Cardiac Drug Update
By Pamela P. Bayles, RN, BSN
• Advances in cardiovascular medicine over the
last decade have dwarfed the major advances
throughout all of history
• Advances over the last ten years have resulted
in a 25% decrease in deaths due to CAD
• This is by and large due to the advances in
cardiac pharmacology
Statins
– Cholesterol lowering by increasing clearance of
LDL from bloodstream
• Cause moderate reduction in triglyceride levels
• Cause small increase in levels of HDL
– Results can be seen after one week and effect
maximal after 4-6 weeks
– Also reduce size of plaques in arteries, stabilize
plaques and reduce inflammation which is am
important component of plaque formation and
rupture
– Reduces C. Reactive Protein levels
– Decreases blood clot formation at site of plaque
rupture
– Increased use over last decade as knowledge of
benefits spread, prices fell and generics became
available
– 60% decrease in # of heart attacks & sudden cardiac
death
– 17% reduction in stroke
Framingham risk score, Heart Protection Study, JUPITER study
ACE-Inhibitors
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Block conversion of angiotensin I to angiotensin II
Medication end with “pril”
Indicated for hypertension, MI, CHF
Slows disease progression
Interferes with ventricular remodeling
In several trials of acute MI:
– Promoted survival, decreased incidence of heart
failure
– Decreased incidence of reinfarction and need for
revascularization
• Side effects: cough, renal insufficiency and
angioedema
– Females at greater risk of angioedema to lower
part of face or airway
– Black females at even great risk
Amiodarone
• Class III Antiarrhythmic approved for use in US in 1985
• Used for ventricular and supraventricular arrhythmias
including:
– Unstable Ventricular Tachycardia refractory to other therapy and
prophylaxis of Recurring Ventricular Fibrillation
– Suppress and prevent recurrence of SVTs refractory to
conventional treatment, esp. assoc. with Wolff-Parkinson-White
syndrome, Paroxysmal Atrial Fibrillation, Atrial Flutter, Ectopic
Atrial Tachycardia, Paroxysmal SVT from AV nodal re-entry
tachycardia in patients with W-P-W syndrome
• Prolongs action potential duration and the
refractory period in all cardiac tissues
• Decreases sinus node automaticity and
junctional automaticity, prolongs AV
conduction and slows automaticity of
spontaneously firing fibers in the Purkinje
system
• Refractoriness is prolonged and conduction is
slowed in accessory pathway in patients with
WPW syndrome
• Available in IV and PO
• Mild negative inotropic effect that is more prominent with IV
than oral administration
• Causes coronary and peripheral vasodilation
• Decreases peripheral vascular resistance (afterload)
• IV: 300 mg for cardiac arrest
– 150 mg bolus over 10 min for dysrhythmias
followed by infusion at 60 mg/hr x 6 hrs., then 30
mg/hr. x 18 hrs.
• PO: 100 – 200 mg daily or BID
• Side effects:
– Pulmonary toxicity
– Interaction with simvastatin at doses >20 mg can
lead to rhabdomolysis which can lead to renal
failure
– Thyroid abnormalities
– Corneal micro-deposits
– Abnormal liver enzymes
– Blue-grey discoloration of skin esp. in lighter skin
tones
Clopidogrel ( Plavix )
• Approved in 1997
• Oral antiplatelet agent used to inhibit clots in CAD, PVD and
with CVA
• Platelet inhibit demonstrated 2 hrs. after single oral dose of
75 mg but onset of action slow
• Dosing indicated for ACS pts. Treated by PCI is a 300 mg
loading dose followed by 75 mg/day along with 75-325 mg of
aspirin/day **
• Indicated for prevention of vascular ischemic events, NSTEMI,
STEMI, for prevention of thrombosis after intracoronary stent
• Side effects include neutropenia and thrombotic
thrombocytopenic purpura (TTP)
** CURRENT-OASIS 7 Trial reduces major cardiovascular events in ACS pts.
during and after PCI
Glycoprotein IIb/IIIa Inhibitors
• New class of antithrombotic agents
– Provide more comprehensive blockade than the combination of
heparin and aspirin
– Work to prevent platelet aggregation and thrombus formation
• Used during Percutaneous coronary interventions with or without
intracoronary stent and for treatment of acute coronary syndromes
• Have demonstrated reduction in combination of death, MI and urgent
coronary revascularization
• Three parenteral agents currently available:
– Abciximab (ReoPro)
– Eptifibatide (Integrilin)
– Tirofibin (Aggrastat)
• Abciximab (ReoPro) used in interventional cardiology as bolus plus
infusion
– Pts. Have show a 35-50% reduction in primary end point of death,
nonfatal MI, refractory ischemia, or urgent revascularization within 30
days esp. in pts. With unstable angina *
• Eptifibatide (Integrilin)and Tirofiban (Aggrastat) used in ACS at onset of CP
or with ischemic change on ECG or any CK-MB elevation above upper
limits of normal
• Used in combination with low-dose thrombolytics in AMI to achieve
reperfusion
*EPIC, EPILOG and EPISTENT trials translated to 35-56& reduction in relative risk for
endpoint regardless of method of revascularization.
Angiomax (Bivalirudin)
• Anticoagulant for use in pts. Undergoing PCI, and in
pts. With or at risk for HIT/HITTS undergoing PCI
• Direct thrombin inhibitor
• Synthetic version of hirudin- naturally occurring drug
found in saliva of medicinal leech
• Onset of action almost immediate after IV bolus
• Prolongs ACT, PT, aPTT that returns to normal within 12 hours
• Horizons AMI and REPLACE-2 trials demonstrated
efficacy and reductions in major bleeding versus
heparin + GP IIb/IIIa inhibitors
• Dosing:
– 0.75 mg/kg loading dose followed by 1.75
mg/kg/hr for up to 4 hrs. then 0.2 mg/kg/hr for
up to 20hr. If needed
– Perform ACT 5” after first bolus and give
additional bolus if needed
Platelet Inhibitors
Inhibit Platelet
Activation
Inhibit Platelet
Aggregation
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ASA
Clopidogrel (Plavix)
Heparin
Angiomax
IIb/IIIa Inhibitors
Abciximab (Reopro)
Eptifibitide (Intregrillin)
Tirofiban (Aggrastat)
Vasopressin
• Antidiuretic hormone, found in humans
• Secreted from posterior pituitary gland in
response to reduction in plasma volume
– Causes kidneys to conserve water
– Raises BP by moderate vasoconstriction
– Doesn’t have negative effect on myocardium
• Used to treat Asystole & Shock
– Increases responsiveness of catecholamines
• 40 units IV during resuscitation
• Infusion 0.01 – 0.06 units/min or 1-4 units/hr
Natrecor ( Nesiritide )
• Approved 8/2001 for treatment of pts. With acute
decompensated CHF who have SOB at rest or with minimal
activity
• Recombinant form of human B-type natriuretic peptide, a
naturally occurring hormone secreted by the ventricles
– Manufactured from E. coli
• Produces dose-dependent reduction in PCWP and systemic
arterial pressure*
*VMAC Trial
• Side effects occur during first 24 hrs of infusion
– Hypotension, VT, angina, bradycardia, HA, abdominal/back
pain
• Bolus of 2 mcg/kg followed by a continuous infusion of 0.01
mcg/kg/min for 48 hours – don’t give in line with other meds
• Monitor BP often
• If hypotension occurs, the dose should be discontinued and
restarted at a dose that is 30% of prior dose
Primacor
• Phosphodiesterase inhibitor with positive inotrope and
vasodilator properties
– Increases CO without increasing HR or myocardial
demand
– Decreases SVR, preload, and afterload
• Improvement in Left ventricular function and relief of CHF
symptoms in patients with ischemic heart disease observed
• Used for short-term management of severe CHF including low
output states following cardiac surgery
• 50 mcg/kg IV slowly over 10 minutes then maintenance
infusion of 0.375 – 0.75 mcg/kg/min
• Side effects:
– Arrhythmogenic
– Decreases potassium
– Thrombocytopenia
– Headache
– Tremors
– Chest pain
• So, what do the next ten years look like?
• Emerging discoveries in the field of
pharmacogenomics are yielding a
personalized era of drug therapy
• Sensors have been developed on chips that
can detect in blood, urine or saliva, protein or
gene patterns that fluoresce known patterns
assoc. with particular disease states.
– Some chips search for SNPs ( single-nucleotide
polymorphyisms) – a DNA sequence variation that
occurs between members of a species & have
been shown to be a predictive of heart disease.
• What’s already in the pipeline?
– Cardiac myosin activators
• Enhance contractility without altering intracellular
calcium levels
• Treat CHF
– Alpha natriuretic peptide medications
• Regulate Na+ and fluid homeostasis
• Decrease PCWP and SVR
• For acute decompensated HF
– More stem cells research
– Computers & imaging techniques
• Less invasive techniques but more information