Flashcards in anti-arrythmic drugs Deck (37):
what happens when the left vagus is hyperstimulated
predisposes the heart to atrioventricular (AV) blocks.
What are the principle intracellular cations of the heart?
K+ is the principal cation
Phosphate and the conjugate bases of organic acids are the dominant anions.
Extracellularly, Na+ is the predominant cation and Cl- is the predominant anion.
what are pacemaker channels of the HCN family
hyperpolarization-gated, cyclic nucleotide-gated channels with autorhythmicity potential
The activity of these channels in the SA node cells causes the membrane potential to slowly become more positive depolarized until, eventually, calcium channels are activated and an action potential is initiated.
depolarization of myocites
1. depolarization of myocardial cells causes the opening of voltage- gated calcium channels and entry of Ca2+ from the t-tubules.
2. This influx of calcium causes calcium-induce calcium release from the sarcoplasmic reticulum, and the increase in myoplasmic free Ca2 concentration causes muscle contraction.
3. After a delay (the absolute refractory period), Potassium channels reopen and the resulting flow of K+ out of the cell causes repolarization to the resting state.
cardiac action potential
Phase 0 – Sodium channels open (Na+ in)
Phase I – Sodium channels close, Potassium channels begin to open (K+ out)
Phase II – Calcium and Potassium channels open (Ca ++ in and K+ out)
Phase III – Calcium channels close
Phase IV – Cells return to resting membrane potential (-70 mV)
Two voltage-dependent calcium channels
L-type calcium channel (“L” for “long lasting”) . Sustaining channels
T-type calcium channels (“T” stands for “transient”) voltage-gated calcium channels. Initiating channels
what are common causes of arrythmias?
ischemic and damaged heart tissue, electrolyte disturbances, pH imbalance and other factors involved in the conduction of depolarization from the SA node to the ventricles. DRUGS
Anti-arrhythmic drug therapy is aimed at?
affecting either specialized ion channels or by affecting sympathetic tone.
Anti-arrhythmic drug classes: 1 a, 1b, 1c
Ia – Sodium channel blockade--slows phase 0, prolong action potential and slow conduction
Ib – Sodium channel blockade--shortens phase 3--repolarization and decrease the duration of the action potential by blocking or inactivated sodium channels.
Ic – Sodium channel blockade--markedly slows phase 0 depolarization
Anti-arrhythmic drug classes: II, III, IV
II – Beta adrenergic receptor blockade : beta blockers which diminish phase 4 depolarization, thus depressing automaticity.
III – Potassium channel blockade: prolong phase 3 repolarization without altering phase 0.
IV – Calcium channel blockade: slow phase 4 depolarization and slow conduction, particularly at the AV node.
Class I/ Na+ channel blockers
• Quinidine/ Quinidex - (Ia)
• Procainamide/ Pronestyl (Ia)
• Mexiletine/ Mexitil (Ib)
• Lidocaine/Xylocaine (Ib)
• Flecainide/Tambocor (Ic)
• Disopyramide / Norpace - (Ic)
• Class: Anti-arrhythmic - Class Ia
• Indication: A-flutter, A-fib, AV and
• MOA: Sodium channel blocker. Diminished inward flow of sodium at phase 0 results in decreased automaticity and a lengthened refractory period.
• Char: PO, IV. Less commonly used because of significant adverse effect profile.
Side effects: Potentially pro-arrhythmic,
nausea, vomiting, diarrhea. Cinchonism.
• Symptoms of cinchonism include blurred vision, tinnitus, nausea, vomiting headache, disorientation and possible psychotic states.
• May induce an abnormal rhythm of ventricular tachycardia known as Torsade de Pointes.
• Class: Anti-arrhythmic Class Ib
• Indication: Ventricular arrhythmias,
particularly recurrent v-tach after MI
• MOA: Blocks open sodium channels and
shortens phase 3 repolarization.
• Char: PO, IV
• Side effects: Drowsiness, confusion, potentially pro-arrhythmic.
• Class: Anti-arrhythmic - Class Ic
• Indication: Treatment of many types of supraventricular tachycardias, including Wolff-Parkinson-White syndrome (WPW) paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia and ventricular tachycardia.
• MOA: Sodium channel blocker
• Char: PO, IV, Narrow therapeutic index
Simply put, Flecainide works by regulating the flow of sodium in the heart, thus slowing nerve impulses.
Flecainide/ Tambocor SE
• Side effects: Potentially pro-arrhythmic. Not indicated for patients with a history of M.I. or ventricular arrhythmia related to acute ischemic event.
patients with structural heart disease should NOT take this drug
Class II/ Beta blockers
• Atenolol/ Tenormin
• Acebutolol/ Sectral
• Betaxolol/ Kerlone
• Bisoprolol/ Zebeta
• Carvedilol/ Coreg
• Metoprolol/ Toprol, Lopressor
• Nadolol/ Corgard
• Propranolol/ Inderal
• Timolol/ Blocadren
Class: Anti-arrhythmic - Class II
• Indication: Tachyarrhythmias such as A- flutter, A-fib, atrioventricular and ventricular arrhythmias, paroxysmal supraventricular tachycardias (PSVT), hypertension, angina.
• MOA: Beta 1 blockade reduces sympathetic effects on myocardium. Reduced phase 4 depolarization and decreased automaticity in the SA node, AV node and the Purkinje fibers.
Atenolol/ Tenormin SE
• Char: PO, IV.
• Side effects: Bradycardia, hypotension, dizziness. Bronchoconstriction is possible but occurs less frequently in selective beta blockers. Depression, fatigue, impotency.
Class III/ K+ channel blockers
• Amiodarone/ Cordarone
• Bretylium/ Bretylol
• Sotalol/ Betapace
Class: Anti-arrhythmic - Class III
• Indication: Ventricular arrhythmias.
• MOA: Potassium channel blockade. Prolongs phase 3.
• Char: PO, IV. Amiodarone contains high level of iodine.
• Side effects: Dizziness and light headedness. Pulmonary fibrosis possible. Blue-gray coloring of skin can occur as a result of iodine deposition.
Class IV/ Ca++ channel blockers
• Verapamil/ Calan, Isoptin
• Amlodopine/ Caduet
• Bepridil/ Vascor
• Diltiazem/ Cardiezem
• Felodipine/ Plendil
• Isradipine/ Dynacirc
• Nicardipine/ Cardene
• Nifedipine/ Adalat
Verapamil/ Calan, Isoptin
Class: Anti-arrhythmic - Class IV
• Indication: A-flutter, A-fib and paroxysmal supraventricular tachycardias (PSVT), hypertension, angina.
• MOA: Calcium channel blockade causes a slowing of phase 4 depolarization, resulting in slowed AV conduction. Suppression of both SA and AV node activity often results in decreased heart rate.
Verapamil/ Calan, Isoptin SE
• Char: PO
• Side effects: Dizziness, flushing, headaches, hypotension.
• Adenosine/ Adenocard
• Digoxin/ Lanoxin
• Adenosine is primarily formed from the breakdown product of adenosine triphosphate (ATP).
• Adenosine acts directly on sinus pacemaker cells and vagal nerve terminals to decrease chronotropic and ionotropic activity.
• Adenosine is recommended as the initial drug of choice for PSVT.
Class: Anti-arrhythmic - endogenous nucleoside
• Indication: Abolishes acute paroxysmal supraventricular tachycardias (PSVT)
• MOA: Prolongs the refractory period and decreases automaticity in the AV node.
• Char: IV only. Duration of action is ~15 seconds.
• Side effects: Low toxicity but often causes transient hypotension and chest pain.
• Atropine is a tropane alkaloid extracted from the plant, Deadly nightshade (Atropa belladonna) and other plants of the family Solanaceae.
• Indication: Cardiac use is in treatment of
• MOA: Anticholinergic agent - Atropine is a competitive inhibitor of the muscarinic acetylcholine receptors thus it can be thought of as a parasympatholytic.
• Char: IV. PO. Can be also given via an endotracheal tube.
Blurred vision, dilated pupils, dry mouth and increased heart rate are usually among the first toxic effects of atropine.
Use of atropine as a cardiac drug is generally confined to emergency treatment of life threatening bradycardia with hypotension.
Additional uses of atropine include:
• Topical atropine is used as a cycloplegic to temporarily paralyze accommodation and as a mydriatic to dilate the pupils.
• Oral atropine can be used to treat diarrhea as it decreases secretions and slows peristalsis.
• Given preoperatively, atropine decreases bronchial and salivary secretions.
• Used to treat organophosphate poisoning.
nerve gases act by destroying enzyme stores of acetylcholinesterase, which results in the prolongation of the action of acetylcholine.
• By blocking the action of acetylcholine, atropine serves as an antidote for poisoning by organophosphate containing insecticides and nerve gases.
Organophosphate poisoning SLUDGE
• The classic symptoms in acute organophosphate poisoning are muscarinic in nature:
• S for salivation
• L for lacrimation
• U for urination
• D for diarrhea
• G for gastric distress
• E for emesis
• Toxicity due to atropine results in decreased secretions; flushed, dry, warm skin, visual changes and delirium with hallucinations.
• “Dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a hatter.”
• The specific antidote for atropine toxicity (or tropane alkaloid toxicity) is physostigmine, a reversible acetylcholinesterase inhibitor.
• Digitoxin has a much longer half life and is now seldom used because of increased risks of toxicity.
• Both digoxin and digitoxin have a very low therapeutic index –
￼Compared to digoxin, digitoxin has longer half life (~ 7 days), is absorbed more readily, is more highly protein bound and is more extensively metabolized before excretion.
Class: Anti-arrhythmic - cardiac glycoside
Indications: CHF. Slows ventricular response to atrial fibrillation and atrial flutter.
• MOA: Inhibits the Na+/K+ ATPase pump which serves to increase inward current of sodium followed by a greater influx of calcium. Cardiac contraction is enhanced by the increased concentration of intracellular calcium.
Slows ventricular rate in atrial fibrillation or flutter by increasing the sensitivity of AV node to vagal stimulation.
• Digoxin also allows increased renal perfusion.
Digoxin/ Lanoxin CHAR/SE
• Char: PO, 36 hour half life, may cause characteristic flattening or even inversion of the T wave on EKG.
• Side effects: Digitalis intoxication – observed more frequently in patients with hypokalemia as may occur in patients on thiazides, lasix or other potassium wasting diuretics.