CARDIAC PHARMACOLOGY

Gerald Caesar O. Libranda, MD

 OVERVIEW

CARDIOVASCULAR A & P REVIEW

GROSS ANATOMY
CELLULAR ANATOMY

DRUGS THAT AFFECT THE CARDIAC SYSTEM

 Cardiovascular Disease
Cardiovascular Disease:
Major cause of death and disability in the US
950,000 die each year, 40% before reaching a hospital

Number one reason: underlying coronary artery or Ischemic heart

disease
Number one presenting rhythm precipitating cardiac arrest:
ventricular fibrillation
Risks:
Age
Heredity
Male
Cigarette smoker:
High lipids
Sedentary lifestyle
History
Pertinent past history of strokes, diabetes, hypertension

Copy DC Dave Murphy

 Anatomy and Physiology
Anatomy Electrophysiology
Layers/myocardium SA node
Chambers AV Junction
Valves His-Purkinje
Veins Myocardial cells
Sinus Electrical potential
Autonomic Nervous
system
 Myocardial Cells
Action potential

Depolarization
Repolarization
Critical electrolytes
Sodium, potassium, calcium
Excitability
 Channels
In cardiac muscle, sodium and calcium ions can enter the cell
through two separate channel systems in the cell membrane:
Fast channels
Slow channels
Fast channels are sensitive to small changes in membrane potential
As the cell drifts toward threshold level (the point at which a
cell depolarizes), fast sodium channels open
Results in a rush of sodium ions intracellularly and in very
rapid depolarization
Slow channel selectively permeable to calcium and to a lesser
extent to sodium
 Action Potential
The cardiac action potential can be divided into
5 phases (phases 0 through 4)
Phase 0 (rapid depolarization phase)
Phase 1 (early rapid depolarization phase)
Phase 2 (plateau phase)
Phase 3 (terminal phase of rapid
repolarization)
Phase 4
DRUGS THAT AFFECT THE
CARDIAC SYSTEM
 OVERVIEW
CARDIAC GLYCOSIDES
SYMPATHOMIMETICS
ANTICHOLINERGIC DRUGS
ANTIDYSRHYTMICS
ELECTROLYTES
THROMBOLYTICS
ANTICOAGULANTS
ANTIHYPERTENSIVES
ANALGESICS
 Digoxin
Cardiac Glycoside that has a positive
inotropic effect on the heart
Given for:
CHF
Afib / A Flutter / PAT
Derived from the Foxglove (Digitalis)
plant
 Digoxin
Inhibits sodium potassium ATPase
(Sodium potassium exchange pump)
Results in increased quantity of Ca in
sarcoplasmic reticulum
Increased Ca will result in greater
contractile strength
Increased contractile strength results in
increased glomerular pressure (Mild
diuretic)
 Digitalis Toxicity
Neurological
Visual Disturbances
Flashing lights
Altered color vision
GI Disturbances
Cardiac Rhythm Disturbances
Hyperkalemia
K and Digoxin both bind to the same site
on the sdoium/K pump
 SYMPATHOMIMETICS
ADRENERGIC
SPECIFIC MEDS:
EPINEPHRINE / NOR-EPIPINEPHRINE
VASOPRESSIN
DOPAMINE
ISUPROTERENOL
DOBUTAMINE
 EPINEPHERINE (ADRENALIN)

CATECHOLAMINE
ALPHA, BETA 1, AND BETA 2 STIMULATION
INDICATIONS / CONTRAINDICATIONS
 PRECAUTIONS (EPI)

MAY BE DEACTIVATED BY ALKALINE SOLUTIONS

CAUSES AN INCREASE IN MYOCARDIAL OXYGEN DEMAND
IVP EPI 1:1,000 SHOULD NOT BE ADMINISTERED TO ANY
PERSON WITH A PULSE
 VASOPRESSIN
NATURALLY OCCURRING ANTIDIURETIC HORMONE
CAUSES VASOCONSTRICTION
INCREASES CIRCULATION TO BRAIN (CONSTRICTION) WITHOUT
BETA 1 EFFECTS
DOSE: REPLACES EPINEPHRINE 40 UNITS IV
IF NO RESPONSE IN 10 TO 20 MINUTES, CONSIDER RETURNING TO EPI
 DOPAMINE (INATROPIN)

PRE-CURSOR TO EPI & NOREPI WITH EFFECTS VARYING

UPON DOSAGE
INDICATIONS:
HYPOTENSIVE / SHOCK LIKE PATIENTS IN THE ABSENCE OF
HYPOVOLEMIA
 DOPAMINE
DOSES:
RENAL DOSE
1 5 MICRO/KG/MIN
STIMULATION OF DOPAMINERGIC RECEPTORS THAT RESULT
IN RENAL, MESENTERIC, AND CEREBRAL VASODILATION
BETA DOSE
5 - 15 MICRO/KG/MIN
BETA 1 EFFECTS
 DOPAMINE

ALPHA DOSE
> 15 MICRO/KG/MIN
VENOUS CONSTRICTION
 ISOPROTERONOL (ISUPREL)
SYNTHETIC CATECHOLIMINE THAT STIMULATES BETA 1 &
BETA 2 (NO ALPHA) RECEPTORS
INCREASES INOTROPIC & CHRONOTROPIC ACTIVITY
INDICATIONS:
TORSADES DE POINTS
SYMPTOMATIC BRADYCARDIAS UNRESPONSIVE TO ATROPINE
 DOBUTAMINE (DOBUTREX)
SYNTHETIC CATACHOLAMINE WITH BETA 1 STIMULATING
EFFECTS
PRIMARY INOTROPIC EFFECT
INDICATIONS:
CHF

DRIP FORMAT
 ANTICHOLINERGIC
ATROPINE
PARSYMPATHOLYTIC
INHIBITS ACH AT POSTGANGLIONIC PARASYMPATHETIC RECEPTOR SITES
(MUSCARININC)
USED FOR SYMPTOMATIC BRADYCARDIAS AND TO ANTAGONIZE
EXCESS MUSCARINIC RECEPTOR STIMULATION FROM OPP / NERVE
AGENTS
 ATROPINE SULFATE

CONCERNS:
GLAUCOMA
GI PROBLEMS
MAY INCREASE THE SIZE OF INFARCT
ARRHYTHMIA VS DYSRHYTHMIA
ANTIDYSRHYMTHMICS

Sodium Channel Blockers

Beta Blockers
K+ Channel Blockers
Ca Channel Blockers
 ANTIDYSRHYTHMICS
TREAT & PREVENT CARDIAC RHYTHM
DISTURBANCES
GENERAL MECHANISM OF ACTION:
ACT DIRECTLY ON CARDIAC CELL MEMBRANE
INDIRECT ACTION THAT AFFECTS THE CARDIAC CELLS
 ANTIDYSRHYTHMICS
CARDIAC RHYTHM DISTURBANCES:
ISCHEMIA
HYPOXIA
H ION DERANGEMENTS
ELECTROLYTE IMBALANCES
EXCESSIVE CATECHOLIMINE RELEASE
SCARRED / DISEASED TISSUE
DRUG TOXICITY
ANTIDYSRHYTHMICS

Impulse Formation
Impulse Conduction
 ANTIDYSRHYTHMICS
ALL HAVE SOME ABILITY TO SUPPRESS AUTOMATICITY
CLASS I SODIUM CHANNEL BLOCKERS
CLASS II BETA BLOCKERS
CLASS III POTASSIUM CHANNEL BLOCKING
CLASS IV CALCIUM CHANNEL BLOCKING
 CLASS I SODIUM CHANNEL
BLOCKING

MECHANISM OF ACTION: SLOW CONDUCTION

CLASS IA PROCAINAMIDE
CLASS IB HAVE NO EFFECT ON CONDUCTION VELOCITY
LIDOCAINE & DILANTIN
CLASS IC PROFOUND SLOWING OF CONDUCTION
LIFE THREATENING DYSRHYTHMIAS ONLY
 PROCAINAMIDE
SUPPRESSES PHASE 4 DEPOLARIZATION
REDUCES AUTOMATICITY OF ECTOPIC FOCI
INDICATIONS:
PVCS REFRACTORY TO LIDOCAINE
VT WITH A PULSE REFRACTORY TO LIDOCAINE
WIDE COMPLEX PSVTS

DOSE: 20 MG/MIN INFUSION

 LIDOCAINE
ANTIDYSRHYTHMIC
DECREASES PHASE 4 DIASTOLIC DEPOLARIZATION
DECREASES ECTOPY & THE FIBRILLATION THRESHOLD
INDICATIONS
CONTRAINDICATIONS
HYPERSENSITIVE
2ND & 3RD DEGREE HEART BLOCK
 CLASS II BETA BLOCKERS
REDUCE STIMULATION OF BETA RECEPTORS
PRIMARY USE IN HTN
 CLASS III K CHANNEL BLOCKERS
BLOCK K CHANNELS
INCREASE CONTRACTILITY WITH NO EFFECT ON
AUTOMATICITY & CONDUCTION VELOCITY
INCLUDES:
BRETYLIUM
AMIODORONE
 AMIODARONE
ANTIDYSRHYTHMIC
MULTIPLE MECHANISMS OF ACTION:
PROLONGS DURATION OF THE ACTION POTENTIAL

INDICATIONS
RECURRING VF & VT
TACHYCARDIAS
 AMIODARONE
CONTRAINDICATIONS:
PULMONARY EDEMA
HYPOTENSION

PRECAUTIONS:
MAY PRECIPITATE HYPOTENSION & BRADYCARDIA WHEN GIVEN
WITH BETA BLOCKERS & CA CHANNEL BLOCKERS
 BRETYLIUM
USED FOR PATIENTS WHO FAIL TO RESPOND TO
LIDOCAINE
EXACT MECHANISM UNSURE
 CLASS IV CALCIUM CHANNEL
BLOCKING

BLOCKING THE FLOW OF CALCIUM ACROSS THE CELL

MEMBRANE MAY AFFECT THE AUTOMATICITY &
CONDUCTIVITY OF CARDIAC CELLS
 Calcium
Muscle Contraction
Impulse propagation (Slow channels)
 Calcium Channel Blocker
Works to block some of the calcium
channels in smooth muscle.Dilated
Vessels
Blocks the slow Ca channels of Cardiac
cellsdecreased conduction velocity
Common Generic Ca Channel
Blockers
Amlodipine (Norvasc, Lotrel)
Bepridil (Vascor)
Diltiazem (Cardizem)
Felodipine (Plendil, Lexxel)
Isradapine (Dynacirc)
Nifedipine (Adalat, Procardia)
Verapamil (Calan, Isoptin)
DILTIAZEM (CARDIZEM)
INDICATIONS
SYMPTOMATIC A-FIB AND A-FLUTTER

CONTRAINDICATIONS
HYPOTENSION LESS THAN 90MMHG
2ND OR 3RD DEGREE AV BLOCK
HYPERSENSITIVITY
 CARDIZEM DOSAGE
.25 MG/KG SLOW IV PUSH ( OVER 2 MINUTES)
REPEAT IN 15 MINUTES @ .35MG/KG
CONSIDER 5 10 MG SLOW PUSH FOR OLDER PATIENTS
& BORDERLINE BLOOD PRESSURE
 VERAPAMIL (ISOPTIN)

EFFECTS LOCALIZED TO SA & AV NODE

DECREASES ATRIAL AUTOMATICITY
REDUCES SMOOTH MUSCLE VASCULAR TONE
DECREASES CONTRACTILITY
 ADENOSINE
FORMED BY THE BREAKDOWN OF ATP
SLOWS SVTS BY SLOWING CONDUCTION THROUGH AV NODE
CAN BE USED DIAGNOSTICALLY IN WIDE COMPLEX TACHYCARDIAS
OF UNKNOWN ORIGIN
CAN BE EFFECTIVE WITH WPW
 ADENOSINE
NOT EFFECTIVE WITH A-FIB, A-FLUTTER, OR V TACH
ADVERSE REACTIONS
TECHNIQUES
 ANTIHYPERTENSIVES
THE IDEAL ANTIHYPERTENSIVE:
MAINTAIN ADEQUATE BP
MAINTAIN PERFUSION
REDUCE WORKLOAD OF HEART
NO UNDESIRABLE EFFECTS
ALLOW FOR LONG TERM ADMINISTRATION
 ANTIHYPERTENSIVES
DIURETICS
SYMPATHETIC BLOCKING AGENTS
VASODILATORS
ACE INHIBITORS
CALCIUM CHANNEL BLOCKERS
 DIURETICS
RENAL EXCRETION
THIAZIDES (HCTZ)
LASIX

K+ SPARING AGENTS PREVENT LOSS OF K+

SPIRONOLACTONE
 BETA BLOCKERS
CONTROL OF HYPERTENSION THROUGH BLOCKING
OF BETA RECEPTORS
BETA BLOCKADES
INOTROPIC EFFECTS
CHRONOTROPIC EFFECTS
DROMOTROPIC EFFECTS
 Common Beta Blockers
Atenolol (Tenormin)
Labetalol (Tandate)
Levobunolol
Metoprolol (Betaloc, Lopressor)
Nadolol (Corgard)
Propranolol (Inderal)
Timolol maleate (Timoptol)
 The Beta Blocker OD
Through the production of cAMP, increased
Glucagon levels in the body will result in
increased myocardial contractile strength
(Positive Inotropic response)
cAMP is a second messenger that causes a
release of catecholamines, and therefore
vasoconstriction
 ACE Inhibitors
Angiotensin Co-enzyme Inhibitors
Angiotensinogen & Renin = Angiotensin I
Angiotensin I is converted to Angiotensin II
Angiotensin II causes the release of Aldosterone
(hormone) from adrenal cortex
Aldosterone causes the retention of sodium in
the proximal and distal tubules
 Common ACE Inhibitors
Captopril (Capoten)
Enalopril maleate (Innovace)
Fosinopril (Staril)
Lisinopril (Zestril)
Perindopril (Coversyl)
Quinopril (Accupro)
Ramipril (Tritace)
Trandolapril (Gopten, Odrik)
 OTHER ANTIHYPERTENSIVE

CALCIUM CHANNEL BLOCKERS MAY BE USED FOR HTN IF

OTHER TREATMENTS ARE UNSUCCESSFUL
MAO INHIBITORS MAY BE USED
 VASODILATOR DRUGS

ACT ON SMOOTH MUSCLE OF VASCULATURE

 VASODILATORS
DECREASE PERIPHERAL VASCULAR RESISTANCE, PRELOAD,
(OR BOTH) AND THEREFORE DROP BP
SOME DILATE ARTERIOLES
DECREASES PVR (AFTERLOAD)
HYDRALAZINE
SOME DILATE BOTH ARTERIOLES AND VEINS
DECREASES BOTH AFTERLOAD AND PRELOAD
SODIUM NITROPRUSSIDE
 ANTICOAGULANTS
PLATELETS AND FIBRIN CLOTS REPAIR DAMAGED VESSELS
3 MAJOR RISK FACTORS:
STASIS
LOCALIZED TRAUMA
HYPERCOAGULABLE STATES
 THE BASICS OF CLOTS
CLOTTING FACTORS: CREATED IN LIVER (VITAMIN K)
PLASMINOGEN TRAPPED IN A CLOT AS WELL AS MANY OTHER
PLASMA PROTEINS
PLASMIN FORM WHEN NATURAL T-PA IS RELEASED FORM
ENDOTHELIAL CELLS AND DIGEST CLOTS
 ANTICOAGULANT
PREVENT THROMBUS BY DECREASING COAGULABILITY
EXAMPLES:
WARFARIN
HEPARIN
 WARFARIN SODIUM
COUMADIN
INTERFERES WITH THE HEPATIC SYNTHESIS OF VITAMIN K DEPENDENT
CLOTTING FACTORS
RESULTS IN THE DEPLETION OF CLOTTING FACTORS

INDICATIONS:
A-FIB
UNLABELED: MI
 HEPARIN
INHIBITS THE FORMATION OF FIBRIN CLOTS
 ANTIPLATELET AGENTS
ASA
SALICYLATE
INHIBITS SYNTHESIS OF PROSTAGLANDINS
(MEDIATORS OF INFLAMMATION)
INHIBITS PLATELET AGGREGATION
 THROMBOLYTIC AGENTS
DISSOLVE CLOTS BY PROMOTING THE DIGESTION OF
FIBRIN
GOAL: ESTABLISH RE-PERFUSION
 THROMBOLYTIC
ALTEPLASE & RETEPLASE
HUMAN TISSUE ENZYME
CONVERTS PLASMINOGEN INTO FIBRINOLYSIN
STREPTOKINASE
ENZYME ISOLATED FROM STREPTOCOCCI BACTERIA
CONVERTS PLASMINOGEN TO PLASMIN
UROKINASE
ISOLATED FROM HUMAN URINE
CONVERTS PLASMINOGEN TO PLASMIN