Cardiac Pharmacology

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
Layers/myocardium Chambers Valves Veins Sinus

Electrophysiology

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

Channels can enter the cell In cardiac muscle, sodium and calcium ions

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:
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:
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 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 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 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
Cardiac A & P Review Cardiac Glycosides Antidysrhythmics Antihypertensives Anticoagulation