Effect of drugs on heart rhythm

Činnost srdce je řízena vegetativním nervovým systémem prostřednictvím mediátorů. Mediátorem sympatického nervového systému je noradrenalin, mediátorem parasympatiku je acetylcholin. Činnost srdce je také ovlivňována adrenalinem z dřeně nadledvin. Acetylcholin srdeční činnost tlumí, zatímco noradrenalin působí na srdce budivě. Účinek mediátorů je zprostředkován specifickými receptory umístěnými na buněčné membráně. Srdeční činnost závisí na přítomnosti vápníku v extracelulárním prostoru a v endoplazmatickém retikulu.

Mezi léky ovlivňující rytmus (a další funkce) srdeční pumpy patří mimo jiné kardioinhibitory, kardiotonika a antiarytmika.

Cardioinhibitors
Cardioinhibitors (drugs that reduce heart activity) act negatively chronotropically (by reducing heart rate) and inotropically (by reducing the contractility of the heart muscle), which leads to a reduction in cardiac output and blood pressure. These changes reduce the activity of the heart and thus the consumption of oxygen by the myocardium. The mechanisms of action of these drugs also include a reduction in electrical conduction (negative dromotropic action).

The mechanical and metabolic effects of these drugs predispose them to the treatment of hypertension, angina pectoris and myocardial infarction. Thanks to their effect on the electrical activity of the heart, they are also suitable for the treatment of cardiac arrhythmias. Some cardioinhibitors (especially certain &beta;-blockers) are used in the treatment of heart failure.

Hypertension
It is caused by an increase in cardiac output or an increase in systemic vascular resistance. Cardioinhibitors decrease heart rate and stroke volume, leading to decreased cardiac output and thus lowering blood pressure.

Angina pectoris and myocardial infarction
Cardioinhibitors (by reducing heart rate, contractility and arterial pressure) reduce the work of the heart and its demands for oxygen. They can thus relieve the patient of anginal pains, which arise most often due to a lack of oxygen during greater exertion. The importance in the treatment of myocardial infarction lies not only in increasing the ratio of oxygen supply and demand, but also in the ability to inhibit post-infarction heart tissue remodeling.

Cardiac arrhythmia
Cardioinhibitors alter pacemaker activity and conduction through the heart and are therefore useful in the treatment of arrhythmias caused by both abnormal automation and conduction.

Heart failure
Although it may seem paradoxical that cardioinhibitors would be used in heart failure when the myocardium is functionally suppressed, clinical studies have shown that certain cardioinhibitors have been shown to improve heart function in certain types of heart failure. This effect may be derived from their blocking of the excessive sympathetic effects on the heart that damage the failing heart.

Classes of drugs and their general mechanisms of action
Clinically used cardioinhibitors can be divided into three groups: beta-blockers, calcium channel blockers and centrally acting sympatholytics.

Beta-blockers (antagonists of beta-adrenergic receptors)
It binds to &beta;-adrenergic receptors in the conduction system and in the working myocardium. Both types are found in the heart: &beta;-1 and &beta;-2 adrenoreceptors. However, &beta;-1 predominates numerically and functionally. These receptors primarily bind noradrenaline released from sympathetic adrenergic nerve endings. It also weighs adrenaline and noradrenaline circulating in the blood. β-Blockers prevent the binding of these ligands to the receptors by competing with them for the binding site. They reduce the effects of the sympathetic (ie, they are sympatholytics) that normally stimulate chronotropy, inotropy, and dromotropic. Their effect even increases if sympathetic activity is increased. Clinically used &beta;-blockers are either non-selective (&beta;-1 or &beta;-2) blockers or relatively selective &beta;-1-blockers (relative selectivity can be lose the medicine). Some of the &beta;-blockers have other effects besides &beta;-blocking. The third generation of β-blockers are substances that additionally have vasodilating effects by acting on the β-adrenoreceptors of blood vessels.

Some beta-blockers, after binding to the &beta;-adrenoceptor, partially activate while preventing the binding of noradrenaline. These so-called partial agonists (partial &beta;-blockers) thus provide a certain background of sympathetic activity, even if they prevent normal or increased sympathetic effects. We speak of them as carriers of their own sympathomimetic activity (intrinsic sympathomimetic activity, ISA). Some of the β-blockers are also carriers of membrane stabilizing activity (MSA), which is also found in sodium channel blockers belonging to antiarrhythmics.

&beta;-adrenoceptors are coupled to Gs-proteins which activate adenyl cyclase. The increase in cAMP activates cAMP-dependent protein kinases (PK-A), which phosphorylate calcium channels and thus cause increased calcium flux into the cell. The increase in intracellular calcium during action potentials leads to increased release of calcium from the sarcoplasmic reticulum, which ultimately increases inotropy (contractility). Gs-protein activation also leads to an increase in heart rate (chronotropy). PK-A protein kinases also phosphorylate parts of the sarcoplasmic reticulum, leading to increased calcium release through ryanodine receptors (ryanodine-sensitive calcium channels) associated with the sarcoplasmic reticulum. This provides more calcium for its binding to troponin-C, increasing inotropy. PK-A can further phosphorylate myosin light chains, which may contribute to the positive inotropic effect of β-adrenoceptor stimulation. They are used to treat hypertension, angina pectoris, myocardial infarction and arrhythmias.

Hypertension
&beta;-blockers lower arterial blood pressure by reducing cardiac output. They can thus represent an effective treatment for hypertension, especially if they are used together with diuretics. In some patients, hypertension is caused by emotional stress, which activates the sympathetic system, in others, for example, pheochromocytoma, which increases the level of circulating catecholamines. Even in these cases, treatment with β-blockers is successful. In addition, β-blockers inhibit the activity of the renin-angiotensin-aldosterone system. Acute treatment with β-blockers is not very effective in lowering blood pressure due to the compensatory increase in vascular resistance in the systemic circulation. The hypotensive effect of the substances of this group is already detectable during the first days of treatment, but they reach their full effect only after 2-3 weeks of administration.

Angina pectoris and myocardial infarction
The antianginal effect of β-blockers is attributed to their depressant effect on heart rate, contractility and their hypotensive effects. &beta;-blockers reduce the work of the heart and thereby the need for oxygen saturation of the myocardium (see above).

Cardiac arrhythmia
The antiarrhythmic properties of β-blockers (class II antiarrhythmics) are related to their ability to inhibit the sympathetic influence on cardiac activity. The sympathetic nerve increases the frequency of excitation in the sinuatrial node, which increases the sinus rhythm. Furthermore, it increases the speed of transfer of excitation to the myocardium of the ventricles and stimulates the formation of ectopic excitations. These sympathetic effects are mediated mainly through β-1-adrenoceptors. Therefore, β-blockers may reduce these effects, thereby reducing sinus rhythm, AV conduction velocity (which may block reentry mechanisms), and inhibiting abnormal pacemaker activity. β-Blockers also affect non-pacemaker action potentials by increasing action potential duration and relative refractory period. This effect may play a major role in preventing arrhythmias caused by the reentry phenomenon.

Heart failure
Most heart failure patients suffer from systolic dysfunction, i.e. the contractile function of the heart is limited (ie loss of inotropy). Although the mechanism by which β-blockers help in heart failure is not entirely clear, it is certain that they improve heart function and reduce mortality.

Abbreviations: HTN - hypertension, Arrhy - arrhythmia, MI - myocardial infarction, CHF - congestive heart failure, ISA - intrinsic sympathomimetic activity

Calcium channel blockers (calcium-channel blockers, CCB)
It binds to L-type calcium channels (slow calcium channels ) in the cardiomyocyte membrane and nodal tissue. These channels are responsible for regulating the influx of calcium into the myocardial cell, which stimulates its contraction. In cardiac node tissue (SA and AV node), these channels have a role in pacemaker currents and the initial phase of action potential generation. By blocking the entry of calcium into the cell, these drugs act negatively inotropically (reduce the force of cardiac contraction), negatively chronotropically (reduce heart rate) and reduce the speed of impulse transmission through the cardiac conduction system (negatively dromotropically, especially on the AV node). In the smooth muscle of the vessels, they cause relaxation and a decrease in peripheral resistance with a decrease in blood pressure. They are used in the treatment of hypertension, angina pectoris and arrhythmias.

Hypertension
By causing the smooth muscle in the vessel wall to relax, CCBs reduce systemic vascular resistance, thereby lowering blood pressure. These drugs act mainly on arterial resistance vessels, with a minimal effect on venous capacitance vessels.

Angina pectoris
The antianginal effects of CCBs are derived from their vasodilatory and cardiac depressant effects. Systemic vasodilatation lowers arterial pressure, which leads to a reduction in ventricular afterload, thereby reducing oxygen demand. The more heart-selective CCBs (verapamil and diltiazem) reduce heart rate and myocardial contractility, making them excellent anti-angiogenic drugs (by reducing myocardial oxygen demand). CCBs can also cause dilation of the coronary arteries, thus preventing their spasm (Prinzmetal's angina pectoris).

Cardiac arrhythmia
The antiarrhythmic group CCB (class IV antiarrhythmics) works mainly by reducing the conduction velocity and prolonging repolarization, especially in the atrioventricular node. Delayed action of the AV node helps prevent the reentry mechanism that can cause supraventricular tachycardia.

Classes of calcium channel blockers
We distinguish three classes of CCB. They differ not only in their basic chemical structure, but also in their relative selectivity to cardiac or vascular calcium channels. Most CCBs acting on vascular smooth muscle are 'dihydropyridines. They are therefore mainly used to reduce vascular resistance and blood pressure, i.e. to treat hypertension. They are not used to treat angina pectoris, due to their strong vasodilatory and pressure-lowering effect, which can lead to reflex cardiac stimulation (tachycardia and increased inotropy), which leads to a dramatic increase in myocardial oxygen consumption. Dihydropyrinidines include the following specific drugs:
 * amlodipine;
 * felodipine;
 * isradipine;
 * nicardipine;
 * nifedipine;
 * nimodipine;
 * nitrendipine.

(note: some newer substances such as amlodipine or isradipine are also called second generation dihydropyridines .)

Non-dihydropyridines include two other classes of CCBs. Verapamil (phenylalkylamine class) is relatively selective for the myocardium and is less effective as a systemic vasodilator. This drug is very important in the treatment of angina pectoris and arrhythmias. Diltiazem (benzothiazepine class) is intermediate between verapamil and dihydropyridines in terms of selectivity for vascular calcium channels. It reduces heart rate and has a vasodilating effect. By these mechanisms, it is able to lower blood pressure without causing the same degree of reflex cardiostimulation as the dihydropyridines.

Side effects and contraindications
Dihydropyrinidine CCBs can cause congestion, headaches, excessive hypotension, edemas, and reflex tachycardia. From the point of view of activation of sympathetic reflexes and lack of direct effects on the heart muscle, they are not very suitable for the treatment of angina pectoris. Long-acting dihydropyridines have been shown to be safer antihypertensives due to reduced reflex responses. Cardiac-selective non-dihydropyridine CCBs can cause excessive bradycardia, impairment of electrical conduction (AV node block), and decreased contractility. Therefore, they should not be used by patients with chronic bradycardia, cardiac conduction disorders or heart failure. CCBs (mainly non-dihydropyridines) should also not be prescribed to patients who are being treated with &beta;-blockers.

Centrally acting sympatholytic
The sympathetic nervous system plays a major role in the regulation of arterial blood pressure. It increases heart rate (positive chronotropic effect), myocardial contractility (positive inotropic effect) and conduction velocity in the heart (positive dromotropic effect). The sympathetic adrenergic fibers that innervate the heart and blood vessels are postganglionic efferent nerve fibers. The cell bodies of these nerves are located in the prevertebral and paravertebral sympathetic ganglia. The sympathetic preganglionic fibers that lead to the ganglia from the spinal cord originate in the medulla oblongata of the brainstem. Sympathetic excitatory neurons are found here, which have a significant basal activity that gives the heart a certain tone under basal conditions. These neuronss receive signals from other, vagal neurons from the nucleus tractus solitarii (receives signals from peripheral baroreceptors and chemoreceptors) and from neurons in the hypothalamus. Together, this neuronal system regulates sympathetic (and parasympathetic) transmission to the heart and blood vessels. Sympatholytic drugs can block the sympathetic adrenergic system at three levels. The first, peripheral sympatholytics - antagonists &alpha; and &beta;-adrenoceptors – they block the effect of noradrenaline on the effector organ (heart or blood vessels). The other are the so-called ganglion blockers, which block the transmission of the impulse in the sympathetic ganglia. The third group consists of drugs that block sympathetic activity inside the brain. We call them centrally acting sympatholytics.

Centrally acting sympatholytics block sympathetic activity by binding and activating α2-adrenoceptors in the membrane of medulla cells that regulate cardiac activity. This reduces the sympathetic effect on the heart and cardiac output decreases. These medicines are only used to treat hypertension.

Therapeutic indications
Centrally acting α-2-adrenoceptor agonists are used to treat hypertension, but are not used as first-line drugs because of their side effects in the brain. They are usually prescribed in combination with diuretics to prevent fluid build-up that would increase blood volume and thus reduce the effect of the drug. These drugs are suitable for patients with kidney disease, as they do not affect renal function.

Specific Medicines
Several different centrally acting antihypertensives are used in clinical practice: Clonidine, guanabenz and guanfacine are structurally similar drugs and have identical antihypertensive effects. α-methyldopa is a structural analog of dopa and must first be converted to α-methynoradrenaline, which only functions as an α-2-adrenoceptor agonist in the medulla oblongata and reduces sympathetic stimulation. α-Methyldopa is the drug of choice in the treatment of hypertension in pregnancy, when its teratogenicity has not been proven.
 * clonidine;
 * guanabenz;
 * guanfacine;
 * α-methyldopa.

Side effects and contraindications
Side effects of centrally acting sympatholytics include sedation, xerostomia, bradycardia, orthostatic hypotension, impotence, and nausea. Swelling may occur during long-term therapy.

Cardiotonics
Cardiotonics (cardiostimulants) potentiate heart function by increasing heart rate (chronotropy) and myocardial contractility (inotropy), which increases cardiac output and arterial pressure. Many of them also have a positive dromotropic and lusitropic effect. Some of these drugs cause systemic vasodilation, while others have vasoconstrictive effects. The effects of these drugs on the heart muscle predispose them to use in heart failure, cardiogenic shock and hypotension. In the treatment of heart failure, procedures that reduce the demands on myocardial function are preferred over cardiotonics- ie reduce afterload or preload, or both (diuretics, organic nitrates, calcium channel blockers, ACE inhibitors).

Heart failure and cardiogenic shock
The main cause of heart failure and hypotension caused by acute heart failure (cardiogenic shock) is loss of myocardial contractility, which leads to reduced organ perfusion and hypotension. Cardiac function can be improved by reducing afterload, increasing preload (increased fluid volume) and increasing cardiac contraction. Cardiotonics work by this mechanism. Sympathomimetics or phosphodiesterase inhibitors are used for short-term therapy and may be harmful if used for a long time. In contrast, cardiac glycosides (digitalis and others) are safe and effective in the long-term treatment of heart failure.

Circulatory shock
It is a form of shock caused by hypovolemia (for example in bleeding conditions) or vasodilation during infection (septic shock). Cardiotonics, especially sympathomimetics such as beta-agonists, are used to improve (ie increase) blood pressure. They are often used in conjunction with infusions and vasoconstrictor drugs.

General classes of drugs and their mechanisms of effect
Cardiotonics can be divided into four basic classes: beta-adrenoceptor agonists (beta-agonists), cardiac glycosides (digitalis and others), phosphodiesterase inhibitors and calcium sensitizers.

Beta-agonists
These are sympathomimetics that bind to cardiac β-adrenoreceptors. Activation of β-1 and β-2 adrenergic receptors leads to an increase in heart rate and contractility, which increases cardiac output. Their activation also has a positive dromo- and lusitropic effect. These drugs are indicated for both acute and refractory heart failure and circulatory shock. Β-Adrenoceptor agonists bind to β-receptors in the heart and smooth muscle. They also have effects in tissues other than the heart, especially in the smooth muscle of the bronchi (relaxation), liver (stimulating glycogenolysis) and kidney (stimulating renin release). They therefore cause cardiac pacing (increased heart rate, contractility, rate of transfer, relaxation) and systemic vasodilation. An increase in arterial pressure may occur, but not necessarily, as a decrease in vascular resistance interferes with an increase in cardiac output. Thus, the final effect on blood pressure depends on the relative effect on cardiac or vascular receptors. β-agonists cause β-receptor down-regulation, which limits their use to short-term. As they are catecholamines (and have low bioavailability), they must be administered by intravenous infusion. The principle of operation of β-adrenergic receptors - see above.

Specific drugs and their therapeutic use
The table shows several different β-agonists that are used clinically to treat heart failure and circulatory shock. These are either natural catecholamines or their analogues. Almost all have a certain degree of α-agonist activity. For some of these drugs, receptor selectivity is highly dose dependent.

Side effects and contraindications
The main side effect of β-agonists is cardiac arrhythmias. Because they increase myocardial oxygen demand, they can accelerate the development of angina pectoris in patients with coronary artery disease. They can also cause headache and tremors.

Cardiac glycosides (digitalis)
They have been used for more than 200 years to treat heart failure. They represent a family of compounds derived from the plant Digitalis purpurea (foxglove). These drugs inhibit Na + / K + ATPase in cardiac sarcolemma, leading to an increase in intracellular calcium through the Na + / Ca 2+ -exchange system. The increase in intracellular calcium subsequently stimulates the release of additional calcium from the sarcoplasmic reticulum, its binding to troponin C, which increases contractility.

Due to the long half-life of digitalis, this fact should be considered when dosing. It should be administered for several days to reach its therapeutic plasma level (0.5-1.5 ng / ml ).. Digitalis has a relatively narrow therapeutic window. Plasma concentrations higher than 2.0 ng / ml can be toxic. Digitalis toxicity is manifested by (sometimes life-threatening) cardiac arrhythmias. Digibind (immune mechanism) or potassium supply are used to reduce digitalis levels (especially if toxicity is associated with hypokalemia).

Therapeutic use:

Heart failure
Digitalis compounds have cardiotonic effects and are used in heart failure. Although new and more effective drugs are already available, digitalis is still widely used. Clinical studies in patients with heart failure have shown that digoxin, when used in combination with diuretics and vasodilators, increases cardiac output and ejection fraction and reduces filling and capillary wedge pressures. This reduces congestion in the lungs and the risk of edema. Heart rate changes slightly. These effects are expected with a drug that increases inotropy.

Atrial fibrillation a flutter
Atrial fibrillation a atrial flutter lead to an accelerated ventricular rate that can affect their filling (reducing their filling time). Digoxin and other drugs in this group are useful in reducing the ventricular rate, which was initiated by the increased rate of atrial contractions. The mechanism of this beneficial action of digoxin is its parasympathomimetic effect. Activation of the vagus can reduce the rate of conduction through the atrioventricular node to the point that some impulses are blocked. A smaller number of pulses is then fed to the chambers and the frequency of the chamber contractions decreases. In addition, digoxin increases the relative refractory period in the AV node.



Specific drugs from the group of glycosides
Note: Oubain is no longer used today.

Side effects and contraindications
The most significant side effect of digitalis is cardiac arrhythmias, especially atrial tachycardia and atrioventricular block. The drug is contraindicated in patients with hypokalemia, AV block or Wolff-Parkinson-White syndrome. Impaired renal function leads to increased plasma concentrations of digitoxin as it is eliminated by the kidneys.

Phosphodiesterase inhibitors
These are drugs that inhibit the enzyme( cAMP-dependent phosphodiesterase, PDE) responsible for reducing cAMP. This leads to an increase in cAMP levels, which has a positive inotropic and chronotropic effect in the heart. cAMP is the second messenger in the pathway initiated by the binding of catecholamines to beta1-adrenergic receptors coupled to Gs-proteins. This is followed by activation of the adenyl cyclase and the formation of cAMP. cAMP (by reaction with other intracellular messengers) increases contractility, heart rate and conduction velocity.

These drugs are used to treat acute and refractory heart failure, but not chronic heart failure. The drugs used target cAMP-dependent phosphodiesterase (PDE3) isoform 3.

Therapeutic indication
The pacing and vasodilatory properties of PDE3 inhibitors predispose them to the treatment of heart failure. Artery dilation reduces the afterload of a failing ventricle and leads to an increase in ejection fraction and organ perfusion. Reduction of afterload leads to a secondary decrease in preload, which increases the mechanical efficiency of the dilated heart and reduces the oxygen requirements of the failing myocardium. The pacing effect of these drugs increases inotropy, which leads to an increase in heart rate and ejection fraction. However, tachycardia is also the result, so drugs are dosed to minimize the positive chronotropic effect. Baroreceptor reflex,which occurs in response to hypotension, may also contribute to tachycardia. Clinical trials have shown that long-term therapy with PDE3 inhibitors increases the mortality of heart failure patients. These drugs are very useful in the treatment of acute decompensated heart failure. They are always used together with other drugs such as diuretics, ACE inhibitors, β-blockers or digitalis.

Specific drugs
PDE3 inhibitors are milrinone a amrinone (possibly emoximone and piroximone ). (PDE5 inhibitors are used to treat erectile dysfunction).

Side effects and contraindications PDE3 inhibitors
The most common and at the same time most serious side effect of PDE3 inhibitors are ventricular arrhythmias, some of which can reach life-threatening proportions. Some patients may experience headaches and low blood pressure.

Calcium sensitizers
They represent the latest class of cardiostimulants. These drugs increase the sensitivity of troponin-C to calcium, so more calcium binds to it, which increases the contractility of the heart. These drugs are currently undergoing clinical trials for possible use in heart failure. These include, for example, some phosphodiesterase III inhibitors (sulmazol, imobendan, levosimendal).

Antiarrthytmics
Antiarytmika (též antidysrytmika) jsou léčiva používaná k terapii poruch srdečního rytmu, v některých případech i preventivně. Ovlivňují srdeční kontraktilitu a hemodynamiku.

Farmakoterapie arytmií závisí na typu arytmie, délce jejího trvání, závažnosti a stavu srdečního svalu. Arytmie dělíme na tachyarytmie a bradyarytmie.

Mechanismy vzniku tachyarytmií mohou být zvýšená dráždivost, zvýšená automaticita nebo reentry. Z diagnostiky mechanismu vzniku arytmie se odvíjí léčba – snížení excitability a automaticity, léčba ischémie.

Terapeutické použití
Hlavním cílem léčby antiarytmiky je znovunastolení normálního srdečního rytmu a převodu; případně alespoň k prevenci těžších až smrtelných arytmií. Snižují či zvyšují rychlost vedení vzruchu, mění vzrušivost buněk srdce a potlačují abnormální automacii.

Všechna antiarytmika mění membránovou vodivost následujícími mechanismy:


 * Blokádou rychlých sodíkových kanálů. Tyto kanály určují rychlost depolarizace membrány během akčního potenciálu, což může pomáhat odstranit tachyarytmie způsobené mechanismem reentry.
 * Ovlivněním průběhu akčních potenciálů a zejména relativní refrakterní periody. Prodlužováním relativní refrakterní periody může často docházet k odstranění tachykardií. Tyto léky ovlivňují draselné kanály a oddalují fázi repolarizace.
 * Blokádou pomalých kalciových kanálů. Tyto léky snižují sinusovou frekvenci zpomalováním depolarizace pacemakerových buněk. Rovněž snižují rychlost vedení vzruchu AV uzlem.
 * Blokádou aktivity sympatiku, která může být rovněž příčinou vzniku arytmií, proto léky blokující β1–adrenergní receptory jsou užívány k potlačení tohoto vlivu sympatiku na srdce. Jelikož jsou β-adrenoceptory spřažené s iontovými kanály, β-blokátory nepřímo mění i tok iontů přes membránu, zejména kalcia a draslíku.
 * V případě AV blokády se někdy používají léky inhibující vagové vlivy (například atropin, antagonista muskarinového receptoru). AV blokáda se může objevit během léčby β-blokátory.
 * V některých případech je komorová frekvence nepřiměřená, jelikož je iniciována síňovým flutterem či fibrilací síní. Vzhledem k tomu, že je velice důležité zamezit komorové tachykardii, léky se často používají ke zpomalení vedení vzruchu AV uzlem. K tomuto se často používají blokátory kalciových kanálů a β-blokátory. Ze stejného důvodu lze využít i parasympatomimetického účinku digitalisu.

Antiarytmika mají často proarytmický efekt, proto je vhodné je užívat pouze u symptomatických arytmií, zhoršujících kvalitu života nebo prognózu nemocného.

Třídy léčiv používaných k terapii arytmií

 * 1) Třída I – Blokátory rychlých sodíkových kanálů – kardioverze fibrilace síní aj.
 * 2) Ia – blokáda Na+ kanálů – chinidin,
 * 3) Ib – blokáda Na+ kanálů – lidokain, trimekain, fenytoin
 * 4) Ic – blokáda Na+ kanálů – propafenon, flekainid
 * 5) Třída II – β-blokátory (viz výše) – kontrola komorové odpovědi při supraventrikulární tachykardii,
 * 6) Třída III – Blokátory draselných kanálů (např. amiodaron) – supraventrikulární i komorová tachykardie,
 * 7) Třída IV – Blokátory vápníkových kanálů (verapamil, diltiazem) – pouze supraventrikulární tachyarytmie.
 * 8) Další:
 * 9) adenosin,
 * 10) doplnění elektrolytů (soli hořčíku a draslíku),
 * 11) srdeční glykosidy (digitalis),
 * 12) atropin (antagonista muskarinového receptoru),
 * 13) bradiny (blokátory SA uzlu).

Antiarytmika třídy Ia
Blokáda sodíkového kanálu antiarytmiky třídy Ia prodlužuje trvání akčního potenciálu a mírně prodlužují repolarizaci.


 * Chinidin

K farmakologické kardioverzi fibrilace a flutteru síní. Má mnoho nežádoucích účinků.
 * Prokainamid

Užíván k léčbě komorových a supraventrikulárních arytmií.


 * Disopyramid

K léčbě tachyarytmií, zejména po infarktu.

Antiarytmika třídy Ib
Blokují sodíkový kanál, ale mají malý vliv na rychlost nárůstu akčního potenciálu. Zkracují dobu repolarizace.


 * Lidokain, trimekain

Užívány zejména v terapii komorové tachykardie.

Antiarytmika třídy Ic
Blokují sodíkový kanál, výrazně zpomalují rychlost nástupu akčního potenciálu a vedení vzruchu. Doba repolarizace je jimi málo ovlivněna.


 * Propafenon

Užíván k léčbě fibrilace síní a komorové tachykardie.

Antiarytmika třídy I se v dnešní době běžně nepoužívají, kromě propafenonu a flecainidu (obě ze třídy Ic).

Antiarytmika třídy II
Jde o β-adrenergní blokátory. Snižují fosforylaci vápníkového kanálu. Negativně ovlivňují frekvenci spontánní depolarizace v SA a AV uzlu. Dobu repolarizace neovlivňují.

Antiarytmika třídy III
Blokují draslíkové kanály, prodlužují akční potenciál a tlumí působení sympatiku. Prodlužují refrakteritu síní, převodního systému a komor. Užívají se při fibrilaci síní a komorové tachykardii.


 * Amiodaron

Má pomalý nástup účinku a mimořádně dlouhý poločas eliminace (až 100 dní), musíme proto monitorovat jeho plazmatickou hladinu. Jde o nejúčinnější antiarytmikum při potlačení komorových a supraventrikulárních tachykardií. Je indikován po akutním infarktu myokardu, u vysokého rizika náhlé smrti srdeční a poruše systolické funkce levé komory srdeční. Amiodaron má nežádoucí negativně inotropní efekt, což vyžaduje opatrné užití u srdečního selhání. Zároveň je ale jediné antiarytmikum, které snižuje riziko vzniku fibrilace síní (např. opět u srdečního selhání). Má četné nežádoucí účinky, především poruchy štítné žlázy (hypotyreóza, vzácně i hypertyreóza), bradykardie, plicní fibróza, hepatotoxicita a korneální depozita.


 * Sotalol

Prodlužuje trvání akčního potenciálu a zpomaluje fázi repolarizace. Používání se omezuje z důvodu jeho nižšího antiarytmického působení.

Antiarytmika třídy IV
Blokátory vápníkových kanálů verapamil a diltiazem inhibují vedení v AV uzlu. Dobu repolarizace neovlivňují. Užívají se zejména u supraventrikulárních tachykardií.

Adenosin
Adenosin působí stimulací draselných kanálů. Podává se nitrožilně pro své krátké působení. Snižuje automacii sinusového uzlu a zpomaluje vedení vzruchu v síňokomorovém uzlu. Zpomaluje odpověď srdečních komor při supraventrikulární arytmii (je lékem první volby). Je možné ho podat i v těhotenství.

Bradiny
Bradiny působí selektivně v sinusovém uzlu, kde zpomalují spontánní diastolickou depolarizaci. Jejich efekt je pouze na zpomalení srdeční frekvence.

Hlavní indikací bradinů je angina pectoris.