Antiarrhythmics Flashcards
Name the 4 Classes of Antiarrhythmic drugs.
Sodium Channel Blockers, BBs, Potassium Channel Blockers, CCBs (Specifically Verapamil and Diltiazem).
Key to understanding Antiarrhythmic agents is what?
Depolarization and Repolarization of the myocyte.
Class I Antiarrhythmics are which drugs and block which channels?
Voltage gated fast sodium channels responsible for upstroke in Phase 0. This decreases the slope and velocity of Phase 0. You cannot forget that they also block Potassium channels that mediate Repolarization at phase 3.
Sodium channels fluctuate between which 3 states? Class IA bind the channel during which state?
Resting, Open, then Closed. Quinidine, Procainamide, and Disopyramide bind channels in the Open state.
Class IB Antiarrhythics bind sodium channels during which states?
Both Open and Closed states.
Class IC Antiarrhythmics are potent blockers of which state?
Open state, and take the longest to dissociate.
Class IA Sodium channel blockers are especially helpful for which cardiac condition?
SVT or Vtach
ADRs of Class IA Antiarrhythmics are very High Yield. What are Tinnitus, HA, and visual problems, possible hearing loss part of?
Cinchonism.
Describe Cinchonism and DIL. Which drugs in Class IA can have these adverse effects on the pt?
Cinchonism is HA, tinnitus, hearing, loss, visual changes. DIL has fever, arthralgias, myalgias, rash.
What can Disopyramide cause as an adverse effect? And what can all 3 of Class IA cause?
Disopyramide can result in Heart Failure. All three can cause the fatal Torsades de Pointes due to the QT prolongation that occurs by blocking the repolarization of the Potassium channels at Phase 3.
All 3 can also cause Thrombocytopenia, tho mechanism is not well understood.
Which drugs fall under Class IB Sodium Channel Blockers and what is their mechanism?
Lidocaine and Mexiletine. (Technically also Phenytoin but it is more of an antiseizure drug). These drugs shorten the action potential.
When do we clinically prefer to use Class IB antiarrhythmics?
Especially post-MI and Digitoxin induced arrhythmias. Also used in Acute Vtach.
1B is Best Post-MI is to remind you of what?
That Lidocaine and Mexilitine are the DOC for post-MI or ischemic pts.
What is a serious potential adverse effect of Class IB drugs?
Anytime there is too much sodium, there is a risk of Cardiovascular depression. Both are also very lipophilic and can stimulate or depress the CNS as well.
Which of the Class IB Antiarrhythmics is classically known for triggering seizures?
Lidocaine think Seizures.
Flecainide and Propefenone are rarely used clinically due to dangerous side effects. Which class of drugs is this?
Class IC. NEVER GIVE POST-MI. Can cause serious arrhythmias.
Post MI you want to decrease the ARP by using what class of drugs?
A class IA drug will prolong the ARP because it increases the action potential (AP) duration. A class IB drug will decrease the AP and therefore decrease the ARP. A class IC drug will not change the ARP. Regardless of ARP action, all class I drugs decrease the slope of phase 0.
Describe the G protein pathway of Beta blocking in the heart.
β-Receptor antagonists work by inhibiting β-receptors, hindering the G-protein/cAMP mechanism. By reducing the amount of cAMP and protein kinase A (PKA) produced, β-receptor antagonists decrease the Ca2+ currents within the AV node. (Decreased production of cAMP and PKA reduces the Na+ current via phosphorylation-mediated downregulation of expression and other mechanisms)
In which phase do BBs decrease the slope? How do BBs affect the HR?
β-receptor antagonists decrease the slope of phase 4 and phase 0. β-Receptor antagonists are known to slow the heart rate (negative chronotropic effect).
Describe the phases of the AV node cardiac potential.
Phase 0: L-type calcium channels open, causing depolarization.
Phases 1 and 2 are absent.
Phase 3: Potassium channels open, causing repolarization. These channels can be affected by a number of pharmacologic mechanisms.
Phase 4: Funny channels with a slow leak of potassium out of the cell cause a transient depolarization toward threshold.
How do Beta blockers affect cAMP and Protein Kinase A?
β-Receptor antagonists cause a decrease in cAMP.
β-Receptor antagonists cause a decrease in PKA.
What does Torsades de Pointes look like on ECG?
Google images.
ADRs of Adenosine?
Adenosine is not known to cause TdP. Causes flushing, dyspnea, and chest pain, as well as high-grade atrioventricular (AV) block.
Esmolol is known for…
Esmolol is extremely short acting (15–20 minutes) BB, so it has few major adverse effects
Lidocaine toxicity cardiac associations…(ignore the seizures for a second ;)
ADRs of lidocaine are third-degree AV heart block, altered AV node conduction, and depressed SA node automaticity.
Propranolol can cause what on the heart…
Bradycardia and HoTN.
Side effects of verapamil include…
Bradycardia, dizziness, and transient hypotension, if it is administered without calcium pretreatment.
Name drugs most commonly associated with causing TdP’s fatally rapid ventricular rhythm by elongating the QT interval (by blocking K+’s repolarization in Phase 3 of the slope)
Procainamide, Quinidine, fluoroquinolones, amiodarone, sotalol, tricyclic antidepressants, risperidone, SSRIs, methadone, ondansetron, and erythromycin.
What is a typical rate for Torsades?
Fatally rapid ventricular rate is variable between 250 and 350 and is usually transient.
Causes of TdP?
Low potassium level and potassium channel blockers such as Amiodarone or Sotalol. It can also occur as a result of congenital abnormalities, such as long QT syndrome. Administration of quinidine. Quinidine is a class Ia sodium channel blocker. It also has a concentration-based potential to block potassium channels, extending the QT interval and causing torsades. This can occur at even subtherapeutic levels.
Amiodarone’s MOA is prolonging phase 3 repolarization of potassium, but also affects other phases. Most high yield however are its toxicities…
Pulmonary fibrosis, hepatotoxicity, and hypothyroidism or hyperthyroidism. And Corneal deposits. Blue/gray skin deposits, photodermatitis.
In pts taking Amiodarone, remember to check pulmonary function, liver function, and thyroid function tests.
If defibrillation convert the Vtach to sinus rhythm…what do we give the pt according to ACLS?
Epinephrine followed by Amiodarone.
What Sxs are suggestive of DIL? Which medications can induce it?
Pleuritic chest pain, a right pleural effusion, and positive antinuclear antibodies and antihistone antibodies (but not anti-double-stranded DNA [anti-dsDNA] antibodies). A collection of fluid around the lungs or heart. Other Sxs include fever, fatigue, myalgia, rash, arthralgia, and arthritis.
SHIPPPEM mnemonic.
Sulfa drugs, Hydralazine, Isoniazid, Procainamide, Penacillamine, Phenytoin, Etanercept, Methyl-Dopa.
Adenosine is a very short-acting drug useful in terminating certain forms of SVT by hyperpolarizing the cell and decreasing atrioventricular (AV) node conduction. Adverse Effects are…
Flushing, hypotension, chest pain, bronchospasm, and a sense of impending doom
MOA of Ivabradine and what is its special clinical use?
is used to treat stable angina in patients who cannot take β-blockers. It works by inhibiting funny channels, thus prolonging phase IV of the cardiac action potential.
DOC for Paroxysmal SVT? What are its ADRs?
Adenosine. Flushing, Chest pain, Bronchospasm, Impending doom, Coronary Steal Syndrome.
What is Adenosine’s structure and which 2 other chemicals have a similar structure and can inhibit its effects?
Purine structure. Caffeine and Theophylline (asthma drug) are also purines and can inhibit the Adenosine receptor.
Ivabradine’s MOA?
Inhibits funny Na+ channels in Phase 4, thereby slowing down SA nodal firing and depolarization.
What are Ivabradine’s clinical uses?
Treatment of angina in those who are not able to take beta blockers. May also be used in HF.
But Ivabradine is not involved in contractility, just chronotropy.
What are the ADRs of Ivabradine?
Visual light disturbances. And due to slowing of SA node, could cause possible bradycardia or reflex increase in BP.
Mg++ is whose babysitter and how so?
Mg is K+’s babysitter in that whenever Potassium is abnormal, Mg is given to adjust the situation.
Mg helps eliminate K+ in the urine and is a cofactor for the ubiquitous Na-K+ ATPase.
What are two serious events in which Mg++ is given as an antiarrhythmic?
- TdP! 2. Digoxin toxicity - to stimulate the action of Na-K ATPase being inhibited by digoxin.
How does Adenosine cause bronchospasm?
Adenosine can cause mast cell degranulation in the lungs and thereby leading to the anaphylactic response.
What is an ideal antiarrhythmic for Wolff-Parkinson-White?
Ibutilide or Sotalol but these are also infamous for causing TdP.
