ANTI ARRHYTHMIC DRUGS

 Arrhythmia may be defined as a condition which

occurs due to any abnormality in the normal rhythm
of the heart.
Or
 Improper beating of the heart (irregular – too fast or
too slow)
 Rhythm of heart – determined by pace maker site
called SA node, contain – specialized cells undergo
spontaneous generation – action potential at 100 to
110 action potential per minute
Classification
 Quinidine sulphate

MOA: Exerts anti arrhythmic effect by depressing flow rate of

Na+ ions into cells – during phase 0 – cardiac action
potential. Slow impulse conduction – AV node, reducing rate
of phase 0 – depolarization & prolonging refractory period
Met: 1oly – liver by hydroxylation, small amt excreted – liver.
Met – hydroxylated derivatives at quinoline ring – 1st pass o-
demethylation
Uses: To treat supraventricular & ventricular ectopic
arrhythmias, atrial & ventricular premature beats, atrial
fibrillation
Adr: Dizziness, nausea, vomiting
 Quinidine sulphate

5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol; sulfuric
acid
 PROCAINAMIDE HCL

MOA: It is Na+ channel blocker, stabilizes

neuronal memb by inhibiting ionic fluxes –
initiation & conduction of impulse – effecting
local anesthetic action
Met: N-acetyl transferase met of procainamide
HCl
Uses: Life threatening ventricular arrhythmias
Adr: Lupus syndrome, bradycardia, hypotension,
blood dyscrasias, cardiac toxicity
 PROCAINAMIDE HCL

4-amino-N-(2-diethylaminoethyl) benzamide
 DISOPYRAMIDE PHOSPHATE

MOA: Increase in Na+ permeability of cardiac myocyte

during phase 0 of cardiac action potential, decrease
inward Na+ current
Met: Undergoes hepatic CMP3A4 met, N-dealkylated
met. Renal excretion
Uses: Ventricular arrhythmias, ventricular tachycardia,
ventricular pre-excitation & cardiac dysrhythmias
ADR: 1oly anticholinergic – nature & include dry
mouth, blurred vision, constipation & urinary
retention
DISOPYRAMIDE PHOSPHATE

4-(Diisopropylamino)-2-phenyl-2-(pyridin-2-yl)butanamide
monophosphate
synthesis
 Phenytoin sodium

MOA: It acts on Na channel on neuronal cell memb, limiting

spread of seizures activity & reducing seizure propagation.
Stabilize threshold against hyperexcitability – reduce memb
Na+ gradient
Met: Relatively slow & involves aromatic hydroxylation by
CYP2C to p-hydroxylated inactive met.
Major met: 5-p-hydroxy phenyl 5-phenyl hydantoin. Excreted –
kidney as glucuronide conjugation
Uses: Tonic- clonic & complex partial seizures, prevention of
seizures during neurosurgery
ADR: Skin rashes – itchy, red, swollen, blistered skin, tightness
of chest
 Phenytoin sodium

5,5-diphenylimidazolidine-2,4-dione
 Lidocaine HCl

MOA: It blocks Na+ & K+ ion channels & regulates intracellular

& extracellular Ca+2 concentration through ligand – gated ion
channel. Block voltage gated Na+ channel
Met: Rapid, 1oly involves N-deethylation to yield
monoethylglycinexylide amidase – catalysed hydrolysis into
N-ethylglycine
Uses: local / regional anesthesia, lumber & caudal epidural
blocks
Adr: Emetic & convulsant properties, dizziness, paresthesia,
epileptic seizures
 Lidocaine HCl

2-(diethylamino)- N-(2,6-dimethylphenyl)acetamide hydrochloride

 Tocainide HCL

MOA: It acts on Na+ channels – neuronal cell memb,

limiting spread of seizures activity & reduce seizure
propagation. It binds to onactiove state of Na+
channels
Met: 1st pass hepatic degradation
Uses: Ventricular arrhythmias, ventricular tachycardia,
life threatening
ADR: GI disturbances, CNS effects
 Tocainide HCL

N-(2,6-dimethylphenyl)alaninamide
hydrochloride
 Mexiletine hcl

MOA: Inhibits inward Na current req – initation &

conduction of impulses, reducing rate – raise of
action potential, phase 0. It decrease effective
refractory period – purkinje fibres in heart
Met: Met by oxidative & reductive process by CYP2D6
– liver. Its met p-hydroxymexiletine & hydroxy
methyl mexiletine
Uses: Ventricular tachycardia, sympthomatic premature
ventricular beats & prevention of ventricular
fibrillation
 Mexiletine hcl

1-(2,6-dimethylphenoxy)propan-2-
amine
 Lorcainide hcl

MOA: It inhibits ATP hydrolytic action of myocardial

Na+K+ATPase in-vitro – conce of dependent manner
Met: N-dealkylated derivatives, suppress chronic
premature ventricular manner
Uses: Normal heart rhythm, premature ventricular
constriction, ventricular tachycardia & wolff -
parkinsonism white syndrome
ADR: Headache, dizziness, sleep distrubances
 Lorcainide hcl

N-(4-chlorophenyl)-N-(1-isopropylpiperidin-4-yl)-2-phenylacetamide
hydrochloride
 amiodarone

MOA: It blocks K+ currents – cause repolarization of

heart muscle during 3rd phase – cardiac action
potential
Met: Liver via CYP2C8 & major met
desethylaminodarone, has antiarrhythmic properties
Uses: Life threatening ventricular arrhythmias
ADR: Abdomianl pain, difficult in breathing, irregular
heart beat, nausea / vomiting, shortness of breath
 amiodarone

butyl-1-benzofuran-3-yl)-[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone
 sotalol

MOA: It is antiarrhythmic drug. It has both beta-

adrenoreceptor- blocking & cardiac action potential –
prolongation. Racemic mix d- & l- sotalol
Met: Not met, nor bound to significant protein
elimination – renal excretion. 80% of drug –
eliminated unchanged
Uses: Life threatening ventricular arrhythmias
 sotalol

N-{4-[1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl}methanesulfonamide
 COAGULANT & ANTICOAGULANT

Theory of blood clotting introduced – 1905 – 4 factors –

thromboplastin, prothrombin, fibrinogen & ionized
calcium
Coagulant drugs: Anti-inhibitor coagulant complex –
regulate blood coagulation. Hemophilia – defect in
blood coagulation
AntiCoagulant drugs: Blood thinner, decrease blood
ability to clot. Decrease clots – blood clots blocking
blood vessels
 MENADIONE

MOA: It is a Vit-K3 and is involved as a cofactor in the

carboxylation of glutamic acid residues of certain
proteins in the body.
These proteins are vit-k3 dependent coagulation factors
II, VII, IX and X.
Uses: Nutritional supplements & treatment of
hypoprothrombinemia, anti neoplastic agent
Adr: Dizziness, difficult in breathing, chest pain,
nausea, vomiting
MENADIONE

2-Methylnaphthalene-1,4-dione
 ACETOMENADIONE

MOA: It maintains normal blood clotting and acts by

reducing excessive bleeding
Uses: Treatment nutritional deficiencies.
Adr: Drowsiness, dizziness, Hypotension, Headache
Met: Hepatic, Renal.
ACETOMENADIONE

2- methyl,1,4-napthelenediol-diacetate
 WARFARIN

MOA: It is an anticoagulant that acts by decreasing the

synthesis of prothrombin, factor VII, IX, and X by
antagonizing the effect of Vit-K3
Uses: - Retinal vascular Occlusion, pulmonary embolism,
cardiomyopathy
Adr: Fetal bleeding, neonatal death, necrosis,
Osteoporosis
 WARFARIN

4-Hydroxy-3-(3-oxo-1-phenylbutyl)- 2H-chromen-2-one
Synthesis
 ANISINDIONE

MOA: It is an anticoagulant that acts by reducing

prothrombin activity of blood. Anisindione prevents
formation - I, VII, IX & X factors.
Uses:- prophylaxis & treatment of venous thrombosis &
treatment of atrial fibrillation, treatment of pulmonary
embolism
Adr: Abnormal bleeding, bleeding from nose, blood in
urine
 ANISINDIONE

2-(4-methoxyphenyl)indene-1,3-dione
 CLOPIDOGREL

MOA: It is a antiplatelet drug that acts by inhibiting platelet

aggregation by blocking the G1-coupled platelet ADP
(adenosine diphosphate) receptor.
It is a prodrug and is activated by the help of cytochrome
enzyme.
On activation it is irreversibly binds and inhibits ADP
receptor which is involved in the activation of platelets
and their aggregation.
Uses: Reduction of atherosclerotic, recent stroke, myocardial
infarction
Adr: Neutropenia, hemorrhage, cardiovascular edema
 CLOPIDOGREL

Methyl (2S)-2-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-
yl)acetate