Antiarrhythmic Drugs

Physiology of normal cardiac muscle / electrical activity of heart:

See physiology lectures, especially concepts such as excitability, irritability etc

Proposed mechanisms of cardiac arrhythmias:

 Enhanced automaticity:

Pathological damage to conducting fibers or cardiac m  unstable RMP 

spontaneous depolarization during diastole (ie depolarizes before SA node).
Ischaemia = common mechanism and can also cause myocardial muscle cells to
assume electrical characteristics similar to pacemaker cells. Similar changes also
possible due to hypokalaemia (unstable ph-4)

 Re-entry + reciprocating mechanisms:

- Cause for many common A + V arrhythmias

- Arise in anatomical sites that possess opportunity for differential rates of
conduction along alternative pathways
- Occurs where: a) Impulses can pass down alternative pathways with
different conduction times + refractory periods
b) When impulses can be blocked
- Can be present in AV bundle, terminal Purkinje + damaged atrial and
ventricular muscle

 Pathological after-potentials:

Pathological changes in ischaemic myocardium may cause generation of spontaneous

after-potentials after the AP. These “oscillations” may reach threshold potential and
hence depolarization.
May be related to entry of calcium or Na along ion-specific channels.

 Heart blockade: eg from damage (usually from ischaemia) to the Av node or

ventricular conduction system.

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 Classification of antiarrhyhtmic drugs (AAD)
(Vaughan – Williams + Singh)

 Class 1:
Membrane stabilizers. Inhibit fast Na-current ( ph 0 )  slowing ph 0
depolarization and / or decreasing rate of depolarization of ph 4.

- Class 1a: lengthen AP duration: Quinidine, procainamide, disopyramide

- Class 1b: shorten AP duration (fast dissociation): lignocaine, phenytoin, mexiletine, tocamide
- Class 1c: no effect on AP duration (slow dissociation): flecainide, lorcainide

 Class 2: Anti-sympathetic = B-blockers ( + bretylium)

Decrease slope of ph 4 of SA node + conducting tissue ( + ? slope of ph 0 )
Other: - prolong effective refractory period (ERP) of AV conduction tissues
- Shortens AP duration + ERP of Purkinje cells

 Class 3:
Prolong AP duration + ERP, with no effect on ph 0. Due to K-channel blockade
(prolongs repolarization of ph 3 ) = both conduction cells and muscle
Eg: Amiodarone, sotalol, bretilium

 Class 4: = Calcium Channel Blockers ( CCB’s)

Blocks slow inward ca-channel ( L-type) +  ph 2 and ph 3, mainly in AV-node
Eg: Verapamil, diltiazem

 Class 5: digoxin

 Other drugs: adenosine, Mg

Clinical Classification: ( ie conditions more effective against)

A) Narrow complex tachy-arrhythmias: adenosine, B-blockers, verapamil, digoxin

B) Broad complex tachy-arrhythmias: amiodarone, procainamide, lignocaine, bretylium

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 Class 1:

Membrane stabilizing by blocking fast Na-channels, thus slowing rate of

depolarization of ph 0 and /or that of ph 4.

Class 1 a: Lengthen the AP duration (and so the refractory period of cardiac muscle)

Quinidine, procainamide , dysopyramide

Procainamide:

Of the class 1a drugs, = most commonly used. Re-introduced in ACLS guidelines

(2a) above lignocaine in stable VT (doubtful / not practical in VF /pulseless VT).

Mechanisms:

 Blocks Na-entry: slows rate of depolarization ph 0

 Increases threshold potential for excitation
 Directly prolongs the refractory period (relative to the AP) of conducting
tissues and myocardial cells. (Suppress re-entry)
 Anti-muscarinic effects (less marked than quinidine) – may antagonize 
vagal tone. (dysopyramide = most potent anti-muscarine effects)

ECG:  QT,  QRS and  PR

Uses: - More commonly for ventricular arrhythmias (long-term use limited by s/e’s )
- ACLS: Stable VT (PSVT 2nd line): load 20mg/min up to 17mg/kg ( 1000mg)

Kinetics:

OBA: ~ 85%
Vd: 2,2 l/kg
Metabolism: partly metabolized + partly excreted unchanged in urine. Hydrolyzed in
liver + plasma, and also acetylated in liver to active metabolite N-acethylprocainamide 
excreted renally.
T1/2 elim 3-4 hrs ( needs frequent administration)

Side-effects / toxicity:

 Cardiac:  QT (torsade de pointes), hypotension (esp iv, but less c/f quinidine)
 GIT: minor disturbances, also hypersensitivity reactions, occasional rash
 SLE-type syndrome with chrnic Rx

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Class 1b: Also Na-channel blockers, but shortens duration of AP.
Phenytoin, lignocaine, mexiletine, tocainide

Lignocaine: (as antiarrhythmic) Amide LA

Electrophysiological effects:

 Shortened repolarization (ph 3) due to ca-ch or K-ch block  shorten AP + ERP,

especially in Purkinje preterminal fibers (good at preventing re-entry +
established reciprocal rhythms).
 Depresses ph 4 diastolic depolarization
 Prolongs rise time of ph 0 due to Na-ch blocking in cardiac muscle
 Increase threshold for depol of cardiac muscle cells
 Little effect on AV-node

Uses: primarily for ventricular (broad complex) arrhythmias, especially if induced by MI

or cardiac surgery ( of little use in atrial arrhythmias).

Dosage: 75 –100mg ivi bolus, followed by constant infusion of 2-4 mg / min ( opt s-[ ] =
2-4 ug/ml). At therapeutic levels, there is little effect on HR, BP or contractility and also
less chance of central toxicity.

Kinetics:
OBA only 30% , so only for ivi use
Vd: 0.8 –2 l/kg, PPB 60 –80% pKa 7.7 , lipid soluble
Metabolism: Liver ( half-life  in liver disease, CHF + drugs that  liver blood flow)
T1/2 elim 1.5 hrs ( SS at ~ 7hrs with infusion)

Toxicity:
 CNS: peri-oral / tongue tingling, tinitis   seizures / CNS depression ( s-[ ] 5-
10ug / ml)
 Cardiac: cvs collapse / arrest ( s-[ ] > 10 ug /ml) (CC:CD 7:1)
 With careful titration, toxicity quite low and effects quickly reversed
 Convulsive threshold for lignocaine reduced with hypoxaemia, hyperkalaemia,
acidosis.

Mexiletine: very similar to lignocaine, but is orally active (OBA ~ 90%). S/e’s however
= common ( nystagmus, tremor, nausea), so has low therapeutic index. Sometimes used
in chronic pain, where there is a positive response to lignocaine ivi infusion.

Phenytoin: sometimes used to acutely Rx lignocaine resistant VT, digitalis-induced toxic

arrhythmias, + chronically Rx congenital long QT-syndrome.

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Class 1c: Not affecting duration of AP.
Flecainide, loracainide

Flecainide:

Fluorinated LA analogue of procainamide

Electrophysiological:

 Decreasing Na entry  prolongs rise of ph 0

 AP + ERP not affected
 Prolongs conduction in all junctional tissues, thus  conduction in intra-atrial,
nodal + intraventricular tissues.
 Also has negative inotropic effects  may ppt CCF in susceptible pts

Uses: (fairly similar to amiodarone)

 Atrial, junctional + ventricular arrhythmias , eg paroxysmal SVT and VEB’s,

VT( non-sustained) or as prophylaxis against. NB: Effective @ WPW / accessory
pathway narrow complex tachy-arrhythmias.
 used oral

Kinetics:

OBA high
Vd: PPB 35-45%
Hepatic metabolism ~ 50%
T1/2 ELIM 14-20 HRS  thus OD dosage

S/E’s: - Can induce new arrhythmias / cause wide QRS complexes

- Nausea, dizziness, tremor
- Can ppt CCF (negative inotropy)

Lorcainide: membrane stabilizer, - depresses ph 4, no ant-arrhythmia

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Class 2:
Anti-sympathomimetics ie B-blockers

Electrophysiologic / effects:

 Reduce slope of ph 4 (thus  HR ) in slow response cardiac cells.

 ERP in AV-node = prolonged (thus effective in SVT’s)
 ERP + AP in Purkinje fibers = shortened (  re-entry )
  CO ( HR +  contractility)
 Most have membrane stabilizing ( LA) properties, except atenolol and nadolol.
 Note: Sotalol prolongs ph 3 repolarization and thus AP ( = Class 3 effect)

Usage:

Generally used for atrial (narrow complex) tachyarrhythmias (PSVT, sinus tachy etc) ie
esp where arrhythmia due to  sympathetic activity or  catecholamines.
Can be used in AF with or without digoxin to suppress a rapid ventricular response ( rate
control) *** avoid in WPW *** ( can  cond via accessory path by blocking AV cond)
Also commonly used post MI ( antiarrhythmic properties in addition to anti-anginal )

For more detail, see BB’s elsewhere. Esmolol, with its rapid on + offset is particularly
handy in OT for sudden onset SVT’s (might abolish it, or slow atrial flutter down
temporarily so as to diagnose it as such). Esmolol also handy to use therapeutic-
diagnostic ( eg in pt where BB relatively CI’ed) – if response good, - consider longer
acting drug like metoprolol.

Side-effects / precautions:

 Bronchospasm (less so with B1-selectives)

 Avoid in heart block / take care in combination with negative dromotropic CCB’s
eg verapamil, diltiazem
 Diabetics: may mask symptoms of hypoglycaemia / cause hypoglycaemia
 Can worsen acute CCF (OK to use in compensated CCF).
 Other: fatigue, cold extremities (Raynaud’s !), bad dreams (propranolol)
 Avoid in WPW

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Class 3:
Prolongs repolarization (ph 3) by blocking K-channels   AP and  ERP

Amiodarone, sotalol, bretylium

Amiodarone: (Need to know this drug well for the exam as well as for theatre)

A Benzofuran derivative (structural similarities with thyroxine)

Electrophysiologic: (has properties of all classes!)

 Main = class 3 ( repol in conducting syst + myocardium)   AP + ERP

 Also has class 1, 2 and 4 effects
 Antifibrillatory effects at ventricular muscle
 Initial effects when given ivi is not class 3, but = prolonging intranodal conduction.
 ECG: QT prolonged
Usage:

 Mainly in arrhythmias associated with anomalous pathways ( eg WPW)

 Used in other ventricular + supraventricular arrhythmias when standard drugs
ineffective / toxicity. (Note: In AF only if CVS stable and < 48hrs)
 ACLS

Dosages:
 Non-resuscitation: Oral loading 200mg tds for 1/52  200mg bd (5days) 200mg o.d
for 6 weeks (or maintenance).
 ACLS: - Non-arrest: load 15mg/min over 10 min (150mg / 100mlD5W)  then
1mg/min q 6hrs then 0.5mg/min q 18hr + onward (mix 900mg in 500ml D5W)
- Arrest: 300mg iv push (in 20ml D5W) may rpt 150mg x1 in 3-5min
- Max dose ivi over 24 hrs = 2,2 g
Kinetics:

ABS: OBA 60-80% (little 1st pass metab)

Vd: 70 l/kg = due to extensive tissue / prot binding, also accumulates in fat, skin, thyroid + well
perfused organs like liver and muscle. ~96% PPB
Metabolism: Liver, -main metabolite N-desethylamiodarone (antiarrhythmic)  accumulates
with chronic Rx
Elim: mainly excreted into bile (some enterohep circ). Minimal renal excretion
Note: biphasic elimination with t1/2’s 3-10 days and 26-107 days  this is reason why loading
dose needed to achieve relatively rapid plasma + tissue [ ]’s.
T1/2 elim 28 days (ave)
Onset = slow ( 2-7days if po ) , and effects may persist 4-6 weeks after stopped

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Side effects / toxicity: NB
  CVS: (non-competitive alpha + beta adrenergic blocker, latter = class 2 effect)
- Bradycardia: usually mild, but marked if in combination with drugs like
BB’s, CCB’s, digoxin, halothane). NB: bradycardia resistant to atropine.
Minimal direct myocardial depressant effects.
- Vasodilator (alpha blocker)   SVR (SVR +HR MAP, esp ivi).
- Torsade de pointes ( QT) (less c/f other class 3 drugs)
- NB: all above can be exacerbated by concurrent GA / drug interactions
 Resp: Pulmonary deposits +/- pneumonitis. Pulmonary fibrosis +/- alveolitis
can occur in 5-15% in chronic Rx and has high mortality. Two patterns seen:
- Slower onset with progressive dyspnoea + infiltrates on CXR
- Acute onset with cough, dyspnoea, hypoxia (mimics pneumonia)
- Post-op pts at risk of developing ARDS ( potential hazard if on high FiO2)
 Thyroid: Occasional hypothyroidism +/- hyperthyroidism = 2-4% (amiodarone
is an iodinated drug / resemblance to thyroxin).
 Liver: Enzyme induction (asymptomatic  in liver enzymes), hepatitis possible
 CNS: Peripheral neuropathy (long term high doses), myopathy.
 Skin: Photosensitivity, hyperpigmentation, rash. (Slate-grey skin colour may
rarely persist on discontinuation).
 Eyes: Corneal microdeposits (reversible + hardly ever causes probs with
vision).
 Other: Displacement of digoxin from protein binding sites, potentiates
warfarin’s effect.

SAQ: What are the side effects of amiodarone and what problems may develop
during concurrent anaesthesia?

Bretilium:

Prolongs ph 3 (  AP + ERP)
Also noradrenergic neuron blocker (like guanethidine) initially  NA release
Antifibrillatory effect on ventricular muscle ( more NB than class 3 effect)

Usage: - Not a 1st line drug, but uniquely effective in resistant/refractory VT + VF.
- 5-10mg/kg iv (of use in resistant arrhythmias from bupivacaine).
Effects: Initial  in BP (NA release) BP (Noradren neuron blockade)
Does not depress myocardial contractility
Kinetics: elimination primarily renal dose adj in renal failure ( not necessary with
amiodarone)
Side effects: - orthostatic hypotension (NB)
- N+V
- Parotid pain with long term oral use

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Class 4:
Calcium Channel Blockers (CCB’s)

 Phenylalkylamines: verapamil (mainly cardiac effects)

 Benzothiazepines: diltiazem (cardiac and peripheral vascular effects)
 Dihydroperidines: nifedipine, amlodipine (mainly peripheral vascular effects)

Calcium channels: = voltage gated channels (VOC) in excitable membranes. Four types:
 L-type; = “slow” channels = in heart and VSM
 T,P,N-types: = synaptic stimulus-secretion coupling
 NB: CCB’s almost exclusively selective for the L-type channels: Nifedipine
reduces the number, verapamil+diltiazem reduce the conductivity + kinetics of
reactivation of the channels. Recovery phase of inactivation is prolonged.

Pharmacological effects:

A) Heart:
 Electrophysiological:
- Verapamil (l-isomer) + diltiazem: Inhibits inward flux of ca-ions (ph 2 +
spontaneous diast depol ph 4 ) = mainly in SA + AV nodes,  prolong
conduction + ERP
- Nifedipine: no significant depressant effects on SA + AV
- Verapamil (d-isomer): blocking effect on fast Na-ch’s, ie membrane
stabilizing effect (LA effect)
 Effects: negative chronotropy, dromotropy and inotropy (reflex tachy with
nifedipine)
B) VSM:
 Calcium entry  vasodilatation (mainly the dihydroperidines, eg nifedipine)
Thus, the CCB’s have similar anti-HTN efficacy, but differ in their effects on
SA/AV node and peripheral vasodilatation.

Verapamil Diltiazem Nifedipine

BP   
Chronotropy   (reflex)
Dromotropy   0
Inotropy   0 - /
SVR  slight  mod marked
Coronary dilatation +/- ++ +/-
Reflex symp stimulation 0/+ 0/+ ++

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Main uses:
  Essential HTN: preferably those with more specific vasodilating and less
negative inotropy in pts with CCF. Little or no effect in normotensives
 Antiarrhythmic: Narrow complex tachyarrhythmias ( eg SVT’s)
Verapamil: 75-150ug/kg (5-10mg) slow ivi q 3-5 min eg in stable PSVT
Depending on conduction thru accessory pathway, verapamil may not be
effective in eg WPW / should avoid ( ist choice = amiodarone)
 Coronary artery vasospasm: (eg angina at rest with ST changes on ECG)
Verapamil ivi or nifedipine po/sl = equally effective
 Exercise induced angina pectoris:
Improvement of balance b/w O2 supply vs demand
Beneficial effect of nifedipine-like drugs = due to peripheral vasodilation rather than
coronary artery dilatation (similar to GTN). Diltiazem commonly used.
 Cerebral artery vasospasm:
Nimodipine = the drug of choice
4-14 days after SAH. (Spasm? due to influx of ca-ionscontraction of VSM in
large cerebral arteries.
Nimodipine = lipid-soluble analogue of nifedipine (can cross BBB well)
 Premature labour: nifedipine

Drug interactions:

Therapy with CCB’s can be continued until time of surgery without risk of significant
DI’s, especially re conduction of cardiac impulses.

1) Anaesthetic drugs:
- May exacerbate myocardial depression + peripheral vasodilatation produced by
volatiles
- Despite above, clinically not unacceptable depressant effects (except if pre-existing
LV-dysfunction)
2) NDNMB’s:
- CCB’s potentiate effects of both depolarizing + non-depol NMB’s (like Mg etc)
- Antagonism of of NM-blockade may be impaired due to  pre-synaptic release of
Ach in presence of a CCB.
3) LA’s:
- Verapamil’s d-isomer has potent LA effects
- May increase risk of LA toxicity when regional anaesthesia given with verapamil
4) Potassium-containing solutions:
CCB’s slow the inward movement of K, and hyperkalaemia may occur after exogenous K
infusion.
5) Dantrolene: Has been associated with myocardial depression + hyperkalaemia with
CCB’s.
6) Digoxin: - plasma [ ] may be increased
7) PLT fx: ca-mediated functions opposed

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Verapamil Diltiazem Nifedipine Nicardipine Nimodipine
Dosage:
Po (mg) 60-160 tds 60-90tds 10-20 tds 20 tds 240 od
Iv 75-150ug/kg 75-150ug/kg 5-15ug/kg
Abs:
Po >90% >90 >90
OBA 10-20% 40% 65-70% 30% 5-10%
Onset:
Po <30min 30 <20 20-60 30-90
SL 3
Ivi 1-3min 1-3 1-3
PPB: 90% 70-80 90 98 99
Cl:
Hepatic % 15 60 <15 45 80
Renal 70 35 80 55 20
Active metab’s: yes yes no
T1/2 elim: hrs 6-12 3-5 2-5 3-5 2

Verapamil:

Phenylalkylamine, synthetic derivative of papaverine

Presented as racemic mixture ( l-isomer = selective for L-channels, d-isomer for Na-ch’s)

Effects:
- Direct depressant of SA node + negative dromotrope for AV-node
- Negative inotrope: not prominent except in pre-existing LV dysfx
- Mild vasodilating properties, -SVR mildly decreased
- Less reflex tachycardia (beneficial in IHD)
Main uses:
- Acute + chronic SVT : In A-flutter + AF, slows ventricular response + may
restore SR ( ACLS order of Rx stable PSVT: CCB>BB>digoxin>DC version
- HTN
- Angina + coron vasospasm
Side effects:
- Bradycardia: can ppt CHB if on other Rx that slows down AV-conduction
- ***Avoid in WPW***: can  conduction thru accessory path by blocking AV
conduction. (Also possible with digoxin)
- Ppt or worsen CCF
- Hypotension

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Diltiazem:

Benzothiazepine

CVS effects ~ verapamil

Used in angina + HTN
Exerts minimal cardiodepressant effects + unlikely to interact with BB’s to further
decrease contractility.

Nifedipine:

Dihydropyridine

 the number of slow ca-channels

Effects:
- Greater coronary + peripheral vasodilator effects ( SVR)
- Minimal effect on capacitance vessels
- Little or no direct effect on SA + AV node (indirect via baroreflex mediated
sympathetic stimulation)

Used:
- Angina: - esp if due to coronary vasospasm
- HTN
- Premature labour suppression

Side effects:
- Abrupt discontinuation  coronary artery spasm
- Hypotension
- Reflex tachycardia

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 Other antiarrhythmics:

Digoxin:

Digoxin = one of 3 digitalis glycosides derived from foxglove leaves (digitalis lanata),
the other 2 being ouabain + digitoxin (fwiw, foxglove appears on the College’s coat of
arms – heart warming…)

Is chemically a glycoside: consists of a sugar (digitoxose) + aglycone ( digitoxigenin).

The pharmacological + therapeutic effects = due to digitoxigenin.

Mechanism action / effects:

A) Direct:
Due to inhibition of the Na/K/ATPase   ic [Na]  indirectly inhibits the 3Na+/Ca2+
exchanger, which is dependant on extracellular Na “driving” the pump (ie secondary
active trsprt)   ic [Ca]   contractility + excitability of cardiac myocytes.
Electrophysiologically, the  ic [Ca] causes ERP of the AV node + Hiss bundle, but
decrease the ERP of ventricular muscle cells.
Digoxin seems to have little beneficial effect in normal hearts

B) Indirect:
= Mediated by Vagus + antagonized by atropine.
Causes: - bradycardia (slows rate of depol ph 4 in SA node)
-  Atrial refractory period
-  ERP of AV node + Hiss bundle

Uses:
 AF + A-flutter: (esp if associated with CCF )
- Digoxin both directly + indirectly  ERP of AV + Hiss bundle  
conductivity   ventricular rate +  diastolic filling time ( ie improving O2
balance)
- It may increase the rate of atrial arrhythmias by reducing atrial ERP
(indirect)
 PSVT: slows HR by  vagal tone + may convert PSVT to SR

 Dosage in AF /PSVT: loading 0.75-1mg/d ( 1 or 2 divided doses)

Maintenance: 0.125 –0.5 mg/d
 Chronic CCF: Should possibly not be given if in SR. Positive inotropy not
maintained in long term.

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 Kinetics:

Abs: Complete abs from small intestine, OBA ~ 75%, usually orally given, ivi loading
in more acute. Max s-[ ] within 30-60 min, though effects may take several hrs
Vd: 10 l/kg (concentrated in cardiac + skeletal muscle) PPB 25%
Elimination: almost entirely renal (filtration)  take care in elderly /  renal Fx

T1/2 elim 36 hrs

Side effects: NB Digoxin has a low therapeutic index (TI) … ( LD50/ED50)

 Initial = GIT: N+V, anorexia

 Neurological: headache, fatigue, visual disturbances (frequent)
 Skin rashes (occ)
 Gynaecomastia ( occ)
 Cardiac: NB
- Almost any type of arrhythmia can occur
- Commonest: PVB’s (include coupled beats) , VT , AV-block
- Atrial arrhythmias less common
- Avoid thus in VT, + PVB’s: digoxin can  ventricular excitability (  ERP)
 can lead to VF. NB: ***should also be avoided in WPW ***(like
verapamil)
- May be ppt’ed by electrolyte abn’s:  K +  Mg,  Ca or acid-base changes.

Thus, extreme care in renal failure + care in elderly

Should be monitored by s-levels:
< 1ng/ml = ineffective and > 2,5ng/ml = toxic range ( thus, low TI !)

Management of OD / toxicity:
 Check + correct electrolyte abn’s
 Digoxin-specific antibodies (Digibind)  renally eliminated
 Phenytoin
 Magnesium

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Adenosine:
 Chemical: an endogenous nucleoside consisting of a purine base (adenine) linked to a
pentose sugar (D-ribose)

Origin: produced during normal metabolic activity by actions of various ic enzymes on high
energy phosphates ( AMP,ADP, ATP) + also by conversion of
s-adenosylhomocysteine   adenosine.
Extracellular levels of adenosine increase during hypoxic + ischaemic episodes

Effects:

 Cellular protective effects:

- Vasodilatation: A2 receptors (via NO) = NB coronary dilator ( ie metabolic
autoregulation), also peripheral dilation ( flushing, headaches,  MAP)
- Inhibition of calcium flux
- Release of excitatory neurotransmitters (eg glutamate)
- K-channel activation (hyperpolarization) causes selective AV cond
blockade
-  Energy production thru glucose transport
 Cardiac:
- Cardiac effects mediated by interaction with A1 receptors (Gi   c-AMP)
- Negative inotropic
-  SA node automaticity: slows sinus rate
-  AV node conductivity: prolongs conduction
-  Accessory pathways conductivity
 Other: - Bronchi: constriction
- Renal: afferent arteriolar constriction (TGF)
Uses:
 Diagnosis + management of SVT’s ( narrow complex tachy’s) ( WPW, can
transiently  rate in WPW, - so should ***avoid in WPW***)
 To induce temporary asystole in endoluminal repair of AAA (esp thoracic aneurysm)
 Hypotensive anaesthesia ( 50-300ug/kg/min) ( ATP also used): Increases CO, with
stable HR. Effects rapidly reversed on cessation.

Dosage: In SVT’s iv bolus of 6-12 mg (usually 3mg6mg12mg18mg)

Concurrent dipyridamole may enhance effects
Antagonized by the methylxantines ( eg aminophyline )

Kinetics:
IVI only
Elimination: deamination to inosine in plasma. Also uptake by RBC’s (inhibited by
dipyridamole)
T1/2 elim only 0.6-1,5 sec

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Side effects: ( ? mediated by other adenosine receptor subtypes)
  Nausea, headache, facial flushing (common)
 Bronchospasm
 Chest pain (coronary steal)
 May induce AF/A-flut: decreases atrial ERP (like digoxin) – so not effective in
these conditions
 Bradycardia (severe), even sinus arrest / pause +/- asystole, transient AV block

Magnesium salts:

 35 –40% in cardiac + skeletal muscle

  in plasma Mg2+ associated with variety of arrhythmia’s (hypo Mg2+ associated
with  K+)

 Mechanisms:
- Co-factor for Na/K/ATPase.  Mg can lead to intracellular K depletion
(cannot be repleted until adequate Mg given)
- Possible intrinsic antiarrhythmic actions
- Effects of Mg similar to that of hypokalaemia

 Antiarrhythmic Uses:
- Torsade de pointes
- Digoxin induced arrhythmias (ventricular arrhythmias)
- Possibly in multifocal atrial tachycardia
- ? In post MI arrhythmia prophylaxis ( not recommended)

 Dosage:
- 8 mmol ivi slowly over 15 – 20 min ( 1-2 min in emergent)( 2,47g/5ml
ampoule = 10mmol)
- Followed by 20 mmol over 6 hrs

NB: Look at latest ACLS guidelines re drug usage in cardiac

resuscitation = recent SAQ… pass rate was loooooow

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Addendum:
WPW syndrome:

Mechanism: Congenital accessory pathway b/w atria and ventricles that conducts more
rapidly than AV node, but has a long ERP.

ECG: - short PR, wide QRS with delta waves. ( if in v1 = type A = pathway in L-heart, if
not, =type B = R-heart)

Clinical presentation:
- SVT (usually) or AF / A-flutter
- Suspect in very young pt, HR >300/min, resting ECG delta waves.

Perioperative management:

- Continue anti-arrhythmic Rx peri-op ( usually flecainide or sotalol)

- Avoid drugs causing  HR (atropine, ketamine, pancuronium) and drugs that
will preferentially  conduction via accessory pathway (adenosine, BB’s,
CCB’s, digoxin)

Treatment of arrhythmias:

- Avoid: adenosine, BB’s, CCB’s, digoxin

- Give: amiodarone, procainamide, flecainide = if < 48hrs and CVS stable
- CVS unstable: cardioversion
- > 48 hrs: anticoagulate first, then cardiovert (like AF)

Torsade de Pointes: (polymorphic VT)

Etiology (factors that prolong QT): Hypokalaemia, hypomagnesemia, Drugs:

erythromycin, haloperidol, Class Ia antiarrhythmics, amiodarone, sotalol, cimetidine,
tricyclic antidepressants, methadone, quinidine
Possibly: Ondansetron

Management: 1) Withdrawal of offending drug, correct electrolyte abnormalities.

2) Magnesium
3) Antiarrhythmics: isoproterenol, atropine (to decrease QT-interval)
4) Electrocardioversion (non-synchronised)

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