Exam 2: Antiarrhythmics Flashcards

Question

Class IC Agents

Answer 1

*also block Na+ channels, but dissociate very slowly* * Slow Na+ channel blocker (slow dissociation), so does not vary much during the cardiac cycle * Potent decrease of depolarization rate phase 0 and decreased conduction rate, with increased AP * *But don’t have much effect on AP and the effective refractory pd in ventricular CMs* * *But do shorten the AP on the cells in the Purkinje fibers* * *This difference in effect on different types of cardiac cells **may** contribute to their pro-arrhythmic effects* * Markedly inhibit conduction through the His-Purkinje system * Good for PVCs, better for atrial arrhythmias (WPW) * Suppress the SA Node * Drugs in this class: Flecainide (Prototype), Propafenone (PO) Think B-A-C (B has the least effect on Na+ channels, and C has the MOST)

Answer 2

* **Flecainide - Class IC Prototype** * *Is a fluorinated LA analog of procainamide (????)* * *Delays conduction in the bypass tracts – so good for reentry rhythms* * *Main use was for prophylaxis in pAfib* * Effective in the treatment of suppressing ventricular PVCs and ventricular tachycardia; **also atrial tachyarrhythmia's**; Wolff-Parkinson-White syndrome (reentry rhythm) * Oral agent * Has pro-arrhythmic side effects\*\*\* * Used to be used ventricular ectopic beats – no longer recommend – higher incidence of sudden death associated with VF if the pt had an MI *Rhyme Time: Flecainide, good for WPW, caused VF in post-MI's!*

Answer 3

Class 1C * Suppression of ventricular and atrial tachyarrhythmias * Oral agent * Has pro-arrhythmic side effects\*\*\* – torsades, VF *pro-pafenone, pro-torsades*

Answer 4

* Fast Na+ channel blocker (fast dissociation) * *Binds to the open channels, dissociates quickly. It dissociates in time for the next AP, but premature beats are what will be aborted* * Alters the action potential by inhibiting sodium ion influx via rapidly binding to and blocking sodium channels (fast) * Produces little effect on maximum velocity depolarization rate, but *shortens repolarization* → ↓ AP duration and shortens refractory period * Decreases automaticity * *Also binds to cells that are deplorized, such as in ischemia/diseased – suppresses Na+ channel in that tissue as well (other classes of drugs don’t do that)* * Drugs in this class: Lidocaine, Mexilitine (PO), Phenytoin (Dilantin) * "IB - I BE fast (dissociates quickly), I B(ind) to ischemic cells (used on MI patients)"* * IB - lido IV, mexili-tene, pheny-T, only V (ventricular)* * ALSO QPC, **LMP** (lettuce mayo pickles)*

Answer 5

* Lidocaine\* - Class IB Prototype * Used as LA, induction – blunt laryngeal reflexes * Used in the treatment of ventricular arrhythmias * Is no longer recommended for preventing ventricular fibrillation after acute MI (Stoelting, 5th ed. p. 523) * *Changed that recommendation bc they found* *↑ mortality d/t bradyarrhythmias and asystole* * Particularly effective in suppression reentry rhythms: ventricular tachycardia, fibrillation, PVCs * *Raises VF threshold (what does that mean), delays rate of spontaneous phase 4 depolarization (**↓ the gradual decrease in K+ ion permeability that normally occurs during that phase)* * *Not effective for SVT* * Pharmacokinetics: * Dose: 1-1.5 mg/kg IV, infusion 1-4 mg/min (max dose 3 mg/kg) * Only used IV bc extensive 1^st pass metabolism PO * 50% protein binding * Hepatic metabolism – think of CYP 450!! * **Active metabolite**, which prolongs elimination half-time. * Metabolism may be impaired by drugs such as cimetidine (Tagamet) and propanolol (inhibitors), or physiologic altering conditions such CHF, acute MI, liver dysfunctioin, GA; or can be induced by drugs like barbiturates, phenytoin (Dilantin), or rifampin (CYP 450 inducers) * 10% renal elimination * **Not a pro-arrhythmic, dissociates so quickly!!** * Adverse effects: _(toxicity) hypotension, bradycardia, seizures, CNS depression_, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment preexisting neuromuscular blockade

Answer 6

Class IB * Chronic suppression of ventricular cardiac tachyarrhythmias * *If you have a pt on mexilitene, make sure you get cardiac clearance for them to have surgery!* * 150-200 mg q8hrs PO * Similar to lidocaine, has an amine side group that helps it avoid the 1^st-pass hepatic metabolism * Also can be used for neuropathic pain Like the PO lidocaine, other IB agent (MPL - mayo pickles lettuce, mexilitene, pheny-t/phenytoin, lidocaine)

Answer 7

Class IB * Effects resemble Lidocaine * Class IB agent * Used in suppression of ventricular arrhythmias **associated with digitalis toxicity** * Can also be used other ventricular tachycardias or torsades de pointes (but would realistically reach for Lido before this) * Given IV (**can precipitate in D5W;** mix in NS) * Can cause pain or thrombosis when given in peripheral IV * Dose: 1.5 mg/kg IV every 5 min (*so think dose* *≅ Lido*) up to 10-15 mg/kg * Causes severe hypotension if given rapidly! “Pheny-to, give it slow!” * Therapeutic blood levels 10-18 mcg/mL * Metabolized by liver * Excreted in urine * Elimination ½ time @24 hours * Adverse effects: CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea, also associated with Stevens Johnson syndrome * Toxicity = CNS disturbances, vertigo, slurred speech * Pheny-T (IB).* * Pheny-to, give it slow, don't mix it with D5W doe, works for 20-foe (T1/2 24 hrs), fucks up your bone mar-row, and your insulin - WHOA! And Verti-go!*

Answer 8

* Class II drugs - Beta-adrenergic antagonists (AKA B-blockers). Depress spontaneous phase 4 depolarization resulting in SA node discharge decrease * Slows rate of depolarization – slow HR – **IN NODAL TISSUE** * Blocks the B-ARs, doesn’t block the Ca++ channels for phase 4 depolarization. * *These are drugs that are used to stop arrhythmias d/t excessive circulating catecholamines, or excessive SNS stimulation.* * Drug-induced slowing of heart rate with resulting decreases in myocardial oxygen requirements is desirable in patients with CAD * Slow speed of conduction of cardiac impulses through atrial tissues and AV node resulting in **prolongation of the P-R interval** on ECG, increased duration of the action potential in atria * Decreased automaticity * Used to treat SVT, atrial and ventricular arrhythmias * Used to suppress and treat ventricular dysrhythmias during MI and reperfusion * *Also decrease mortality in ppl who have had a recent MI – decrease tachyarrhythmias that can occur after MI* * To treat tachyarrhythmias secondary to digoxin toxicity, and SVT (atrial fibrillation or flutter). * Prevents catecholamine binding to beta receptors * Slowing of heart rate * **Decrease myocardial oxygen requirements** (good for CAD/MI patients) * *Decrease rate of atrial contraction in aflutter (said afib but the atria isn’t contracting during afib)* * Drugs in this class: Propanolol, metoprolol, esmolol, all the -olols *"B-AR (blocker), longer P-R"*

Answer 9

Prototype Class I Agent * Prototype * Beta-adrenergic antagonist (**nonselective**) – *not good for asthma d/t bronchoconstriction* * Used to prevent reoccurrence of tachyarrhythmias, both supraventricular and ventricular **precipitated by sympathetic stimulation** * Onset: 2-5 minutes * Peak effect 10-15 minutes, duration 3-4 hours * Elimination half-time 2-4 hours * Cardiac effects: decreased HR, contractility, CO; increased PVR, coronary vascular resistance; however, oxygen demand lowered, *↓ inotropy,* *↓ chronotropy*

Answer 10

(More on this in the other cardiac lecture) Class I Agent * Beta-adrenergic antagonist (selective B1) * *Remember that this doesn’t mean that they are \*exclusive\* for B1, just more selective for it* * Dose: Dose 5 mg IV over 5 minutes; max dose 15 mg over 20 min. * Onset: 2.5 min. * Duration: Half-life 3-4 hours * Metabolized by liver * Can be used in mild CHF

Answer 11

Class I Agent * Beta-adrenergic antagonist (selective B1) * Dose: 0.5 mg/kg IV bolus over 1 min, then 50-300 mcg/kg/min * Duration \<10 minutes * Affects HR without decreasing BP significantly in small doses * Metabolism: hydrolyzed by plasma esterases ≠ PChE *es-molol, (plasma) es-terase*

Answer 12

* Class III Agents – K+ ion channel blockers * Class III drugs block potassium ion channels resulting in prolongation of cardiac depolarization and increasing action potential duration, and lengthening repolarization. * Don’t need to know inward/outward rectifier stuff * Just know that they work on Phase III, and extend repolarization and AP * *ALSO work on Na+, Ca++ channels, and noncompetitively block alpha and beta ARs!* * *Lots of actions! Just know that it 1) extends Phase III, 2) extends repolarization/refractory period, and 3) decreases the membrane excitability of all myocardial cells* * **Decrease the proportion of the cardiac cycle during which myocardial cells are excitable and thus susceptible to a triggering event * Used to treat supraventricular and ventricular arrhythmias * Can prolong QT interval and develop torsades → most Class III drugs are proarrhythmic * Prophylaxis in cardiac surgery patients r/t high incidence of Afib * Preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD * Control rhythm in Afib * Drugs in this class: Amiodarone, Dronedarone, Sotatol, Ibutilide, Dofetilide

Answer 13

Class III prototype * **also has Class I, II, and IV antiarrhythmic properties** * Potassium/ sodium/ calcium channel blocker (Class IV drug during Phase 2), alpha- and beta- adrenergic antagonist * Used for prophylaxis or acute treatment in the treatment of atrial and ventricular arrhythmias (refractory SVT, refractory VT/ VF, AF) * **1st line drug VT/ VF when resistant to electrical defibrillation** * One of the most effective drugs in preventing ventricular arrhythmias in CHF pts, and also used prophylactic/acute tx of atrial OR ventricular arrhythmias * Good for post-MI/abnormal heart tissue, pts who have irritable heart tissue * Dose: Bolus 150-300 mg IV over 2-5 minutes, up to 5 mg/kg, then 1 mg/hr x 6 hrs, then 0.5 mg/hr x 18 hrs * Prolonged elimination half-life (29 days) * Hepatic metabolism, active metabolite * **Biliary/ intestinal excretion** * Therapeutic plasma level 1.0-3.5 ug/mL * Extensive protein binding 96% * Large volume of distribution * *CVAD preferred, phlebitis if given through PIV* * *Monitor K+, susceptible to TDP, lengthening the refractory pd so much* * *↓ incidence of afib post-cardiac surgery (given preop)* * Adverse Effects of Amio – esp if high doses or long time of use * Pulmonary toxicity – acute or **chronic** onset → **fibrosis!!** * Think it’s d/t free oxygen radicals in the lungs * Pulmonary edema * ARDS * Photosensitive rashes * Grey/blue discoloration of skin * Thyroid abnormalities 2% - *amio contains iodine, so pts can develop hypo/hyperthyroidism* * Corneal deposits * CNS/GI disturbance * Pro-arrhythmic effects (torsades de pointes) * Heart block l Hypotension * Sleep disturbances * Abnormal LFT 20% * **Inhibits hepatic CYP P450 – prolonged effect of other CYP 450 metab drugs (coumadin, dig) and muscle relaxants may last longer also**

Answer 14

* Class III drug * lacks iodine, less lipophilic, less SEs

Answer 15

* Class III Antiarrhythmic * Used for conversion of Afib or Aflutter to NSR * Used for the maintenance of sinus rhythm after Afib or conversion of Afib to sinus * Proarrhythmic, prolongs QT interval

Answer 16

* Class II and Class III Antiarrhythmic Drug * Beta-adrenergic antagonist (**nonselective**) and potassium channel blocker * *So combo Class II and III, and also B1 and B2 nonselective* * Used to treat severe sustained ventricular tachycardia and ventricular fibrillation; to prevent reoccurrence of tachyarrhythmias, especially Aflutter and AF * Side effects: prolonged QT interval, bradycardia, myocardial depression, fatigue, dyspnea, AV block * ![]() Caution in patients with asthma * Excreted in urine * Phase III – extend refractory pd, TDP risk

Answer 17

Ca++ Channel Blockers * Calcium ion channel present in: * Cell membranes of skeletal muscle * Vascular smooth muscle * Cardiac muscle * Mesenteric muscle * Neurons * Glandular cells * *Ca++ is the universal messenger in most of our cells* * *There are many different types (L, N, T)* * *We’re focusing on L-type channels* * *Has 5 subunits (Alpha-1,2 beta, etc)* * We’re interested in the alpha 1 subunit – center of the channel, and is the main pathway for Ca++ entry into the cell * So when drugs bind to the L-type channel, they’re ↓ing the entry of Ca++ into the cell! * Calcium channel blockers bind to the receptor on voltage-gated calcium ions maintaining the channels in an inactive or closed state * Selectively interfere with inward calcium ion movement across myocardial and vascular smooth muscle cells. * Classified based on structure: * Phenyl-alkyl-amines - AV node (Verapamil) * **"verapa-phenyl-alkyl-amines"** * Benzothiazepines - AV node (Diltiazem) * **"benzo = diazepam. benzo-thiazepines = diltiazem"** * 1,4-dihydropyridines - arterial beds (Nifedopine) * Drugs in this class: Verapamil, Diltiazem, Nifedipine

Answer 18

* Vascular * Angina * Systemic hypertension * Pulmonary hypertension * *as opposed to vasopressin, which is a potent vasoconstrictor, but DILATES renal afferent arteriole, cerebral and pulmonary vasculature* * Cerebral arterial spasm (ex: post-bleed) * Raynaud’s disease * Migraine * *All good at dilating Coronary Arteries -* *↓s contractility of VSMC* * *Complementary to nitrates since working through a different pathway* * Non-vascular * Bronchial asthma * Esophageal spasm * Dysmenorrhea * Premature labor (prevention of) * Block slow calcium channels * \*primary site AV node * Block slow calcium channels, which **decreases conduction through SA and AV node** and **shortens Phase 2** (the plateau) of the action potential in ventricular myocytes * AP decreased * Impair impulse propagation in nodal tissue * Also ↓ spontaneous phase 4 depol in nodal tissue * Contractility/chronotropy of the heart decreases

Answer 19

* *Verapamil - Blocks the binding site, right in the center* * *Nefedipine – modulates the binding site in smooth muscle*

Answer 20

* Remember that it's Class IV * Mechanism of action: * Calcium channel has several subtypes * L, T, N, P channels * The L type channel is important in determining vascular tone and cardiac contractility * Decreased Ca+ keeps intracellular Ca+ low * Effects: * Decreased contractility * Decreased HR * Decreased activity of SA node * Decreased rate of conduction of impulses via AV node * Vascular smooth muscle relaxation: ↓ SVR & BP (arterial \> venous) * → ultimately decreases workload of the heart and decreased O2 demand (good for angina or CAD, 2^nd line tx for UA) * Used in the treatment of SVT and ventricular rate control in Afib and Aflutter * Good for reentrant tachycardias whose main pathway is the AVN * VSMC is also modulated by Ca++ → VSMC relaxation → vasodilation → ↓ BP! * Used to prevent reoccurrence of SVT * Not used in ventricular arrhythmias * Calcium channel blockers * Verapamil\* – Class IV Prototype * Diltiazem \* * *Ultimately shorten phase 2, shorten AP -**↓* *HR,* *↓* *activity in SA node, dilate Cas (**↓* *SVR,* *↓* *BP)* Calci-um, only atri-um

Answer 21

Class IV * *Blocks the binding site, right in the center - **Verapa-MIDDLE*** * Synthetic Derivative of papaverine * Its levoisomer is specific for the slow calcium channel * Primary site of action is the AV node * Depresses the AV node * Negative chronotropic effect on SA node * Negative inotropic effect on myocardial muscle * Moderate vasodilation on coronary as well as systemic arteries (does this, but not as well as some of the other agents \*prescribed for this issue\* - primarily used as an antiarrhythmic) * Clinical uses * SVT * Vasospastic Angina pectoris * HTN * Hypertrophic cardiomyopathy * Maternal and fetal tachydysrhythmias * Premature onset of labor * Pharmacokinetics- Verapamil * Highly protein bound – 87-98% (presence of other agents such as lidocaine, diazepam, propranolol ↑its activity) * Orally almost completely absorbed with extensive hepatic first pass metabolism and almost none of the drug appears unchanged in the urine. * Oral Peaks in 30-45 minutes, IV 15 minutes * E ½ t is 6-12hrs * Active metabolite: norverapamil * Dose 2.5-10 mg IV over 1-3 minutes (max dose 20 mg) * Continuous infusion 5 ug/kg/minute * **Do not use IV verapamil with ß- blocker (heart block)** * T1/2 6-8 hours * Hepatic metabolism, with active metabolite * Excreted in the urine, and bile * Side effects: myocardial depression, hypotension, constipation, bradycardia, nausea, **prolongs effects of neuromuscular blockers, and can impair antagonism of blockade also** (can impair reversal?) * *Verapamil and diltiazem can also have LA activity, and can* *↑ r/f LA toxicity if giving regional anesthesia* * *Myocardial depression/hypovolemic, can give 1g Ca Gluconate **before** administration of verapamil to decrease the amount of hypotension* * (Bit of a stretch) - **AV-erapamil** (AVN primary site of action, mostly used as an antiarrhythmic), **still ...** does all of the things that Ca-Channel blockers do (neg chronotropy, neg inotropy, vasodilate coronaries/systemic arteries)* * Verapamil-LABOR. idk i feel like it's unique and she's gonna ask about it.*

Answer 22

Class IV * Benzothiazepines derivative * Binds at alpha subunit of the L-type Ca++ channel * Principle site of action is the AV node * 1st line treatment for SVTs * HTN * Intermediate potency between verapamil and nifedipine * Minimal CV depressant effects * Clinical Uses – Similar to verapamil * SVT * Vasospastic Angina pectoris * HTN * Hypertrophic cardiomyopathy * Maternal and fetal tachydysrhythmias * PO or IV * Dose is 0.25-0.35mg/kg over 2 minutes can repeat in 15 minutes * IV infusion 10mg/h * Pharmacokinetics-Diltiazem * Oral onset is 15 minutes and peaks in 30 minutes * 70-80% protein bound/excreted in the bile and urine (inactive metab) * E ½ t is 4-6 hours * Liver disease may require a decreased dose * PD – mixed cardiac and vascular effects, this is why it’s also used for HTN * SEs * Myocardial depression * Hypotension * Constipation * bradycardia

Answer 23

Class IV * Dihydropyridine derivative * Clinical uses * Angina pectoris * Primary site of action is **peripheral arterioles** * **Coronary and peripheral vasodilator properties** \> verapamil * Little to no effect on SA or AV node * ↓ SVR, BP (main use) * Reflex tachycardia * Can produce myocardial depression in pts with LV dysfunction or on beta blockers * Pharmacokinetics * IV, oral or sublingual * Oral – effects in 20 minutes/peaks 60-90 minutes * 90% Protein Bound/hepatic metabolism/ excreted in the urine E ½ t is 3-7hrs *Ni-fed up with your BP, CP!*

Answer 24

* Dihydropyridine * Potent vasodilator * Broken down by plasma esterases * 4-6 mg/hr IV (normal dose), start at 1-2 mg/hr and titrate up to 32 mg/hr * Duke using this. Not on exam.

Answer 25

* Side effects * Cancer!! If taking them for a prolonged pd of time. WTF. * Cardiac problems - *heart blocks, esp if on B-blockers already* * Bleeding = Prolonged, *interfere with plt fn* * GI = constipation * Drug Interactions: * Can potentiate the Myocardial depression and vasodilation from Inhalational agents * Can potentiate Neuromuscular blockers * Verapamil and Beta blockers = heart block * Verapamil-increases risk of Local anesthetic toxicity * Verapamil + dantrolene = (can cause) hyperkalemia due to slowing of inward movement of K+ ions can result in cardiac collapse * CCB interact with calcium mediated Platelet function * Digoxin: CCBs can increase the plasma concentration of digoxin by decreasing its plasma clearance * H2 antagonists * ranitidine and cimetidine alter hepatic enzyme activity and thus could increase plasma levels of CCB * Toxicity of CCB – may be reversed with IV administration of calcium or dopamine * Side effects: * vertigo * headache * flushing * hypotension * paresthesias * muscle weakness * Can induce renal dysfunction\*\* * coronary vasospasm with abrupt discontinuation\*\* - need to be slowly discontinued

Answer 26

* Adenosine * Digoxin * Phenytoin * Atropine * Magnesium

Answer 27

"Other" category used for SVT * Replaced verapamil for tx of SVT * Binds to A1 purine nucleotide receptors (activates adenosine receptors to open K+ channels and increase K+ currents) - ↑ K+ conductance, shortens AP * Slows AV nodal conduction – ME: how does increasing the conductance slow down AVN conductance? I thought it would repolarize quicker and then be ready for the next beat. But maybe bc K+ is coming out quickly, then the whole process is shortened * Stops the arrhythmia from occurring * Creates a *hyperpolarization* of nodal cells → decreases the excitability of AVN cells * Used for acute Rx only * Used for termination of SVT/ diagnosis of VT * Produced endogenously, has effects on nerve tissue, cardiac muscle, plts, “and breathing” * Dose 6mg IV, rapid bolus * Give over ~1 second * Large AC or CVAD, flush immediately * Repeated if necessary after 3 minutes, 6-12 mg IV at that time * Usually 1^st dose effective in ~60% cases * 2^nd dose effective ~90% cases * T1/2 \< 10 seconds * Eliminated by plasma and vascular endothelial cell enzymes * *Enzymes in RBCs. Is taken up by nucleic transporter cells located in the surface of vascular endothelium* * Side effects: excessive AV or SA nodal inhibition, facial flushing, headache, dyspnea, chest discomfort, nausea, bronchospasm * Contraindicated in asthma, heart block (bc it slows the AV conduction so much) * Feel “impending doom” Youtube: * aden-osine → ↓ aden-ylyl cyclase → ↓ cAMP* * Also ↑ K+ efflux – transient heart block in AVN!*

Answer 28

"Other" category * Cardiac glycoside * Increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses thru the AV node * Decreases HR, preload and afterload * Slows AV conduction by increasing AV node refractory period * Positive inotrope- used to treat CHF * We never give this in the OR * Therapeutic range is very narrow * *Binds the Na-K-ATPase pump, and slows the extrusion of Ca++ (Na-Ca++ exchange)* *→ positive inotropy* * *↓ ventricular preload, afterload, wall tension and O2 consumption in the failing heart* * *↓ HR* * *↑ inotropy* * Used for the management of atrial fibrillation or flutter (controls ventricular rate), especially with impaired heart function * Dose: 0.5-1 mg in divided doses over 12-24 hrs * Onset of action 30-60 minutes * T1/2 36 hours * Narrow therapeutic index * Therapeutic levels 0.5-1.2 ng/mL * Weak protein binding * 90% Excreted by kidneys * Reduce dose in elderly/renal impairment * Adverse effects (think of slowing of the AVN) * Arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation * potentiated by **hypokalemia** and **hypomagnesaemia** * Toxicity treatment * Phenytoin for ventricular arrhythmias * Pacing * Atropine

Answer 29

"Other" category * Works at sodium, potassium and calcium channels * Can be used with Very good for torsades de pointes * Dose 1 Gm IV over 20 minutes; can be repeated.

Answer 30

"Other" category * Muscarinic receptor antagonist/anticholinergic * Unstable bradyarrhythmias * 0.4 – 1.0 mg and repeat as necessary * Metabolized by the liver * Onset \<1 minute * DOA 30-60 minutes * **Caution using \<0.4 mg** **→ paradoxical response of intense bradycardia**

Answer 31

"Some block potassium channels" ## Footnote Class I - SOME - SOdium channel blocker Class II - BLOCK - B-blocker Class III - POTASSIUM - Potassium channel blockers Class IV - CHANNELS - Ca++ channel blockers