Cardiac Drugs

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Drug/Class MOA Clinical Use Adverse Rxns Interaction/Notes
Vasopressor
Dopamine Alpha1 agonist at high dose, beta
and D1 agonist at lower doses
leading to increased renal
perfusion and increase HR and
contractility
Vasopressor used in
severe hypotension
and shock
Arrhythmias, angina, HTN,
nausea

Antihypertensive
Fenoldopam D1-like receptor agonist –
arteriolar vasodilation (including
afferent and efferent renal),
natriuresis, and diuresis
IV infusion during
hypertensive
emergencies
Can reduce serum K+ levels Concurrent use with beta blockers could
cause hypotension and should be avoided.
Non-
dihydropyridine
Calcium Channel
Blockers

Verapamil, diltiazem
Inhibits transmembrane
movement of Ca++ and cause
arteriolar smooth muscle
relaxation, decreasing afterload
Useful in pts with
angina pectoris and
SVTs, first line
therapy in pts for
whom diuretics and
-blockers are
contraindicated.
Bradycardia, heart block,
constipation, verapamil
causes severe gingival
hyperplasia, inhibit LES
leading to GERD.
Predominantly act on the heart, so avoid in
SA or AV node. Not useful in LV
dysfunction due to negative inotropic
effects, verapamil can increase digoxin
Dihydropyridine
calcium channel
blockers

Amlodipine,
felodipine, nifedipine
Hypotension, peripheral edema,
slight reflex tachycardia
More selective to smooth muscle, short
acting DHPs increase mortality due to
swings in BP.
Vasodilators
Hydralazine Selectively relaxes arteriolar
smooth muscle, not venous.
Decrease afterload.
Severe HTN or HTN
in pregnant
Reflex tachycardia, drug
induced lupus syndrome,
headache, nausea, flushing,
palpitation
Bidil (hydralazine + isosorbide dinitrate)
more effective in blacks for HF.
Minoxidil Activates ATP-sensitive K+
channels, leading to
hyperpolarization and
vasodilation, decreasing afterload
Reserved for
refractory HTN
Hypotension reflex tachycardia
(aggravate ischemia), flattened
or inverted T waves,
hypertrichosis
Should be combined with -blocker to
prevent reflex tachycardia.
Diazoxide Activates ATP-sensitive K+
channels, leading to
hyperpolarization and
vasodilation, decreasing afterload
Refractory HTN and
HTN emergencies
Reflex tachycardia leading to
mycocardial ischemia, salt and
water retention, increased renin
secretion, hyperglycemia due to
decreased insulin secretion
from pancreas due to opening
K+ channels,

Sodium
Nitroprusside
Metabolized by the blood vessels
to produce NO. Dilates both
arterioles and venules, decreasing
afterload and preload.
Primarily for HTN
emergencies
Toxicity from cyanide or
thiocynate (treat with sulfur
compounds/sodium
thiosulfate), rebound HTN,
increased levels of renin.

Class I
antiarrhythmics
(Na+ channel
blockers)

Ia Slow rate of rise of phase 0 of AP,
prolong QRS (+) and QT
(++), and increases ventricular
refractory period. Intermediate
speed of association/dissociation
with active/inactive channels.
Use dependent
Atrial fibrillation and
ventricular
taccycardia,
alternatives for SVT
Combining drugs with fast and slow rate of
recovery (Mexiletine-fast + quinidine-
intermediate) is useful when neither drug
alone is effective, deaths due to
irreversible ventricular tachycardia
Quinidine Same plus some class III (K+
channel) activity increases
refractoriness, has vagolytic
action (increase AV
conduction), IV use causes
alpha-adrenergic block leading to
hypotension and reflex
tachycardia
Cinchonism (blurred vision,
photophobia, tinnitus,
psychosis, vertigo, headache),
hepatitis, bone marrow
suppression, lupus,
thrombocytopenia, purpuric
rash, class III activity =
torsades, diarrhea could lead to
hypokalemia
Cytochrome P450 metabolism, reduces
clearance of digoxin, metabolism inducible
by Phenobarbital and phenytoin,
Procainamide Similar action to quinidine minus
vagolytic and alpha-adrenergic
blocking. Converted to N-acetyl
procainamide (lacks Na+ blocking
but has class III property).
Alternative for Vtach
and digoxin-induced
Vtachyarrhythmia
Lupus like syndrome NAPA is excrete renally so renal dosing is
necessary. Inconvenient due to short ½
life (dosing 3-8 X/day)
Disopyramide Does not block alpha adrenergic,
but his high Anticholinergic action
Atrial flutter and
fibrillation and
recurrent ventricular
tachycardia or
fibrillation
Dry mouth, constipation,
urinary retention, constipation,
double vision
Avoid in HF and prostatism
Class IB Have little effect on rate of
depolarization. Decrease duration
of AP and decrease QT. Rapidly
interact with Na+ channels

lidocaine Blocks open or inactivated Na+
channels, does not markedly slow
conduction so has little effect on
atrial or AV arrhythmias
Ventricular
arrhythmias during
myocardial ischemia
(MI), DOC for
emergency tx of
cardiac arrhythmias
Seizures, tremor, sedation,
slurred speech, nystagmus is
early sign of toxicity
IV only
Phenytoin Similar to lidocaine Digitalis induced
ventricular
arrhythmias
Nystagmus, ataxia, lethargy, GI
intolerance, gingival
hyperplasia, hirsutism
Inducer of cyt p450
Mexiletine Similar to lidocaine Ventricular
tacchyarrhythmias
GI, fatigue, dizziness, seizures,
sleep upset, visual
disturbances, psychosis, fever,
Oral administration
blood dyscrasias, hepatitis,
Tocainide Ventricular
tacchyarrhytmias
Pulmonary fibrosis, fatal
aplastic anemia, tremor and
nausea

Class IC Depress rate of rise of phase O,
cause marked slowing of
conduction prolonging action
potential QRS (++), QT (+).
Bind and dissociate slowly ( >
10s)

Flecainide Prolongs PR, QRS, and QT Chronic treatment of
atrial fibrillation and
atrial flutter
Increased mortality in pts
convalescing from MI, new
arrhythmias, heart failure
exacerbation
Not recommended in pts recovering from
underlying heart disease
Class II (beta
blockers)
Blocks sympathetic action,
slowing phase 4 depolarization,
slowing automaticity, prolonging
AV conduction, and decreasing
HR and contractility, increase
energy required to fibrillate the
heart
Useful in treating
tachyarrthythmias
caused by
sympathetic activity
and in controlling
reentrant arrythmias
involving the AV
node and in slowing
ventricular response
in atrial fibrillation
and atrial flutter.
Pts with congenital
long QT syndrome
are prone to
arrthythmias caused
by stress so class
II’s are useful.
Arrthythmias
induced by Na+
channel block
respond to -
blockers
Fatigue, bronchospasm,
impotence, heart block,
depression, aggravation of HF,
worsen symptoms of PVD,
increases hypoglycemia in
diabetics, abrupt
discontinuation can result in
arrhythmias, HTN, and angina.
Not to be used in WPW-syndrome, -
blockers with sympathomimetic activity
may not be useful in arrhythmias
Propranolol Also has Na+ channel blocking
action at higher doses

Acebutolol Effectively reduces
ventricular ectopic
beats just as
effectively as
quinidine

Sotalol Also has K+ channel block
Esmolol Cardioselective and rapidly
metabolized
Used to prevent
cardiac arrhythmias

while recovering
from anasthesia
Class III
antiarrhythmics -
Potassium
channel blockers
QT (+++) predisposes to long-QT
syndrome (EAD - torsades), no
change in QRS. Blockade of K+
channels increasing the action
potential duration by slowing
repolarization. Reduces abnormal
automaticity.

Amiodarone Thyroid hormone analog blocks
Na+, Ca++, and K+ channels and
has noncompetitive adrenergic
blocking action. Prolongs AP and
refractory period.
Drug of choice for
ventricular
fibrillation and
sustained
ventricular
tachycardia
Pulmonary fibrosis, blue
skin, hyper or
hypothyroidism,
photosensitivity, corneal
microdeposits, liver toxicity,
testicular dysfunction,
bradycardia, heart block, new
Vfib.
Although increases QT interval, torsades is
rare, oral administration, has half life of
several weeks and distributes
extensively in adipose tissue
Bretylium Prolongs AP duration, no effect
on Na+ channels except at higher
concentrations
Orthostatic hypotension,
increased sensitivity to
catecholamines, initial increase
in arrhythmias, nausea and
vomiting, long QT can
predispose to torsades

Dofetilide, ibutilide Block K+ current and slow inward
Na+ and prolong AP duration
Can be used in pts
with atrial fibrillation
and HF, or with
impaired LV function
Torsades de pointes Should not be used in pts with renal failure
Calcium channel
blockers

Verapamil, diltiazem
AV nodal refractoriness increased,
AV nodal conduction velocity
decreased (PR interval increased)
Used to control
ventricular rate in
Afib and Aflutter.
DAD-mediated Vtach
respond well to
verapamil
Hypotension, constipation,
bradycardia, AV block
Not for use in WPW syndrome or in pts
with depressed cardiac function (HF), not
useful in Vtach, increase digoxin
concentration
Miscellaneous
anti-arrhythmics

Digoxin Increases intracellular Ca++ via
Na/K+ATPase block (lower
extracullar sodium inhibits
Na+/Ca++ exchanger), vagotonic
action slows AV conduction
Very useful in
arrhythmias
involving AV node,
also increased
cardiac contractility
so useful in HF
DAD related tachycardia due to
increased intracellular Ca++,
hypokalemia or
hypomagnisemia predisposes to
digoxin-induced arrhythmias,
bradycardia, AV block
Overdose treated with digoxin antibody
fragments (DigiBind), long half life
Adenosine Activates Ach-sensitive K+
channel by  subunit of trimeric
G-protein, hyperpolarizes the cell
and slows automaticity. Inhibits
electrophysiological effects of
Acute SVTs Flushing, dyspnea, chest
discomfort, asystole,
bronchoconstriction
IV administration
increased cAMP
Magnesium Mechanism unknown Prevents torsades de
pointes and digoxin-
induced arrhythmias
Areflexia, respiratory
depression, bradycardia, AV
block, asystole
IV administration
Coronary Artery
Disease
Angina related to wall stress
(intraventricular pressure, ventricular
radius, wall thicknesss), contractility, HR
Nitrates

Nitroglycerin,
Isosorbide dinitrate,
amylnitrate
(inhalation)

NO   guanylate cyclase  
cGMP  (1)  Potassium
conductance (2)  calcium (3) 
myosin light phosphatase  
phosphorylated MLC = vascular
smooth muscle relaxation
Relax veins >
arteries, reducing
preload and
afterload and
reducing cardiac
oxygen demand
Headache, reflex tachycardia,
orthostatic hypotension
Tolerance develops, concurrent use with
sildenafil (Viagra) can cause severe
hypotension, may increase epicardial
coronary arteries
Beta blockers Decrease HR, decrease
contractility = decrease
myocardial oxygen demand
Not useful in Prinzmetal’s angina (use
Ca++ blockers). Can increase LVEDV due
to slowed HR, which can increase oxygen
demand
Calcium channel
blockers
Decrease contraction, decrease
afterload via arteriodilation,
inhibit coronary vasospasm in
Prinzmetal’s angina. (no effect on
preload)
Constipation, peripheral edema,
pulmonary edema
Contraindicated in WPW and Vtach,
increase digoxin levels

ACEs Reduce preload and afterload
Ranolazine Reduces fatty acid oxidation for
myocardial energy demand,
leading to increased use of
glucose which requires less O2
Chronic angina Constipation, nausea, dizziness,
headache, QT prolongation
Should be combined with a nitrate, beta
blocker, or Ca++ channel blocker,
expensive
Anticoagulants
Heparinoids

Unfractionated
heparin
ATIII-heparinoid complexes bind
with high affinity to factor Xa and
IIa

IV only

Safe for pregnancy (does not
cross placenta or into milk)

Metabolism: fast saturable phase
in liver and slow nonsaturable
phase is renal…1/2 life increases
in hepatic disease
Surgery, thrombosis
prophylaxis
(unstable angina,
post MI), venous
thrombosis or PE,
DIC, Tx of severe
hypertriglyceridemia
Bleeding, (HIT) heparin
induced thrombocytopenia
(causes thrombosis via Hep-pf4
complex binds platelet, anti
hep-pf4 antibody binds Fc
region of platelet and
activates)…risk highest in
bovine > porcine

increase ALT/AST/bilirubin,
osteoporosis, inhibition of
aldosterone and hyperkalemia
Secondary paths of heparin: stimulates
other thrombin antagonists (Plasminogen
activator I, protein C inhibitor). Can
inactivate plasmin, inhibiting fibrinolysis,
high doses decrease platelet activation,
activates release of LPL to decrease TG

aPTT goal is 1.5-2.8 increase
LMWHs and
fondaparinux
Bind with high affinity with Xa,
but NOT to IIa

Can be administered
Advantages: similar
anticoagulant
efficacy, 4 times less
risk of HIT, longer
Disadvantages: Not to be used
in renal failure, protamine
sulfate only partially neutralizes
excess LMWH
Not to be used in pregnancy
subcutaneously half life, renal
clearance, more
predictable kinetics,
does not require
aPTT

Fonaparinux: most
predictable kinetics,
lowest rsk of HIT

Fondaparinux: renally cleared,
no antidote
ATryn (recombinant
ATIII)
Bind and inactivate Xa and IIa
with 4 times higher affinity for
thrombin and decreased ½ life.
Prevention of peri-
operative and peri-
partum
thromboembolic
events in hereditary
ATIII deficient Pts
bleeding
Protein C derivative

Ceptroin,
Drotrecogin Alfa,
Xigris
Protein C proteolyses and
inactivates factor V and VIIIa

Inhibits plasminogen activator
inhibitor  increased fibrinolysis
Used for severe
sepsis and septic
shock

Sepsis 
inactivation of
protein C 
procoagulant state
Bleeding, hypersensitivity Not very effective
Hirudin (direct
thrombin inhibitors)

Derivates: lepirudin,
desirudin, bivalirudin
Produces by salivary gland of
leeches

Binds to thrombin (IIa) and
inhibits   activation XIII

Renal and proteolytic cleavage
elimination
Pts with risk of HIT Monitor with aPTT

Not for use in pts with renal failure
Argatroban
(synthetic thrombin
inhibitor)
Inhibits thrombin

IV administration

Hepatic metabolism
Percutanous
coronary
intervention (PCI),
pts with risk of HIT,
endstage renal
disease (ERSD)
Can be used in renal disease
Warfarin (Coumadin) GGC in liver ER oxidizes KH2 to
KO. Warfarin inhibits Vit K
epoxide reductase, which
normally converts Vit K epoxide
(KO) to active Vit K (KH2)
activation of factors II, VII, IX, X,
proteins C and S. KH2 deficiency
develops an prevents Glu  Gla
 fewer active Vit K dependent
Prophylaxis of
thrombosis end
embolic
complications in
atrial fibrillation and
cardiac valve
replacement
Skin necrosis, not
recommended in pts with newly
diagnosed HIT, can worsen
protein C and S deficiency
before anticoagulant effects
begin

Poorly metabolized by
individuals with CYP2C9*2 and
Oral use, absorbed in gut, slow onset
(days), factor VII has shortest ½ life of 6
hours (depleted first), II has longest ½
life.

Crosses placenta, DO NOT use in
pregnancy

Barbituates phenytoin induce CYP  
clotting factors *3 (require lower dosage)

VKORC1 gene type A sensitive
to warfarin, type B requires
increased dose

Monitor prothombin time (PT),
factors II, VII, X important
determinants of PT

Desired INR 1.5-2.5 normal PT
warfarin activity

Ginseng, herbs with Vit K (alfalfa, green T)
 warfarin action

Cayenne, feverfew, garlic, ginkgo, ginger 
platelet aggregation

Antibiotics, anabolic steroids   warfarin
action

Antidote: Vitamin K, fresh frozen plasma if
immediate reversal needed
Antithrombotics Decrease incidence
of MI, stroke, TIA,
prevent thrombus on
prosthetic valves and
tissue grafts

Aspirin Irreversibly inhibits COX1 and
COX2, COX1 needed for TXA2
formation, TXA2 increases
platelet aggregration and
vasospasm
Peptic ulcers, bleeding, allergy
(bronchospasm), hepatic and
renal toxicity

Dipyridamole Decreases catabolism and uptake
by platelets. Adenosine binds to
platelets   cAMP   platelet
activation

Inhibits phosphodiesterases,
further increasing cAMP
Weak effects in monotherapy Increases aspirin and clopidogrel
antithrombotic efficacy
Purinergic receptor
inhibitors

Clopidogrel,
Prasugrel,
Ticlopidine
Platelets containing purinergic
receptors P2Y1 (GPIIb/IIIa)
and P2Y12 ( cAMP)

Drugs inhibit this action
Combo with aspirin
only recommended
for angioplasty and
stenting

Clopidogrel for TIA
Nausea, vomiting, diarrhea
Rare: hepatotoxicity,
neutropenia, HUS and TTP

Clopidogrel has less toxicity
Clopidogrel has variable absorption due to
variants of drug-efflux transporter, P-
glycoprotein (ABCB1 gene)

Genotype TT = higher efflux
CC = wild type (higher clopidogrel levels)
Glycoprotein IIb/IIIa
inhibitors

Abciximab,
Eptifibitide, Tirofiban
Abciximab – antibody binds to
GPIIb/IIIa receptor, blocking
fibrinogen binding

Eptifibitide/Tirofiban – bind
fibrinogen GPIIb/IIIa binding site

IV administration
High risk PCI Bleeding, thrombocytopenia Abciximab is expensive
Thrombolytics
(They. Dissolve.
Evolving MI and
stroke, DVT and PE

Clots.)
Streptokinase and
urokinase
Streptokinase – forms complex
with plasminogen. SK-
plasminogen complex cleaves
plasminogen to plasmin 
cleaves fibrin
PE, reperfusion with
STEMI, stroke,
prosthetic valve
thrombosis, venous
thrombosis
Activator not localized to clots,
causes antibody production

Major bleeding and intracranial
hemorrhage due to lysis of
fibrin in physiological thrombi
Both are infrequently used

Contraindications: surgery within 10 days,
recent active bleeding, aortic dissection,
HTN
Alteplase (r-tPA) Tissue plasminogen activator

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