Cardiac Pharmacology

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Cardiac Pharmacology
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Overview

• Cardiovascular A P Review
• Gross Anatomy
• Cellular Anatomy
• Drugs that affect the cardiac system

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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
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Anatomy and Physiology

• Anatomy
• Layers/myocardium
• Chambers
• Valves
• Veins
• Sinus

• Electrophysiology
• SA node
• AV Junction
• His-Purkinje
• Myocardial cells
• Electrical potential
• Autonomic Nervous system

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Myocardial Cells

• Action potential
• Depolarization
• Repolarization
• Critical electrolytes
• Sodium, potassium, calcium
• Excitability

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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

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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

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Drugs That Affect the Cardiac System
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Overview

• Cardiac Glycosides
• Sympathomimetics
• Anticholinergic Drugs
• Antidysrhytmics
• Electrolytes
• Thrombolytics
• Anticoagulants
• Antihypertensives
• Analgesics

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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

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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)

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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

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Sympathomimetics

• Adrenergic
• Specific Meds
• Epi / Nor-epi
• Vasopressin
• Dopamine
• Isuprel
• Dobutamine

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Epinepherine (Adrenalin)

• Catecholamine
• Alpha, Beta 1, and Beta 2 Stimulation
• Indications / Contraindications

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Precautions (EPI)

• May be deactivated by alkaline solutions
• Causes an increase in myocardial oxygen demand
• IVP EPI 11,000 should not be administered to any
  person with a pulse

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Vasopressin

• Naturally occurring antidiuretic hormone
• Causes vasoconstriction
• Increases circulation to brain (constriction)
  without Beta 1 effects
• Dose Replaces Epi 40 units IV
• If no response in 10 to 20 minutes, consider
  returning to EPI

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Dopamine (Inatropin)

• Pre-cursor to EPI NorEPI with effects varying
  upon dosage
• Indications
• Hypotensive / shock like patients in the absence
  of Hypovolemia

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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

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Dopamine

• Alpha Dose
• gt 15 micro/kg/min
• Venous constriction

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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

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Dobutamine (Dobutrex)

• Synthetic catacholamine with Beta 1 stimulating
  effects
• Primary inotropic effect
• Indications
• CHF
• Drip format

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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

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Atropine Sulfate

• Concerns
• Glaucoma
• GI Problems
• May increase the size of infarct

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Antidysrhymthmics

• Sodium Channel Blockers
• Beta Blockers
• K Channel Blockers
• Ca Channel Blockers

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Antidysrhythmics

• Treat prevent cardiac rhythm disturbances
• General mechanism of action
• Act directly on cardiac cell membrane
• Indirect action that affects the cardiac cells

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Antidysrhythmics

• Cardiac rhythm disturbances
• Ischemia
• Hypoxia
• H ion derangements
• Electrolyte imbalances
• Excessive catecholimine release
• Scarred / diseased tissue
• Drug toxicity

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Antidysrhythmics
Lethal Dysrhythmias
Disturbances in

• Impulse Formation
• Impulse Conduction

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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

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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

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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

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Lidocaine

• Antidysrhythmic
• Decreases phase 4 diastolic depolarization
• Decreases ectopy the fibrillation threshold
• Indications
• Contraindications
• Hypersensitive
• 2nd 3rd Degree Heart Block

Ventricular Escape Beats
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62 year old status post conversion from v-fib
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Class II Beta Blockers

• Reduce stimulation of Beta receptors
• Primary use in HTN -

More to follow
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Class III K Channel Blockers

• Block K channels
• Increase contractility with no effect on
  automaticity conduction velocity
• Includes
• Bretylium
• Amiodorone

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Amiodarone

• Antidysrhythmic
• Multiple mechanisms of action
• Prolongs duration of the action potential
• Indications
• Recurring VF VT
• Tachycardias

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Amiodarone

• Contraindications
• Pulmonary edema
• Hypotension
• Precautions
• May precipitate hypotension bradycardia when
  given with Beta Blockers Ca Channel Blockers

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Bretylium

• Used for patients who fail to respond to
  Lidocaine
• Exact mechanism unsure

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Class IV Calcium Channel Blocking

• Blocking the flow of Ca across the cell membrane
  may affect the automaticity conductivity of
  cardiac cells

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Calcium
2 Roles Muscle Contraction Impulse propagation
(Slow channels)
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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

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Common Generic Ca Channel Blockers

• Amlodipine (Norvasc, Lotrel)
• Bepridil (Vascor)
• Diltiazem (Cardizem)
• Felodipine (Plendil, Lexxel)
• Isradapine (Dynacirc)
• Nifedipine (Adalat, Procardia)
• Verapamil (Calan, Isoptin)

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Diltiazem (Cardizem)

• Indications
• Symptomatic A-Fib and A-Flutter
• Contraindications
• Hypotension less than 90mmHg
• 2nd or 3rd degree AV Block
• Hypersensitivity

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Cardizem Dosage

• .25 mg/kg slow IV push ( over 2 minutes)
• Repeat in 15 minutes _at_ .35mg/kg
• Consider 5 10 mg slow push for older patients
  borderline blood pressure

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Verapamil (Isoptin)

• Effects localized to SA AV node
• Decreases atrial automaticity
• Reduces smooth muscle vascular tone
• Decreases contractility

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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

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Adenosine

• Not effective with A-fib, A-flutter, or V Tach
• Adverse reactions
• Techniques

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Antihypertensives

• The Ideal Antihypertensive
• Maintain adequate BP
• Maintain perfusion
• Reduce workload of heart
• No undesirable effects
• Allow for long term administration

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Antihypertensives

• Diuretics
• Sympathetic Blocking Agents
• Vasodilators
• ACE Inhibitors
• Calcium Channel Blockers

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Diuretics

• Renal excretion
• Thiazides (HCTZ)
• Lasix
• K Sparing Agents Prevent loss of K
• Spironolactone

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Beta Blockers

• Control of Hypertension through blocking of Beta
  receptors
• Beta Blockades
• Inotropic effects
• Chronotropic effects
• Dromotropic effects

Selective Vs. Non-selective
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Common Beta Blockers

• Atenolol (Tenormin)
• Labetalol (Tandate)
• Levobunolol
• Metoprolol (Betaloc, Lopressor)
• Nadolol (Corgard)
• Propranolol (Inderal)
• Timolol maleate (Timoptol)

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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

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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

What happens to the BP?
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Common ACE Inhibitors

• Captopril (Capoten)
• Enalopril maleate (Innovace)
• Fosinopril (Staril)
• Lisinopril (Zestril)
• Perindopril (Coversyl)
• Quinopril (Accupro)
• Ramipril (Tritace)
• Trandolapril (Gopten, Odrik)

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Other Antihypertensives

• Calcium Channel Blockers may be used for HTN if
  other treatments are unsuccessful
• MAO Inhibitors may be used

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Vasodilator Drugs

• Act on smooth muscle of vasculature

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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

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Anticoagulants

• Platelets and fibrin clots repair damaged vessels
  
• 3 Major risk factors
• Stasis
• Localized trauma
• Hypercoagulable states

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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

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Anticoagulant

• Prevent thrombus by decreasing coagulability
• Examples
• Warfarin
• Heparin

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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

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Heparin

• Inhibits the formation of fibrin clots

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Antiplatelet Agents

• ASA
• Salicylate
• Inhibits synthesis of prostaglandins (mediators
  of inflammation)
• Inhibits platelet aggregation

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Thrombolytic Agents

• Dissolve clots by promoting the digestion of
  fibrin
• Goal Establish re-perfusion

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Thrombolytics

• 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

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Thrombolytics
What does this mean for us???
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Review

• Cardiac A P Review
• Cardiac Glycosides
• Antidysrhythmics
• Antihypertensives
• Anticoagulation