Cardiac Drugs

Firman DullahSMF Ilmu Penyakit Jantung &

Pembuluh DarahRS Bahteramas Kendari

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OVERVIEW

Autonomic nervous system review

Cardiac Drug`s

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Autonomic NervousSystem

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Autonomic Nervous System

Also known as the Visceral Nervous System and Involuntary Nervous System.Is a division of peripherial nervous system system that influences the function of internal organs.

It is regulated within the brain by the Hypothalamus.

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Autonomic Nervous System

Functions– Regulation of cardiac function– Temperature regulation– Fluid & electrolyte balance– Metabolism– Digestion– Excretion

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Autonomic Nervous System

SympatheticFight or flight response

ParasympatheticRelaxation response

NorepinephrineEpinephrine --- released fromadrenal medulla

Acetylcholine

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Actions of autonomic drugs

• Increase the amount of neurotransmitters• Inhibit or augment the breakdown of

neurotransmitters in the synaptic cleft• Interact with post-synaptic receptors

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Receptor Types

AlphaReceptor

Beta

Receptor

Vasoconstrictionureteral contraction

Beta-1----- Increased myocardial contractility & rate

Beta-2-----Vasodilation, bronchodilation Stimulated by norepinephrine & epinephrine 8

Sympathetic Stimuli

• Stress• Hypoglycemia• Postural hypotension• Exercise

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Receptor Types: Parasympathetic

• Decreased heart rate, increased GI motility, relaxation of bladder sphincter– Stimulated by acetylcholine & baroreceptors

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CARDIAC DRUG`S

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CARDIACDRUG`S

* Alpha blockers* Beta blockers

* Nitrates

* ACE Inhibitors (ACE-I)* Angiotensin Receptor

Blockers (ARB)* Calcium Channel Blockers (CCB)

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Alpha blockersDoxazosin (Cardura), Terazosin (Hytrin)

• Action: block alpha-1 receptors smooth muscle relaxation

• Uses:– Prostate enlargement– Hypertension

• Side effects– Orthostatic hypotension • First dose at bedtime• Change position carefully

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Beta blockersBisoprolol(Concor),Propanolol(Inderal), Atenolol(Tenormin), metoprolol (Fapressor), Carvedilol

(VBloc)

• Action: Blocks sympathetic nervous system stimulation – lowers heart rate, BP– reduces myocardial work, lowering oxygen consumption

• Uses: – Blood pressure control– Control of angina– Prolongs survival after MI (prevents arrhythmias)– Prolongs survival in heart failure– Treatment of certain abnormal heart rhythms– Prevention of Migraines

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Beta Blockers

• Cautions:– Worsening heart failure in acute CHF– Bradycardia when combined with calcium channel

blockers • (often combined in angina)

– Diabetics: masking of hypoglycemia– Exacerbation of wheezing in asthmatics

• Adverse effects– Symptomatic bradycardia– Hypotension– Fatigue

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Implications

• Check pulse and BP prior to administration– Goal for pulse in patient with CAD often 50-60, as

tolerated• Patient education– Check pulse– Make sure they know why they are taking it!– Diabetics: hypoglycemia issue

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NITRATE

• Isosorbid Mononitrate, Isosorbid Dinitrate, Isosorbid Trinitrate, Nitroglycerin(NTG).

• Provide an exogenous source of Nitrit Oxide (NO) ---- cAMP ---- Vasodilator.

• Venous dilation predominates.

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Implications

• Beware of nitrat tolerance.• Education and Self monitoring patient`s

needed.• Side Effect : Headache, Flushing and rash,

Dizziness, Postural hypotension and reflex tachycardia.

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ACE InhibitorsCaptopril, Ramipril, Enalapril (Vasotec), Lisinopril (Zestril)

• Blocks conversion of Angiotensin I to Angiotensin II– Blocks vasoconstriction effects of Angiotensin II– Blocks sodium retention effect of Aldosterone• Effects: reduced peripheral vascular resistance, less

fluid retention

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ACE inhibitors

• Uses– Management of heart failure, prolongs survival• Decreases preload and afterload

– Control of high blood pressure• Diabetics: protective effect on kidneys• Works well with HCTZ

– Prolongs survival in MI with LV dysfunction• Prevents enlargement during remodeling phase of

recovery

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ACE Inhibitors

• Adverse effects– Cough ( increase of bradykinin)• Substitute Angiotensin receptor blocker

– Lightheadedness, hypotension– Hyperkalemia– Kidney dysfunction in bilateral renal artery

stenosis• Watch renal function when first started

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Implications

• Check BP prior to giving– Note: in heart failure goal systolic BP may be 85-

90, • it may not decrease BP in these patients• Always check with MD before holding dose

• Monitor creatinine, potassium• Patient education:– Patient must know why it is being taken– Stopping ACE in CHF can cause worsening, leading

to hospitalization!22

Angiotensin receptor blockers (ARB’s)

• Also called Angiotensin II inhibitors• Losartan (Cozaar), Valsartan (Diovan),

Irbesartan, Telmisartan, Candesartan.• Blocks Angiotensin II effects --/-- the AT1

receptor`s.• No effects on bradykinin no cough

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Angiotensin receptor blockers

• Uses:– Substitute for ACE, when not tolerated due

to cough• Heart failure management• Hypertension

–Adverse effects similar to ACE, no cough–Generally well-tolerated

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Calcium Channel BlockersAmlodipine (Norvasc), Diltiazem (Cardizem), Nifedipine (Procardia),

Verapamil (Calan)

• Action: Blocks calcium entry into cells, decreasing the strength of contraction– Relaxation of smooth muscle– Decreased heart work– May slow heart rate

• Uses– Blood pressure control– Angina Control– Heart rate control in atrial arrhythmias

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Calcium Channel Blockers

• Several types of CCB• Adverse effects– Verapamil: constipation– Dizziness, flushing, peripheral edema

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Diuretics

• Prevent sodium reabsorption and facilitates fluid excretion in kidneys.Prevent sodium reabsorption and facilitates fluid

excretion in kidneys.

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Loop diureticsFurosemide (Lasix), Bumetanide (Bumex)• Very potent• Used for fluid overload, especially CHF• Larger doses needed with renal dysfunction • Frequent dose adjustments made• Adverse effects: – potassium and magnesium wasting• Monitor potassium levels with dosage change • Potassium supplements

– Dehydration, hypotension, lightheadedness• Reduce dose, replace fluids

– Ototoxicity with rapid IV administration29

Diuretics• Thaizide Diuretics–Hydrochlorothiazide (HCTZ) –Milder than loop diuretics–Used for hypertension, edema• Often combined with other

antihypertensives for synergistic effect• Adverse effects: potassium and magnesium

loss

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Potassium-sparing Diuretics

• Spironolactone, triamterene• Mild diuretics• Used in combination with other diuretics to

prevent potassium wasting• Side effects: – hyperkalemia

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Implications : diuretics

• DAILY WEIGHTS!– Weights are most accurate indicator of fluid status

changes

• Monitor electrolyte levels– Check potassium level before giving potassium

supplements

• Patient education:– Daily weights– May do sliding scale diuretic doses in CHF management

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Antithrombotic

Platelet Inhibitors

Anticoagulant

Fibrinolytics

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Platelet Inhibitors

PAR receptors

Respond to thrombin and TXA2 to activate Platelets

Aspirin (aspilet, thromboaspilet)

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Platelet Inhibitors

P2Y1, PY12 receptors

Respond to ADP Receptors to activate Platelets

Clopidogrel(Plavix,Vaclo), Prasugrel,Ticlopidine, Ticagrelor

(Brilinta)

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Platelet Inhibitors

GpIIBIIIA receptors

Binds Fibrinogen and and vWF to form platelet

Abciximab,Tirofiban, Eptifibatide

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Anti-coagulant

CLOTTING BLEEDING

Anticoagulants tip the balance towards bleeding

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Anticoagulant

Heparin• Unfractional Heparin(UFH)• Inhibits Factors Xa & the thrombin also

coagulation protease.• Drugs : Inviclot.

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Low Molecular Weight Heparin(LMWH)• One third of the molecular weight of heparin.• Greater bioavailability and a longer plasma

half life than heparin.• Same action with heparin.• Simple and single use but high cost.• Drugs : Fondaparinux(Arixtra),

Enoxaparin(Lovenox), Parnaparin, Dalteparin.

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Warfarin(Vitamin K Antagonist/VKA)• Oral anticoagulant.• Inhibits/inactivation of Vitamin K in hepatic

microsomes.• Needs monitoring and self-guided warfarin

therapy.• Depends on Index Normalized Ratio (INR)

Level.

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Direct Thrombin Inhibitor• Its acyl gluronides are competitive and cause

thrombin enable the conversion fibrin to fibrinogen.

• Dabigatran etexilate (Pradaxa)• No need Monitoring but high in cost

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Anti X-a Agents• Directly inhibits of factor X• Rivaroxaban (Xarelto), Apixaban• No Need Monitoring

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Fibrinolytic

• Thrombolytic/Reperfusion therapy• The generation of plasmin ---plasminogen that

binds to the clot surface to lyse the clot• Needs special preparation and checklist• Be careful of allergic paients --- rare case• Drugs : Streptokinase, Urokinase

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Fibrinolytic

• Tissue Plasminogen Activator (tPA)• Is a naturally occuring enzyme that binds to

fibrin with a greater afinity than streptokinase/urokinase.

• Needs special preparation and checklist• Drugs : Alteplase, Reteplase, Tenecteplase

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AntiArrhytmia

• Divided by Vaughan Wiiliams Class.Class I --- IA, IB & ICClass IIClass IIIClass IV

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Anti-arrhythmic Agents– Classification of anti-arrhythmic agents with the

Vaughan-Williams system (Classes I, II, III and IV) • Based on their effects on certain ion channels and/or

receptors• Class I agents further divided into subclasses IA, IB and IC

based one electrophysiological effects• Class I agents –Mechanism of Action: block Na+ channels, slow

conduction velocity, prolong refractoriness, decrease automaticity of sodium-dependent tissues– Subclasses due to differences in effect on repolarization

(recovery)» Subclass IA – block K+ channels (prolonged recovery phase)

resulting in QRS widening and QT prolongation» Subclass IB – do not block K+ channels but shorten repolarization

phase» Subclass IC – no effect on repolarization phase but profoundly

slow conduction velocity resulting in QRS widening 47

–Subclass indications:»Class IA – Atrial and ventricular

arrhythmias»Class IB – Ventricular arrhythmias»Class IC - Atrial and ventricular

arrhythmias• Class II agents– Mechanism of Action: Beta-adrenergic antagonist

with decreased heart rate– Indications:»Slow ventricular rate in Atrial

Flutter/Fibrillation and Paroxysmal SupraVentricular Tachycardia (PSVT)»Symptomatic Premature Ventricular

Contractions (PVC)48

Anti-arrhythmic Agents

–Classification of anti-arrhythmic agents with the Vaughan-Williams system (Classes I, II, III and IV) continued:• Class III agents –Mechanism of Action: block K+ channels leading to

prolonged repolarization and QT prolongation– Indications:» Amiodarone – Atrial and ventricular arrhythmias» Bretylium – Ventricular arrhythmias » Sotalol – Ventricular arrhythmias» Butilide and dofetilide – conversion of atrial

flutter/fibrillation49

• Class IV agents–Mechanism of action: Ca+2 channel blockers

decreasing the heart rate– Indications: slow ventricular rate in atrial

flutter/fibrillation and PSVT

•Misc. Agents–Digoxin - slow ventricular rate in atrial

flutter/fibrillation and PSVT–Adenosine – endogenous hormone that

slows conduction through cardiac tissue, used to treat PSVT

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Anti Arrhytmia Drug ClassesClass Channel Effect Repolarization Time Drugs

IA Sodium Block Effect ++ Prolongs QuinidineDisopiramideProcainamide

IB Sodium Block Effect + Shortens LidocainePhenitoinMexiletineTocainide

IC Sodium Block Effect +++ Unchanged FlecainidePropafenone

II A pacemaker and Depolarizing current; indirect Ca Channel Block

Unchaged Beta Blocker

III Repolarizing K currents Markedly Prolongs AmiodaroneSotalolIbutilideDofetilide

IV Av Nodal Ca Block Unchaged VerapamilDiltiazem

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Cardiac glycosides

• Definitions--preload, afterload, inotrope, chronotrope, cardiac output

• Clinical effects--increase myocardial contractile force, the positive inotropic action increases CO, RBF and diuresis; decreases preload

• Uses--CHF, arrhythmias (afib and aflutter)

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Cardiac glycosides--Digoxin

• Mechanism of action-inhibition of the Na-K pump and increasing intracellular sodium to activate the Na-Ca carrier to increase calcium concentration inside the cell

• Results in an increase in the force of contraction of myocardial muscle fibers and increase in SV and CO

• Blood volume decreases, venous pressures and EDV decreases and distended heart returns to normal

• Decrease in sympathetic stimulation-renal elimination of sodium and water improves secondary to improved renal perfusion, heart rate decreases (decrease AV conduction)

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Digoxin

• Adverse effects--digitalis intoxication, electrolyte disturbances, cardiac arrhythmias, GI symptoms, visual disturbances, fatigue

• Heart rate must be checked prior to digoxin administration and must be >60 bpm

• Treatment is drug discontinuation and treat symptoms. Check dig.level to be between 0.5 to 2.0 ng/ml

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