for minor surgical
procedures and spinal anesthesia. It has not been proven effective in managing
extravasation caused by vasopressor agents.
Phentolamine The ischemic tissue damage in this patient is caused by persistent
vasoconstriction due to activation of α1 receptors by the extravasated pressor
agent, which increases arteriolar smooth muscle IP3. As a short-acting,
nonselective α-antagonist, phentolamine counteracts the α1 receptor-mediated
vasoconstriction, improving blood flow to the damaged area and preventing
further tissue loss. Terbutaline and topical nitroglycerin ointment may also be
considered in cases of pressor extravasation.
Tamsulosin Tamsulosin is an α1-antagonist that is most commonly used for the treatment of
BPH. Tamsulosin acts selectively on α1A receptors in the prostate gland and has
only minimal effect on peripheral vasomotor tone.
Conivaptan Conivaptan acts as an ADH inhibitor and is used in the treatment of SIADH. It
has not been proven effective in managing extravasation caused by vasopressor
agents.
Heparin Heparin is most commonly used for the treatment of thrombosis or embolic
disease, which could also manifest with a cool, pale extremity. However, signs of
ischemia restricted to the antecubital fossa, as seen in this patient, are more
suggestive of ischemia due to vasopressor extravasation, in which case heparin
would not be effective.
Midodrine Midodrine is an α1 agonist that promotes vasoconstriction and is used for
autonomic insufficiency and orthostatic hypotension. It would only worsen the
symptoms of vasopressor extravasation in this patient.
Inhibition of funny channels Ivabradine is a drug that inhibits the funny current responsible for cardiac
pacemaker activity and thus reduces heart rate. While this medication is
prescribed as a second-line agent for symptomatic treatment of patients with
heart failure, ivabradine overdose would likely cause profound bradycardia
Inhibition of Na+-K+-2Cl--cotransporters Loop diuretics (e.g., furosemide) are drugs that inhibit Na+-K+-2Cl-
cotransporters in the thick ascending loop of Henle within nephrons. This leads to
increased production of urine and a subsequent reduction of blood volume and
cardiac preload. While this medication is commonly prescribed to patients with
heart failure, loop diuretic overdose would likely cause hypotension,
hyponatremia, hypokalemia, hypocalcemia, and metabolic alkalosis
Blockade of aldosterone receptors Aldosterone receptor antagonists (e.g., spironolactone, eplerenone)
competitively inhibit aldosterone receptors in the distal tubule and collecting duct
of nephrons. This leads to decreased Na+ reabsorption and K+ excretion,
subsequently causing diuresis. While potassium-sparing diuretics such as
aldosterone receptor antagonists are commonly prescribed to patients with heart
failure and can cause hyperkalemia, an overdose would likely cause
hypotension, hyponatremia, and metabolic acidosis
Inhibition of Na+/K+-ATPase Cardiac glycosides are drugs that inhibit Na+/K+-ATPases, and digoxin is the
only drug of this class commonly used clinically as a positive inotrope in heart
failure. Digoxin has a narrow therapeutic index, and this patient exhibits
symptoms and laboratory findings consistent with digoxin poisoning. Given his
recent life stressors (job loss, financial worries), the possibility that this patient
overdosed on his prescribed digoxin to attempt suicide should be considered.
,Amboss Cardiovascular USMLE Step 1 | Complete Practice Questions & Verified Answers
Blockade of beta-adrenergic receptors Beta blockers (e.g., metoprolol) are drugs that inhibit sympathetic activation of
beta-adrenergic receptors. They reduce blood pressure by decreasing heart rate,
reducing contractility, and causing peripheral vasoconstriction. While beta
blockers are commonly prescribed to patients with heart failure and can cause
hyperkalemia at high doses, overdose would likely cause hypotension,
bradycardia, bronchospasm, and hypoglycemia
Inhibition of angiotensin-converting enzyme ACE inhibitors (e.g., enalapril) reduce the conversion of angiotensin I to
angiotensin II and thereby reduce blood pressure as well as cardiac preload and
afterload. While this medication is commonly prescribed to patients with heart
failure, ACE inhibitor overdose would likely cause severe hypotension
Blockade of Na+ channels Epithelial sodium channel blockers (e.g., triamterene and amiloride) directly
inhibit epithelial Na+ channels in the distal tubule and collecting duct of
nephrons. This decreases Na+ reabsorption and K+ excretion, which causes
diuresis. Though potassium-sparing diuretics such as epithelial sodium channel
blockers are commonly prescribed to patients with heart failure and can cause
hyperkalemia, an overdose would likely cause hypotension, hyponatremia, and
metabolic acidosis
Inhibition of myocardial Na+/K+ ATPase The primary action of digoxin, inhibition of myocardial Na+/K+ ATPase, results in
a higher intracellular Na+ concentration and reduced efficacy of Na+/Ca2+
exchangers, which leads to higher intracellular Ca2+ concentration and,
subsequently, increased cardiac inotropy.
Inhibition of AV node L-type Ca2+ channels Calcium channel blockers act via the inhibition of AV nodal L-type Ca2+ channels
and can cause PR interval prolongation.
Increase in vagal tone Digoxin indirectly increases vagal tone via inhibition of neuronal Na+/K+ ATPase,
causing a negative chronotropic effect that leads to a PR interval prolongation as
seen in this patient's ECG. This indirect effect on vagal tone can lead to
bradyarrhythmia and increase the risk of AV block. Cardiac glycosides have a
narrow therapeutic index and require close monitoring of serum concentrations.
Hypokalemia increases the risk of digoxin toxicity by enhancing its affinity for
Na+/K+ ATPase. Other ECG findings seen with digoxin use include premature
ventricular beats, T-wave inversion or flattening, downsloping ST-segment
depression, and a decrease in the QT interval.
Activation of Na+/Ca2+ exchanger Digoxin inhibits Na+/K+ ATPase in cardiomyocytes, which then indirectly inhibit,
rather than activate, the activity of Na+/Ca2+ exchangers. This inhibitory effect
leads to higher intracellular Ca2+ concentrations and an increase in cardiac
contractility.
Decrease in intracellular cAMP Beta blockers inhibit the sympathetic activation of β-adrenergic receptors leading
to PR interval prolongation, bradycardia, and decreased cardiac contractility.
Inactivation of potassium channels Inactivation of potassium channels is the mechanism of action of class III
antiarrhythmic drugs such as amiodarone. Side effects of this drug class include
cardiovascular depression, including bradycardia, heart block, and hypotension.
Inactivation of sodium channels Local anesthetics (e.g., bupivacaine) bind to voltage-gated sodium channels of
the nerve fibers and block them, which leads to an inhibition of nerve excitation
and impulse conduction (pain signals). When absorbed systemically, bupivacaine
also acts as a class IB antiarrhythmic drug and can cause hypotension and
bradycardia, as seen in this patient. Ventricular arrhythmias and asystole may
also occur. Of the commonly used local anesthetics, bupivacaine is most likely to
result in cardiovascular toxicity, because of its high potency and long duration of
action.
Activation of acetylcholine receptors Activation of acetylcholine receptors is the mechanism of action of depolarizing
agents such as succinylcholine. Side effects include hypercalcemia,
hyperkalemia, and malignant hyperthermia, which may lead to hypotension and
bradycardia. However, succinylcholine is used for the induction of anesthesia,
not for a brachial plexus block.`
, Amboss Cardiovascular USMLE Step 1 | Complete Practice Questions & Verified Answers
Inactivation of ryanodine receptors Inactivation of ryanodine receptors is the mechanism of action of muscle
relaxants like dantrolene. Side effects of dantrolene include CNS depression, and
infrequently, AV block or tachycardia. However, dantrolene is not an anesthetic
drug used for brachial plexus block but rather can be used to treat toxicity
associated with inhaled anesthetics (e.g., malignant hyperthermia).
Activation of GABA receptors Activation of GABA receptors is the mechanism of action of benzodiazepines
(e.g., midazolam) and barbiturates (e.g., phenobarbital), some of which may be
used for general anesthesia or sedation. Side effects may include CNS and
cardiovascular depression, including bradycardia and hypotension. However,
GABA receptor activation cannot be used to achieve brachial plexus block.
Pulsating headaches Headaches are a common side effect of nitrates and affect approx. 10% of
patients. These headaches are either mild-to-moderate and occur immediately
after drug administration (due to nitric oxide-induced vasodilation) or migraine-
like, occurring several hours after drug intake (due to nitric oxide-mediated
release of neurotransmitters such as calcitonin gene-related peptide and
glutamate, and/or altered ion channel function). Nitrate-induced vasodilation
decreases both preload and afterload and improves myocardial perfusion, but
may also result in cutaneous flushing and hypotension.
Digital vasospasm Digital vasospasm (secondary Raynaud phenomenon) is a potential side effect of
beta blockers. This side effect is mediated by the blockade of beta blockers on
β2-receptors, which causes vasoconstriction.
Hypertensive urgency Nitrates can cause hypotension, rather than hypertensive urgency. Nitrates are
used to treat hypertensive crisis for short-term reduction of blood pressure and
are contraindicated in hypotensive patients.
Nonproductive cough Nonproductive cough is a side effect of ACE inhibitors. This side effect is due to
decreased breakdown of bradykinin, which increases production of arachidonic
acid metabolites (e.g., prostaglandins). The accumulation of prostaglandins in the
upper respiratory tract and the lungs results in nonproductive cough.
Lupus-like syndrome Lupus-like syndrome (drug-induced lupus erythematosus/DILE) is a side effect of
antihypertensives, such as hydralazine and methyldopa. Other drugs that can
lead to DILE include monoclonal TNF-α inhibitors, such as infliximab or
etanercept, procainamide, penicillamine, isoniazid, minocycline, and phenytoin.
Lower extremity edema Lower extremity edema is a common side effect of dihydropyridine calcium
channel blockers (CCBs), particularly amlodipine. CCBs cause vasodilation,
which increases the hydrostatic pressure within the blood vessels, causing
extravasation of plasma into the interstitial space. Although nitrates can rarely
cause lower extremity edema, it is not the most common side effect associated
with this drug class.
Erectile dysfunction Erectile dysfunction is a known side effect of beta blockers, which effect β2-
receptors in the vasculature. Patients taking PDE-5 inhibitors for erectile
dysfunction have an increased risk of life-threatening hypotension if nitrates are
taken within 24 hours of a PDE-5 inhibitor.
Coronary artery vasospasm Coronary artery vasospasm is the underlying mechanism of Prinzmetal angina.
Episodes of Prinzmetal angina typically occur at rest (in contrast to exertional
angina) and common triggers include stress, smoking, alcohol, drugs (e.g.,
cocaine), and triptan use. The transient appearance of anterior ST-segment
elevations (as opposed to depressions) and spontaneous resolution of symptoms
in the setting of recent alcohol use and stress support this diagnosis.
Pulmonary artery occlusion Patients with pulmonary artery occlusion due to pulmonary embolism typically
present with pleuritic chest pain, rather than the substernal pain reported here.
The absence of dyspnea and prominent risk factors for PE (e.g., recent surgery,
immobility, hypercoagulable state) in this patient also make pulmonary artery
occlusion an unlikely cause of his symptoms. Moreover, ECG findings are usually
normal or suggestive of right heart strain (e.g., right bundle branch block, right
axis deviation).
