Cardiac Arrhythmia and Antiarrhythmic Drugs PDF

Part 6 6: Card diac arrrhythmia a and an ntiarrhytthmic d drugs █ Bas sic inform mation ▌Cardiiac action potential  In the restin...

Part 6 6: Card diac arrrhythmia a and an ntiarrhytthmic d drugs █ Bas sic inform mation ▌Cardiiac action potential  In the restin ng state, K+ ions is founnd mainlyy intracellular, whi le + Na and Ca2+ are main nly extrracellular making m the e interior o of the cell electrically negaative.  Conntraction and a relaxa ation occu ur wheen rapid redistribut r ion of ionns acrooss the ce ell membrrane occurrs during 4 phasses known n as “actioon pottential”. Phases s of action n potentia al:  Pha ase 0: rap pid depolarization o of the cell due too rapid influx of Na+.  Phaase 1: sho ort period of rapid re e- + polaarization due to outflow of K.  Phaase 2: “p plateau”: delay d in ree- polaarization due d to slo ow influx o of + ++ Ca.  Phaase 3: seco ond period d of rapid rrepolarization due to rapid out--flow of K+.  Phaase 4: the resting sta ate is restoored. Na+ ions are extruded e o ut the cell and K+ ionss returns back b by thee Na+/K+ pu ump and so s on.  Thee slope of phase 4 determines d s when thee 2nd action n potential starts. When the slop pe is incrreased, th he distanc ce betwee en 2 cardiac cyclees shorte ens (i.e. tachhycardia) and a vice ve ersa. ▌Impulse formattion (automaticity)  Carrdiac auto omaticity refers to the abilitty of certtain cells to self-generate elec ctrical impu ulses that spread thrroughout the heart.  Undder normal condition ns, the SA A node is the t domina ant pacemmaker (i.e. has the high hest autommaticity).  Norrmal myoca ardial cells s don’t havve automatticity i.e. ca annot geneerate impuulses.  Undder certain patholo ogic cond ditions, soome myoc cardial ceells may acquire spoontaneous repetitive firing, thiss is called d abnorma al automa aticity or ectopy. e Theese ectopicc pacemak kers comp pete with th he SA node for contrrol of the heart. h 185  ▌Impulse condu uction  Elecctrical actiivity sprea ads from th he SA nodde to the ventricles v via v the AV V node andd the bund dle of His, and then down thro ough the rig ght and lefft bundless.  In th he ECG, the P wave e represen nts the spreead of dep polarization wave th hrough the atria (atrial contrac ction). Thee QRS commplex rep presents the sprea ad of deppolarizationn wave through the ventricles (ventricular contraction c n). The ST segmentt and T wave w rep resent ventricular reppolarizationn (relaxatio on). █ Card diac arrh hythmia hmia means disturba Arrhyth ance in the e normal heart rhythm m. It resultts from:  AAbnormal impulse ge eneration;  AAbnormal impulse co onduction;;  Both. ▌Abno ormal impu ulse forma ation: Nod mality: e.g dal abnorm g. sinus tac chycardia and a sinus bradycard ia. Extranodal abnormal a ity: e.g. premature e atrial or o ventricuular contrractions (ecttopic beatss). ▌Abno ormal impu ulse condu uction Re--entry: – Thiss is a circcus movement of aan imppulse thatt circulattes aroun nd certtain area in a un nidirection nal fashhion and excites e the conductin ng systtem more than once. – It iss the mosst commo on cause o of atriial flutter and a fibrilla ation (AF). – Wolff–Parkinsson–White syndrome (WP PW) is ana examp ple of an y defined re-entry. WPW natomically syndrome is an atrio oventricula ar re-entra ycardia, ssecondary to an ant tachy acccessory AV V conductin ng pathwa ay (see befo ore). 186  Hea art block: – AV conductio on is delayed (firsst degree)), intermitttent (seccond degrree), or com mpletely blocked b (th hird degree e). █ ANT TIARRHYT THMIC DRUGS  Antiarrhythmic c drugs produce efffects by altering a one or moree of the fo ollowing facttors: 1) Automatici A ty; 2) Coonduction velocity; 3) Refraactory perriod; 4) Mem mbrane ressponsiveness.  Alm most all anttiarrhythmic drugs hhave more e than one mechanissm of actio on. The simplified Vau ughan Williams clas n system assumes ssification a thhat each drug has onee main mechanism of o action: Class II: Na+ chan nnel block kers: Class IA: e.g. qu uinidine, pro ocainamide e, disopyrramide: modderately bllock Na+ channels c d ↑ ERP (e and effective re efractory periiod) and d APD (action poteential dura ation) Class IB: e.g. lidocaine, mexxiletine: weakly w bloc annels and ↓ ERP and ck Na+ cha d APD. Class IC: e.g. flecainid ck Na+ and enone: strrongly bloc de, propafe d K+ channels with no e effect on ERP E or APDD. Class III: Beta-blockers: e..g. propra anolol, biso oprolol, metoprolol m They ↓ AV conductio T on and inhibit phase 4 depolariz zation. Class IIII: K+ chan nnel block kers: e.g. a amiodarone, dronedarone, ib butilide, so otalol T bit mainly K+ channelss and ↑ ER They inhib RP. Class IIV: Ca+ channel bloc ckers: e.g g. verapam mil and dilttiazem T They inhib bit mainly Ca nels and ↑ ERP. C 2+ chann E Other u unclassifie ed drugs: digoxin, a adenosine e, Mg sulp phate 187