Class I= Na channel blockers
--> prolong Phase 0--> slow conduction velocity
--> make membrane return to a more hyperpolarized state, thus --> prolong refractory pd of fast response fibers bc there's a greater difference between the resting state and the threshold for activation of the Na channels to initiate Phase 0
--> suppress Purkinje/His bundle automaticity, caused by myocardial damage--> SA node resumes its dominance.
Class IA) -->slow rate of rise of Phase 0 to Vmax & prolong refractory pd
Class IB) --> conduction block at diseased myocardium, but no effect on Phase 0 or refractory pd
Class IC) --> signif decr conduction velocity, but ~no effect on refractory pd
IA -
-Quinidine - rarely used bc of xx. like quinine it's antimalerial, antipyretic, ototoxik, skel relaxant
-effect d/o dose: low [ ] --> Anti-cholinergic, at high [ ] --> direct EP effets
-SA nd & Atria: low [ ] --> inr HR; low [ ] slows depol- slows Vmax of ph 0--> slow conduction
-AV nd: low [ ] anti-chol effect--> incr conduction at AV nd, high [ ] --> decr conduction velocity and incr effective refractory pd
-HPS/Ventricle: decr ph 4 slow of depol--> inhibit automaticity, with a greater effect at HPS than SA nd, and in ventricles it blocks the Kr delayed rectifier channels (K into cell after repol to trigger next depol)--> prolongs repol'n--> inr dur of AP and incr QT on ECG
-ECG: prolong PR, QRS, and QT, w magnitude related to [ ]
-Hemodynamics: if poor fx, it can worsen it; also inhib alpha1 R--> sm muscle vasc dilation
-Pharm: complete PO avail, onset 1-3hrs, pk 1-2hrs, t1/2 6hr, hepatic metab
-Use: not often used bc of xx, can ctrl ventric arrhythmias, and short QT synd correction
-xx: diarrhea, abd xx, ligh headed, tired, palpn, HA, angina pain, rash (dose related)
-+/- thrombocytopenia
-AV & intraventricular block, VT, decr contractility
-Quinidine Syncope = VT/VF w LOC
-Cinchonis- (w large ds)--> tinnitus, HA, nausea, vision changes, vertigo, auditory acuity cahnges, then confusion, delirium, halluc'n, psychosis if large dose; hypoglycemia
-c/i xx: complete AV block, long QT can get torsades, CHF/hypotension, Digox toxicity and hyperK+ --> incr effect to decr conduction
-Drug-Drug- incr digox [ ]
-acetazolamide, CaCarb, MgOH, cimetidine decr metab of quinidine
-Procainamide -
-Tx SVT, VT, Digox induced arrhythmia
-xx- short t1/2, & side effects when chronically used
-EP Mech: like quinidine, but weaker anti-CH effect. similar ECG effect
-HD Effect: less HD xx w than quinidine, rare if taken PO
-Pharm: very PO bioavail, pks at 1-1.5hrs p adm, t1/2 2.5-4.5hrs (unless sustained release then 6-8hrs), hepatic metab, cleared in urine.
-The metabolite NAPA is cardioactive w class III properties & is eliminated via urine
-Some pts are rapid acetylators, some have renal dysfx --> accum NAPA more than procainamide
-may need slightly higher dose in neonates
-Use: AP mediated tachy, a-fib, ventric xx, and postop JET (along w pt cooling)
-if a-flutter or IART, it might --> slow conduction in flutter circuti allowing 1:1 AV conduction w incr in ventric rate, also it can slow conduction in other macroreentrant circuits, and convert self limted tachy into a slower incessant tachy.
-might be used for Brugada Dx
-Adverse Effects: decr BP, AV block, IV bock, VT, complete HB
-stop if it --> sev prolonged QRS or QT
-lupus like synd w long term use, but sx stop w stopping the Rx
-(rare) hallucinations, mental confusion
-give slowly (max 10mg/kg/min) bc of hypotension risk
-c/i xx- be careful if pt has 2nd deg AV block, BBB
-if prolonged adm, check CBC bc of r/o agranulocytosis
-Drug-Drug Interactions: cimetidine decr its metab. EtOH increases its hep clearance.
-amio or quinidine given at same time can incr procain [ ]
IB -
-Lidocaine- aka Xylocaine- local anesthetic, blocks Na Ch
-acts preferentially in diseased tissue, causing conduction block & interrupts reentrant tachy
-EP Mech:
-SA/atrium- ~no effect at Tx doses
-AV nd- min effects on conduction velocity & ERP
-HPS/Ventricle- reduce membrane responsiveness, decr automaticity
-at low [ ] --> slow ph4 depol at Perkinjes
-at high [ ] --> suppress automaticity, eliminate ph 4 depol
-ECG: no change to PR, QRS, QT (some w short QT). not much change bc it doesnt wk at healthy mycoardium much.
-HD effects- no effect on myocard fx, even w CHF
-Pharm Mech: much first pass metab--> not good orally
-immediate onset w IV, t1/2 1-2hrs. hepatic metab. Clearance decr w CHF, liver xx, cimetidine, beta-blockers.
-Clinical Use: VT/VF. NOT SVT. though amio now 1st line...
-Adverse xx- CNS xx- paresthesias, disorientated, muscle twitch, then psychosis, resp dp, sz. myocardial depression if very high doses
-c/i xx- hyperSn to local anesthestics, sev hepatic dysfx, prev grand mal sz due to lido.
-be careful if 2nd/3rd HB bc it can worsen it and abolish idioventric pacemakers
-Drug-Drug: cimetidine (not ranitidine)--> incr [ ] lidocaine. Incr risk of myocard dp if +Dilantin
-Mexiletine-
-analog of lidocaine, but prevents 1st pass metab.
-Often combine w quinidine to incr efficacy and decr proarrhythmia risk
-EP Mech: slows conduction velocity, ~no effects onrepol
-rate dependent blocking action on Na ch w rapid onset
-HD Effects: caution if already hypOtensive or sev LV dysfx
-Pharm: 90% oral bioavail. Onset 0.5-2hrs, t1/2 10-12hrs. metab by liver via bile, 10% renal
-Use: acute/ch VT/VF; ?for congen long QT
-Adverse xx- narrow Tx window
-hand tramor, then dizzy and blurred vision. Also n/v etc, lightheadedness, cordination xx, but improve w decr dose. CV xx: less common- palpn, CP, angina
-c/i xx- cardiogenic shock, 2nd/3rd degr HB (or h/o of it) if no pacemaker, and caution if SA dysfx or IV conduction xx
-Drug-Drug: phenytoin/rifampin incr hepatic metab.
IC -
-Flecainide-
-slows conduction throughout the heart, espec HPS and ventricles.
-also weakly inhib the delayed rectifier K ch (thus slight repol'n prolong), & inhib abNl automaticity
-EP Mech:
-SA/atrium- decr HR slightly, decr conduction velocity @atria, prolongs action potential
-AV nd- prolong conduction
-HPS/ventricles- slows conduction; may also slow conduction at accessory pathways
-ECG: incr PR, QRS, and to some degr QTc (just bc of incr QRS, NOT bc of a change in repol)
-HD: negative inotropy, so some pts might get decr LV Fx
-Pharm: good PO abs (80-90%) but decr w milk/milk formulas; onset 1-2hrs, t1/2 12-30hrs, liver metab and renal excrete
-Use: atrial arrhythma- espec reentrant mech, and life threatening VT/VF
-be careful if +CHD bc can cause more proarrhythmia xx
-crosses placenta, so ok for fetal tachy (after digox)
-2nd line for SVT in kids unresponsive to betablocker
-start as inpt bc of risk of proarrhythmias
-Adverse xx: dizziness, vision change, nausea, headache, dyspnea initially (first few days)
-some-> worse CHF and prolong PR and QRS
-less pro-arrhythmia than adults (?). #1 proarrhythmia is slow incessant SVT, but also VT/VF in pts s/p CHD repair
-c/i xx: 2nd/3rd HB unless +pacemaker to maint ventric rhythm; cardiogenic shock
-Drug-Drug: cimetidine decr hepatic metab--> incr toxicity; Flec --> incr digox [ ]
-Propafenone-
-blocks Na ch, and weakly blocks K channels too (like flec)
-also, weak beta-R antag, and L type Ca ch blocker
-EP Mech:
-SA nd- slows SA nd
-Atrium- prolong AP and ERP, and decr conduction velocity--> slow a-flutter to a rate that lets more rapid conduction to the ventricle (like other class I Rx), so be careful...
-AV Nd- slows AV nd conduction if given IV
-HPS/ventricle- slows conduction, inhibit automaticity
-ECG: dose dependent incr in PR and QRS
-HD effect: no signif xx on fx, but might decr mycard performance if pt already has ventric dysfx
-Pharm Mech: ~all PO absorbed, t1/2 2-10hrs, liver metab, urine excrete
-Use: SVT, life threatening VT/VF if no structural heart dz. IF CHD, can incr VT/VF
-start as inpt to monitor for arrhythmias
-Adverse xx/Drug-Drug- if give w digox, warfarin, propranolol, metoprolol, it incr serum [ ] of the other drugs. cimetidine will sightly incr its [ ].
-lidocaine, procainamide, quinidine will be additive w it.
-can interact w other drugs to depress AV nd fx, intraventric conduction, or contractility
-common xx- dizzy, light headed, metallic taste, n/v
-sev CHF, cardio shock, AV and IV conduction xx, SSS, also sev brady, low BP, obstructive pulm dz, hep/renal fail. and bc of beta-blocker action use w caution for bronchospasm
Class II = Beta-blockers
-Propranolol-
-aka Indural
-decr sympt stim by competitive bindign to beta adr R
-EP Mech: 1) remove adrenergic influence on heart
2) Membrane stabilization effects via direct effect on heart- (more at higher doses)--> effect to ctrl arrhythmias that aren't related to beta R stim
-SA nd- slow spont rate of cells by decr slopw of phase 4 depol (longer to recover)
-Atrium- local anesthetic--> decr AP amp & excitability
-AV nd- decr AV conduction velocity, incr AV nd refractory pd
-HPS & Ventricle- --> depress catechol stimulated automaticity ; if high dose, it can decr Purkinje responsiveness and reduce AP amp
-ECG: long PR, no change in QRS; QT might be short
-HD xx: decr positive inotropic & chronotropic effect of NE/E, w decr HR & BP, and decr myocard VO2
-Pharm: ...
-Use: SVT (#1 Rx along w atenolol); ventricular ectopy/VT, w suppression of PVCs and NE/E dependent ideopathic VT, and good for congen long QT synd
-Adverse xx: brady, hypotension, bronchospasm if asthma, mood changes/dp (Crosses BBB), school difficulties; infantile hypoglycemia; crosses placenta and can blunt fetal stress response at delivery
-c/i xx- depressed myocard fx, no good if +digox toxicity bc it can --> complete AV block and ventric asystole, asthma
-don't abruptly withdraw it, it can be dangerous bc of up regulation of Beta R's after long term use...
-Atenolol-
-aka Tenormin
-selects B1 R'
-better than Propranolol bc it has longer t1/2, limited BBB crossing so less CNS xx
-ECG & EP Mech like Propranolol
-Use: SVT & ventricular ectopy
-Adverse xx: still can have worsening of bronchospasm so be careful if asthmatic
-c/i xx - asthma is a relative one...
-Nadolol-
-aka Corgard
-Long acting, nonselective Beta antag, w NO membrane stabilizing or intrinsic sympathomimetic fx
-EP Mech/HD xx: just like propranolol
-Use: SVT, long QT; long t1/2 and less CNS xx like Nadolol
-Adverse xx & c/i xx- like propranolol
-Esmolol-
-short acting, IV, b1 blocker.
-no membrane stabilizing activity or sympathomimetic activity
-EP Mech/HD xx like propranolol
-Use: acute SVT Tx, acute VT Tx, and to acutely lower BP.
-rapidly lose effects when you stop the drip bc it is hydrolysed quickly
-Adverse xx & c/i xx- hypotension, nausea, dizzy, headache, dyspnea; c/i xx is CHF/cardio shock
Class III = Prolong Membrane Action Potential Duration
-Prolong Membrane AP, by delaying repol w/o changing depolarization or resting membrane potential
-signif pro-arrythmias bc of AP duration prolongation and risk of torsades de pointes.
-Amiodarone-
-mainly, it prolongs the AP, but also blocks Na and Ca Ch and binds to B receptor (so has class I, II, and IV actions)
-good to Tx most arrhythmias
-EP Mech: complex, ?known completely,
-after long term use, it --> prolong the repol & refractoriness of all cardiac tissues (thus class III)
-SA nd- inhib SA fx, espec if SSS (to the pt they'd need a pacemaker) common xx after Fontan and atrial switches
-HPS/Ventricles- slow AV nd conduction and refractory pd; ch Tx--> prolong AP at ventricles and incr their refractory pd w a decrease in conduction velocity
-ECG: prolong PR, QTC, incr U waves, and change T wave morph
-HD xx: relax smooth muscle, improve myocardial Q; and --> decr SVR so decr LV stroke work and myocardial VO2. IV adm can --> hypotension
-Pharm: poor PO bioavail (35-65%) and slow; protein bound, mainly concentrated in myocardium, adipose tissue, liver, lungs (as oppose to serum), t1/2 serum ranges fr 26-107 days; mainly liver metab w biliary excretion
-Use: broad use, little risk of torsades compared to other class III Rx, but does have other xx
-IV amio- postop pd xx: SVT, a-flutter, a-fb, IART, JET, VT
-ch PO amio- better than IV use, good for SVT and VT in most forms, but limited by xx
-Adverse xx:
-chemical hepatitis, worsen SA dysfx, thyroid dysfx (hyper/hypo), pulm fibrosis (often fatal even if u stop the amio)
-it prolongs QT but only small risk of torsades
-if underlying sinus nd dysfx, then may need pacemaker
-corneal microdeposits common & reversible, but only rare blurred vision/halos
-Skin: photoSn, blue-gray color (incr risk if fair complexion), slow regression if at all after stop Rx
-Inhib periph and intrapituitary conversion of T4 to T3 ==> incr serum T4, decr serum T3, but most pts remain euthyroid. xx = hyper and hypothyroid sx
-hand tremor
-sleep xx- vivid dreams, nightmare, insomnia
-ataxia, staggering, impared ambulation
-periph Sn and motor neuropathy, sev prox muscle weakness uncommon (resolve in a few weeks after stopping Rx)
-C/i xx- SSS, sev brady and 2nd/3rd AV block; crossess placenta and --> fetal brady/thyroid xx
-it is secreted in breastmilk
-Drug-Drug: many drugs
-Digoxin- cut the amio dose in half bc it incr amio [ ]
-Warfarin, flecainide, propafenone, progainamide, phenytoin, quinidine
-Sotalol-
-aka Betapace
-nonselective B blocker at lower doses, and at higher doses class III action by blocking K ch (w AP prolongation)
-EP Mech:
-SA nd/atrium: decrease pacemaker activity, incr atrial refract pd
-AV nd: decr conduction velocity, prolong effective refract pd
-HPS/ventricles: inhib the delayed rectifier K ch--> prolong ERP
-ECG: decr HR, prolong PR, prolong QTc; no change in QRS dur if at Nl dose
-HD xx: some decr SBP and CO bc of beta blocker effects--> decr HR, but no change in SV
-If Nl fx, SV will increase to compensate decr HR so CO stays the same
-Pharm: 50% bioavail, onset 30min, t1/2 4hrs; hepatic metab w urine excretion
-Use: both ventricular and SVT, but limited bc of proarrhythmia ventric xx; 2nd line for fetal arrhyth
-Adverse xx: tired, dyspnea, chest pn, HA, n/v; proarrhythmia
-c/i xx: sev heart failure, poor RV fx, hypoK, long QT bc incr risk of proarrythmia
-Drug Drug: QT prolonging meds (diuretics, thiazides, etc) can incr its class III effects
-Dofetilide-
-pure class III in that it prolongs the AP and the refract pd by selectively inhib the rapid component of the delayed rectifier K ch
-EP Mech: as above, no signif effect on other repolarizing K currents
-exaggerated if pt has hypErkalemia
-less effective at higher HR
-SA nd/atrium: minor slowing of SA rate bc of hyperpolarization of the maximum diastolic potential, and reduces slope of the pacemaker potential...
-AV nd: no effect
-HPS/ventricles: incr ERP (less so than in atria)
-ECG: no change in PR or QRS, but does prolong QT (directly related to [K])
-HD xx: no change in BP, HR, CO SV, or SVR
-Pharm: delayed absorption if w food, but good avail (90%), onset 7-10hrs,
-Use: a-fib, a-flutter; maybe for SVT in CHF pt, or IART w Fontan pt
-Adverse xx: risk of torsades of QT long, 3% of adult trial pts, usually w/in 1st 3 days so start as inpt
-c/i xx: baseline long QT, other QT prolonging Rx, h/o torsades, CR clear low, or use w verapamil, cimetidine, ketoconazole, or K <4, or low Mg, or pregnant/breastfeeding
-Drug Drug- Verapamil, cimetidine, ketoconazole increase its [ ]
-Ibutilide-
-aka Covert
-similar to stoalol, w similar class III effect, but only IV bc of first pass effects
-EP Mech: prolong AP, incr atrial/ventricular - activate slow inward Na current (mainly), and blocks the delayed rectifier K current--> increase the duration of atrial and ventric AP and refractoriness by slowing the initial Na in of the depol, and slows the rectifier K at the end...
-SA nd/atrium: no change in HR, incr atrial ERP without any "reverse use dependence" (works just as well at higher HR) unlike other class III Rx
-AV Nd: may slow AV nd conduction, no change in PR interval
-HPS/Ventricles: incr ERP
-ECG: no change in PR or QRS bc it doesn't effect conduction velocity; dose related QT prolong (d/o dose and rate of infusion)
-HD xx: no signif effect on CO, MAP, PCWP, no effect on cv fx
-Pharm: variale by pt bc of first pass metab, so ng for PO, metab by liver
-Use: refractory a-fib/a-flutter in adults (a-flutter better than a-fib), limited peds use for IART
-Adverse xx: QT prolong w torsades (4%), within 40min of adm, so have ECG going w DC cardioversion ready for 4-6hrs p adm
-also incr/decr BP, brady/tachycardia, AV block
-c/i xx: baseline long QT, h/o torsades, low K, low Mg, pregnant/breastfeeding
-Drug Drug: no signif issues
Class IV = Ca++ Channel Blockers
-block the slow inward Ca++ (L type Ca Ch)
-most pronounced effects on cells dependent on Ca Ch to initiate the AP- SA nd, AV nd
--> slows conduction velocity and incr AV nd refractoriness--> decr ability of AV nd to rapidly conduct an impulse to the ventricle; thus good for SVT, and to decr a-flutter/fib conduction
-Verapamil-
-inhib voltage gated Ca Ch needed to make an AP in slow response myocytes seen in SA/AV nd
-EP Mech:
-SA nd/atrium- decr SA nd rate, but no effects on atrial muscle
-AV nd: slow AV nd conduction, prolong AV nd refract pd
-HPS/ventricles: no effect on intraatrial and intraventric conduction; effects are mainly prox to HPS
-HD xx: no major arterial BP, periph vasc resistance, HR, LVEDP, contractility effect
-Pharm: much first pass metab (90%), w much incr [ ] if hepatic dysfx; t1/2 3-7 hrs
-Use: slow ventric response to atria in a tachyarrhythmia- a-flutter, a-fib; also good w enhanced automaticity xx like ectopic atrial tachy or ideopathic LV tachy; good to stop SVT that involves AV nd
-Adverse xx: PO: not much, some GI xx- upset/constipation, other xx: vertigo, HA, nervous, pruritis
-c/i xx: beta blocker use bc --> exaggerate the HR depression, decr AV nd conduction, and decr myocard contractility.
-limited use in pt <1yo, espec if CHF, bc risk of CV collapse
-caution if ventric dysfx
-Diltiazem-
-similar to Verapamil
-?less ventric depression
-Pharm: less bioavail (45% absorption), t1/2 4-7hrs; metab in liver like verapamil but mainly GI excreted
Other Rx:
-Digitalis Glycosides
-e.g. Digoxin
-positive inotropy, so used for CHF
-also useful for SVT
--> slow AV nd conduction, so good for reentry tachy if AV nd is part of the circuit
-limit AV nd conduction durng a-fib/flutter (less used for this nowadays)
-theoretically better than CCB and BB's which also slow AV nd conduction bc it has positive and not negative inotropy,
-however has only limited AV nd effects in states of high symp tone (e.g CHF)
-risk of shortening effect on the EFP of accessory pathways, it is AVOIDED in older pts w WPW
-used in infants w WPW and SVT - long, safe history of use, but not proven effective in randomized study...
-Adenosine
-endogenous nucleoside (end product of ATP)
-for rapid termination of SVT
-EP Mech:
-Adenosine R' at SA and AV nd via G protein signaling cascade--> open the outward K current activated by ACh.... Adenosine stim--> hyperpolarize the resting membrane potential, decr phase 4 depol slope, and shortening the AP duration ==> complete conudction block that terminates tachy that uses AV nd. NO affect on ventric myocytes bc the adenosine stimulated K ch isn't in ventricles.
-ECG: 10-20sec block, both antegrade and retrograde; see mild sinus slowing initially after use, then a sinus tachy due to vasodilation and hypotension. No effect on QRS or QT
-HD xx: biphasic pressor response: initial brief incr in BP, then vasodilation and 2y tachy
-Pharm: metab by rbc in <10sec...
-Use: acute termination of SVT using AV nd; and to Dx narrow complex tachy by unmasking the a-flutter and ectopic atrial tachy.
-Adverse xx: flushing, chest pn, dyspnea, bronchospasm if +RAD hx; a-fib bc shorten atrial refract pd
-c/i xx: WPW in a-fib..., asthma
-Drug Drug: methylxanthinse (theophylline) antags their effects...
-Mag Sulfate
-can terminate VT, espec polymorphic VT
-Digitalis induced arrhythmias more likely if Mg defic
-low Mg may incr risk of postop JET
-Mg sulfate can be given PO, IM, IV (preferred) if needed rapidly
-Losing DTR = you OD'd
Drug-Device Interactions
-Increase Threshold for Defibrillation:
-Amio, Flec, Lidocaine, Propafenone, Mexiletine
-Decr Threshold for Defibrillation:
-Sotalol, Dofetilide