11 09 15.cardiology pharmacology review.patel

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)


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


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 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 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 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


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 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


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


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


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 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 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


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 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 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 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


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


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


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


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)


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


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)


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 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]

11 09 15.cardiology pharmacology review.patel

Documents

rotations clinical uses

cholesterol adverse

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positive clinical outcomes

risk of adverse effects

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effects constipation

inhibition of hmg