ANTIARRYTHMIC DRUGS SUMMARY

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Vaughan williams system:

1#CLASS I: blocj Na channels

1a: Quani-rocanamide

1b: Lidocaine\mexiletine

1c: Flec-Ecaiainide\propafenone

2#CLASS II: Beta blockers

3#CLASS III: block K channels

4#CLASS IV: block Ca channels

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when do u use these mfs?

-to supress arrythemia-> prevent formation of aberrant impulses

-Most of these mfs can supress one type of arrythmia but cause othe type->assosiated with cardiac arrest and death

-restrict their use to dangerous arrythemia and recurrent symptomatic arrythemia

(Commonly used in persistent recureent ventricular tachcadia+recurrent atrial febrillation)

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-what is the common mechanism of class 2 and 4? lowing sinus and AV node conduction\excerte effect on the SA\AV node graph

-class one\three excert effect in Ventricles and atria

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-phase 0 is depolarization of a single myocyte-QRS is depolariztion of hundreds of thousands of myocytes

-what happens if Na channels were blockd bu antiarr druf-> phase 0 takes longer to occur-> lenghtened QRS complex

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-drugs that block K channel lengthen phases 1,2,3->prolong QT interval

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1-Class 1:

prolong QRS

some affect K channels->prolong QT

can prolong AP duraton and effective refractory period

A-CLASS 1A:

-Block Na+K->INC QRS\QT\ERT\AP DURATION

-Quanidine:

Oral-Dec recurrence of Atr. Feb

Assosiated w INC mortality

Not used much cuz better are avelable

-Procanamide:

IV

Slow conduction in accesoray pathways(WOLF PARKINSON WHITE SYNDROME)

Slow arrthymia assoisated with bypass tract(WPW)

DRUG INDUCED SLEEEEEEEE (also assosiated with hydralazine+INH(tb drug)) which can lead to rash, arthristis, anemia(stop that mf)

ANA positive test

What is the uniqe feature of this bittch?ANTI HISTON ANTIBODIES(not in regular SLE but drug induced)

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B-CLASS 1B:

Block >DEC QT\ERP\APD(slightly shrinking)

Lidocaine\mexiletine

HAVE LEAST EFFECT ON AP OF CLASS 1 DRUGS

Most of the bining in when myocytes are in depolarized state where membrane potential is +

Ischemia Inc number of myocytes in depolarized state and they can't maintain their negative membrane potential

useful in ISCHEMIC ARRHYTHMIAS\ventricular tachycardia?cuz fast HR-Lots of depolarized Na channels+ischemic tissue

Rapidly unbind when myocytes exit depolarized state-?less effective in DEC HR cuz they unbind quick and less drugs are actually bound and producing their effect

WHY ARE THEY MORE EFFECTIVE WHEN HR IS FASTER? cuz less time to unbind before NA nels open again

-How can LIDOCAIN terminate arrythemia?

through aboloishing RE-ENTRY THROUGH converting unidirectional block->Bidirectional block and the circut in which electricity s looping is blocked

LIDOCAIN Local anathesia

LIDO AMD MEXI may cause CNS stimulation (tremor\agitation)

Tremor in patient taking oral mexi is a sign of? TOXICITY

What are the CVS side effects?

-excessive Na block

-Bradycardia\heart block\hypotension

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C-CLASS 1C:

Flec-Ecaiainide\propafenone

pure Na channel block->INC QRS-DOESN'T AFFECT QT OR AP DURATION

VERY SLOW UNBINFIG->limited use due to toxicity(proarrythemic effects+possiblilty of cardiac arrest)

only used in patients with structurally normal heart

reduce atr. feb recurrenc

MUST MONIOR THIS BITHCH FOR QRS PROLOGATION CUZ INC RISK OF CARDIAC ARREST

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What is the use dependance?

Na channels states? Resting(Baseline potential)\open(Phase 0)\inactive(positive AP)

Inc drug binding at certin state

CLASS ONE ACT BEST ON OPEN\INACTIVE-class 1C show most use dependance

Drugs that exhibit use depend->more effect on FAST HR

Na channels

are open\inactive where myocytes are depolarized\inactive starts from begining of Q->end of T

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2-CLASS 3:

-Amiodarone\sotalol\doferilide\Ibutilide

-DO NOT AFFECT QRS

-INC QT\APD\ERP

-What is the fered complication of qt prologation->TORSADE DE POINTES->CARDIAC ARREST

{TdP caused by by 1A and 3 REALLY IMP}

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-Amiodarone:

lowest incidence of TDP of all class 3

HAS CLASS 1,2,4 EFFECTS:

1:prolong QRS

2\4:slow HR, delay AV conduction

Very effective\

supressed ATRIAL FIB AND VENTRICULAR TACHYCARDIA

Hoghly LIPID SOLUBLE

Accumulates in LIVER\LUNG\OTHER TISSUES->SIDE EFFECTS(Less likely at low dose)

Half life 58 DAYS

steady state reaches? very long washout

SAFE IN RENAL DISEASE(BILIARY EXCRETION)

risk accumulates over time

young patient+indefinite therapy->GREATER RISk->often used in older patients 80-90 (cuz less likely to use for long time to develop toxicity)

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SIDE EFFECTS?

Hyper\hypothtyroidism: cuz contain IODINE

Inc LFT cuz usually mld\asymptomatic\ if marked inc stop drug)

Photosensetivity (easily sunburnt)

BLUE-GRAY DISCOLORATION(blue man syndrome) less common\mostly in face

Corneal deposits: cuz secreted by lacrimal glands->accumulate on corneal surface->cat whiskers apperance on cornea (BUT NO VISION PROBLEMS USUALLY AND SEEN IN CHRONIC THERAPY)

FEARED COMPLICATIONS ARE FROM ACCUMULATION IN LUNGS:

Pulmonary fibrosis->most common cause of deathffoamy macrophages in air spaces filled with amiodarone+hospholoipids(HONEYCOMBING PATTERN ON CXR)

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what do we need to do when we establish amiodarone?

-CHEST X RAY

-ULMONARY+LIVER+THYROID FUNCTION TESTS

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Sotalol+dofetidile

Class 3 effects-may lead to TDP

CONSIDER when patient start these mfs?

admit patient to hospital to monitor heart rythem on telemetry and check QT by EKG everyday(first few days have highest risk and if normal?discharge that mf)

Sotalol has BETA BLOCKING EFFECT TOO

can be used in cardiomyopathy

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{{{{ERSE USE DEPENDANCE}}}}

K channels fluctuate between 3 states

CLASS 3 bind in resting state and exhsibit reverse use dependance

as in the exert their greatest effects when the channel is not in use->MORE EFFECT IN PATIENTS WHO ARE BRADYCARDIAC

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COMMONALY USED IN ATRIAL FEB

recurrest episode of symptomatic atrial feb->start sota\doefiti

cardioversion to restore heart sinus rythem

sinus rythem persists on therapy

what are some other mfs that are also used in this manner?FLECANIDE\PROPAFENONE\AMIODARONE

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IBUTILIDE: IV- half life 2-12 Hrs

used for chemical cardioversion

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What is cardioversion?

termination of arrythemia\often atrial feb\flutter

-ELECTRICAL-REQUIRES SEDATION

-CHEMICAL0NO SEDATION-IBUTILIDE-MAY CAUSE TORSADE->need monitioring for several hours

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3-CLASS 2(BETA BLOCKERS):

Main effect on pacemaker cells (SA\AV)

DEC PHASE 4 SLOPE->Longer to reach -40 mv->deploarize less frequently

PROLONG REPOLARIZTION-PHASE 3->longer for av node to de and repolarize

DEC HR\COND VELOCITY

INC PR

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4-CLASS 4 (CCB)

VERAPAMIL+DILITIAZEM

slow HR AND AV CONDUCTION

DEC HR\COND VELOCITY

INC PR

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AV block:

Beta blockers\CCB->DEC AV conduction

an possibly lead to TYPE 1 AV BLOCK(Prolonger PR)

Or wenkebach (mobitz 1)

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BB and CCB:

1-atrial feb: control ventricular rate and make patients to feel better

(this is solely antiarrythemic)

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BB:

patients with risk of sudden cardiac death\INC risk of systolic HF patient cuz of ventricular tchycardia\febrillation

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5-Digoxin:

TWO CARDIAC EFFECTS:

1-INC contractility (SHF W\ DEC LVEF)

2-Slow AV node conduction (Atrial feb)

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HOW DOES THIS MF INC CONTRACTILITY?

inhibit Na-K ATPase->Na trapped inside the cell

other pumps b

ring Na inside and ca outside but with inc intracelluler calcium->less active->More ca inside myocytes->INC CONTRACTILITY

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HOW DOES THIS MF SLOW AV CONDUCTION?

Through INC vagus nerve tone->slow HR in rapid Atrial FEB cuz fewer impulses will reach ventricles->slower HR

SIMILAR EFFECT TO BB AND CCB IN AV NODE

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toxicity?

-Renal clearance->inc risk of toxicity in chronic kidney disease

-HYPOKALEMIA

due to many diuretics especially look pnes)

digoxin+furosemide->TOXICITY

Levele often need to be monitered

-GI:nausea-vomit-pain-Anorexia

-Neurological: lethargy-fatigue-deliriumonfusion-disorentaion-weakness

-Visula changes: altered vision color-blindness-SCOTOMAS

-Cardiac arrhythmia

-Why does the cardiac toxicity happen? MORE NA IN CELL

->Inc resting potential in atrial\ventricular cells

Inc automaticity

TOXIC RYTHM: extra beats(atrial\junction\ventricular)

Evidence of AV node block

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How to treat digoxin toxicity?

DIGIBIND

tigent binding fagment (FAB)

oduced in sheeps

Dig bound to albumin (hapten)->Ab->fragments

CRECTS HYPERKALEMIA AND SYMPTOMS

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6-Adenosine:

nucloside base used to make ATP with short half life

GIVEN IV FOR ACUTE SVT in emergancy room

receptors in many places (purinergi receptors0)

(((AV NODE\VASCULAR SMOOTH MUSCLES)))

effects are blocked byy theophylline and caffeine--> cuz block adenosine receptors cuz they have similar adenosine structure

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AV nodal cells:

activate K+ channel->K out->hyperpolarization->longer time to depolarize

BLOCKS CA INFLUX

Results in: Slowing AV conduction

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SVT:

Useful in it cuz most common tachycardia is AV NODAL RENTRANT TACHYCARDIA (AVNRT) where u have a slow and fast pathway->electrical circut in av node-> arrthymia

why useful? slow av conduction and break circut->terminate arrythemia

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REMEMBER THAT THERE ARE ADENOSINE RECEPTORES OUTSIDE AV NODE

-vasodilation\flushing\hypotension

some develp dyspneachest pain

short half life? effects quickly resolve

MUSTT WARN PATIENTS BEFORE GIVING SVT cuz they may feel uncomfortable for a bit

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7-Magnisum

USED FOR ACUTE MANAGEMENT OF TDP

BLOCK CA INFLUX

CA INFLUX->EARLY AFTERDEPOLARIZTION

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8-Atropine

Muscrininc receptor antagonist

parasymp block-> INC HR AND AV CONDUCTION

se in BRADYCARDIA(especially if from AV block)->INC HR

many side effects related to muscurnic block:

DRY MOUTH

CONSTIPATION

URINARY RETENTION(especially in men who may have benigin prostatic hypertrophy)

CONFUSION (elderly)

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Digoxin