Block 2-Reymann (Anti-arrhythmic)

Question 1

Classes of drugs

Answer 1

1. Fast channel blockers (Na+): Quinidine, Lidocaine, Flecainide
2. Beta-adrenoceptor blockers (Ca+2): Propranolol, atenolol, esmolol, sotalol
3. Inhibitors of repolar (K+): Amiodarone, Bretylium, dofetilide
4. CCB: Verapamil & Dilitiazem
5. Unclassified: Adenosine, Atropine, Digoxin, & Mg+2

Question 2

Mechanism of Arrhythmias

Answer 2

• Main promoting factors:
• Ischemia-Hypoxia (^{<strong>Delayed Afterdepolar</strong>})
• Acidosis, alkalosis, electrolyte imbalance
• Excessive autonomic input (catecholamine exposure)
• Drug toxicity (Digitalis)-Delayed afterdepolar
• Overstretching of cardiac fibers
• Scarred or functionally impaired tissue
• ALL occur from:
• Disturbances in impulse formation or conduction
• Or combo of both

Question 3

Examples of Arrhythmias

Answer 3

1. Premature Vent beat = 1 or 2 Depressed QRS out of normal Ekg
2. PSVT(parox suprevent tachy) = Equally spaced sinus rhythm Pwaves & QRS peak are close together
3. Atrial Fib = NO sinus ^{<u><strong>(IRREG/IRREG BEAT)</strong></u>}
4. Atrial flutter (AV block/2nd degree) = Depressed P wave w/small QRS peak
5. Atrial flutter w/1:1 Av conduction = Pwave connected to QRS
6. Monomorphic vent tachy = All QRS wave pointing down
7. Torsades de pointed (Bradycardia) = Irregular P wave & QRS w/splits
8. Vent fib = Death

Question 4

Therapy of Cardiac Arrhythmias

Answer 4

• Eliminate or minimize precipitating factors
• Define type of arrhythmia(suprevent or vent)
• Most ANTI-arrhythmic drugs can cause arrhythmias-Minimize risks of combined DRUG therapy
• Termination of ongoing arrhythmias
• Prevention of recurrent arrhythmias (could LEAD to death)

Question 5

Class 1 (Fast Na+)

Answer 5

• Subclasses:
• 1A = prolonged (quinidine, procainamide, disopyramide)
• 1B = Accelerated (lidocaine, mexlietine, tocainide)
• 1C = little effect (Flencainide, Propafenone)
• Mech:
• recovery of Na+ channel is Voltage-dependent
• Na+ channel blocker delays recovery=Prolonged ERP
• Shifts voltage-response relationship

Question 6

Class 1A quinidine PK & PD

Answer 6

• Anti-malaria drug & isomer of quinine
• PK:
• Oral , IV & 1/2 life 1 hour
• Hepatic metab, 20% unchanged in renal excretion
• Digitalis interaction
• PD:
• Blockade of Na+ channels in activated site=^{<u><strong>Reduction in Vmax PHASE 0</strong></u>}
• Blockade of K+channels=_{<u><strong>Prolonged AP</strong></u>}
• Antimuscarinergic effect (@ low doses)=^{<u><strong>Increase in AV-conduction </strong></u>}(death)
• Alpha blocker activity @ high conc

Question 7

Class 1A quinidine Use & EKG

Answer 7

• Use:
• Treat paroxysmal supravent tachy
• Conversion of Atrial flutter or fib to Sinus rhythm (Second line treatment)
• Need to use prior digitalization=Protective block (3:1)
• Recovery from block is slower & less complete in depolarized cell than in FULLY polarized tissue
• Result: Prolongation of refractory period in depolarize tissue
• Blockade of K+=Prolongation of AP, ERP & reduction of MAX re-entry
• EKG=
• Long QRS ^{<u><strong>(delayed cond in Punkinje &amp; HIS)</strong></u>}
• Long QT & alterations in T
• Variable PR ^{<u><strong>(slow AV-conduction)</strong></u>}

Question 8

Class 1A quinidine (SE)

Answer 8

• SE:
• Paradoxical-Increase in sinus & AV conduction due to ANTI-muscar (atropine)-
• Removal of protective AV-block
• Vent tachy (3:1, 2:1, 1:1 AV)
• Torsades- polymorphic Vent tachy (quinidine syncope)
• Slowing of conduction-QRS prolongation greater than 30-50% indicates toxicity
• Extracardiac effects:
• Antimalarial activity
• Hypotensive due to Alphablocker
• Can cause GI issues
• CNS Tinnitis in high doses

Question 9

Procainamide Class 1A

Answer 9

• Protected from enzymatic hydrolysis-LESS CNS effects
• PK:
• Oral & IV (arrythemia & hypotension)
• Hepatic metab, Variable rate of acetylation of NAPA
• PD: LIKE QUINIDINE
• Less muscarinergic than quinidine
• SE: LIKE QUINIDINE
• CNS can lead to psychosis
• Much more hypersensitivity - fever, rashes, arthritis, lupus like (ANA)
• USE:
• same as quinidine
• Sustained Vent arrhythmias w/Acute MIs

Question 10

Lidocaine Class 1B

Answer 10

• Amide local anaesthetic
• PK:
• Only IV binds to alpha1acid-glycoprotein
• PD:
• Blockade of activated & inactivated Na channels= MORE prounounced effect on tissues w/long plateus (punkje & vent)
• Little to NO effect on K+ channels-^{<strong>shortening of APD</strong>}
• Main effect on depolarized, ^{<strong>Arrhythmogenic tissue</strong>}
• SE:
• Cardiac exacerbation of arrhythmias less than 10%
• CNS tremor, paresthesias in TOXIC lvls coma or convulsions
• Interactions: Agents that interfere w/hepatic perfusion or hepatic microsomal metab

Question 11

Lidocaine Class 1B Uses

Answer 11

• Drug of choice in _supression of VENT tachy & Afib _
• Supression of arrhythmia associated w/Depolarization (^{<u><strong>POST MI &amp; Digitalis Toxicity)</strong></u>}
• Rx: IV loading dose 100-200mg
• Monitor plasma lvls
• Not for chronic use POST MI

Question 12

Mexiletine & Phenyioin Class 1B

Answer 12

• Mex orally active version of lidocaine
• PK: Oral 1/2 life of 8-20 hours
• PD: same as lidocaine
• SE: happens with frequent dosing
• Neurologic-nausea, tremor, lethargy
• Allergies-rash, fever, Agranulocytosis ^{<u><strong>(Low WBC @ Bone marrow)</strong></u>}
• _Phenytoin antiepileptic drug _
• PK: IV 1/2 less than 17 hrs
• PD: same as lidocaine
• _SE: _
• Neurologic-sedation, double vision, vertigo
• Gingival hyperplasia ^{<u><strong>(swollen gums)</strong></u>}

Question 13

Flecainide & Propafenone Class 1C

Answer 13

• Very SLOW dissociation from Na channel DURING recovery.
• Used in life threatening-refactory arrhythmia ONLY
• Flecainide=Increased Mortality rate in POST-MI pts treated for premature Vent contractions
• Use only oral for atrial arrhythmias

Question 14

Beta-Blockers Class 2

Answer 14

• _Anti-arrhythmic properties due Beta-blockade _
• Propranolol ^{<u><strong>(non-selective)</strong></u>}
• Atenolol^{<u><strong> (B1)</strong></u>}
• Esmolol^{<u><strong> (SHORT acting 1/2 life 9min)</strong></u>}
• Sotalol ^{<u><strong>(non-selective &amp; K+ channel blocker)</strong></u>}
• Cardio effects:
• Depress SA-node = sinus bradycardia
• Depresses auto of punkenje fibers
• Prolongs ERP of AV node
• SUPPRESSES ectopic vent depolar
• (-) ionotrope

Question 15

Beta-Blockers Class 2 (Propranolol)

Answer 15

• Cardio SE:
• Hypotension
• Aggravation of CHF
• Asystolia ^{<u><strong>(weakening of contraction/SYSTOLE)</strong></u>}
• Extracardiac SE:
• Predisposed Asthma & diabetes
• Peripheral occulsive disease
• Use:
• Decrease risk of sudden death in ^{<u><strong>POST MI</strong></u>}
• Control of supravent tachy
• Exercise or stress induced ^{<u><strong>Vent arrhythmias</strong></u>}
• Ischemic heart disease ^{<u><strong>(agina)</strong></u>}

Question 16

Class 3 Inhibitors of Repolarization Mech.

Answer 16

• Prolongs AP & ERP through inhibition of K+ channels
• Amiodarone
• Bretylium ^{<u><strong>(Indirect sympatholytic-Antihypertensive)</strong></u>}
• Sotalol ^{<u><strong>(prolongs repolar-Class 3 OR Class 2 Beta-blocker)</strong></u>}
• Dofetilide ^{<u><strong>(like sotalol w/LESS SEs)</strong></u>}
• Ibutilide^{<u><strong> (PURE class 3 ONLY ICU)</strong></u>}
• On AP/ERP will see ^{<u><strong>LONGER Plateu phase</strong></u>}

Question 17

Class 3: Amiodarone

Answer 17

• Can also be Class 1A
• PK:
• 1/2 life 30-120 days
• Metabolite desthylamiodarone
• Loading dose take 2 weeks for steady state
• PD:
• Blockade of inactivated Na+ channels MOST effects seen on Punkenje/Vent
• Blockade of K+ channels=Long AP
• Weak Ca+2 channel & NON-comp Beta-Blocker
• SE:
• conc in tissues (30 Fold) can be found in every organ ^{<u><strong>- BINDS TO PROTEIN</strong></u>}
• Pulm fibrosis (5-15%)
• corneal deposits
• photodermatitis (25%)
• Skin discoloration (5%)
• Thyroid dysfunction (5%) -iodine
• GI-Liver toxicity

Question 18

Class 3: Sotalol (beta 1-blocker)

Answer 18

• B1 blocker & K+ channel blockers
• PK:
• Oral & IV
• PD:
• Blockade of K+ channel=prolongation of AP
• Nonselective B-blocker
• SE:
• Same SEs as Beta-blockers
• Proarrythmic - ^{<strong>Torsades des pointes</strong>}
• USE:
• Treat prophylaxis of severe Vent tachy & atrial tachy

Question 19

Class 4: CCB

Answer 19

• decrease SA & AV nodal activity & protects vent
• Verapamil & Dilitiazem: Block L-type Ca+2 channels & inactivated state
• Most pronouced effect on AV-conduction
• USE:
• Treat Re-entrant ^{<u><strong>(circle current)</strong></u>} supravent tachy
• Reduction of Vent rate in atrial fib & flutter
• Treat ischemic HD^{<u><strong> (angina)</strong></u>}
• Treat Hypertension
• Additive effect w/beta blockers

Question 20

Misc class (Adenosine)

Answer 20

• Neutotransmitter-GI coupled=Lowered cAMP
• Hyperpolarize K+ channels open
• PK:
• IV w/half life 10seconds degraded by Adenosine deaminase to inactive inosine
• PD:
• Purine-P1 receptor agonist
• Enchances K+ conductance & inhibits cAMP mediated Ca+2 influx:
• Hyperpolarize in AV-node
• Use:
• Slowing AV node to prevent PSVT
• SE:
• Transient due to 10 sec 1/2 life
• Flushing
• AV-block 3
• Bronchoconstriction-presist for 30 min in asthmatics (Gq/M3)

Question 21

Misc class

Answer 21

• K+ supplements
• Mg+2:
• Functional Ca+2 antagonist
• Use:
• In treatment of torsades des pointed ^{<strong>(vent arrythemias)</strong>}
• Digitalis-induced arrhythmias
• Prevention of arrythemia in ^{<u><strong>ACUTE MI</strong></u>}
• Digoxin - Can SLOW AV conduction
• Atropine - Used in bradyarrhythmia to decrease Vagal tone

Question 22

Drug therapy for Atrial Fib

Answer 22

• Slow down vent rate:
• (-) dromotropic agents (stimulation to heart)
• Digoxin
• Verapmil, dilitiazem
• Beta-adrenoreceptor blockers
• Induce/Maintain sinus rhythm:
• Blockade of fast AP
• 1A=Quinidine
• 1C=Felcainide & propafenon
• 3= amiodarone & dofelitide