Cardiology Pharmacology
ReviewDhiren Patel, PharmD, CDE
Assistant Professor of Pharmacy PracticeMassachusetts College of Pharmacy and Health
Sciences - Boston
Clinical Pharmacy Specialist / Certified Diabetes Educator
VA Boston Healthcare System
E-mail: [email protected]
Patient CasePatient Case A 50 yo man with diabetes receives the results of a A 50 yo man with diabetes receives the results of a
FLP that reveals hypercholesterolemia. His FLP that reveals hypercholesterolemia. His physician recommends lifestyle changes and physician recommends lifestyle changes and initiates therapy with a statin. Which of the initiates therapy with a statin. Which of the following mechanisms describes the action of following mechanisms describes the action of statins in reducing serum levels of LDL cholesterol?statins in reducing serum levels of LDL cholesterol?
A.A. Inactivation of 3-hydroxy-3-methlyglutaryl Inactivation of 3-hydroxy-3-methlyglutaryl coenzyme A synthasecoenzyme A synthase
B.B. Competitive inhibition of 3-hydroxy-3-Competitive inhibition of 3-hydroxy-3-methlyglutaryl coenzyme A reductasemethlyglutaryl coenzyme A reductase
C.C. Positive feedback to increase 3-hydroxy-3-Positive feedback to increase 3-hydroxy-3-methlyglutaryl coenzyme A lyase activitymethlyglutaryl coenzyme A lyase activity
HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitors
Drug (Trade Name)
Atorvastatin (Lipitor)
Fluvastatin (Lescol)
Lovastatin (Mevacor)
Pravastatin (Pravachol)
Rosuvastatin (Crestor)
Simvastatin (Zocor)
Board worthy!Board worthy! MOA: MOA:
Inhibits HMG-CoA Inhibits HMG-CoA reductase, reductase, which prevents which prevents the conversion to the conversion to mevalonate preventing mevalonate preventing cholesterol synthesischolesterol synthesis
Adverse effects:Adverse effects: Hepatotoxicity, myalgias, Hepatotoxicity, myalgias,
myopathymyopathy, rhabdomyolysis , rhabdomyolysis Special Considerations:Special Considerations:
New patients can’t be New patients can’t be started on simvastatin 80mgstarted on simvastatin 80mg
Do not combine with fibrates Do not combine with fibrates
Clinical Pearls for Clinical Pearls for RotationsRotations Clinical uses:Clinical uses:
Dyslipidemia, s/p MI, diabetic patientsDyslipidemia, s/p MI, diabetic patients First line agent (mortality data, pleotropic effects)First line agent (mortality data, pleotropic effects) Initial recommended starting dose of any statin will Initial recommended starting dose of any statin will
provide ~30% reduction in LDLprovide ~30% reduction in LDL Subsequent dose increases will only provide an Subsequent dose increases will only provide an
additional 6-7% reduction in LDL, however, will additional 6-7% reduction in LDL, however, will increase risk of adverse effects by 50%increase risk of adverse effects by 50%
Consider metabolism pathway when selecting Consider metabolism pathway when selecting statinsstatins CYP3A4 – atorvastatin, simvastatin, lovastatinCYP3A4 – atorvastatin, simvastatin, lovastatin Sulfation – pravastatin (DOC if concerned about Sulfation – pravastatin (DOC if concerned about
DDIs or AEs)DDIs or AEs) CYP2C19, CYP2C9 – rosuvastatin CYP2C19, CYP2C9 – rosuvastatin
Statin dose conversion Statin dose conversion tabletable
LDL Reduction
lovastatin (Mevacor)
pravastatin (Pravachol)
simvastatin (Zocor)
fluvastatin (Lescol)
atorvastatin (Lipitor)
rosuvastatin (Crestor)
25-32% 20mg 20mg 10mg 40mg -- --
31-39% 40mg 40mg 20mg 80mg 10mg --
37-45% 80mg 80mg 40mg -- 20mg 5mg
48-52% -- -- 80mg -- 40mg 10mg
55-60% -- -- -- -- 80mg 20mg
60-63% -- -- -- -- -- 40mg
Patient CasePatient Case A 50 yo man with moderate familial A 50 yo man with moderate familial
hypertriglyceridemia is treated with hypertriglyceridemia is treated with gemfibrozil. Which of the following is gemfibrozil. Which of the following is the primary mechanism of action? the primary mechanism of action?
A.A. Binding of bile acids in the intestine Binding of bile acids in the intestine
B.B. Inhibition of hepatic VLDL secretion Inhibition of hepatic VLDL secretion
C.C. Inhibition of HMG-CoA reductase Inhibition of HMG-CoA reductase
D.D. Stimulation of HDL productionStimulation of HDL production
E.E. Stimulation of lipoprotein lipase Stimulation of lipoprotein lipase
FibratesFibrates
Drug (Trade Name)
Gemfibrozil (Lopid)
Fenofibrate (Tricor)
Fenofibric acid (Trilipix)
Board worthy!Board worthy! MOA: MOA:
Decreases TGs by up-regulating lipoprotein Decreases TGs by up-regulating lipoprotein lipaselipase
Adverse effects:Adverse effects: Increased LFTsIncreased LFTs, abdominal pain, HA, dyspepsia, , abdominal pain, HA, dyspepsia,
fatiguefatigue Special Considerations:Special Considerations:
Do not use in combination with statin Do not use in combination with statin (risk>benefit)(risk>benefit)
Could use fibrate over statin if TGs > 500 due Could use fibrate over statin if TGs > 500 due to risk of pancreatitis to risk of pancreatitis
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses: Clinical uses: (limited)(limited) HypertriglyceridemiaHypertriglyceridemia
Treating triglycerides is not associated with Treating triglycerides is not associated with positive clinical outcomes!positive clinical outcomes!
DosingDosing Fenofibrate is dosed once dailyFenofibrate is dosed once daily Gemfibrozil is dosed twice daily (30 mins Gemfibrozil is dosed twice daily (30 mins
before food)before food) Consider lifestyle modifications, weight loss, Consider lifestyle modifications, weight loss,
and omega 3 fatty acids for management of TGsand omega 3 fatty acids for management of TGs
Patient CasePatient Case Drugs such as cholestyramine and colestipol have Drugs such as cholestyramine and colestipol have
been shown to decrease circulating serum LDL been shown to decrease circulating serum LDL cholesterol and to slightly elevated TGs. These cholesterol and to slightly elevated TGs. These drugs work by which of the following mechanisms?drugs work by which of the following mechanisms?
A.A. Decreased peripheral lipolysisDecreased peripheral lipolysis
B.B. Increased lipoprotein lipase activity Increased lipoprotein lipase activity
C.C. Inhibition of cholesterol absorption at the small Inhibition of cholesterol absorption at the small intestine brush borderintestine brush border
D.D. Binding and excretion of bile-soluble lipidsBinding and excretion of bile-soluble lipids
E.E. Inhibition of the rate-limiting enzyme of Inhibition of the rate-limiting enzyme of cholesterol formationcholesterol formation
Bile Acid ResinsBile Acid Resins
Drug (Trade Name)
Colestipol (Colestid)
Colesevelam (Welchol)*
Cholestyramine (Questran)
*Has approved indication for diabetes mellitus
Board worthy!Board worthy! MOA: MOA:
Prevents intestinal reabsorption of bile acids Prevents intestinal reabsorption of bile acids Bile acids needed to make cholesterolBile acids needed to make cholesterol
Adverse effects:Adverse effects: GI side effects GI side effects (constipation, abdominal pain, (constipation, abdominal pain,
flatulence, nausea)flatulence, nausea)
Special Considerations:Special Considerations: Decrease absorption of fat soluble vitamins Decrease absorption of fat soluble vitamins
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses:Clinical uses: Dyslipidemia (Decreases LDL)Dyslipidemia (Decreases LDL) Off label uses: diarrhea and pruritusOff label uses: diarrhea and pruritus
DosingDosing Colesevelam: Give other oral drugs >4h Colesevelam: Give other oral drugs >4h
beforebefore Colestipol: Give other oral drugs >1h Colestipol: Give other oral drugs >1h
before or 4h afterbefore or 4h after Cholestyramine: Give other oral drugs Cholestyramine: Give other oral drugs
>1h before or >4-6 after>1h before or >4-6 after
Board worthy!Board worthy!
Ezetimibe (Zetia)Ezetimibe (Zetia) MOA: MOA:
Inhibits the intestinal Inhibits the intestinal absorption of exogenous absorption of exogenous cholesterolcholesterol
Adverse effects: Adverse effects: (minimal)(minimal) Diarrhea, Fatigue, Diarrhea, Fatigue,
Cholelithiasis Cholelithiasis Special Considerations:Special Considerations:
Does not effect cholesterol Does not effect cholesterol made by livermade by liver
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses: (limited)Clinical uses: (limited) Dyslipidemia (lower LDL)Dyslipidemia (lower LDL)
Has not been demonstrated to improve clinical outcomes Has not been demonstrated to improve clinical outcomes in combination with statin therapy!in combination with statin therapy! ENHANCE trial (used surrogate endpoints)ENHANCE trial (used surrogate endpoints)
Vytorin did not result in a significant difference in Vytorin did not result in a significant difference in changes in intima–media thickness, as compared changes in intima–media thickness, as compared with simvastatin alonewith simvastatin alone
ARBITER-6-HALTS trialARBITER-6-HALTS trial Compared with ezetimibe, niacin had greater Compared with ezetimibe, niacin had greater
efficacy regarding the change in mean carotid efficacy regarding the change in mean carotid intima–media thicknessintima–media thickness
Dosing (10mg daily not any more effective than 5mg)Dosing (10mg daily not any more effective than 5mg)
Board worthy!Board worthy!Niacin (Niaspan)Niacin (Niaspan) MOA: MOA:
Inhibits lipolysis in adipose tissue Inhibits lipolysis in adipose tissue Reduces hepatic VLDL secretion into circulationReduces hepatic VLDL secretion into circulation
Adverse effects:Adverse effects: FlushingFlushing, itching, headache, hepatotoxicity, itching, headache, hepatotoxicity
Special Considerations:Special Considerations: Use with caution in patients with history of Use with caution in patients with history of
diabetes and goutdiabetes and gout Contraindicated in patients with PUD and severe Contraindicated in patients with PUD and severe
hepatic impairmenthepatic impairment
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses:Clinical uses: Dyslipidemia (Increases HDL)Dyslipidemia (Increases HDL)
AIM-HIGH StudyAIM-HIGH Study Adding Niacin to a statin dose NOT improve Adding Niacin to a statin dose NOT improve
cardiovascular outcomes and might increase cardiovascular outcomes and might increase strokesstrokes
DosingDosing Start with 500mg and increase by 500mg Start with 500mg and increase by 500mg
every 4 weeksevery 4 weeks Flushing can be minimized if aspirin dose is Flushing can be minimized if aspirin dose is
given ½ hour before given ½ hour before
Patient CasePatient Case Class I antiarrhythmics are Na+ channel Class I antiarrhythmics are Na+ channel
blockers that slow or block cardiac conduction, blockers that slow or block cardiac conduction, especially in depolarized cells. Which of the especially in depolarized cells. Which of the following class I antiarrhythmics will increase following class I antiarrhythmics will increase both the action potential and the effective both the action potential and the effective refractory period?refractory period?
A.A. Mexiletine Mexiletine
B.B. ProcainamideProcainamide
C.C. Flecanide Flecanide
D.D. Propafenone Propafenone
E.E. Tocainide Tocainide
Patient CasePatient Case An elderly man presents with complaints of ringing An elderly man presents with complaints of ringing
in his ears, blurred vision, and upset stomach. He in his ears, blurred vision, and upset stomach. He is taking multiple medications. His wife states that is taking multiple medications. His wife states that he has had a few episodes of confused, delirious he has had a few episodes of confused, delirious behavior over the past few weeks. Which of the behavior over the past few weeks. Which of the following agents might be responsible for this following agents might be responsible for this man’s syndrome? man’s syndrome?
A.A. Allopurinol Allopurinol
B.B. Hydralazine Hydralazine
C.C. Niacin Niacin
D.D. QuinidineQuinidine
E.E. SpironolactoneSpironolactone
Anti-arrhythmicsAnti-arrhythmics
Class 1 (Na+ Channel Class 1 (Na+ Channel blockers)blockers)
Drug (trade name)
1A
Quinidine
Procainamide
Disopyramide (Norpace)
1B
Lidocaine (Xylocaine)
Tocainide (Tonocard)
Mexiletine (Mexitil)
Phenytoin (Dilantin)
1C
Flecainide (Tambocor)
Propafenone (Rythmol)
Board worthy!Board worthy! MOA: Na+ channel blockers MOA: Na+ channel blockers
Slow or block conduction especially in Slow or block conduction especially in depolarized cellsdepolarized cells
Decrease slope of phase 0 depolarizationDecrease slope of phase 0 depolarization Class IA: Class IA:
Increases AP duration, ERP and QT Increases AP duration, ERP and QT intervalinterval
Class IB: Class IB: Decreases AP durationDecreases AP duration
Class IC: Class IC: No effect on AP durationNo effect on AP duration
Board worthy!Board worthy!Adverse effects:Adverse effects: Class IAClass IA
Quinidine – cinchonism, thrombocytopenia, Quinidine – cinchonism, thrombocytopenia, torsades de pointestorsades de pointes
Procainamide – reversible SLE-like syndromeProcainamide – reversible SLE-like syndrome Class IBClass IB
Cardiovascular depression and CNS related Cardiovascular depression and CNS related AEsAEs
Class ICClass IC ProarrhythmicProarrhythmic
Clinical PearlsClinical Pearls Class IAClass IA
Affect both atrial and ventricular arrhythmiasAffect both atrial and ventricular arrhythmias Class IBClass IB
Useful in acute ventricular arrhythmias Useful in acute ventricular arrhythmias (especially post-MI) and in digitalis-induced (especially post-MI) and in digitalis-induced arrhythmias arrhythmias
Class ICClass IC Useful in V-tachs that progress to VF and in Useful in V-tachs that progress to VF and in
intractable SVTintractable SVT Usually used only as last resortUsually used only as last resort Contraindicated post MIContraindicated post MI
Patient CasePatient Case A 57 old smoker with a long history of A 57 old smoker with a long history of
chronic obstructive lung disease presents to chronic obstructive lung disease presents to the physician with a BP of 150/90 mm Hg. the physician with a BP of 150/90 mm Hg. Which of the following anti-hypertensives is Which of the following anti-hypertensives is contraindicated in this patient? contraindicated in this patient?
A.A. Acebutolol Acebutolol
B.B. Atenolol Atenolol
C.C. Esmolol Esmolol
D.D. Metoprolol Metoprolol
E.E. NadololNadolol
Patient CasePatient Case A 45 yo woman is brought to the hospital after A 45 yo woman is brought to the hospital after
collapsing on the sidewalk in front of the hospital. collapsing on the sidewalk in front of the hospital. Her friend reports that the patient has no known Her friend reports that the patient has no known medical conditions. Initial evaluation reveals severe medical conditions. Initial evaluation reveals severe hypotension, and she is given IV norepinephrine. hypotension, and she is given IV norepinephrine. Which of the following drugs antagonize both the Which of the following drugs antagonize both the vascular and cardiac actions of the given medication? vascular and cardiac actions of the given medication?
A.A. AtenololAtenolol
B.B. Esmolol Esmolol
C.C. CarvedilolCarvedilol
D.D. MetaproterenolMetaproterenol
E.E. BisoprololBisoprolol
Class II – Beta blockers Class II – Beta blockers (Selective)(Selective)
Drug (Trade Name)
Acebutolol (Sectral)Atenolol (Tenormin)Betaxolol (Kerlone)Bisoprolol (Zebeta)Metoprolol Tartrate (Lopressor)Metorolol Succinate (Toprol XL)Esmolol (Brevibloc)*only available as IV formulation
Board worthy!Board worthy! MOA: MOA:
Selectively blocks betaSelectively blocks beta11-adrenergic receptors -adrenergic receptors in the heart and vascular smooth musclein the heart and vascular smooth muscle
Adverse effects:Adverse effects: Dizziness, Dizziness, fatigue,fatigue, impotenceimpotence BradycardiaBradycardia
Special Considerations:Special Considerations: Up regulation of receptors is seen in chronic Up regulation of receptors is seen in chronic
use so it is important to not abruptly use so it is important to not abruptly discontinue medicationdiscontinue medication
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses:Clinical uses: TachycardiaTachycardia AnginaAngina ArrhythmiasArrhythmias HypertensionHypertension
Decreases post MI mortalityDecreases post MI mortality Proven to decrease mortality in heart Proven to decrease mortality in heart
failurefailure Bisoprolol, metoprolol succinate, carvedilolBisoprolol, metoprolol succinate, carvedilol
May mask symptoms of hypoglycemia May mask symptoms of hypoglycemia
Class II – Beta blockers (Non-Class II – Beta blockers (Non-Selective)Selective)
Drug (Trade Name)
Nadolol (Corgard)
Pindolol (Visken)
Propranolol (Inderal)
Sotalol (Betapace)
Timolol
Board worthy!Board worthy! MOA: MOA:
Blocks the beta-1 and beta-2 receptors Blocks the beta-1 and beta-2 receptors in the heart and vascular smooth in the heart and vascular smooth musclemuscle
Adverse effects:Adverse effects: Dizziness, fatigue, Dizziness, fatigue, sleep disturbancessleep disturbances
Special Considerations:Special Considerations: Causes increase airway resistance – Causes increase airway resistance –
contraindicated in asthmatics contraindicated in asthmatics Use with caution in patients with Use with caution in patients with
diabetes receiving hypoglycemic drugs diabetes receiving hypoglycemic drugs
Clinical Pearls for Clinical Pearls for RotationsRotations Clinical uses:Clinical uses:
ArrhythmiasArrhythmias AnginaAngina Other indications: pheochromocytoma, Other indications: pheochromocytoma,
tremor, migraine prophylaxis, portal tremor, migraine prophylaxis, portal hypertensionhypertension
Carvedilol (Coreg) and Labetolol Carvedilol (Coreg) and Labetolol (Normodyne)(Normodyne) Antagonists at beta-1, beta-2 and alpha-1 Antagonists at beta-1, beta-2 and alpha-1
receptorsreceptors Added benefit of vasodilatationAdded benefit of vasodilatation
Class III – K+ channel Class III – K+ channel blockersblockers
Drug (Trade Name)
Amiodarone (Cordarone, Pacerone)
Ibutilide (Corvert)
Dofetilide (Tikosyn)
Sotalol (Betaspace, Sorine)
Bretylium
Board worthy!Board worthy! MOA: MOA:
Block the potassium channels, prolonging Block the potassium channels, prolonging repolarizationrepolarization
Increases AP duration, ERP and QT intervalIncreases AP duration, ERP and QT interval Adverse effects: Adverse effects:
Sotalol – torsades de pointesSotalol – torsades de pointes Ibutilide – torsadesIbutilide – torsades Bretylium – new arrhythmias, hypotensionBretylium – new arrhythmias, hypotension Amiodarone – pulmonary fibrosis, hepatotoxicity, Amiodarone – pulmonary fibrosis, hepatotoxicity,
hypo/hyperthyroidism (check PFTs, LFTs, TFTs)hypo/hyperthyroidism (check PFTs, LFTs, TFTs)
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses:Clinical uses: Ventricular arrhythmiasVentricular arrhythmias Atrial fibrillation and flutterAtrial fibrillation and flutter
Sotalol also has Class II activitySotalol also has Class II activity Amiodarone has Class I, II, III, and IV Amiodarone has Class I, II, III, and IV
activityactivity Amiodarone does not have any negative Amiodarone does not have any negative
inotropic effects and lowest incidence inotropic effects and lowest incidence of Torsades de pointesof Torsades de pointes
Patient CasePatient Case
A physician decides to place a pt on CCB for A physician decides to place a pt on CCB for treatment of her angina. CCBs can relax the treatment of her angina. CCBs can relax the smooth muscle of blood vessels and can also smooth muscle of blood vessels and can also have various effects on cardiac contractility, have various effects on cardiac contractility, conduction, and HR. Which of the following conduction, and HR. Which of the following CCBs would be most effective in reducing HR CCBs would be most effective in reducing HR and contractility?and contractility?
A.A. DiltiazemDiltiazem
B.B. NifedipineNifedipine
C.C. NimodipineNimodipine
D.D. VerapamilVerapamil
Patient CasePatient Case A 56 yo woman arrives in the ED complaining of A 56 yo woman arrives in the ED complaining of
dizziness and headache. Her BP is 210/140. dizziness and headache. Her BP is 210/140. She is currently not taking any medications and She is currently not taking any medications and has not seen a doctor for several years. The has not seen a doctor for several years. The physician decides to address her HTN urgently. physician decides to address her HTN urgently. Which of the following drugs is contraindicated?Which of the following drugs is contraindicated?
A.A. IV diltiazemIV diltiazem
B.B. IV labetaololIV labetaolol
C.C. IV metoprololIV metoprolol
D.D. Oral captoprilOral captopril
E.E. SL nifedipineSL nifedipine
Class IV – Calcium Channel Class IV – Calcium Channel BlockersBlockers
Drug (Trade Name)
Dihydropyridines
Amlodipine (Norvasc)
Felodipine (Plendil)
Nifedipine (Adalat CC, Procardia XL)
Isradipine (Dynacirc)
Nisoldipine (Sular)
Non-dihydropyridines
Verapamil (Calan)
Diltiazem (Cardizem)
Board worthy!Board worthy! Dihydropyridines MOA: Dihydropyridines MOA:
Selectively Selectively binds to L-type voltage-gated binds to L-type voltage-gated calcium channels in calcium channels in vascular smooth musclevascular smooth muscle
Non-dihydropyridines MOA:Non-dihydropyridines MOA: Binds to L-type voltage-gated calcium channels Binds to L-type voltage-gated calcium channels
in in sinoatrial node, atrialventricular node, and sinoatrial node, atrialventricular node, and vascular smooth musclevascular smooth muscle
Adverse effects: Adverse effects: Peripheral edema, constipation, flushing, Peripheral edema, constipation, flushing,
headacheheadache AV block, bradycardia, CHF (Non-DHPs)AV block, bradycardia, CHF (Non-DHPs)
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses:Clinical uses: Hypertension Hypertension Arrhythmias: afib, aflutter, PSVTArrhythmias: afib, aflutter, PSVT Angina: vasospastic, Prinzmetal, Angina: vasospastic, Prinzmetal,
exertionalexertional Verapamil is a stronger negative Verapamil is a stronger negative
inotrope than diltiazeminotrope than diltiazem DHPs drug of choice for HTNDHPs drug of choice for HTN
Patient CasePatient Case A 25 yo white woman with no PMH presents to A 25 yo white woman with no PMH presents to
the ED for a “racing heartbeat.” It is the ED for a “racing heartbeat.” It is determined that she has paroxysmal determined that she has paroxysmal supraventricular tachycardia. Which of the supraventricular tachycardia. Which of the following is the drug of choice used for following is the drug of choice used for diagnosing and abolishing AV nodal arrhythmias diagnosing and abolishing AV nodal arrhythmias by virtue of its effectiveness and its low toxicity?by virtue of its effectiveness and its low toxicity?
A.A. AdenosineAdenosine
B.B. BretyliumBretylium
C.C. LidocaineLidocaine
D.D. SotalolSotalol
Other anti-arrhythmicsOther anti-arrhythmics
AdenosineAdenosine Slows down AV node conduction time and Slows down AV node conduction time and
interrupts AV node re-entry pathwaysinterrupts AV node re-entry pathways DOC in diagnosing/abolishing DOC in diagnosing/abolishing
supraventricular tachycardiasupraventricular tachycardia Short acting (15 secs)Short acting (15 secs)
MagnesiumMagnesium Effective in torsades de pointes and Effective in torsades de pointes and
digoxin toxicitydigoxin toxicity
Board worthy!Board worthy!
DigoxinDigoxin MOA:MOA:
Direct inhibition of Na+/K+ ATPaseDirect inhibition of Na+/K+ ATPase Stimulates vagus nerveStimulates vagus nerve
Adverse effects:Adverse effects: Cholinergic side effects, Cholinergic side effects, blurry yellow visionblurry yellow vision
Special considerations:Special considerations: Increased risk of digoxin toxicity if pt is Increased risk of digoxin toxicity if pt is
hypokalemic and impaired renal functionhypokalemic and impaired renal function
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses:Clinical uses: CHF (increases contractility)CHF (increases contractility) Afib (decreases conduction at AV node Afib (decreases conduction at AV node
and depression of SA node)and depression of SA node) Monitor levels of digoxinMonitor levels of digoxin
CHF: 0.5-0.8 ng/mLCHF: 0.5-0.8 ng/mL Afib: 0.8-2 ng/mLAfib: 0.8-2 ng/mL
Digoxin toxicityDigoxin toxicity DigiFabDigiFab
Patient CasePatient Case A patient who is being treated for a A patient who is being treated for a
hypertensive crisis that occurred 2 hours ago hypertensive crisis that occurred 2 hours ago is medicated with IV nitroprusside. Which of is medicated with IV nitroprusside. Which of the following is the expected action of this the following is the expected action of this drug? drug?
A.A. Constriction of arterioles alone Constriction of arterioles alone
B.B. Constriction of both arterioles and venules Constriction of both arterioles and venules
C.C. Constriction of venules alone Constriction of venules alone
D.D. Dilation of arterioles alone Dilation of arterioles alone
E.E. Dilatation of arterioles and venules Dilatation of arterioles and venules
NitratesNitrates
Drug (Trade Name)
Nitroglycerin (available in various forms)
Isosorbide dinitrate (Isordil)
Isosorbide mononitrate (Imdur)
Board Worthy!Board Worthy! MOA:MOA:
Vasodilates by releasing nitric oxide in smooth Vasodilates by releasing nitric oxide in smooth musclemuscle Increases cGMP and smooth muscle Increases cGMP and smooth muscle
relexationrelexation Decreases preloadDecreases preload
Adverse effects:Adverse effects: Reflex tachycardia, hypotension, HA, flushingReflex tachycardia, hypotension, HA, flushing
Special considerations:Special considerations: Contraindicated with PDE-5 inhibitors (severe Contraindicated with PDE-5 inhibitors (severe
hypotension)hypotension)
Clinical PearlsClinical Pearls
Clinical uses:Clinical uses: AnginaAngina
Various formulations available such as oral, Various formulations available such as oral, IV, topical ointment, transdermal, IV, topical ointment, transdermal, sublingual,sublingual,
Onset: nitroglycerin > isosorbide dinitrate Onset: nitroglycerin > isosorbide dinitrate > isosorbide mononitrate> isosorbide mononitrate
Dilate veins > arteries Dilate veins > arteries Can develop tolerance (drug free periods to Can develop tolerance (drug free periods to
avoid tolerance)avoid tolerance)
Board Worthy!Board Worthy!Hydralazine (Apresolin)Hydralazine (Apresolin) MOA:MOA:
Peripheral vasodilatorPeripheral vasodilator Increases cGMP and causes smooth muscle Increases cGMP and causes smooth muscle
relaxationrelaxation Adverse effects:Adverse effects:
Compensatory tachycardia, headache, nauseaCompensatory tachycardia, headache, nausea Lupus like syndromeLupus like syndrome
Special considerations:Special considerations: Contraindicated in angina/CAD Contraindicated in angina/CAD
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical Uses:Clinical Uses: Severe hypertensionSevere hypertension CHFCHF
Vasodilates arterioles > veins (afterload Vasodilates arterioles > veins (afterload reduction)reduction)
First line therapy for HTN in pregnancy with First line therapy for HTN in pregnancy with methyldopamethyldopa
Combination hydralazine and isosorbide dinitrate Combination hydralazine and isosorbide dinitrate when added to standard heart failure medications when added to standard heart failure medications improved symptoms and reduced risk of death improved symptoms and reduced risk of death and hospitalizations in African Americansand hospitalizations in African Americans
Board worthy!Board worthy!Ranolazine (Ranexa)Ranolazine (Ranexa) MOAMOA
Unknown Unknown Inhibits late sodium current, reducing Inhibits late sodium current, reducing
sodium-induced calcium overload in myocytessodium-induced calcium overload in myocytes Adverse effects:Adverse effects:
Constipation, nausea, Constipation, nausea, prolonged QT interval, prolonged QT interval, syncopesyncope
Special considerationsSpecial considerations Use with caution in renal impairmentUse with caution in renal impairment
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical useClinical use Chronic angina (not indicated for acute Chronic angina (not indicated for acute
angina)angina) Counsel patients on orthostatic Counsel patients on orthostatic
hypotensionhypotension Contraindicated in liver cirrhosisContraindicated in liver cirrhosis Should avoid grapefruit juice Should avoid grapefruit juice
Anti-plateletsAnti-platelets
Patient CasePatient Case A 65 yo patient has experienced several TIAs A 65 yo patient has experienced several TIAs
over the past few months. Because his general over the past few months. Because his general health is poor, he is not considered an health is poor, he is not considered an appropriate candidate for carotid appropriate candidate for carotid endarterectomy. The decision is made to treat endarterectomy. The decision is made to treat him medically. Which of the following agents him medically. Which of the following agents would be most appropriate for this therapy? would be most appropriate for this therapy?
A.A. Aspirin Aspirin
B.B. Coumadin Coumadin
C.C. Dipyridamole Dipyridamole
D.D. Heparin Heparin
Board worthy!Board worthy!AspirinAspirin MOA: MOA:
Acetylates and irreversibly inhibits Acetylates and irreversibly inhibits cyclooxygenase (COX-1 and COX-2)cyclooxygenase (COX-1 and COX-2)
Adverse EffectsAdverse Effects: : Gastric ulceration, bleeding, tinnitusGastric ulceration, bleeding, tinnitus
Special Considerations:Special Considerations: Reye’s syndrome (use with caution in Reye’s syndrome (use with caution in
children)children)
Clinical uses:Clinical uses: AntipyreticAntipyretic AnalgesicAnalgesic Anti-platelet drug Anti-platelet drug
(ACS, MI prevention, (ACS, MI prevention, TIA/thromboembolic stroke prevention)TIA/thromboembolic stroke prevention)
Use with caution in patients with asthmaUse with caution in patients with asthma Increases bleeding time but does not effect Increases bleeding time but does not effect
PT or PTT PT or PTT
Clinical Pearls for Clinical Pearls for RotationsRotations
Patient CasePatient Case A patient admitted to the ED with CP is diagnosed A patient admitted to the ED with CP is diagnosed
with MI. On discharge, the pt is prescribed aspirin with MI. On discharge, the pt is prescribed aspirin but develops an allergic hypersenitivity reaction. but develops an allergic hypersenitivity reaction. Ticlopidine is prescribed instead as a maintenance Ticlopidine is prescribed instead as a maintenance anticoagulant. Which of the following is the MOA?anticoagulant. Which of the following is the MOA?
A.A. It binds to the active site of cyclo-oxygenase via It binds to the active site of cyclo-oxygenase via acetylationacetylation
B.B. It blocks the binding of plasmin to fibrinIt blocks the binding of plasmin to fibrin
C.C. It hinders the production of thromboxane A2It hinders the production of thromboxane A2
D.D. It prevents fibrinogen from binding to plateletsIt prevents fibrinogen from binding to platelets
E.E. It stimulates platelet adenylyl cyclaseIt stimulates platelet adenylyl cyclase
ThienopyridinesThienopyridines
Drug (Trade Name)
Ticlopidine (Ticlid)
Clopidogrel (Plavix)
Prasugrel (Effient)
Board worthy!Board worthy! MOAMOA::
Inhibit platelet aggregation by irreversibly Inhibit platelet aggregation by irreversibly blocking ADP receptorsblocking ADP receptors Inhibit fibrinogen binding by preventing Inhibit fibrinogen binding by preventing
glycoprotein IIb/IIIa expressionglycoprotein IIb/IIIa expression AdverseAdverse Effects:Effects:
Ticlopidine- neutropeniaTiclopidine- neutropenia Bleeding – clopidogrel and prasugrelBleeding – clopidogrel and prasugrel
Special ConsiderationsSpecial Considerations:: Use with caution in patients that are poor Use with caution in patients that are poor
metabolizers of 2C19 (Black Box Warning)metabolizers of 2C19 (Black Box Warning)
Clinical usesClinical uses: : Acute coronary syndromeAcute coronary syndrome Coronary stentingCoronary stenting Thrombotic event preventionThrombotic event prevention
Use of PPIs and Plavix controversialUse of PPIs and Plavix controversial Prasugrel is not recommended in patients 75 years Prasugrel is not recommended in patients 75 years
of age and older, except for high-risk situations of age and older, except for high-risk situations (diabetes, history of prior myocardial infarction)(diabetes, history of prior myocardial infarction) May be a good option for poor metabolizers of May be a good option for poor metabolizers of
2C19 and chronic PPI users as it isn’t 2C19 and chronic PPI users as it isn’t significantly affectedsignificantly affected
Clinical Pearls for Clinical Pearls for RotationsRotations
Drug (Trade Name)
Tirofiban (Aggrastat)
Eptifibatide (Integrilin)
Abciximab (Reopro)
Glycoprotein IIb/IIIa Glycoprotein IIb/IIIa inhibitorinhibitor
MOA: MOA: Inhibits aggregation of platelets by reversibly Inhibits aggregation of platelets by reversibly
antagonizing fibrinogen binding to the GP antagonizing fibrinogen binding to the GP IIb/IIIa receptorIIb/IIIa receptor
Adverse Effects:Adverse Effects: Bleeding, bradyarrythmia, dizziness (tirofiban)Bleeding, bradyarrythmia, dizziness (tirofiban) CP, hypotension, nausea, backache (abciximab)CP, hypotension, nausea, backache (abciximab) Hypotension, bleeding (eptifibatide)Hypotension, bleeding (eptifibatide)
Special considerations:Special considerations: Tirofiban can not be used in patients allergic to Tirofiban can not be used in patients allergic to
aspirinaspirin
Board worthy!Board worthy!
Clinical useClinical use Acute coronary syndromeAcute coronary syndrome PCIPCI Myocardial ischemia Myocardial ischemia
Abciximab has the most potential to Abciximab has the most potential to cause allergic reactionscause allergic reactions
Tirofiban and eptifibatide requires Tirofiban and eptifibatide requires renal dosingrenal dosing
Clinical Pearls for Clinical Pearls for RotationsRotations
Anti-thrombinsAnti-thrombins
Patient CasePatient Case A 62 yo white man complains of left thigh and leg pain A 62 yo white man complains of left thigh and leg pain
and swelling that are exacerbated by walking. One and swelling that are exacerbated by walking. One week earlier, the patient underwent cardiac week earlier, the patient underwent cardiac catheterization. The patient is currently vacationing catheterization. The patient is currently vacationing and has spent 28 hours in a car. Which of the following and has spent 28 hours in a car. Which of the following drugs, which might be prescribed in this instance, drugs, which might be prescribed in this instance, works by inhibiting the enzyme epoxide reductase? works by inhibiting the enzyme epoxide reductase?
A.A. Acetylsalicylic acid Acetylsalicylic acid
B.B. Dipyridamole Dipyridamole
C.C. Heparin Heparin
D.D. StreptokinaseStreptokinase
E.E. Warfarin Warfarin
Heparin vs. WarfarinHeparin vs. WarfarinHeparin Warfarin
Activates antithrombin (decreases action of IIa and Xa)
Interferes with synthesis of vitamin K clotting factors (II, VII, IX, X)
Monitored by PTT Monitored by PT/INR
Given IV or SQ Given orally
Toxicity treated with protamine sulfate
Toxiciity treated with vitamin K and fresh frozen plasma
Rapid anticoagulation 2-3 days before anticoagulation
Can be used in pregnancy
Can’t be used in pregnancy
Direct Thrombin Direct Thrombin InhibitorsInhibitors
Drug (Trade Name)
Argatroban
Dabigatran (Pradaxa)
Desirudin(Iprivask)
Lepirudin (Refludan)
Bivalirudin (Angiomax)
Board worthy!Board worthy!
MOA: MOA: Reversibly binds and inhibits the active Reversibly binds and inhibits the active
site on site on thrombinthrombin Adverse effects: Adverse effects:
Bleeding, hemorrhageBleeding, hemorrhage Special Considerations:Special Considerations:
Dabigatran, lepirudin, bivalirudin, Dabigatran, lepirudin, bivalirudin, desirudin: renal eliminationdesirudin: renal elimination
Argatroban: hepatic eliminationArgatroban: hepatic elimination Predictable dose-responsePredictable dose-response
Clinical Pearls for Clinical Pearls for RotationsRotations Clinical uses:Clinical uses:
HITHIT VTEVTE DVTDVT PEPE AfibAfib PCIPCI
Monitory therapy with PTTMonitory therapy with PTT None have antidotes for reversalNone have antidotes for reversal All are continuous IV infusions All are continuous IV infusions except except
dabigatran dabigatran Expensive: $800-$1000/dayExpensive: $800-$1000/day
Low Molecular Weight Low Molecular Weight HeparinsHeparins
Drug (Trade Name)
Dalteparin (Fragmin)
Tinzaparin (Inohep)
Exoxaparin (Lovenox)
Board worthy!Board worthy!
MOA: MOA: Inhibits thrombin and Inhibits thrombin and Factor XaFactor Xa
Adverse effects: Adverse effects: (lesser degree than (lesser degree than heparin)heparin) Bleeding, hemorrhageBleeding, hemorrhage HIT, osteoporosis (chronic)HIT, osteoporosis (chronic)
Special Considerations:Special Considerations: Use with caution in renal impairment Use with caution in renal impairment
and obese patientsand obese patients
Clinical Pearls for Clinical Pearls for RotationsRotations
Clinical uses: Clinical uses: DVTDVT PCIPCI N/STEMIN/STEMI
No therapeutic monitoring No therapeutic monitoring Can be dosed subcutaneously as an Can be dosed subcutaneously as an
outpatientoutpatient Weight-based dosingWeight-based dosing
Thank you!Thank you!
Dhiren Patel, PharmD, CDE
Assistant Professor of Pharmacy PracticeMassachusetts College of Pharmacy and Health
Sciences-Boston
Clinical Pharmacy Specialist / Certified Diabetes Educator
VA Boston Healthcare System
E-mail: [email protected]