Pharmacology

Question 1

How do calcium channel blockers slow the heart rate?

Answer 1

Calcium channel blockers appear to change the threshold necessary to activate an action potential without changing the slope of phase 4 depolarization.

Question 2

How do beta-blockers cause bradycardia? How is it different from calcium channel blockers?

Answer 2

Beta-blockers decrease phase 4 depolarization so that it takes longer to reach the threshold for action potential activation

Question 3

How does adenosine cause sinus bradycardia?

Answer 3

Adenosine causes hyperpolarization without changing phase 4 depolarization

Question 4

Besides it’s beta blocker activity, why might sotalol slow the heart rate

Answer 4

By blocking K+ channels, the AP is prolonged so the time it takes for phase III to decay delays the onset of phase 4 and therefore, the next depolarization is delayed.

Question 5

Which enzyme system is most important for the metabolism of antiarrhythmic drugs? Name 3 AA drugs that are metabolized with this enzyme?

A. serum esterases

B. CYP2C9

C. CYP3A4

D. P-glycoprotein

E. CYP1A2

Answer 5

C. CYP3A4

Amiodarone, Dofetilide, Diltiazem, Verapamil

Question 6

Which antiarrhythmics are metabolized by CYP2D6?

Answer 6

flecainide, propafenone, lidocaine, carvedilol, metoprolol, propranolol

Question 7

Due to genetic polymorphisms, about 7% of individuals in which race(s) have deficiency in the CYP2D6 enzyme?

Asian

Caucasian

African American

Answer 7

About 7% of Caucasians and AA are deficient in CYP2D6.

Question 8

A caucasian man with known CYP2D6 deficiency would have difficulty metabolizing which antiarrhythmic medications?

Answer 8

flecainide, metoprolol, Lidocaine, carvedilol, propafenone

Question 9

Which agents are inducers of CYP2D6?

Answer 9

rifampin, ethanol, phenytoin, and phenobarbital.

Question 10

Which agents are inhibitors of CYP2D6?

Answer 10

amiodarone, cimetidine, delavudin, fluoxetine, paroxetine, quinidine, and ritonavir.

Question 11

Into which of the Vaughn-Williams class does Propafenone belong? What other drugs are in this class?

Answer 11

Class IC

Flecainide, Encainide, Moricizine

Question 12

2 patient’s identicle in size are given the same dose of propafenone. One becomes bradycardic, the other doesn’t. Why?

Answer 12

The bradycardic patient is likely to be a slow metabolizer. The parent compound has betablocker activity. The fast metabolizer will have less beta-blocker effect.

Question 13

propafenone increases the plasma concentrations of what drugs?

Answer 13

digoxin, warfarin, metoprolol and propranolol

Question 14

Which of the three newer oral anticoagulants is predominantely renally eliminated?

Answer 14

Dabigatran.

Rivaroxaban and Apixaban are predominantly hepatically cleared.

Question 15

Which of the newer oral anticoagulants work by inhibiting factor Xa?

Answer 15

Rivaroxaban, Apixaban. Dabigatran works by inhibiting the action of free and bound fibrin.

Question 16

Which of the newer oral anticoagulants is dialyzable?

Answer 16

dabigatran

Question 17

Which drugs inhibit P-glycoprotein and can raise drug levels for drugs handled by this transporter?

Answer 17

quinidine, verapamil, amiodarone, dronedarone, cyclosporin, antifungals, HIV protease inhibitorcarvedilol, atorvastatin

Question 18

Which medications are transported by P-glyc, oprotein?

Answer 18

Digoxin, amiodarone, dofetilide, dabigatran, rivaroxaban, apixaban

Question 19

By what mechanism does amiodarone or dronedarone increase increase the plasma levels of dabigatran, rivaroxaban, and apixaban by 2 fold.

Answer 19

By inhibiting p-glycoprotein transport out of the cell.

Question 20

Which of the following AA meds are not dialyzable in the setting of an overdose?

Procainamide

Flecainide

Amiodarone

Dofetilide

Answer 20

Flecainide and Amiodarone

Question 21

Which of the AA is rated class B in pregnancy?

Answer 21

Sotalol

Question 22

What effect does verapamil have on dofetelide peak concentrations? How does this happen?

Answer 22

Peak dofetilide concentrations are increased by 40% by simultaneous injestion with verapamil. This is thought to be mediated by verapamil’s ability to increase hepatic and portal blood flow causing increased absorption of dofetilide.

Question 23

Why do you have to lower the dose of adenosine in transplanted hearts?

Answer 23

Adenosine receptor density is higher on transplanted (denervated) hearts.

Question 24

What is the drug interaction between amiodarone and Statins?

Answer 24

Amiodarone inhibits CYP3A4, which results in increased statin levels.

Question 25

Which drug interaction with amiodarone is not present with dronedarone?

Answer 25

Unlike amiodarone, dronedarone does not increase INR in patients on warfarin therapy.

Question 26

Why is it important to have an AV nodal blocking agent in place when using flecainide or procainamide for an atrial tach?

Answer 26

These drugs are vagolytic and can facilitate conduction through the AV node.

Question 27

Procainamide is considered a class Ia antiarrhythmic agent but it's metabolite is different. What is it and what kind of antiarrhythmic is it?

Answer 27

N-acetylprocainamide (NAPA) is a pure class III agent and excreted by the kidney.

Question 28

Disopyramide is no longer used much as an antiarrhythmic agent. What is it's main use?

Answer 28

Disopyramide is a class Ia sodium channel blocker. It's vagolytic effects leading to urinary retension and dry mouth limit its use. It can also cause TdP. It is a negative inotrope and so may be used as a lucitropic agent in HCM. Can also be used in vasovagal syncope.

Question 29

Into what Vaughan-Williams class does Lidocain fall? What other drugs are in this class?

Answer 29

IB. The other drug in this class includes Mexelitine.

Question 30

Why might beta blockers be effective in helping with the bradycardia portion of the "tacky- brady" syndrome in patients with heart failure?

Answer 30

In a heart failure canine model, researchers from Japan (Masahiro Ogawa) published in HR 2009 found that surges of sympathetic activity followed by sympathetic withdrawal was handled abnormally by the sinus node in this dog model of heart failure. By performing stellate ganglion ectomy researchers were able to prevent sinus pauses presumably by preventing the surges of sympathetic activity and resultant pauses when the surge withdrew.

Question 31

In a retrospective review of a large cohort of LQTS patients treated with Bblockers, what percentage exeperienced a symptomatic hypoglycemic episode? What was the common trigger in all cases?

Answer 31

In a study out of the Mayo Clinic published in Aug 2015 Heart Rhythm, researchers found nine children (3%; 7 boys; average corrected QT interval 486 ± 35 ms) developed 13 episodes (0.005 events per 100 treatment years) of beta-blocker–associated hypoglycemia (mean initial glucose 21 ± 7 mg/dL), including 3 of 157 patients with LQTS type 1 (LQT1; 1.9%) and 6 of 105 with LQTS type 2 (LQT2; 5.7%). The mean age at hypoglycemic event was 3.5 ± 2 years (range 7 months to 9 years). Decreased caloric intake before the event was identified in all patients and a concomitant viral infection in 3.

Question 32

Name 6 risk factors for drug induced proarrhythmia.

Answer 32

1. female gender 2. structural heart disease 3. metabolic and electrolyte abnormalities 4. bradycardia and conduction disease 5. increased drug bioavailability 6. silent channelopathies

Question 33

What lab tests should be monitored in a patient on Mexiletine?

Answer 33

Rare marked leukopenia, agranulocytosis, and thrombocytopenia have been reported. Marked elevations of AST (\>1000 units/L) and rare instances of severe liver injury, including hepatic necrosis, have also been reported.

Question 34

Propranolol was used in an early therapeutic trial for Brugada syndrome paired against ICD therapy. The trial was stopped early due to higher mortality in the drug arm. What property of propranolol might have made this a bad choice for Brugada syndrome?

Answer 34

Propranolol has sodium channel blocking properties that could have exacerbated the electrical disturbance in Brugada. This is not a bblocker class medication effect (not seen in nadolol or metoprolol), but rather seems idiosynchratic to propranolol.