Download ANTI-ARRHYTHMIC DRUGS

ANTI-ARRHYTHMIC
DRUGS
Dr. Marjan Nassiri-Asl
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5/3/2017
Normal rhythm
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Atrial arrhythmia
5/3/2017
Ventricular Arrhythmia
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5/3/2017
ANTI – ARRHYTHMIC DRUGS
SA node
ELECTROPHYSIOLOGY
OF
ATRIA
NORMAL
AV node
CARDIAC
His-Purkinje System
RHYTHM
4
VENTRICLES
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ANTI – ARRHYTHMIC DRUGS
IONIC BASIS OF MEMBRANE ELECTRICAL ACTIVITY
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Transmembrane potential of cardiac cells
is determined by the concentrations of
the ions:
– Sodium, Potassium, Calcium
The movement of these ions produces
currents that form the basis of the cardiac
action potential
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ANTI – ARRHYTHMIC DRUGS
PHASES OF ACTION POTENTIAL
Phase 1
>Limited depolarization
>Inactivation of fast
Na+ channels→ Na+
ion conc equalizes
>↑ K+ efflux & Cl- influx
Phase 2
>Plateau Stage
>Cell less permeable to Na+
>Ca++ influx through slow
Ca++ channels
>K+ begins to leave cell
Phase 0
>Rapid depolarization
>Opening fast Na+
channels→ Na+ rushes
in →depolarization
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Phase 3
>Rapid repolarization
>Na+ gates closed
>K+ efflux
>Inactivation of slow
Ca++ channels
Phase 4
>Resting Membrane Potential
>High K+ efflux
>Ca++ influx
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ANTI – ARRHYTHMIC DRUGS
CLASS I: Sodium Channel Blocking Drugs
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
IA

IB

IC
-
lengthen AP duration
Intermediate interaction with Na+ channels
Quinidine, Procainamide, Disopyramide
shorten AP duration
rapid interaction with Na+ channels
Lidocaine, Mexiletene, Tocainide, Phenytoin
no effect or minimal AP duration
slow interaction with Na+ channels
Flecainide, Propafenone, Moricizine
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ANTI – ARRHYTHMIC DRUGS
CLASS I: Sodium Channel Blocking Drugs
CLASS IA:
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QUINIDINE
Depress pacemaker rate
Depress conduction & excitability
Slows repolarization & lengthens AP duration
→ due to K+ channel blockade with reduction of
repolarizing outward current → reduce maximum
reentry frequency → slows tachycardia
(+) alpha adrenergic blocking properties →
vasodilatation & reflex ↑ SA node rate
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ANTI – ARRHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: QUINIDINE
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
Pharmacokinetics:
– Oral → rapid GI absorption
– 80% plasma protein binding
– 20% excreted unchanged in the urine →
enhanced by acidity
– t½ = 6 hours
– Parenteral → hypotension

Dosage: 0.2 to 0.6 g 2-4/ day
5/3/2017
ANTI – ARRHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: QUINIDINE
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
Therapeutic Uses:
– Atrial flutter & fibrillation
– Ventricular tachycardia
– IV treatment of malaria

Drug Interaction:
– Increases digoxin plasma levels
5/3/2017
ANTI – ARRHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: QUINIDINE
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Toxicity:
– Antimuscarinic actions → inh. vagal effects
– Quinidine syncope (lightheadedness, fainting)
– Arrhythmia or asystole
– Depress contractility & ↓ BP
– Widening QRS duration
– Diarrhea, nausea, vomiting
– Cinchonism (HA, dizziness, tinnitus)
– Rare: rashes, fever, hepatitis, thrombocytopenia,etc
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‫‪ANTI – ARRHYTHMIC DRUGS‬‬
‫‪CLASS IA: QUINIDINE‬‬
‫نکات مهم‬
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‫استفاده از محلول های تزریقی بی رنگ (نور سبب کریستالیزه شدن و قهوه‬
‫ای رنگ شدن محلول می گردد)‬
‫شروع درمان با دوز کم‬
‫کنترل بیمارازنظرنشانه های حساسیت به دارو (اختالالت تنفس ی)‬
‫به هنگام تجویز دارو مرتبا فشارخون اندازه گیری شود‬
‫مانیتورینگ قلبی بیمار‪ :‬طوالنی شدن فاصله‪ ، PR‬محو موج ‪ P‬و‬
‫‪.....‬دالیل قطع دارو هستند‬
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: PROCAINAMIDE
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
Less effective in suppressing abnormal ectopic
pacemaker activity
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More effective Na+
depolarized cells
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Less prominent antimuscarinic action

(+) ganglionic blocking properties → ↓PVR →
hypotension (severe if rapid IV or with severe LV
dysfunction)
5/3/2017
channel
blockers
in
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: PROCAINAMIDE
PHARMACOKINETICS:
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Oral, IV, IM
N-acetylprocainamide (NAPA) → major
metabolite
Metabolism: hepatic
Elimination: renal
t½ = 3-4 h
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: PROCAINAMIDE
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
Dosage:
Loading IV – 12 mg/kg at 0.3 mg/kg/min or less
rapidly
Maintenance – 2 to 5 mg/min

Therapeutic Use:
2nd DOC in most CCU for the treatment of
sustained ventricular arrhythmias asstd. with MI
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: PROCAINAMIDE

Toxicity:
- new arrhythmias
- LE-like syndrome
- pleuritis, pericarditis, parenchymal
pulmonary disease
- nausea, rash, fever, hepatitis,
agranulocytosis
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5/3/2017
‫‪ANTI – ARHYTHMIC DRUGS‬‬
‫‪CLASS IA: PROCAINAMIDE‬‬
‫نکات مهم‬
‫‪ ‬عدم استفاده ازمحلول تغییررنگ یافته‬
‫‪ ‬انفوزیون آهسته وریدی‬
‫‪ ‬درحالت انفوزیون بیماردرازکشیده و مرتبا فشارخون اندازه‬
‫گیری شود‬
‫‪ ‬پایداری محلول تزریقی پروکائین آمید دردکستروز‪ %5‬به مدت‬
‫‪ 24‬ساعت دردمای اتاق و یک هفته دریخچال‬
‫‪5/3/2017‬‬
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‫‪ANTI – ARHYTHMIC DRUGS‬‬
‫‪CLASS IA: PROCAINAMIDE‬‬
‫نکات مهم‬
‫‪ ‬بدلیل جذب ناکافی دارو باید با معده خالی مصرف شود‬
‫‪ ‬در بیمار تحت درمان خوراکی کنترل بیمار از نظر عالئم‬
‫لوپوس اریتماتوز‬
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‫‪ANTI – ARHYTHMIC DRUGS‬‬
‫‪CLASS IA: PROCAINAMIDE‬‬
‫تداخل پروکائین آمید‬
‫لیدوکائین‬
‫بیکربنات سدیم‬
‫افزایش عوارض جانبی دارو‬
‫کاهش دفع کلیوی دارو و افزایش‬
‫اثر آن‬
‫افزایش خطر آریتمی کشنده‬
‫فلوروکینولون ها‬
‫افزایش غلظت دارو‬
‫تری متوپریم‪ ،‬سایمتدین‬
‫داروهای آنتی کولینرژیکی سبب افزایش اثر آنتی کولینرژیکی‬
‫‪5/3/2017‬‬
‫آنها میگردد‬
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: DISOPYRAMIDE
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
More marked cardiac antimuscarinic effects
than quinidine → slows AV conduction

Pharmacokinetics:
- oral administration
- extensive protein binding
- t½ = 6 to 8 h
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IA: DISOPYRAMIDE
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Dosage: 150 mg TID up to 1 g/day
Therapeutic Use: Ventricular arrhythmias
Toxicity:
- Negative inotropic action
- Urinary retention, dry mouth, blurred
vision, constipation, worsening glaucoma
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE
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IV route only
Arrhythmias asstd with MI
Potent abnormal cardiac activity suppressor
Rapidly act exclusively on Na+ channels
Shorten AP, prolonged diastole → extends time
available for recovery
Suppresses electrical activity of DEPOLARIZED,
ARRHYTHMOGENIC tissues only
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE
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Pharmacokinetics:
- Extensive first-pass hepatic metabolism
- t½ = 1 to 2 hrs
Dosages: loading- 150 to 200 mg
maintenance- 2-4 mg
Drug Interaction:
Propranolol, Cimetidine – reduce clearance of
Lidocaine
Therapeutic Use:
DOC for suppression of recurrences of
ventricular tachycardia & fibrillation in the first few
days after AMI
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE

Toxicity:
–
–
–
–
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SA nodal standstill or worsen impaired
conduction
Exacerbates ventricular arrhythmias
Hypotension in HF
Neurologic: paresthesias, tremor, nausea,
lightheadedness,
hearing
disturbances,
slurred speech, convulsions
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: LIDOCAINE
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Attention!!
‫شکل تزریقی آن باید فاقد ماده نگهدارنده و اپی نفرین باشد‬
‫عدم افزودن آن به خون و مشتقات آن‬
5/3/2017
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: TOCAINIDE & MEXILETENE
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Congeners of lidocaine
Oral route - resistant to first-pass hepatic
metabolism
Topic use: ventricular arrhythmias
Elimination t½ = 8 to 20 hrs
Dosage: Mexiletene – 600 to 1200 mg/day
Tocainide – 800 to 2400 mg/day
S/E: tremors, blurred vision, lethargy, nausea,
rash, fever, agranulocytosis
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IB: PHENYTOIN
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Anti-convulsant with anti-arrhythmic properties
Suppresses ectopic pacemaker activity
Useful in digitalis-induced arrhythmia
Extensive, saturable first-pass hepatic metabolism
Highly protein bound
Toxicity: ataxia, nystagmus, mental confusion,
serious dermatological & BM reactions,
hypotension, gingival hyperplasia
D/I: Quinidine, Mexiletene, Digitoxin, Estrogen,
Theophyllin, Vitamin D (Enz inducer)
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IC: FLECAINIDE
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Potent blocker of Na+ & K+ channels
No antimuscarinic effects
Used in patients with supraventricular
arrhythmias
Effective in PVC’s
Hepatic metabolism & renal elimination
Dosage: 100 to 200 mg bid
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ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IC: PROPAFENONE
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(+) weak β-blocking activity
Potency ≈ flecainide
Average elim t½ = 5 to 7 hrs.
Dosage: 450 – 900 mg TID
Topic use: supraventricular arrhythmias
Adv. effects: metallic taste, constipation,
arrhythmia exacerbation
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS I: SODIUM CHANNEL BLOCKERS
CLASS IC: MORICIZINE
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Antiarrhythmic phenothiazine derivative
Used in ventricular arrhythmias
Potent Na+ channel blocker
Do not prolong AP duration
Dosage: 200 - 300 mg orally tid
Adv. effects: dizziness, nausea
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ANTI – ARHYTHMIC DRUGS
CLASS II: BETA ADRENOCEPTOR BLOCKERS
Propranolol, Esmolol, Sotalol
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↑ AV nodal conduction time (↑ PR interval)
Prolong AV nodal refractoriness
– Useful in terminating reentrant arrhythmias that
involve the AV node & in controlling ventricular
response in AF & A.fib.
Depresses phase 4 → slows recovery of cells, slows
conduction & decrease automaticity
Reduces HR, decrease IC Ca2+ overload & inhibit after
depolarization automaticity
Prevent recurrent infarction & sudden death in
patients recovering from AMI
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS II: BETA ADRENOCEPTOR BLOCKERS
Specific agents:

Propranolol
Esmolol

Sotalol
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– (+) MSA
- short acting hence used
primarily for intra-operative &
other acute arrhythmias
– has K+ channel blocking
actions (class III)
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ANTI – ARHYTHMIC DRUGS
CLASS II: BETA ADRENOCEPTOR BLOCKERS
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“membrane stabilizing activity”
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“intrinsic sympathetic activity”
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Less antiarrhythmic effect
Acebutolol, celiprolol, carteolol, labetalol, pindolol
Therapeutic indications:
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Exert Na+ channel blocking effect at high doses
Acebutolol, metoprolol, propranolol, labetalol,
pindolol
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Supraventricular & ventricular arrhythmias
hypertension 5/3/2017
Metoprolol
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
Cardioselective, are the most widely used
blockers in the treatment of hypertension

Sustained-release metoprolol is effective in
reducing mortality from HF and is
particularly useful in patients with
hypertension and HF
5/3/2017
Atenolol
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Less effective than metoprolol in preventing the
complications of hypertension.
5/3/2017
Labetalol
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Has a 3:1 ratio of β:α antagonism after oral dosing
BP is lowered by reduction of systemic vascular
resistance (via α blockade) without significant
alteration in HR or C.O.P
Is useful in treating the hypertension of
pheochromocytoma and hypertensive emergencies
(combined β- and α-blocking activity)
5/3/2017
Carvedilol
Nonselective β and α-adrenoceptor blocker
 Metabolized in the liver
 The average half-life is 7–10 h
 Reduces mortality in patients with HF and
is therefore particularly useful in patients
with both HF and hypertension
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‫اسمولول‬
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β1-selective blocker that is rapidly metabolized
via hydrolysis by RBC esterases
It has a short half-life (9–10 min)
Is administered by constant IV infusion
Is used for management of intraoperative and
postoperative hypertension, and sometimes for
hypertensive emergencies, particularly when
hypertension is associated with tachycardia
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Pharmacokinetics
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Steady-state blood concentrations are
reached within 30 min with doses of 50300 µg/kg per min
The time to ss may be reduced to 5 min
by giving an appropriate loading dose.
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Pharmacokinetics
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Blood concentrations decline in a biphasic
manner with a distribution half-life of about
2 min
Esmolol has low lipid solubility and is about
55% bound to plasma proteins
It is excreted in urine, primarily as the deesterified metabolite.
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Pindolol, Acebutolol, &
Penbutolol
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Partial agonists, ie, β blockers with some
intrinsic sympathomimetic activity (ISA)
They lower blood pressure by decreasing
vascular resistance and appear to depress
C.O.P or HR less than other β blockers
Significantly
greater
agonist
than
antagonist effects at β2 receptors
Beneficial for patients with
bradyarrhythmias or peripheral vascular
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disease
ANTI – ARRHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
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Prolong effective refractory period by
prolonging Action Potential
– Amiodarone
- Ibutilide
– Dofetilide
– Sotalol
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ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
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Drugs that prolong effective refractory period by
prolonging action potential
Prolong AP by blocking K+ channels in cardiac
muscle
Amiodarone → prolong AP duration
Bretylium & Sotalol → prolong AP duration &
refractory period
Ibutilide & Dofetilide → “pure” class III agents
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ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
CLASS III: AMIODARONE
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Approved only in serious ventricular arrhythmias
Broad spectrum of action on the
Very effective Na+ channel blocker but low affinity
for activated channels
Markedly lengthens AP by blocking also K+
channels
Weak Ca++ channel blocker
Non-competetive inhibitor of β receptors
Powerful inhibitor of abnormal automaticity
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ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
CLASS III: AMIODARONE
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Slows sinus rate & AV conduction
Markedly prolongs the QT interval
Prolongs QRS duration
↑ Atrial, AV nodal & ventricular refractory
periods
Antianginal effects – due to noncompetetive α
& β blocking property and block Ca++
influx in vascular sm.m.
Perivascular dilatation - α blocking property
and Ca++ channel-inhibiting
effects
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
CLASS III: AMIODARONE
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Pharmacokinetics:
t½ = 20 to 100 days
effective plasma conc: 1-2 μg/ml
Dosage: - Loading – 0.8 to 1.2 g daily
- Maintenance – 200 to 400 mg daily
Drug Interaction: reduce clearance of warfarin,
theophylline, quinidine, procainamide, flecainide
Therapeutic Use: Supraventricular & Ventricular
arrhythmias
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
CLASS III: AMIODARONE
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Toxicity:
- fatal pulmonary fibrosis
- Yellowish-brown microcrystals corneal deposits
- photodermatitis & grayish blue discoloration
- Paresthesias, tremor, ataxia & headaches
- Hypo - / hyperthyroidism
- Symptomatic bradycardia or heart block
- heart failure
- Constipation, hepatocellular necrosis, inflam’n,
fibrosis, hypotension
5/3/2017
‫‪ANTI – ARHYTHMIC DRUGS‬‬
‫‪CLASS III: AMIODARONE‬‬
‫نکات مهم‬
‫‪ ‬بدلیل جذب ناکافی دارو باید با معده خالی مصرف شود‬
‫‪ ‬محافظت پوست بیمار از نور در طول درمان و حداقل ‪ 4‬ماه پس از‬
‫قطع آن‬
‫‪ ‬انجام آزمایشات مرتب برای ارزیابی کارتیروئید‬
‫‪ ‬برای تزریق داخل وریدی آمیودارون در محلول تزریقی دکستروز‬
‫‪ %5‬رقیق شده و انفوزیون گردد‬
‫‪ ‬انفوزیون مکرر وریدی می تواند سبب درد و التهاب موضعی گردد‬
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‫‪ANTI – ARHYTHMIC DRUGS‬‬
‫‪CLASS III: AMIODARONE‬‬
‫نکات مهم‬
‫‪‬‬
‫درهنگام انفوزیون وریدی تجهیزات کافی برای کنترل وضع قلب باید‬
‫دردسترس باشد‬
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‫‪ANTI – ARHYTHMIC DRUGS‬‬
‫‪CLASS III: AMIODARONE‬‬
‫تداخل آمیودارون‬
‫داروهای ضد‬
‫انعقاد‬
‫بتا بلوکرها‬
‫تشدید اثرداروها‬
‫افزایش خطر کاهش‬
‫فشار خون و برایکاردی‬
‫افزایش خطر بلوک‬
‫‪CCBs‬‬
‫دهلیزی‪-‬بطنی و‬
‫هیپوتانسیون‬
‫دیگوکسین ‪ 5/3/2017‬احتمال افزایش سطح‬
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ANTI – ARHYTHMIC DRUGS
CLASS III: POTASSIUM CHANNEL BLOCKERS
SOTALOL
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Nonselective
B-blocker
that
also
slows
repolarization & prolongs AP duration
Effective antiarrhythmic agent
Used in supraventricular & ventricular arrhythmias
in pediatric age group
Renal excretion
Dosage: 80 – 320 mg bid
Toxicity: torsades de pointes
B-blockade symptoms
5/3/2017
ANTI – ARRHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS

Blocks cardiac calcium currents
→ slow conduction
→ increase refractory period
*esp. in Ca++ dependent tissues (i.e. AV node)

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Verapamil, Diltiazem, Bepridil
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS
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VERAPAMIL
 Blocks both activated & inactivated calcium
channels
 Prolongs
AV nodal conduction & effective
refractory period
 Suppress
both
early
&
delayed
afterdepolarizations
 May antagonize slow responses in severely
depolarized tissues
 Peripheral
vasodilatation
→
Effective
in
Hypertention & vasospastic
disorders
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS
VERAPAMIL
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Oral administration → 20% bioavailability
t½ = 7 hrs
Liver metabolism
Dosage:
IV: 5-10 mg every 4-6 hrs or infusion of 0.4 ug/kg/min
Oral: 120-640 mg daily, divided in 3-4 doses
Use: SVT, atrial fib
Toxicity: AV block, sinus arrest
constipation, lassitude, nervousness,
peripheral edema
5/3/2017
ANTI – ARHYTHMIC DRUGS
CLASS IV: CALCIUM CHANNEL BLOCKERS
DILTIAZEM & BEPRIDIL
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55
Similar
efficacy
to
verapamil
in
supraventricular arrhythmias & rate
control in atrial fibrillation
5/3/2017
ANTI – ARRHYTHMIC DRUGS
Miscellaneous:
56

ADENOSINE
→ inhibits AV conduction &
increases AV refractory period

MAGNESIUM
→ Na+/K+ ATPase, Na+, K+,
Ca++ channels

POTASSIUM
→ normalize K+ gradients
5/3/2017
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
DIGITALIS


57
Indirectly alters autonomic outflow by
increasing
parasympathetic
tone
&
decreasing sympathetic tone
Results in decreased conduction time &
increased refractory period in the AV node
5/3/2017
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
ADENOSINE




58
A nucleoside that occurs naturally in the body
t½ ≈ 10 seconds
Enhances K+ conductance & inhibits cAMPinduced Ca++ influx → results in marked
hyperpolarization & suppression of Ca++dependent AP
IV bolus: directly inhibits AV nodal conduction &
↑ AV nodal refractory period
5/3/2017
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
ADENOSINE
 DOC for prompt conversion of paroxysmal SVT to
sinus rhythm due to its high efficacy & very short
duration of action
 Dosage: 6-12 mg IV bolus
 D/I:
 theophylline, caffeine – adenosine receptor
blockers
 Dipyridamole–
adenosine
uptake
inhibitor
[enhancer]
 Toxicity: flushing, chest burning, atrial
fibrillation,
headache, hypotension, nausea,
paresthesia
59
5/3/2017
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
MAGNESIUM


60
Effective in patients with recurrent
episodes of torsades de pointes (MgSO4 1
to 2 g IV) & in digitalis-induced arrhythmia
Mechanism unknown → influence Na+/K+
ATPase, Na+ channels, certain K+ and
Ca++ channels
5/3/2017
ANTI – ARHYTHMIC DRUGS
MISCELLANEOUS ANTIARRHYTHMIC AGENTS:
POTASSIUM



61
Therapy directed toward normalizing K+ gradients &
pools in the body
Hypokalemia:
 ↑ risk of early & delayed afterdepolarization
 ↑ ectopic pacemaker activity esp if (+) digitalis
Hyperkalemia:
 Depression of ectopic pacemakers
 Slowing of conduction
5/3/2017