Download Antiarrhythmic Drugs

Antiarrhythmic drugs
Antiarrhythmic drugs can be classified according to their effects on the electrical behavior of
myocardial cells during activity into:
(The Vaughan Williams classification)
Class IA, B, C: Sodium channel blockers (membrane stabilizing drugs).
Class II: beta-blockers.
Class III: potassium-channel blockers.
Class IV: calcium-channel blockers.
Class IA: Na cannel blockers
Drugs
Quinidine
(Kinidin Durules)
*Procainamide
(Pronestyl)
MOA
Decreases myocardial
conduction velocity and
excitability. Depresses
myocardial contractility.
Suppresses automatically in
His-Purkinje system.
Primarily increases the effective
refractory period of atrial and
ventricular sodium-dependent
tissue.
As quinidine.
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Disopyramide
(Norpace )
As quinidine.
Sodium channel blocker
with moderate
anticholinergic properties.
Sodium channel blocker with
weak anticholinergic properties.
Sodium channel blocker with
strong anticholinergic
properties.
Uses
•Atrial flutter or fibrillation
•Ventricular tachycardia
•Paroxysmal
supraventricular tachycardia
As quinidine.
As quinidine.
Pregnancy
risk factor
Pharmacokinetics
C
Metabolism: extensively
hepatic.
Half-life elimination:
Adults: 6-8 hr
Excretion: urine.
2
C
Metabolism: hepatic via
acetylation to produce N-acetyl
procainamide (NAPA) (active
metabolite).
Half-life elimination:
Adults: 2.5-4.7 h (relatively
short half-life)
Excretion: urine (25% as NAPA)
C
Duration:1.5-8.5 h
Metabolism: hepatic
Half-life elimination:4 -10 h
Excretion: urine.
Dosing
Adults: PO: 100-600
mg/dose q4-6h; begin at 200
mg/dose & titrate to desired
effect (maximum 3-4g/d).
I.M.: 400mg/dose q2-6 h;
initial dose: 600mg
(gluconate).
I.V.:200-400 mg/dose
diluted & given at a rate ≤10
mg/min.
Adjustment • Kidney disease:
of dosage Creatinine clearance <10
mL/min: administer 75% of
normal dose.
• Liver disease:
No recommendations
available. Dose should be
titrated on the basis of
effectiveness and toxicity.
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Adults: PO: 250-500mg/dose q36 h or 500mg to 1g q6h extended
release; usual dose 50mg /kg/d;
max: 4g/d.
I.M.:0.5 – 1g q4-8h until oral
therapy is possible.
I.V.: loading dose: 15-18 mg /kg
administered as slow infusion
over 25-30 min or 100-200 mg
/dose repeated q5 minas needed
to a total dose of 1g;
maintenance dose: 1-4 mg/min
by continues infusion.
• Kidney disease:
Creatinine clearance10–50
mL/min; administer q6–12h;
Creatinine clearance 10
mL/min: administer q8–24h.
• Liver disease:
Reduce dose by 50%.
• Elderly: May require reduced
dosage.
Adults:
<50 kg: 100 mg q6h or 200-mg
extended-release (CR) capsule
q12h.
>50 kg: 150 mg q6h or 300-mg
extended-release (CR) capsule
q12h.
If no response ↑ to 200 mg q6h.
max. dose required for patient
with sever refractory
ventricular tachycardia is 400
mg q6h.
• Kidney disease:
Clcr 15-30 ml/min: ↓ dose 75%
Clcr 30-40 ml/min: ↓ dose 50%
• Liver disease:
100 mg q6h or 200mg q12h
(CR)
Monitoring • CBC with differential and
parameters platelets, liver & renal
function.
• ECG, pulse, and BP
continuously during IV
administration.
• Symptoms of arrhythmia:
palpitations, shortness of
breath, chest pain, syncope.
Route of
administration
Contraindications
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Oral, IV, IM.
Hypersensitivity to
quinidine, history of
quinidine induced Torsade
de pointes, myasthenia
gravis, heart block greater
than 1st degree,
thrombocytopenia
associated with previous
quinidine administration.
ECG, blood pressure, CBC,
platelet count; cardiac & blood
pressure monitor required during
I.V. administration.
ECG, blood pressure, urinary
retention, CNS anticoagulant
effect (confusion, agitation,
hallucination….)
Oral, IV, IM.
Oral only.
Hypersensitivity to procaine and
ester-type local anesthetics,
complete heart block, seconddegree AV block after
procainamide, systemic lupus
erythematosus, Torsade de
pointes, concurrent cisapride
long QT syndrome.
Patients with uncompensated
HF because of its negative
inotropic actions,
hypersensitivity to
disopyramide, 2nd or 3rd
degree heart block,
cardiogenic shock, Torsade de
pointes, congenital QT
prolongation, SSS
ADR
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• Common: diarrhea,
nausea, vomiting, fever,
rash, anorexia,
lightheadedness.
• Serious: arrhythmias,
hypotension, cinchonism
(hearing loss, vertigo,
confusion, delirium),
inflammatory syndromes
(bronchospasm, hemolytic
anemia, vasculitis,
thrombocytopenia,
agranulocytosis,
pneumonitis, lupus-like
syndrome), hepatic injury,
optic neuritis, respiratory
depression.
• Common: dizziness, diarrhea.
• Serious: lupus-like syndrome,
ventricular fibrillation, bone
marrow depression, AV block,
widened QRS complex, QT
prolongation, pericarditis,
confusion, depression, hemolytic
anemia, pleural effusion.
Anticholinergic S.E:
• Common: dry mouth,
constipation, blurred vision.
• Serious: hypotension, heart
failure, urinary retention,
chest pain, syncope, AV block,
widening QRS complex, or QT
interval, psychosis, depression,
hypoglycemia, confusion.
• Quinidine increases
D-D
interactions effects/toxicity of digoxin,
verapamil, depolarizing
and nondepolarizing muscle
relaxants, warfarin,
procainamide, TCA,
phenothiazines, reserpine.
• Drugs that increase
effects/toxicity of quinidine:
amiodarone,
cimetidine, alkalinizing
agents, sodium bicarbonate,
antihistamines, pimozide,
succinylcholine, other
neuromuscular blocking
drugs.
• Drugs that decrease
effects/toxicity of quinidine:
Phenobarbital,
rifampin, phenytoin.
200 mg (43.25 SR)
Price
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• Drugs that increase effects/
toxicity of procainamide:
lidocaine,
amiodarone, antihypertensives,
nitrates, antihistamines,
antidepressants, atropine,
phenothiazines, cimetidine,
ranitidine, quinidine,
trimethoprim, pimozide.
• Procainamide increases
effects/toxicity of neuromuscular
blocking agents, class IA or III
antiarrthymics, phenothiazines,
macrolide antibiotics,
ketoconazoles, lidocaine,
quinidine.
• Drugs that increase
effects/toxicity of
disopyramide:
anticholinergics, oral
hypoglycemic agents, insulin
and erythromycin.
• Drugs that decrease
effects/toxicity of
disopyramide: rifampin,
phenytoin, phenobarbital,
other inducers of hepatic
microsomal enzymes.
• Disopyramide increases
effects of warfarin.
10 ml vial(£1.90)
100mg(48-cap pack= £14,71)
150mg(48-cap pack= £19.52)
Class IB: Na channel blockers
Drug
MOA
*Lidocaine (Xylocaine)
Suppresses myocardial conduction automaticity, block both the initiation &
conduction of nerve impulse by ↓ the neural membrane permeability to Na ions,
which results in inhibition of depolarization with resultant blockade of conduction.
• Ventricular arrthymias from MI, digitalis intoxication; DOC for ventricular
Uses
ectopy, VT, VF.
B
Pregnancy risk factor
Onset of action: single bolus dose: 45-90 sec
Pharmacokinetics
Duration:10-20 min
Protein binding: 60%-80% to alpha1 acid glycoprotein
Metabolism: 90% hepatic
Half-life elimination: biphasic: initial:7-30 min, terminal:1.5 – 2h
Adults: IV bolus 50–100 mg, rate 25–50 mg/min. Repeat q3–5min until symptoms
Dosing
are reversed. Follow with IV infusion 20–50 mg/kg, rate 1–4 mg/min.
Maximum: 200–300 mg/h.
Adjustment of dosage • Kidney disease: None.
• Liver disease: In acute hepatitis and uncompensated cirrhosis: decrease dose by
50%.
• Elderly: Use with caution. Initial dose should be reduced by 50% and then
increased slowly as needed.
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Monitoring
parameters
Route of
administration
Contraindications
ADR
D-D interactions
Price
8
• BP, respiratory status, and ECG continuously during intravenous administration.
IV, IM, topical.
Hypersensitivity to amide local anesthetics, 2nd - or 3rd -degree heart block (when no
pacemaker is present), Stokes–Adams syndrome.
CNS:
• Common: headache, shivering.
• Serious: hypotension, seizures, hallucinations, respiratory arrest, heart block,
arrthymias, anaphylaxis, coma.
• Drugs that increase effects/toxicity of lidocaine: amiodarone,blockers,
INHclarythromycin…
• Drugs that decrease effects/toxicity of lidocaine: phenytoin, Phenobarbital.
• Lidocaine increases effects/toxicity of succinylcholine, amphetamine, blockers,
BZD
0.5% Injection , (5vials, 20 ml )34,85 SR
Class II: ß blockers
Drug
MOA
*Propranolol (Inderal )
Competitive blocker of --adrenergic receptors in heart and blood vessels which
result in ↓ HR, myocardial contractility, BP and myocardial oxygen demand.
Uses
Management of HTN, angina pectoris, pheochromocytoma, essential tremor,
supraventriular arrhythmia, ventricular tachycardia, migraine prophylaxis.
Pregnancy
risk factor
C (manufacture); D( 2nd & 3rd trimesters)
Pharmacokinetics Onset of action: oral: 1-2 hrs.
Duration: 6 hrs.
Protein binding: 68%
Metabolism: hepatic
Half-life elimination: 4-6 h
Excretion: urine
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Dosing
Adjustment of
dosage
Essential tremor: 20-40 mg BID initially, maintenance dose usually 120-320 mg/d
HTN: initially 40 mg BID; increase dosage every 3-7 days, usual dose: ≤320 mg divided
into 2-3 doses/d, max daily dose: 640 mg; usual dosage range 40 – 160 mg/d in 2
divided doses.
Migraine headache: initially 80 mg/d q 6-8 hrs; increased by 20 – 40 mg/dose q 3-4
weeks to max. of 160 -240 mg/d.
Post MI: 180-240 mg/day in 3-4 divided doses.
Pheochromocytoma: oral adult 30-60 mg/d in divided doses.
Stable angina: 80-320 mg in doses divided 2-4 times/d
Tachyarrhythmia: P.O:10-30 mg/dose q 6-8 hrs.
I.V:1mg/dose; repeat q5min up to a total of 5mg; titrate initial dose to desired response.
Thyrotoxicosis: 10-40 mg/dose q 6 hrs.
• Kidney disease: not dialyzable.
• Liver disease: Use caution.
• Elderly: Use caution. Increased risk for CNS and cardiovascular side effects.
BP, Pulse, cardiac & BP monitor required for I.V. administration.
Monitoring
parameters
Oral, IV.
Route of
administration
Contraindications Hypersensitivity, Cardiogenic shock, asthma, CHF unless it is secondary to
tachyarrhythmia treated with a blocker, sinus bradycardia and AV block greater than
first degree, bronchial asthma, COPD, pregnancy (2nd & 3rd trimester).
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ADR
D-D interactions
Price
11
Common: hypotension, bradycardia, HF, peripheral VC, GIT disturbance, sexual
dysfunction …
Drugs that increase effects/toxicity of propranolol: alpha blocker, rifamycin (CYP1A2
inhibitors), aminoquinoline, acetylcholinestrase inhibitors, amiodarone, digoxin,
dipyridamole, verapamil, diltiazem, chlorpromazine, qinidine, other antihypertensive.
Drugs that decrease effects/toxicity of propranolol: CYP1A2 inducers, NSAID.
blockers may ↓ the effect of sulfonylurea.
1mg/ml, 10 AMP( 14.25 SR)
Class III: K channel blockers
Drug
MOA
Uses
*Amiodarone (Cordarone )
Prolongs action potential duration as well as refractory period in myocardial tissue, ↓
AV conduction & sinus node function.
Class I, II, III & IV actions.
• Ventricular tachyarrhythmia after MI or VF
• Life threatening recurrent ventricular fibrillation or hemodynamically unstable
ventricular tachycardia.
D
Pregnancy risk
factor
Pharmacokinetics Onset of action: oral: 2days to 3 weeks.
Duration: after discontinuing therapy 7-50 days
Distribution: Vd: 66 L/kg; cross placenta
Protein binding: 96%
Metabolism: hepatic
Half-life elimination: 26-107 days(very long half-life)
Excretion: feces.
Adults: PO 800–1600 mg/day in 1-2 doses for 1–3 weeks, then when adequate
Dosing
arrhythmia control is achieved, ↓ to 600-800 mg/d in 1-2 doses for 1 month;
Maintenance: 400 mg/d.
I.V. initially 5 mg/kg over 20–120 minutes with ECG monitoring.
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Adjustment of
dosage
Monitoring
parameters
• Kidney disease: None.
• Liver disease: probably necessary in substantial hepatic impairment. No specific
guidelines available.
• Elderly: None.
• Baseline and follow-up serum electrolytes, BUN and creatinine, thyroid functions,
liver enzymes.
• Ophthalmic examinations for signs of granular corneal deposits (brown colored).
Advise patient to instill methylcellulose ophthalmic solution frequently to minimize
problem.
• Pulmonary function test to monitor signs and symptoms of pulmonary toxicity.
• ECG for the following parameters: heart rate and rhythm, reduction of T-wave
amplitude, Q-T prolongation.
• Signs and symptoms of thyroid dysfunction, including both hyper- and
hypothyroidism, pale skin, edema of extremities and periorbital region.
Oral, IV.
Route of
administration
Contraindications Sinus node dysfunction, bradycardia accompanied by syncope, AV block (second or
third degree).
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ADR
D-D interactions
price
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Common: headache, dizziness, fatigue, muscle weakness, solar dermatitis,
photosensitivity, discoordination, hyperlipidemia, nausea, vomiting, constipation,
anorexia, tremor, paresthesias, visual disturbances.
Serious: pulmonary fibrosis and/or interstitial pneumonitis (17%), hepatotoxicity,
hypotension (16%), pulmonary infiltrates, dysrhythmias, hypothyroidism,
hyperthyroidism, cardiovascular collapse, CHF, thrombocytopenia, optic neuritis or
neuropathy, corneal microdeposits, peripheral neuropathy.
Drugs that prolong QT interval: amitriptyline, clarithromycin, quinidine,
disopyramide, procainamide….
Drugs which delay AV conduction: verapamil, diltiazem, digoxin, blockers
Amiodarone may ↑ the levels of digoxin, INH, warfarin.
200mg (28.45 SR)
Class IV: CCB
Drug
MOA
Uses
*Verapamil (Isoptin)
*Diltiazem (Tildiem)
Inhibits calcium movement across cell
As verapamil
membranes.
Produces a relaxation coronary vascular
smooth muscle & coronary VD, ↑
myocardial oxygen delivery in patient with
vasospastic angina; slow automaticity &
conduction of AV node.
Orally: treatment of angina pectoris & HTN. Orally: treatment of HTN; stable angina.
I.V.: for SVT; rate control of AV & flutter. I.V.: AF or atrial flutter ;SVT
C
C
Pregnancy risk
factor
pharmacokinetics Onset of action: peak effect: oral: immediate
release: 1-2 h; I.V.:1-5 min.
Duration: oral: immediate release: 6-8 h
I.V.:10-20 min.
Protein binding: 90%
Metabolism: hepatic
Half-life elimination: single dose: 2-8 h,
multiple doses: 4.5 12 h.
Excretion: urine.
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Onset of action: oral: immediate release:
30-60 min.
Distribution: Vd; 3-13 L/kg
Protein binding: 70-80%
Metabolism: hepatic
Half-life elimination: immediate release 34.5 h
Excretion: urine & feces.
Dosing
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• Angina:
Adults: Initial: PO 80–120 mg TID.
Maintenance: PO 240– 480 mg/d in3-4
divided dose.
• Hypertension:
PO 80–360 mg/d in 2 divided dose.
• Supraventricular tachyarrhythmia:
Adults: Initial: IV 2.5–5 mg given over 2
min, second dose of 5-10 mg may be given
15-30 min after initial dose. Max. total dose:
20mg.
• Angina:
Adults: capsule, extended release: Initial:
PO 120–180 mg OD
Max.dose: 480 mg/d
Tablet, extended release: 180 mg OD; may
↑ at7-14 day intervals.
Max. recommended dose: 360 mg/d.
Tablet, immediate release: usual starting
dose: 30 mg 4times/d; usual range: 180360 mg/d.
• Hypertension:
capsule, extended release: initial:180240mg OD; usual dose rang:180-240mg/d
Tablet, extended release:180-240mg OD;
usual dosage range120-540mg/d
•AF, atrial flutter, PSVT:
I.V: Initial bolus dose: 0.25 mg/kg over
2min. repeat bolus dose: 0.35 mg/kg over
2 min.
Continuous infusion: initial infusion rate
of 10 mg/hr ; rate may be ↑ in 5mg /hr
increment up to 15 mg /hr as needed.
Adjustment of
dosage
Monitoring
parameters
Route of
administration
Contraindications
ADR
17
• Kidney disease: Clcr <10ml/min;
Administer at 50% to75% of normal dose.
• Liver disease: Reduce dose by 20%-50%
& monitor ECG.
• Kidney disease: Use with caution.
• Liver disease: Use with caution.
• Elderly: Use with caution.
Monitor BP closely & status of liver and
kidney function.
LFT, BP, ECG
Oral, IV.
Oral, IV.
Hypersensitivity to verapamil, sever LV
dysfunction, hypotension, cardiogenic
shock, SSS, 2nd or 3rd AV block.
Hypersensitivity to calcium blockers, sick
sinus syndrome, 2nd or 3rd degree AV
block, severe hypotension, acute MI with
pulmonary congestion.
• Common: Cough headache, edema,
gingival hyperplasia, constipation.
• Serious: CHF, bradycardia, first-,
second-, and third-degree AV block.
Hypotension, dizziness, nausea
• Common: headache, edema.
• Serious: CHF, AV block, hypotension,
depression, bradycardia.
D-D interactions
price
• Drugs that increase effects/toxicity of
verapamil: use of verapamil with
amiodarone, blockers lead to bradycardia
& ↓ COP.
Aspirin & concurrent verapamil use may
↑ bleeding time.
The levels/effects of verapamil ↓by:
carbamazepine, barbiturate, phenytoin.
As verapamil.
40 mg TAB (26.4SR)
80 mg TAB (20.25 SR)
60 mg TAB(25.5 SR)
*Available in KAUH
Done by: Rasha R. Subahi. Pharm.D Candidate.
Perceptor : Prof. Osama M. Ibrahim
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