Hi everybody, welcome back. This is anti-arrhythmic drugs part two. These are case questions. For those of you studying for the boards, it's meant to replicate the types of questions that you might see on the board exams. These are my disclosures. So case one, a 23-year-old female has a history of occasional PSVT that she has always been able to terminate with valsalva maneuvers. She is now pregnant with increasing episodes that no longer terminate with valsalva. She presents to the emergency department with the ECG shown in tracing one. I will show you on the next slide. Her vital signs are stable. The best treatment is A, DC cardioversion followed by atenolol, B, adenosine followed by sotolol, C, ibuprofen amide followed by flecainide, and D, ibuprofen amide followed by digoxin. This is the tracing and I'll go back to the questions. Give you a moment to take a look at this. And again, here are the questions, A, B, C, and D. And the tracing again. So the right answer is B, adenosine followed by sotolol. It seems increasingly that we are being consulted by our OB colleagues to treat either the mother or the fetus for SVTs. And so it is really important to understand what the guidelines say and what the FDA category of risk is. So the ECG in this patient suggests an AVRT or maybe an atypical ADNRT, but it is a PSVT of some sort. And the treatment of SVT in pregnancy is of course complicated by the safety of the antiarrhythmic medication on the fetus. And really few of the medications have been studied. The FDA ranks the safety category of beta blockers as B or C except for atenolol, which you need to know about, which is a class D FDA category. Most antiarrhythmic drugs are FDA category C except for sotolol, which is B, and you need to know that amiodarone is D. The 2015 ACC AHA HRS guideline for the management of adult patients with supraventricular tachycardias also address the situation of pregnancy. The class 1 recommendation for acute therapy is cardioversion or adenosine as first options when vagal maneuvers fail. For ongoing therapy, the guideline recommendation is a class 2A for digoxin, sotolol, fluconide, propanol, metoprolol, propranolol, and varapamil. And that's why the best answer for this patient was B, adenosine first, followed by sotolol. And here is the reference information from the guideline document for 2015 with the levels of evidence for your reference. I also just pulled out this statement from that 2015 guideline. It's useful just to read through this in terms of thinking about how to manage these patients during pregnancy. All right. Case 2. A 69-year-old female with preserved ejection fraction heart failure, or HFPEF, and persistent atrial fibrillation has failed several antiarrhythmic drugs. Two months ago, she had catheter ablation for atrial fibrillation, but with early recurrence. She prefers to try another antiarrhythmic drug prior to a repeat ablation. Dronetarone will be started. Other medications that she takes includes warfarin and digoxin. So which of the following change should you make? A, decrease warfarin dose by 50%, B, switch warfarin to the bigotrin, C, decrease digoxin dose by 30% to 50%, or D, switch warfarin to apixaban. The correct answer is to decrease the digoxin dose by 30% to 50%. So unlike amiodarone, warfarin does not need to be adjusted when prescribing dronetarone. That was answer A. Dronetarone can increase the concentration of the bigotrin due to being inhibitor of PGP, so answer B is really not the best answer. Similarly, dronetarone can increase apixaban concentration due to being both an inhibitor of CYP3A4 as well as PGP, answer D. There's an interaction between dronetarone and digoxin via PGP, and it is recommended to decrease the digoxin concentration by 30% to 50%, which is answer C. Case 3, blockade of ITO by which of the following drugs has been postulated to be a benefit in patients with the Bregada syndrome? A, dofetilide, B, procainamide, C, quinidine, and D, amiodarone. Well, the answer is quinidine. Blockade of the transient and recurrent ITO by which of the following drugs has been postulated to be a benefit, and that is quinidine and not dofetilide, procainamide, or amiodarone. This is because quinidine blocks ITO and has been recommended in symptomatic patients with Bregada syndrome. This is an earlier study from circulation where the control ECG is demonstrated with a Bregada type 2 ECG pattern. Procainamide unmasks it to a type 1 Bregada ECG pattern, whereas quinidine nearly normalizes the ECG pattern completely. Case 4, which of the following agents might be expected to be beneficial in symptomatic patients with Long QT syndrome type 3? Sotilol, dofetilide, rinolazine, or quinidine. The answer to this is rinolazine because rinolazine blocks the late inward sodium current and can shorten repolarization in patients with Long QT 3 type 3. This is from a publication in 2008 from Art Moss's group where IV rinolazine was administered, and as the dose increases, you can see that the change in the QTC decreased. Case 5, a 51-year-old man with a history of a documented episode of atrial fibrillation two months ago. He presents to the emergency room with palpitations that started as he was eating dinner one hour ago. He took 450 milligrams of propranolol as instructed. He is on no other medications. His ECG is shown in tracing 1 on the next slide. The question is, which of the following is the next best therapy? A, IV metoprolol, B, IV propionamide C, DC cardioversion, or D, activate acute coronary syndrome protocol? Here is the ECG tracing. These are rhythm strips lead 2, V2, and V5. The answer is IV metoprolol. The ECG shows classic atrial proarrhythmia that's associated with class 1C drugs that is organization of AFib to AFlutter, slowing of the atrial cycle length which can promote one-to-one conduction with increased conduction delay which results in aberrant conduction. Slowing the heart rate by increasing the AV conduction delay should be the first therapy which is answer A. IV propionamide is another class 1 drug and potentially could worsen the conduction abnormalities. Cardioversion would be an option if the patient was highly symptomatic, but he's also just recently eaten as was given to you in the stem of the question. The ECG is just simply not consistent with acute coronary syndrome. Case 6, a 76-year-old male with paroxysmal atrial fibrillation and the history of prior bypass surgery, LVEF is 32%, near heart isolation class 2 heart failure. Six months ago, he was started on oral amiodarone load for increased episodes. He is currently taking 300 milligrams per day and has had no further AF episodes and is feeling well. Today, he comes to the clinic and you note that he has trouble getting up from a chair and seems to be off balance. No other physical exam findings are abnormal. The next best therapy is stop the amiodarone, change to dunetarone, change to propothenone, and decrease the amiodarone dose. So the answer is decrease the amiodarone dose. Now, in the real clinical situation, a thorough physical exam would be needed to really identify better the cause of this patient's trouble getting up out of a chair, but that should trigger in your mind when you're taking care of patients that this patient may have the neurologic toxicity that affects primary proximal muscles, such as the thighs, and makes it hard for people to get up out of a chair. So as was told you in the lecture, amiodarone is associated with dose-dependent neurologic toxicity, particularly in the elderly, and this form of amiodarone toxicity usually can be reduced or reversed with dosage reduction, which is answer D. Since the patient was doing well, dose reduction is reasonable as a first step rather than stopping amiodarone altogether, which was answer A. Propothenone is contraindicated in patients with coronary disease, so answer C is wrong. Nacetolol would be a reasonable medication if amiodarone cannot be continued. Phase 7. A 55-year-old man with remote prior myocardial infarction develops atrial fibrillation. He takes daily simvastatin 40 milligrams, as well as metoprolol succinate 50 milligrams, and warfarin 5 milligrams. You elect to start dronetaril 400 milligrams BID. Which of the following additional steps would you advise? A. Discontinue metoprolol. B. Decrease the warfarin dose to 2.5 milligrams daily. C. Discontinue simvastatin and start atorvastatin. Or D. Discontinue simvastatin and start rosuvastatin. The answer is discontinue simvastatin and start rosuvastatin. So, there's no clinical indication to stop his metoprolol. He has coronary disease, and it provides rate control for AF, and warfarin does not need to be adjusted when taking dronetaril, which was answer B. This is different from amiodarone, because dronetaril is not an inhibitor of CYP2C9. Dronetaril and amiodarone inhibit simvastatin metabolism by CYP3A4, answers C and D. Atorvastatin and lovastatin are also metabolized primarily by CYP3A4, so C is not correct. Rosuvastatin, on the other hand, is not metabolized by CYP3A4 and can be used safely with dronetaril and amiodarone, which is answer D. Case 8. Your patient calls to tell you that he has begun to take St. John's wort because he feels depressed. Which of the following has a potential adverse interaction with St. John's wort? A. Sotilol, B. Dulfetilide, C. Pravastatin, and D. Atenolol. The answer is B, Dulfetilide. St. John's wort is an herbal supplement that is often promoted for depression. It has many potential drug interactions as an inducer of both PGP, as well as several of the CYP450 isozymes, including CYP3A4. As an inducer, it may result in a reduction of drug efficacy. Dulfetilide is a substrate for CYP3A4 and thus taking St. John's wort could decrease drug concentration. The other drugs listed are not CYP3A4 substrates, answers A, C, and D. I think this is important because seeing patients in clinics, sometimes their herbal supplements are not listed and it's probably worth remembering medications like this that could have a significant drug-drug interaction. Patients taking St. John's wort in our clinics ought to be told, in general, not to take it. A 68-year-old man is admitted with fever and cough. He has a history of hypertension and paroxysmal atrial fibrillation, successfully treated with a stable dose of an antiarrhythmic drug. Tuberculosis is diagnosed and his antimicrobial regimen includes rifampin. Which of the following medications, if being taken, should be discontinued? Lisinopril, atenolol, dronetarone, or sotolol? The answer is dronetarone. Rifampin is a potent CYP3A4 inducer and of the agents listed, only dronetarone is metabolized by this pathway. Adding rifampin could significantly reduce dronetarone drug concentration. Lisinopril, atenolol, and sotolol are all excreted by the kidneys and do not undergo hepatic metabolism and are therefore not affected by rifampin. Case 10. A 76-year-old woman presented with AFib one month ago. She was started on warfarin, 4 mg per day. She's being started today on amiodarone, 600 mg per day, in preparation for a scheduled cardioversion in three weeks. Appropriate management at this time would be increase warfarin to 6 mg a day, decrease warfarin to 2 mg a day, continue warfarin at 4 mg per day, or discontinue warfarin. The correct answer is B, decrease warfarin to 2 mg per day. Amiodarone potentiates warfarin through its inhibition of CYP2C9 and a 30 to 50% reduction in warfarin dose is recommended. There's not a need to discontinue warfarin. INRs must be checked weekly. That's the end of part two of the pharmacology lectures with the representative cases. I hope you will find these cases helpful to you. Thank you for your attention.

anti-arrhythmic drugs

pregnant patient

PSVT

safety

atrial fibrillation