anti-arrythmic drugs

Question 1

what happens when the left vagus is hyperstimulated

Answer 1

predisposes the heart to atrioventricular (AV) blocks.

Question 2

What are the principle intracellular cations of the heart?
Anions?

Extracellularly?

Answer 2

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.

Question 3

what are pacemaker channels of the HCN family

Answer 3

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.

Question 4

depolarization of myocites

Answer 4

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.

Question 5

cardiac action potential

Answer 5

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)


Question 6

Two voltage-dependent calcium channels

Answer 6

L-type calcium channel (“L” for “long lasting”) . Sustaining channels

T-type calcium channels (“T” stands for “transient”) voltage-gated calcium channels. Initiating channels

Question 7

what are common causes of arrythmias?

Answer 7

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

Question 8

Anti-arrhythmic drug therapy is aimed at?

Answer 8

affecting either specialized ion channels or by affecting sympathetic tone.

Question 9

Anti-arrhythmic drug classes: 1 a, 1b, 1c

Answer 9

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

Question 10

Anti-arrhythmic drug classes: II, III, IV

Answer 10

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.

Question 11

Class I/ Na+ channel blockers

Answer 11

• Quinidine/ Quinidex - (Ia)
• Procainamide/ Pronestyl (Ia)
• Mexiletine/ Mexitil (Ib)
• Lidocaine/Xylocaine (Ib)
• Flecainide/Tambocor (Ic)
• Disopyramide / Norpace - (Ic)

Question 12

Quinidine/ Quinidex

Answer 12

• Class: Anti-arrhythmic - Class Ia
• Indication: A-flutter, A-fib, AV and
ventricular arrhythmias.
• 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.

Question 13

Quinidine/Quinidex SE

Answer 13

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.

Question 14

Mexiletine/ Mexitil

Answer 14

• 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.


Question 15

Flecainide/ Tambocor

Answer 15

• 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.

Question 16

Flecainide/ Tambocor SE

Answer 16

• 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

Question 17

Class II/ Beta blockers

Answer 17

• Atenolol/ Tenormin
• Acebutolol/ Sectral
• Betaxolol/ Kerlone
• Bisoprolol/ Zebeta
• Carvedilol/ Coreg
• Metoprolol/ Toprol, Lopressor
• Nadolol/ Corgard
• Propranolol/ Inderal
• Timolol/ Blocadren

Question 18

Atenolol/ Tenormin

Answer 18

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.

Question 19

Atenolol/ Tenormin SE

Answer 19

• Char: PO, IV.
• Side effects: Bradycardia, hypotension, dizziness. Bronchoconstriction is possible but occurs less frequently in selective beta blockers. Depression, fatigue, impotency.

Question 20

Class III/ K+ channel blockers

Answer 20

• Amiodarone/ Cordarone
• Bretylium/ Bretylol
• Sotalol/ Betapace

Question 21

Amiodarone/ Cordarone

Answer 21

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.


Question 22

Class IV/ Ca++ channel blockers

Answer 22

• Verapamil/ Calan, Isoptin 
• Amlodopine/ Caduet
• Bepridil/ Vascor
• Diltiazem/ Cardiezem
• Felodipine/ Plendil
• Isradipine/ Dynacirc
 • Nicardipine/ Cardene 
• Nifedipine/ Adalat


Question 23

Verapamil/ Calan, Isoptin

Answer 23

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.

Question 24

Verapamil/ Calan, Isoptin SE

Answer 24

• Char: PO

* Side effects: Dizziness, flushing, headaches, hypotension.

Question 25

Other anti-arrhythmics

Answer 25

* Adenosine/ Adenocard * Atropine * Digoxin/ Lanoxin

Question 26

Adenosine/ Adenocard

Answer 26

* 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.

Question 27

Adenosine/ Adenocard 

Answer 27

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.

Question 28

Atropine

Answer 28

• Atropine is a tropane alkaloid extracted from the plant, Deadly nightshade (Atropa belladonna) and other plants of the family Solanaceae.

Question 29

Atropine

Answer 29

Class: Anti-arrhythmic • Indication: Cardiac use is in treatment of bradycardia. • 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. 

Question 30

Atropine SE

Answer 30

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. 

Question 31

Additional uses of atropine include:

Answer 31

* 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.

Question 32

Organophosphate poisoning SLUDGE 

Answer 32

* 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

Question 33

Atropine overdose

Answer 33

* 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.

Question 34

Cardiac glycosides | •

Answer 34

* 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.

Question 35

Digoxin/ Lanoxin

Answer 35

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.

Question 36

Digoxin/ Lanoxin CHAR/SE

Answer 36

* 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.

Question 37

Digitalis intoxication

Answer 37

* Cardiac signs: arrhythmias, including bradycardia, partial or complete heart block. * GI: nausea, vomiting, anorexia and diarrhea. * CNS: drowsiness and fatigue. * Visual disturbances: blurred vision, double vision, flickering dots or flashes of light, halos may appear around objects. TX: Digoxin immune Fabs that attach to Digoxin molecules and rapidly remove them from receptor sites.(from sheep IgG)