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1、Pharmacology,Drugs that Affect the Cardiovascular System,Topics,Electrophysiology Vaughn-Williams classification Antihypertensives Hemostatic agents,Cardiac Function,Dependent upon Adequate amounts of ATP Adequate amounts of Ca+ Coordinated electrical stimulus,Adequate Amounts of ATP,Needed to: Main
2、tain electrochemical gradients Propagate action potentials Power muscle contraction,Adequate Amounts of Calcium,Calcium is glue that links electrical and mechanical events.,Coordinated Electrical Stimulation,Heart capable of automaticity Two types of myocardial tissue Contractile Conductive Impulses
3、 travel through action potential superhighway.,A.P. SuperHighway,Sinoatrial node Atrioventricular node Bundle of His Bundle Branches Fascicles Purkinje Network,Electrophysiology,Two types of action potentials Fast potentials Found in contractile tissue Slow potentials Found in SA, AV node tissues,Fa
4、st Potential,-80,-60,-40,-20,0,+20,RMP -80 to 90 mV,Phase 1,Phase 2,Phase 3,Phase 4,controlled by Na+ channels = “fast channels”,Fast Potential,Phase 0: Na+ influx “fast sodium channels” Phase 1: K + efflux Phase 2: (Plateau) K + efflux AND Ca + + influx Phase 3: K+ efflux Phase 4: Resting Membrane
5、Potential,Cardiac Conduction Cycle,Slow Potential,-80,-60,-40,-20,0,Phase 4,Phase 3,dependent upon Ca+ channels = “slow channels”,Slow Potential,Self-depolarizing Responsible for automaticity Phase 4 depolarization slow sodium-calcium channels leaky to sodium Phase 3 repolarization K+ efflux,Cardiac
6、 Pacemaker Dominance,Intrinsic firing rates: SA = 60 100 AV = 45 60 Purkinje = 15 - 45,Cardiac Pacemakers,SA is primary Faster depolarization rate Faster Ca+ leak Others are backups Graduated depolarization rate Graduated Ca+ leak rate,Potential Terms,APD,ERP,RRP,relative refractory period,effective
7、 refractory period,action potential duration,Dysrhythmia Generation,Abnormal genesis Imbalance of ANS stimuli Pathologic phase 4 depolarization Ectopic foci,Dysrhythmia Generation,Abnormal conduction Analogies: One way valve Buggies stuck in muddy roads,Reentrant Circuits,Warning!,All antidysrhythmi
8、cs have arrythmogenic properties In other words, they all can CAUSE dysrhythmias too!,AHA Recommendation Classifications,Describes weight of supporting evidence NOT mechanism Class I Class IIa Class IIb Indeterminant Class III,View AHA definitions,Vaughn-Williams Classification,Class 1 Ia Ib Ic Clas
9、s II Class III Class IV Misc,Description of mechanism NOT evidence,Class I: Sodium Channel Blockers,Decrease Na+ movement in phases 0 and 4 Decreases rate of propagation (conduction) via tissue with fast potential (Purkinje) Ignores those with slow potential (SA/AV) Indications: ventricular dysrhyth
10、mias,Class Ia Agents,Slow conduction through ventricles Decrease repolarization rate Widen QRS and QT intervals May promote Torsades des Pointes!,PDQ: procainamide (Pronestyl) disopyramide (Norpace) qunidine (Quinidex),Class Ib Agents,Slow conduction through ventricles Increase rate of repolarizatio
11、n Reduce automaticity Effective for ectopic foci May have other uses,LTMD: lidocaine (Xylocaine) tocainide (Tonocard) mexiletine (Mexitil) phenytoin (Dilantin),Class Ic Agents,Slow conduction through ventricles, atria & conduction system Decrease repolarization rate Decrease contractility Rare last
12、chance drug,flecainide (Tambocor) propafenone (Rythmol),Class II: Beta Blockers,Beta1 receptors in heart attached to Ca+ channels Gradual Ca+ influx responsible for automaticity Beta1 blockade decreases Ca+ influx Effects similar to Class IV (Ca+ channel blockers) Limited # approved for tachycardias
13、,Class II: Beta Blockers,propranolol (Inderal) acebutolol (Sectral) esmolol (Brevibloc),Class III: Potassium Channel Blockers,Decreases K+ efflux during repolarization Prolongs repolarization Extends effective refractory period Prototype: bretyllium tosylate (Bretylol) Initial norepi discharge may c
14、ause temporary hypertension/tachycardia Subsequent norepi depletion may cause hypotension,Class IV: Calcium Channel Blockers,Similar effect as blockers Decrease SA/AV automaticity Decrease AV conductivity Useful in breaking reentrant circuit Prime side effect: hypotension & bradycardia,verapamil (Ca
15、lan) diltiazem (Cardizem) Note: nifedipine doesnt work on heart,Misc. Agents,adenosine (Adenocard) Decreases Ca+ influx & increases K+ efflux via 2nd messenger pathway Hyperpolarization of membrane Decreased conduction velocity via slow potentials No effect on fast potentials Profound side effects p
16、ossible (but short-lived),Misc. Agents,Cardiac Glycocides digoxin (Lanoxin) Inhibits NaKATP pump Increases intracellular Ca+ via Na+-Ca+ exchange pump Increases contractility Decreases AV conduction velocity,Pharmacology,Antihypertensives,Antihypertensive Classes,diuretics beta blockers angiotensin-converting enzyme (ACE) inhibitors calcium channel blockers vasodilators,Blood Pressure = CO X PVR,Cardiac Output = SV x HR PVR = Afterloa
