pharma fouda 2_p91-95.pdf

Quinid dine (subc class 1A)) Mecha anism and pharmac cological e effects  It bblocks acttivated Na+ channe els leading g to decrrease the rate of phase-0...

Quinid dine (subc class 1A)) Mecha anism and pharmac cological e effects  It bblocks acttivated Na+ channe els leading g to decrrease the rate of phase-0 p dep polarization n, decrease e excitabil ity, and ↑ APD A and ERP. E  It blocks mus scarinic and α rece eptors lead ding to atroopine-like action (va agolytic) andd hypotenssion.  Quinidine hass complex x effect on n AV cond duction due d to direect and vaagolytic actions: – A At low dosses: its vag golytic acti on predom minates → ↑ AV conduuction. – A At therapeeutic dosess: its directt action pre edominate es → ↓ AV cconductionn  It ha as –ve inottropic effecct and antiimalarial efffect (again nst P. falcip iparum). peutic use Therap es  Quinidine wass used for many ye ears to tre eat suprav ventricularr and ventricular arrh hythmias, anda to maintain sinu us rhythm after conversion from m atrial fluttter and fibriillation; ho owever, it is rarelyy used todday becauuse of avaailability of o more ective and less toxic drugs. effe Advers se effects and preca autions – Cin nchonism: tinnitus (i.e. hearing g of ringin ng or hiss), headachhe, blurred d vision, vom miting, and d diarrhea. – Hyp potension: after rapid i.v. infussion due to o α-recepto ors blockad de. – Parradoxical tachycard dia: quinid dine has atropine-lik a ay ↑ AV ke action aand, it ma connduction an nd cause "paradoxic " cal tachycaardia". Digitalis or verrapamil should be give en before quinidine q to offer rate b ↓ AV con e control by nduction. – Quiinidine syn uinidine ↑ Q ncope: qu QT intervall and may predisposse the patie ent to a seriious type of o arrhythmmia (torsad de de pointtes). Quinid dine therefo fore should d not be give en to patie ents with lo ong QT synndrome or with otherr drugs thaat ↑ QT inte erval. Procainamide (subclass ( s 1A)  Thiss drug is equiva alent to quinidine e as an n antiiarrhythmic c agent and has simiilar cardiac c and toxic c effe ects. Like quinidine, q its use now w is very lim mited.  Add ditional adverse effect: procaina amide is s mettabolized by b hepatic c acetylatio on; 30% of o patientss (slow acetyla ators) dev velop drug g-induced systemic c lupuus erythem matosus (SLE) after loong term th herapy. 188 Lidocaine (subclass 1B)  Lidocaine (lignocaine) is exclusively Na+ channel blocker; it is highly selective for damaged tissues.  It undergoes extensive first-pass metabolism so, it is not given orally.  It is given only i.v. for acute suppression of ventricular arrhythmia associated with acute MI (not for long-term treatment). The usual dose is 50-100 mg i.v. half of this dose may be repeated after 5-10 min if necessary.  It has no effect on AV conduction, so it is not used for supraventricular arrhythmia.  Most adverse effects are neurologic. N.B.  Mexiletine is very similar to lidocaine but can be given orally. It is used primarily for long-term treatment of ventricular arrhythmias associated with previous MI.  Phenytoin is antiepileptic drug with class 1B activity. It is used primarily in the treatment of digitalis-induced tachyarrhythmia. It has a limited role in the treatment of other ventricular arrhythmias. The IV loading dose is 250 mg given over 10 minutes. Flecainide (subclass 1C)  It blocks both Na+ and K+ channels leading to decrease the rate of phase-0 depolarization and slows AV conduction. Due to its complex effects on cardiac tissue, the APD is not altered.  It is used for atrial and ventricular arrhythmia and for maintenance sinus rhythm after conversion from atrial flutter and fibrillation.  Flecainide increases the incidence of ventricular fibrillation and sudden death after MI (proarrhythmic effect), so it is contraindicated for patients with ischemic heart disease or structural heart disease (e.g. LV hypertrophy). █ Class II: Beta blockers Mechanism of action They ↓ sympathetic stimulation, inhibit phase 4 depolarization, depress automaticity, prolong AV conduction, ↑ heart rate and ↓ contractility. Therapeutic uses  All arrhythmia induced by sympathetic overactivity.  Arrhythmia due to thyrotoxicosis. 189   Arrh hythmia asssociated with w HOCM M.  Suppraventricu ular arrhyth hmia (AF).  Arrh hythmia duue to mitral valve pro olapse. █ Clas ss III: Amiodarone e  It iss structura ally related to thyroxiine. It con ntains ~ 40 0% iodine.. Droneda arone is che emically sim milar to ammiodarone b but does not n contain n iodine.  Amiodarone has h long t½ t and la rge Vd so o, it can accumulate a e in many tissues lead ding to wid de range off adverse eeffects. Mecha anism of action a  Bloccks mainlyy K+ chann nels → slow wing of pha ase 3 → ↑ ERP.  Bloccks Na+ chhannels → ↓ excitabiliity.  Βloc 2+ cks Ca channels → – ve inotropic and chro onotropic effects. e Therap es: (most ty peutic use ypes of arrrhythmia)  Suppraventricu ular and ve entricular a arrhythmia.  WPW syndrom me.  hythmia resistant to other Arrh o druggs. Advers se effects – Dosse-related pulmonarry toxicity (fibrosis) is th he most im mportant ad dverse effeect. – Hep patic toxic city. – Thy yroid dysfuunction: hypo- h or hyyperthy- roid dism becau use of its io odine conttent. – Corrneal micrrodeposits s: reversib le, does not affect vision. – Braadycardia and heart block. – Pho otosensitivvity leading to gray-b blue skin disccoloration in sun-expposed area as. █ Clas ss IV: CCB Bs (verap pamil and d diltiazem m) Mecha anism of action: a ey ↓ SAN a The activity and d AV conduction Therap peutic use es 190  Non n-dihydrop pyridines (v verapamil and diltiazzem) are primarily p ussed to reduce HR in s chycardia (SVT) and arrhythmia supraventrricular tac a associateed with HO OCM.  CCB Bs have no role in the chronic c managem ment of ve entricular ttachycarddia (VT). IV vverapamil should neever be ussed in the acute ma anagementt of VT, as s it may cauuse hemodynamic co ollapse. █ Othe er antiarrrhythmic agents: A Adenosin ne  It iss a purinergic A1 rec ceptor ago onist; this leads to opening o off K+ channnels and 2+ inhibition of CaC chann nels (i.e. h hyperpolariization) in the AV co onducting system and d directly in nhibits AV V nodal con nduction.  It ha as very shoort half-life e of 8-10 se econds.  It iss the drug of choice for immed diate terminnation of paroxysma p al supravenntricular tach hycardia (including WPWW synd drome). It is given as s a bolus dose of 6 mg i.v. folloowed, if neecessary, by b a dose o of 12 mg.  The e drug is le ess effectiv ve in the prresence off adenosine e receptorr blockers such s as theophylline or caffeine e.  It is contraindicated in pa atients with h asthma because b it can c cause bronchos spasm. █ Non-pharmac cological methods s DC carrdioversio on  It iss applicatio on of directt current (e electric sho ock) to the chest wall for emerrgency co ntrol of an ny type of a arrhythmia a especiallyy rapid AFF in an un nstable patiient (i.e. hyypotensivee).  Thee patient should be e hepariniized befo ore the procedure.  Folllowing elec ctrical card dioversion , patients should s be aanticoagulated for att least 4 we eeks. Laser a ablation  It iss used for many m types of arrhyt hmias.  A ccatheter is inserted into i a speecific area of the heaart. A spec cial machin ne directss energy th hrough the catheter to small areas a of thhe heart muscle m thatt causes the abno ormal hea art rhythm m. This eneergy "disc connects" the pa athway of o the abnnormal rhytthm.  Lasser radiofrrequency ablation is the definite d trea atment of WPW W synd drome. 191  Artificiial pacemakers and d implanta able cardio overter defibrillators  Theey are batttery-powered electroonic devic ces that are implanted d under the e skin or in n the ches st cavity to mmonitor and pace thee heart. █ Man nagementt of cardiac arrestt Cardiac c arrest innvolves ce essation off cardiac mechanic m al activity as confirm med by absencce of signss of circulattion (absen nt pulse an nd apnea). s Causes  Corronary heart disease (~80%).  Carrdiac disea ase: e.g. HO OCM, Brug gada synd drome.  Carrdiac arrhytthmia espe ecially ven ntricular.  Oth hers: traumma, electrolyte imbala ance, electrical shock k, drugs, eetc. Pattern ns of arres st  Com mplete asyystole: the ECG is flatt line.  Venntricular fib brillation: ECG showss fibriillation wavves.  Pulsseless elec ctrical activ vity (PEA): Theere is some e electrical activity (o other thann VF) witho out detecta able pulse. Manag gement  The e ultimate goal of treatment is to presserve life by early CPR 30:2 2 i.e. cycles of 30 chest c comp pressions ffollowed by b 2 rescuee breaths.  Adm ectrical deffibrillation at 360J then repeat CPR for 2 min. minister ele →N No responsse → Epine ephrine 1 mg i.v. /3-5 min with h CPR. →NNo responsse → DC shock s with CPR for 2 min. →NNo responsse → Amio odarone 3 00 mg i.v. with CPR.. →NNo responsse → DC shock s with CPR. ock – Drug Sho g – Shock – Drug – S Shock 192