farmaci antiaritmici. indications for treatment co one typically treats those arrhythmias that: -...
TRANSCRIPT
![Page 1: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/1.jpg)
FARMACI ANTIARITMICI
![Page 2: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/2.jpg)
Indications for Treatment
CO
One typically treats those arrhythmias that:
- asynchronization (multifocal VT, VFib) - contractions too infrequent (bradycardia)- contractions too frequent (tachycardia)- AFlutter VTach - Sustained VT VFib- AFib thrombus Cardioversion embolus
(Rx: anticoagulate for 2-3 weeks prior to DC cardioversion)
Berne & Levy 1996
Are likely to convert to a more serious arrhythmia Cause vascular stasis
![Page 3: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/3.jpg)
Treatments for Arrhythmias
Electrical
- DC Cardioversion (AFib, VT, VFib)- Implantable Cardioverter-Defibrillators (ICD) (VT, VFib)- Pacemaker (SAN Dx., AVN Block)
Carotid Sinus Massage
Life style modification
- Rx. For PSVT (can also vagal tone by: occular pressure, diving reflex, ValSalva, phenylephrine, edrophonium)-Rx. For AVN bypass tracts, WPW
- “Type A” behavior- smoking, weight, hypertension, etc.
Catheter-mediated or surgical ablation
Drugs
![Page 4: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/4.jpg)
SISTEMA SISTEMA CARDIOVASCOLARECARDIOVASCOLARE
CC
![Page 5: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/5.jpg)
C. SISTEMA CARDIOVASCOLARE
C01 TERAPIA CARDIACA
- C01A Glicosidi Cardiaci
- C01B Antiaritmici, Classe I e III
- C01E Altri preparati cardiaci
C07 BETABLOCCANTI
C08 CALCIOANTAGONISTI
- C08D Calcioantagonisti selettivi con effetto cardiaco diretto
![Page 6: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/6.jpg)
Potenziale d’Azione
Na+ in Ca++ in K+ outNa+out/ K+in Na+out/ K+in
+25
-100
![Page 7: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/7.jpg)
Potenziale d’Azione
Riposo: -60 -95 mV Pompa Na-K ATPasi dipendente: 3Na est. vs 2 K in
Depolarizzazione al potenziale soglia: -40 -60 mV Depolarizzazione rapida (fase 0): +10-20 mV
Apertura canali del Na (miocardio atriale e ventric.) Apertura canali Ca (nodo SA ed AV)
Ripolarizzazione rapida (fase 1): 0 mV Inattivazione canali del Na
Plateau (fase 2): 0 mV Apertura canali del Ca / Contrazione cellulare
Ripolarizzazione (fase 3): -60 -95 mV Inattivazione corrente in di ioni positivi Apertura canali del K
![Page 8: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/8.jpg)
Arrhythmia
Heart condition where disturbances in Pacemaker impulse formation Impulse conduction Combination of the two
Results in rate and/or timing of contraction of heart muscle that is insufficient to maintain normal cardiac output (CO)
To understand how antiarrhythmic drugs work, need to understand electrophysiology of normal contraction of heart
![Page 9: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/9.jpg)
Normal heartbeat and atrial arrhythmia
Normal rhythm Atrial arrhythmia
AV septum
![Page 10: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/10.jpg)
Ventricular Arrhythmia
Ventricular arrhythmias are common in most people and are usually not a problem but…
VA’s are most common cause of sudden death
Majority of sudden death occurs in people with neither a previously known heart disease nor history of VA’s
Medications which decrease incidence of VA’s do not decrease (and may increase) the risk of sudden death treatment may be worse then the disease!
![Page 11: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/11.jpg)
Contraction of atria
Contraction of ventricles
Repolarization of ventricles
![Page 12: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/12.jpg)
Differences between nonpacemaker and pacemaker cell action potentials
PCs - Slow, continuous depolarization during rest Continuously moves potential towards threshold for a
new action potential (called a phase 4 depolarization)
![Page 13: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/13.jpg)
Mechanisms of Cardiac Arrhythmias
Result from disorders of impulse formation, conduction, or both
Causes of arrhythmias Cardiac ischemia Excessive discharge or sensitivity to autonomic
transmitters Exposure to toxic substances Genetic (channelopathies) Unknown etiology
![Page 14: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/14.jpg)
Disorders of impulse formation
No signal from the pacemaker site
Development of an ectopic pacemaker May arise from conduction cells (most are capable of spontaneous
activity) Usually under control of SA node if it slows down too much
conduction cells could become dominant Often a result of other injury (ischemia, hypoxia)
Development of oscillatory afterdepolariztions Can initiate spontaneous activity in nonpacemaker tissue May be result of drugs (digitalis, norepinephrine) used to treat other
cardiopathologies
![Page 15: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/15.jpg)
Disorders of impulse conduction May result in
Bradycardia (if have AV block) Tachycardia (if reentrant circuit occurs)
Reentrant circuit
![Page 16: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/16.jpg)
Circulation. 2007;116:2325-2345
Aritmie cardiache e canalopatie (channelopathies)
![Page 17: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/17.jpg)
![Page 18: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/18.jpg)
![Page 19: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/19.jpg)
Sindrome di Brugada E’ una patologia che può provocare sincopi e morte
cardiaca improvvisa in soggetti di giovane età (tipicamente tra la terza e quarta decade di vita),
Quadro elettrocardiografico: di sopraslivellamento del tratto ST nelle derivazioni precordiali destre associato a blocco di branca destra
modalità di trasmissione di tipo autosomico dominante.
nel 1998 mutazioni sul gene SCN5A, sono state dimostrate in alcune famiglie con SB. Al contrario di quanto accade per le mutazioni di SCN5A che causano LQT3, esse portano ad una perdita parziale o totale di funzione del canale, e quindi ad una riduzione della corrente del sodio.
![Page 20: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/20.jpg)
![Page 21: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/21.jpg)
Meccanismi D’Azione Degli Antiaritmici Aumentato automatismo
Riduzione frequenza di scarica focus ectopico Rallentamento depolarizzazione diastolica Innalzamento potenziale di soglia Aumento depolarizzazione a riposo
Aritmie da rientro Eliminazione blocco unidirezionale Aumento velocità di conduzione
Miglioramento / omogeneizzazione velocità di cond. Creazione blocco bidirezionale
Rallentamento velocità di conduzione Allungamento periodo refrattario
![Page 22: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/22.jpg)
Classificazione dei Farmaci Antiaritmici (I)
Classe I: Bloccanti canale del Na Classe IA:
Riduzione Vmax ed aumento durata PdA (chinidina, procainamide, diisopiramide)
Classe IB: Vmax invariata e riduzione durata PdA
(lidocaina, mexiletina, tocainide, moricizina) Classe IC:
Moderata riduzione Vmax, marcato rallentamento velocità di conduzione, allungamento del periodo refrattario
(flecainide, propafenone)
![Page 23: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/23.jpg)
Classificazione dei Farmaci Antiaritmici (II)
Classe II: Beta Bloccanti
(propranololo, metoprololo, atenololo...)
Classe III: Bloccanti del canale del K con rallentamento della
ripolarizzazione
(amiodarone, bretilio, dofetilide, ibutilide, sotalolo*)
Classe IV: Calcioantagonisti
(verapamile, diltiazem)
![Page 24: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/24.jpg)
Effetto proaritmico
Aggravamento aritmia preesistente
Induzione di nuova aritmia
Modifica caratteristiche circuito di rientro
Aumento della disomogeneità tra diverse aree di miocardio
Induzione di postdepolarizzazioni
![Page 25: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/25.jpg)
Chinidina (I) Effetti elettrofisiologici diretti
Rallentamento fase 0 (depolarizzazione rapida) Allungamento PdA Allungamento Periodo Refrattario Lieve eff. inotropo negativo
Effetti neurovegetativi Vagolitica: freq. cardiaca/ vel conduz AV Alfa bloccante: vasodilatazione / att. simpatica riflessa /
freq. cardiaca/ vel conduz AV Modificazioni ECGrafiche
Frequenza sinusale / conduz. AV : = Durata QRSe QT:
![Page 26: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/26.jpg)
Chinidina (II) Forme farmaceutiche
Solfato, poligalatturonato, cloridrato, gluconato Dosi:
Chinidina solfato: 300-600 mg ogni 6 ore Steady state in 24-48 ore
Indicazioni: Tachiaritmie sopraventricolari e ventricolari Cardioversione FA
Associazione con dig, betablocc, verapamile ! Profilassi recidive di FA
mortalità vs placebo! (2.9 vs 0.8%: 12/413 vs 3/387 pazienti) (Coplan et al. Circ.1990)
![Page 27: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/27.jpg)
Chinidina (III)
Effetti collaterali Causa di sospensione terapia nel 30% dei casi
Gastroenterici SNC (cefalea, acufeni, parestesie, confusione...) (cinconismo) Ematologici (trombocitopenia, anemia emolitica) Cardiaci
Bradicardia / disturbi conduzione AV Tachiaritmie (0.5-2% dei casi)
• Torsioni di punta / T.V. / F.V.
![Page 28: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/28.jpg)
Altri antiaritmici della classe IA
Procainamide Rispetto alla chinidina:
Simili effetti (inclusi quelli proaritmici) Minore durata d’azione (circa 4 ore)
Diisopiramide Rispetto alla chinidina:
>>> Effetto inotropo negativo >>> Effetto vagolitico (possibilità di secchezza fauci,
ritenzione urinaria, stipsi, glaucoma...) Utilizzato nella cardiomiopatia ipertrofica
![Page 29: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/29.jpg)
Lidocaina (I) Effetti elettrofisiologici diretti
assenti sulla fase 0 (depolarizzazione rapida) PdA Periodo Refrattario Periodo Refrattario Relativo (PReff/PdA) Nessun effetto inotropo negativo
Effetti ECGrafici e neurovegetativi assenti
Attività bloccante dei canali Na in presenza di acidosi, tachicardia, depolarizzazione, > K extr, ischemia Omogeneizzazione caratteristiche elettrofisiologiche aree
ischemiche e non
![Page 30: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/30.jpg)
Lidocaina (II) Metabolismo
Epatico Via di somministrazione e posologia
e.v. bolo di 1-2 mg/kg (circa 100 mg) ripetibile infusione a 1-4 mg/min
Indicazioni Tachiaritmie soprattutto dell’IMA
Effetti collaterali SNC: vertigini, parestesie, confusione, convulsioni, coma
![Page 31: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/31.jpg)
Mexiletina (e tocainide) Effetti elettrofisiologici diretti
Simili alla lidocaina Possibilità di somministrazione anche orale Indicazioni
Tachiaritmie ventricolari Efficacia scarsa ( 5-50% per os) Possibilità d’associazione con farmaci delle classi I e III
Effetti collaterali SNC: simili alla lidocaina Gastroenterici: pirosi, nausea, vomito... Proaritmico (tocainide)
![Page 32: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/32.jpg)
Propafenone e flecainide Effetti elettrofisiologici e miocardici
velocità depolarizzazione rapida (fase 0) () durata Potenziale d’Azione Periodo refrattario effettivo Velocità di conduzione Contrattilità miocardica Lieve attività betabloccante e calcioantagonista
Modificazioni ECGrafiche = Frequenza sinusale intervallo PR (conduzione AV) durata QRS e QT
![Page 33: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/33.jpg)
Propafenone e flecainide (II) Indicazioni
Trattamento acuto e cronico Aritmie ipercinetiche sopra- e ventricolari Cardioversione della fibrillazione atriale (associazione con digitale...) Profilassi recidiva di FA
Posologia (propafenone) orale: 150-300 mg x 3/die e.v.: 0.5-2 mg/kg in 3-5 min+infusione a 1-2 mg/min
Effetti indesiderati Bradicardia, blocchi AV, blocchi di branca Effetto proaritmico Insufficienza cardiaca
![Page 34: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/34.jpg)
CAST Trial: Metodi Presupposti
La frequenza e complessità dell’extrasistolia ventricolare è predittiva della mortalità nel postinfarto
Ipotesi La soppressione delle aritmie ventricolari con la terapia antiaritmica
determina una miglior prognosi Casistica
2372 infartuati (6 giorni-2 anni) con extrasistolia ventricolare frequente (> 6 BPV/ora) e riduzione lieve-moderata della funzione VSinx (FE < 40-50%)
Protocollo Somministrazione in doppio cieco di placebo o dell’antiaritmico
dimostratosi preliminarmente efficace nel sopprimere l’aritmia (> 80% riduzione BPV)
![Page 35: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/35.jpg)
CAST Trial: Risultati Incidenza di morte aritmica ed arresto cardiaco a 10 mesi
Significativamente maggiore nei pazienti trattati con flecainide/encainide vs placebo: 4.5 vs 1.2 %
Mortalità totale Significativamente aumentata nei pazienti trattati con
flecainide/encainide vs placebo: 7.7 vs 3 % Implicazioni:
Anche se ben tollerata acutamente, la terapia antiaritmica può determinare una > mortalità
Possibile effetto sinergico con l’ischemia nella creazione di circuiti di rientro
Non indicazione al trattamento delle tachiaritmie ventricolari asintomatiche
![Page 36: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/36.jpg)
Arrhythmogenic Mechanisms of Sympathetic Activation
Direct Abnormal electrophysiology
Increased automaticity Triggered activity (delayed afterdepolarizations)
Reentrant circuits Nonuniform effects on conductivity and repolarizations
Increased sensitivity to arrhythmogenic mechanisms Ischemia / infarction Electrolyte disturbances (e.g. hypokaliemia) Drugs (digitalis, diuretics, antiarrhythmics)
Indirect Acute coronary syndromes LV dilatation and remodeling Electrolyte abnormalities
![Page 37: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/37.jpg)
Beta bloccanti Effetti elettrofisiologici e miocardici
= () Velocità depolarizzazione e durata PdA durata periodo refrattario contrattilità
Effetti ECGrafici Frequenza sinusale () durata PR = durata QRS () durata QT
Effetti indiretti, dipendenti dall’attivazione adrenergica Indicazioni:
Tachiaritmie sopra- e ventricolari soprattutto da iperattività adrenergica (QT lungo, PVM); Postinfarto
![Page 38: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/38.jpg)
Effects of Beta Blockers on the Mortality of Postinfarction Patients: Metanalysis of 27 Controlled Trials (>27,000 patients)
0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 1,8 2
Selective
Non selective
With ISA
Without ISA
Non fatal reinfarction
Non sudden
Sudden
OVERALL
Type of beta blocker
Mode of death
(Yusuf et al. Prog Cardiovasc Dis 1985;27:335)
Odds ratio (active:control)
![Page 39: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/39.jpg)
Effects of Beta Blocking Agents on the Incidence of Sudden Death in Postinfarction Patients
0
5
10
15
-4% -41% -12% -47% -45%
Suddendeath
(% patients)
Placebo Beta1 selective Non-selective
AtenololISIS-1
n.s.
MetoprololMetanalysis
<.0001
PropranololBHAT
No CHF CHFn.s. <.05
TimololNorwegian
<.0001
(modified from Eichorn & Bristow, AJC 79:794;1997)
![Page 40: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/40.jpg)
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II)
0
0,6
0,8
1
0 200 400 600 800
Su
rviv
al
Time after inclusion (days)
34% all cause death(95% CI: 0.54-0.81; P<0.0001)
44% sudden death (95% CI: 0.39-0.80; P<0.0011)
(CIBIS II, Lancet 1999;353:9)
Bisoprolol
Placebo
![Page 41: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/41.jpg)
Sotalolo (I)
Azione beta bloccante (L-sotalolo) + azione tipo antiaritmico tipo III (L- e D-sotalolo)
Effetti elettrofisiologici e miocardici = () Velocità depolarizzazione durata PdA durata periodo refrattario contrattilità
Effetti ECGrafici Frequenza sinusale () durata PR durata QRS durata QT
![Page 42: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/42.jpg)
Sotalolo (II)
Indicazioni Trattamento acuto e cronico Aritmie ipercinetiche sopra- e ventricolari Profilassi recidiva di FA Profilassi delle AIV maligne (efficace nel 25-40%pz)
Posologia orale: 120-320 mg/die suddivisi in 2-3 somministraz.
Effetti indesiderati Bradicardia, blocchi AV, blocchi di branca Effetto proaritmico Insufficienza cardiaca Effetti indesiderati dei beta bloccanti
![Page 43: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/43.jpg)
Effetti del d-Sotalolo sulla Mortalità in Pazienti con Disfunzione Vsinx Postinfartuale
(Survival With ORal D-sotalol Trial)
0,86
0,88
0,90
0,92
0,94
0,96
0,98
1
0 60 120 180 240 300Time from randomization (days)
Pro
port
ion
eve
nt fr
ee
(waldo et al., Lancet 1996; 348:7)
Placebo
D-Sotalolo
Relative risk=1.6595% CI= 1.15-2.36p= 0.006
![Page 44: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/44.jpg)
Amiodarone (I) Antiaritmico tipo III + bloccante fase 0, alfa e beta
bloccante, calcioantagonista ed inibizione T3 T4 Effetti elettrofisiologici e miocardici
= () Velocità depolarizzazione durata PdA durata periodo refrattario velocità conduzione
Effetti ECGrafici Frequenza sinusale, () durata PR durata QRS, durata QT
Effetti emodinamici Debole azione inotropa negativa Lieve azione vasodilatatrice sistemica
![Page 45: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/45.jpg)
Amiodarone: Farmacocinetica
Biodisponibilità: 40-70% Inizio comparsa degli effetti di tipo beta bloccante a 5-10 gg efficacia
antiaritmica a 5-6 settimane dall’inizio terapia Metabolismo epatico / Metabolita attivo: desetilamiodarone Accumulo in polmoni, fegato, tess. adiposo, cute, cornea... Concentrazione miocardica = 10-50 volte quella plasmatica senza
rapporti precisi tra di loro Eliminazione in due fasi:
50% del farmaco eliminato dai tessuti meglio perfusi entro 5-10 gg dalla sospensione
25-120 gg. dagli altri tessuti
![Page 46: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/46.jpg)
Amiodarone: posologia e modalità di somministrazione
Per via orale 1a settimana: 400 mg x 3/die 2a settimana: 400 mg x 2/die 3-4a settimana: 200 mg x 2-3/die Successivamente: minima dose efficace: 200-400 mg/die /
possibile intervallo di 1-2 giorni Controlli ogni 1-3 gg. dell’ECG nelle prime settimane
/(ospedalizzazione) In assenza di carico: steady state in 256 gg!
Per via e.v. 2.5-10 mg/kg in 20-30 min + infusione continua
![Page 47: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/47.jpg)
Amiodarone: indicazioni
Tutte le tachiaritmie sopra- e ventricolari
Cardioversione e profilassi delle recidive
Prevenzione della morte improvvisa (effetto antifibrillatorio)
Cardiomiopatia ipertrofica ostruttiva
Postinfarto (pz. non beta bloccati)
(Insufficienza cardiaca)
Cardiomiopatia dilatativa idiopatica (?)
![Page 48: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/48.jpg)
Amiodarone: Effetti collaterali
Dose dipendenti (n.s. vs placebo a 300 mg/die) Fibrosi polmonare (rara con < 300 mg/die) Epatopatia (> enzimi epatici; cirrosi epatica rara) Cutanei (fotosensibilizzazione, colorazione bluastra) Microdepositi corneali Ipertiroidismo (1-2%) ipotiroidismo (2-4%) Disturbi gastroenterici Bradiaritmie Tachiaritmie (eff. proaritmico raro)
![Page 49: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/49.jpg)
GESICA TrialGrupo de Estudio de la Sobrevida en
lnsuficiencia Cardiaca en Argentina
516 pz. con IC randomizzati ad amiodarone (300 mg/die) o terapia standard
Pz in classe IV: 31% IC non ischemica : 60% Con amiodarone,
riduzione: 28% Mortalità totale 27% morte improvvisa 23% morte per IC
progressiva Effetto indipendente
dalla presenza di tachicardia ventricolari non sostenute all’ECG dinamico
40
45
50
55
60
65
70
75
80
85
90
95
100
0 90 180 270 360 450 540 630 720
Amiodarone
Placebo
Log rank testp=0.024
Sop
ravv
iven
za (
%)
Giorni dalla randomizzazione
![Page 50: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/50.jpg)
Survival trial of Antiarrhythmic Therapy in CHF (CHF-STAT)
674 pazienti con IC , FE < 40% e > 10 BPV/ora randomizzati ad amiodarone (300 mg/die)
Pz in classe III/IV: 42% IC non ischemica: 30% Non significativa
modificazione: Mortalità totale Incidenza di morte
improvvisa Tendenza a miglioramento in
cardiopatia non ischemica Con amiodarone:
miglioramento FE Soppressione BPV n.s. effetti collaterali
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 6 12 18 24 30 36 42 48 54
Amiodarone
Placebo
Mesi
Sop
ravv
iven
za (
%)
![Page 51: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/51.jpg)
Ibutilide
class III Success rate: In 34-50% patients of AF or AFL Iv during the 30-min, 2 mg dosing or ensuing 30-
40 minutes More effective than iv procainamide or sotalol Adverse effect:
torsade de pointes Can be treated and prevented by with iv MgSO4 Can be limited by cautious use in patients at higher risk
![Page 52: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/52.jpg)
Ibutilide
Higher risk patient Bradycardia Hypokalemia Hypomagnesemia Ventricular hypertrophy or failure Female gender
![Page 53: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/53.jpg)
Effetti emodinamici acuti dei principali gruppi di calcioantagonisti
Diidropiridinici(es. nifedipina)
Fenilalchilamine(es. verapamile)
Benzotiazepine(es. diltiazem)
Resistenzeperiferiche
Resistenzecoronariche
Frequenzacardiaca
()
Conduzione A-V ( )
Contrattilità ( )
![Page 54: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/54.jpg)
The different binding sites of CCBs result in differing pharmacological effects
Voltage-dependent binding (targets smooth muscle)
Use-dependent binding (targets cardiac cells)
Cellmembrane
1
out
in
+20
-80
mV 2
DiltiazemVerapamil
1
1
out
in
+20
-80
-30 2
1
Nifedipine
CellmembranemV
![Page 55: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/55.jpg)
Effetti collaterali dei calcioantagonisti Nifedipina (18%)
Edemi malleolari Cefalea Vertigini Rash cutaneo Ipotensione Cardiopalmo Aggravamento dell’angina
Verapamile (10%) Stipsi Blocco AV, bradicardia Insufficienza cardiaca Vertigini, Cefalea
Diltiazem (5%) Blocco AV, bradicardia Vertigini, Cefalea, rash cutaneo
![Page 56: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/56.jpg)
Reentry - VM/PF Junction
V. SeptumR.VentricleVent. Wall
Ventricular Apex
PF twigVentricular Cavity
Unidirectional Block
Subendocardial Ischemia
![Page 57: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/57.jpg)
Subendocardial Ischemia
Reentry - VM/PF Junction
V. SeptumR.VentricleVent. Wall
Ventricular Apex
3 Requirements:• 2 Parallel pathways• Unidirectional block• CT > ERP
Ventricular Cavity
Unidirectional Block
Reentrant Circuit Established
![Page 58: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/58.jpg)
Class I & III Effects on Reentry (Ventricular)
Ventricular Apex
PF twig
Reentrant Circuit Established
Sustained V Tach:
3 Reentry Requirements:
• 2 Parallel Pathways
• Undirectional Block
• CT>ERP
Subendocardial Ischemia
Class I Drug Effects:• ERP
• Selective Block at Depold. Vm
Normal Sinus Rhythm
Class III:
APD ( ERP >CT )
Block IKr
![Page 59: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/59.jpg)
Class II - Blockers
• AV Node ERP - AVN reentry - rate control during atrial tachycardia
• Reduce exercise-induced arrhythmias (catecholamine-induced)
• Clinical trials: - significantly reduce incidence of re-infarction & sudden death after an MI (prevent / reverse remodeling).
![Page 60: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/60.jpg)
Class IV Drugs (diltiazem, verapamil)
Ca channel blockers inhibit L-type Ca
channels by the same State & Vm-
dependent mechanism as Na channel
blockers inhibit Na channels.
Mechanism of Action:
50
0
% Ca Channels Blocked diltiazem
50
100
![Page 61: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/61.jpg)
Normal ERP
AVN Rentry
His Bundle
Normal ERP
PSVT: •140-220 min -1• sudden onset• palpitations,dizziness
PrematureAtrial Beat
Ischemia Atrium
Long ERP
“Dispersion of Refractoriness”
![Page 62: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/62.jpg)
Class IV & AVN Rentry
His Bundle
Normal ERP
PSVT: •140-220 min -1• sudden onset• palpitations,dizziness
Ischemia
Atrium
Long ERP
+ diltiazem
ERP>CT
Long ERP
![Page 63: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/63.jpg)
Class IV - Clinical Study
• 8 Pts. with a history of AVN Reentry
• Defined AVN ERP
• Induced PSVT by Programmed Electrical Stimln.
• Administered i.v.boluses of diltiazem, verapamil or nifedipine
• Remeasured AVN ERP
![Page 64: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/64.jpg)
Class IV & Human AVN ERP
500
400
200
300
500
400
200
300
500
400
200
300
C D C CV N
P<0.05 P<0.05 P<0.05
diltiazem verapamil nifedipine
AVN ERP (msec)
Kawai et al., 1981
![Page 65: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/65.jpg)
Different Treatments for AVN Reentry
Prophylactic Rx: diltiazem (Cardizem ®)
verapamil (Isoptin, Calan ®) propranolol (Inderal ®)
Acute Rx: adenosine (Adenocard ®) -for rapid i.v. administration (6 or 10 mg) - t1/2 <10 secs; >90% effective
![Page 66: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/66.jpg)
Different Treatments for Rate Control
diltiazem (Cardizem ®) verapamil (Isoptin, Calan ®) propranolol (Inderal ®) digoxin (Lanoxin ®) amiodarone (Cordarone ®)
During Atrial Tachyarrhythmias - “Protect the ventricle”
![Page 67: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/67.jpg)
Major Side Effects
Anticholinergic Class Ia - m2 blockade (quinidine, disopyramide) - ganglionic blockade (procainamide)
![Page 68: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/68.jpg)
Quinidine & Atrial Flutter
• O2 demand>supply• CO
Antimuscarinic!
200
300
400
500
0 5 10 15
Bea
ts (
min
-1)
Minutes
Quinidine3 mg/kg
Rx: +Digoxin (protect the ventricle)
Ventricular
Atrial
![Page 69: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/69.jpg)
Major Side Effects
Negative Inotropic Effects Class IV (verapamil, diltiazem) Class II (propranolol, other -blockers) Class Ia (quinidine, procainamide)
Bronchoconstriction Propranolol (2-blockers)
Neurologic Side Effects Class Ib (lidocaine) - CNS stimulation or depression - ringing in ears, metallic taste, slurred speech
Anticholinergic Class Ia - m2 blockade (quinidine, disopyramide) - ganglionic blockade (procainamide)
![Page 70: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/70.jpg)
Major Side Effects (cont.) Proarrhythmia
(Class I 10%) (Class Ic > Class Ia & Class Ib)
![Page 71: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/71.jpg)
Proarrhythmia
V. SeptumR.VentricleVent. Wall
Ventricular Apex
PF twigVentricular CavitySubendocardial
Ischemia
“Mild ischemia”
![Page 72: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/72.jpg)
Proarrhythmia
V. SeptumR.VentricleVent. Wall
Ventricular Apex
PF twigVentricular CavitySubendocardial
Ischemia
+ Class I or III(ERP)
![Page 73: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/73.jpg)
Proarrhythmia
V. SeptumR.VentricleVent. Wall
Ventricular Apex
PF twigVentricular Cavity
Unidirectional Block
Subendocardial Ischemia
+ Class I or III(ERP)
“Drug Induced Arrhythmia”
![Page 74: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/74.jpg)
Major Side Effects (cont.)
Proarrhythmia (Class I 10%) (Class Ic > Class Ia & Class Ib)
Torsade de Pointes (Quinidine, Sotalol, Class III)
![Page 75: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/75.jpg)
Torsade Mechanism (EADs)
Roden, ‘96
(INa, ICa, INa/Ca)?
Multifocal Ventricular Tachycardia
![Page 76: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/76.jpg)
Major Side Effects (cont.) Drug-Specific: Quinidine: syncope, cinchonism, diarrhea
Procainamide: systemic lupus-like syndrome (20-25% of all patients after 1 year)
Amiodarone: pulmonary fibrosis, constipation, corneal deposits (100% >1 yr), bluish skin, hypo- or hyper-thyroidism, peripheral neuropathy, elevated transaminases.
![Page 77: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/77.jpg)
Regional Selectivity
• Class Ib - Rx for Ventricular arrhythmias only
• Class Ia - Rx for Ventricular & Atrial arrhythmias
0
% Na Channels Blocked
100lidocaine
atrial
ventricular
atrial
ventricularVm
(mV)
20
0
![Page 78: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/78.jpg)
The generation of pacemaker potentials relies on a complex interplay between different types of currents carried by cation channels.
I(f) is an inward current activated by hyperpolarization of the membrane potential and by intracellular cyclic nucleotides such as cAMP.
Specific agents have been developed for their ability to selectively reduce heart rate by lowering cardiac pacemaker activity where f-channels are their main natural target. These drugs include alinidine, zatebradine, cilobradine, ZD-7288 and ivabradine.
Nuovi farmaci in fase di studio
![Page 79: FARMACI ANTIARITMICI. Indications for Treatment CO One typically treats those arrhythmias that: - asynchronization (multifocal VT, VFib) - contractions](https://reader036.vdocument.in/reader036/viewer/2022062512/5542eb67497959361e8d3136/html5/thumbnails/79.jpg)
Drugs of the FutureDrugs Fut 2007, 32(3): 245
ISSN 0377-8282Copyright 2007 Prous ScienceCCC: 0377-8282DOI: 10.1358/dof.2007.032.03.1072639
Gap junction modifying antiarrhythmic peptides: Therapeutic potential in atrial fibrillationHaugan, K., Petersen, J.S.
Rotigaptide is a synthetic AAP* analogue that prevents metabolic stress-induced atrial conduction velocity (CV) slowing and rapidly reverts established atrial CV slowing in vitro. …
in dog models of ischemia-related AF and chronic atrial dilatation-induced AF, rotigaptide has significant antiarrhythmic effects. Rotigaptide also has a favorable safety profile.
*antiarrhythmic peptide