Download Cardiac Pharmacology

Cardiac Pharmacology
Overview
• Cardiovascular A & P Review
• Gross Anatomy
• Cellular Anatomy
• Drugs that affect the cardiac system
Cardiovascular Disease
Cardiovascular Disease:
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Major cause of death and disability in the US
950,000 die each year, 40% before reaching a hospital
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Number one reason: underlying coronary artery or Ischemic heart
disease
Number one presenting rhythm precipitating cardiac arrest:
ventricular fibrillation
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Risks:
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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
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Layers/myocardium
Chambers
Valves
Veins
Sinus
Electrophysiology
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SA node
AV Junction
His-Purkinje
Myocardial cells
Electrical potential
Autonomic Nervous
system
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
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
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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:
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Epi / Nor-epi
Vasopressin
Dopamine
Isuprel
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 Epi 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
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:
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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
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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
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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 Ca across the cell
membrane may affect the automaticity &
conductivity of cardiac cells
Calcium
2 Roles:
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
cells…decreased conduction velocity
Common Generic Ca Channel
Blockers
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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)
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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:
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Maintain adequate BP
Maintain perfusion
Reduce workload of heart
No undesirable effects
Allow for long term administration
Antihypertensives
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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
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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
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Captopril (Capoten)
Enalopril maleate (Innovace)
Fosinopril (Staril)
Lisinopril (Zestril)
Perindopril (Coversyl)
Quinopril (Accupro)
Ramipril (Tritace)
Trandolapril (Gopten, Odrik)
Other Antihypertensives
• 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
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
Thrombolytics
Review
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Cardiac A & P Review
Cardiac Glycosides
Antidysrhythmics
Antihypertensives
Anticoagulation