introduction to arrhythmia, their causes and mechanisam, classification in brief

1. Presented by
Miss. Ashvini Vijay Govande
Assistant Professor
Kandhar College of Pharmacy, Kandhar

2.  Arrhythmia: refers to any change from the normal sequence
of electrical impulses.
 Types-
1) Bradycardia- decreases heart rate
2) Tachycardia- increases heart rate
3) Ventricular tachycardia- abnormality in ventricle causes
increases in heart rate
4) Atrial flutter- heart beat is increases and irregular (between
250-300)
5) Atrial fibrillation- heart beat rises irregularly above 300

3.  Causes:
 Myocardial hypoxia
 Ischemia
 Trauma
 Drugs
 Electrolyte disturbance
 Mechanism-
1) Abnormal generation of impulses
a) altered normal autonomicity
b) abnormal autonomicity
c) after depolarization- i) early ii) delayed
2) abnormal conduction of impulses
a) re-entery
b) conduction block- I, II, III

4. 1) Membrane stabilizing agents-
a) Minimal phase O depressors (shorten repolarization and slow
conduction (1+))
Lidocaine, phenytoin, mexiletine, tocainide.
b) Moderate phase O depressors (prolong repolarization and slow
conduction (2+))
Quinidine, procainamide, disopyramide, moricizine
c) Marked phase O depressors (no effect on repolarization and slow
conduction (3+ to 4+))
Encainide, flecainide, indecainide, lorcainide, propafenone
2) β-adrenergic blokers-
Propranolol, acebutolol, esmolol
3) Drug causing repolarization-
Amiodarone, bretylium, sotalol
4) Ca2+ channel blockers-
Verapamil, diltiazem

5.  Lidocaine: It is a local anasthetic and cardiac depressant used
as an antiarrhythmia agent.
 MOA: It is stabilizes the neuronal membrane by inhibiting the
ionic fluxes required for the initiation and conduction of
impulses thereby effecting local anesthetic action. It alters
signal conduction in neuron by blocking the fast voltage gated
sodium channels in the neuronal cell membrane that are
responsible for single propogation.
 Indication: Peripheral nerve block, epidural, spinal, surgical
anasthesia, insect bites, minor burns, cystoscopy, painful
cystitis.
 Contraindications: Hypersensitivity, child below 12 yrs of
age, elderly, hepatic impairment, pregnancy.

6.  Side effects: Vomiting, nausea, blurred vision, tinnitus,
constriction of the pupils of eyes, anaphylaxis, status
asthamticus, urticaria, rash, edema, tissue necrosis, cardiac
arrest, hypotension, fetal bradycardia, myocardial depression,
tremors, shivering, drowsiness, loss of consciousness,
convulsion, disorientation.
 Pharmacokinetics: Onset action 4-17min, duration of action
3-6hrs, plasma half life by iv injection is about 13min by 1M
injection 90min, half life is increased in liver disease. It is
metabolized by liver, cross placenta, excreted in urine.
 Drug interaction: It decreases action of lidocaine. Lidocaine
with other drugs like MAOIs tricyclic antidepressants,
phenothiazine cause hypertension.

7.  Dosage: varies by route of anasthesia. IV route 50-100 mg
alimentary bolus, followed by 20-40mg every 10-20 min. Or 1-
3 mg/min infusion.
 Brand name: 2% lidocaine hydrochloride injection USP,
agonEaze, Amniocentesis tray 1%, Arthrogram tray 1%.
Atelocollagen implant 3% intradermal. Injection Gesicaine
(Lignocaine hydrochloride) 30ml vial. Gesicaine with
adrenaline 2%, 30ml Xylocaine, xylocaine with adrenaline
xylocaine heavy 5%.

8.  It is antiepileptic drug.
 MOA: The primary site of action appears to be motor cortex where
spread of seizure activity is inhibited. It acts on sodium channels on
the neuronal membrane and limiting the spread of seizure activity. It
promotes sodium efflux from neuron.
 Pharmacokinetic:
 Absorption: Well absorbed orally, bioavailability is 85%, food
influences absorption.
 Distribution: volume of distribution 0.5-1.0L/kg
 Protein binding: 90%
 Metabolism: liver
 Elimination: Drug is excreted in the bile as inactive metabolite
which are then reabsorbed from the intestine and excreted in urine.
 Half life: 22hrs

9.  Adverse effect: Rash, Gum hypertrophy, ataxia, nystagmus,
slurred speech, confusion, drug induced lupus, agranulocytosis,
aplastic anemia, hepatitis and anticonvulsant hypersensitivity
syndrome.
 Drug interaction: several drug may inhibit or induce the
metabolism of phenytoin such as amiodarone (increased level),
erythromycin (increased level), fluconazole (increased level),
rifampicin (decreased level), folate supplement (decreased level),
fluoroquinolnes (decreased level).
 Uses: Anticonvulsant, antiarrhythmic, mucle relaxant
 Dose: Dilantin 25mg, 100mg cap, 100mg/4ml oral, suspension,
100mg/2ml inj., Epsolin 100mg tab, 100mg/2ml inj., Epton 50,
100mg tab, 25 mg/ml syr, Fentoin-ER 100 mg

10.  Is a lidocaine analogue
 MOA: It inhibits the inward sodium current required for the
initiation and conduction of impulses, thus reducing the rate of rise
of the action potential. It achieve this by reducing sodium current by
inhibiting sodium channel.
 Indication: Ventricular tachycardia, during cardiac surgery.
 Contraindications: Hypersensitivity, cardiogenic shock, pregnancy,
lactation, liver disease, myasthenia gravis.
 Side effects: Vomiting, nausea, diarrhoea, anorexia, dry mouth,
hepatitis, altered taste, gastro intestinal bleeding, blurred vision,
hearing loss, tinnitus, dizziness, headache, confusion, tremors,
convulsion, weakness, change sleep pattern, hypotension, syncope,
cardiogenic shock, skin rash, dry skin, alopecia, edema, fever,
decreased libido.

11.  Pharmcokinetics: Orally peak 2-3hrs, plasma half life 12hrs,
metabolized by liver, excreted by kidney, breast milk.
 Drug interaction: The action of mexilitine decrease by
cimetidine, smoking decreases action of drug. Metoclopramide
increases action of mexilitine.
 Dosage: Adult: orally 400mg then 200mg after 8hrs then same
dose of 200mg after next 8hrs.
 Brand name: mexilitine: capsule Mexitil 50mg, 150mg,
injection mexitil 250mg/10ml vial.
 Treatment of overdose: Injection diazepam for convulsions,
injection dopamine for circulatory depression, monitor ecg,
medical oxygen inhalations.

12.  It is a primary amine analogue for lidocaine.
 MOA: It acts on sodium channel on neuronal cell membrane,
limiting the spread of seizure. The anti-arrhythmic action are
mediated through effects on sodium channels in purkinji fibers.
 Indication: Ventricular arrhythmias
 Pharmacokinetic: Oral administration, bioavailability 100%,
unaffected by food. 10% drug bound to plasma protein, plasma
half life is approximately 15hrs, may be prolonged up to 35hrs
in patient with severe renal function impairment. Excreted in
urine.
 Brand name: Tonocard Tab 400mg

13.  Quinidine sulphate: Quinidine is an isomer of quinine which
is a natural alkaloid occurs in cinchona bark.
 Molecular formula: C40H50N408;2H20
 Molecular weight: 782.9
 MOA: It acts on sodium channels on the neuronal cell
membrane, limiting the spread of seizure. The antiarrhythmic
action are mediated through effects on sodium channels in
purkinje fibers.
 Pharmacological actions:
1) Cardiac effect: The effect occurs due to vagolytic and
myocardial depressant action. Quinidine reduces the sodium
influx.

14. 2) Excitability: it decreases excitability of the cardiac tissue.
3) Cardiac contractility: it depresses entery of calcium ion to
cardiac muscle and exerts negative inotropic effect on heart
due to this cardiac contractility is decreased.
4) Conduction velocity: slows down the rate of conduction in
heart muscle. It decreases conduction velocity of cardiac
muscles.
5)BP: in oral dose or iv administration produce fall in bp by
producing direct relaxant action on arterial smooth muscles.
There is dilation of arteries.
6) Depolarization: It slows the rate of depolarization by
depressing sodium ion into cell. It prolongs depolarization-
repolarization cycle. The rate of contraction is decreased.

15. 7) Skeletal muscles: relax skeletal muscle.
8) CNS: causes convulsion due to its adverse effect on the
CNS.
9) Cinchonism: at higher dose or prolong use causes
cinchonism characterized by light headedness,
giddiness, tinnitus, blured vision, hearing loss.
10) GIT tract effect: when administerd orally causes
vomiting, nausea, diarrhoea and irritation to git tract.
 Indication: aterial fibrillation, paroxymal atrial
tachycardia, premature ventricular contraction.
 pharmacokinetic: Orally onset action ½ hr, peak conc.
5-6hrs, serum half life 6-7hrs, duration of action 8hrs,
metabolisd in liver, excreted through kidney.

16.  Dosage:
 Adult: Orally 200mg 3-4 times a day, maximum dose
4gms/day.
 Child: Orally 6mg/kg body weight per day in ¾ equal divided
dose.
 Drug interaction: Increased effect of warfarin, digoxin. Drugs
like cimetidine, thiazides, antacids, propranolol increase effect
of quinidine. The effect of quinidine is decreased with drug
like barbiturates, rifampin, phenytoin, nifedipine.
 Contraindications: Myasthenia gravis, hypersensitivity,
severe heart block, hypotension, lactation, paediatric, elderly
reduces dose.

17.  Side effects: Cinchonism, blurred vision, disturbed color
vision, hearing loss, vomiting, nausea, diarrhoea,
hepatotoxicity, hypotension, bradycardia, respiratory
depression, skin rash, urticaria, angioedema, swelling,
hemolytic anemia, thrombocytopenia, agranulocytosis,
headache, confusion, restlessness, syncope, irritability.
 Brand name: Qunidine: Tablet quinidine, natcardine quininga
100mg, 200mg, 300mg tablets.
 Treatment overdose: Administer dopamine for circulatory
depression, diazepam for convulsion, oxygen inhalation, ECG.

18.  Procainamide is an amide derivative of local anaesthetic procaine.
 MOA: It is sodium channel blocker. It stabilizes the neuronal
membrane by inhibiting the ionic fluxes required for the initiation
and conduction of impulses thereby effecting local anasthetic action.
It depresses the excitability of cardiac muscle to electrical
stimulation, slow conduction in atrium bundle and ventricle.
 Indication: Atrial fibrillation, ventricular tachycardia, proximal
atrial tachycardia.
 Dosage: Adult: 1-1.25gm maintenance dose 500mg every 4-6hrs.
 Contraindication: Hypersensitivity, myasthenia gravis, severe heart
attack, pregnancy, lactation, renal disease, respiratory depression,
children.
 Side effects: vomiting, nausea, anorexia, diarrhoea, hepatomegaly,
headache, dizziness, restless, confusion, irritability, psychosis, skin
rash, urticaria, edema, hemolytic anemia, agranulocytosis.

19.  Pharmacokinetics: Orally peak conc. 1-2 hrs, duration of
action 3 hrs, plasma half life 3 hrs. Metabolized in liver,
excreted in urine.
 Drug interaction: increased effect of procainamide with
cimetidine, barbiturate decrease effect of procainamide.
Toxicity is increased with other antidysrhythemic drug.
 Brand name: Procainamide: Tablet Pronestyl 250mg,
Injection pronestyl 100mg/ml.

20.  MOA: It inhibits fast sodium channels. In animal studies
disopyramide decreases the rate of diastolic depolarization in
cells with augumented automaticity, decreases the upstroke
velocity and increases the action potential duration of normal
cardiac cell.
 Indication: Ventricular arrhythmias, sustained ventricular
tachycardia, ventricular pre-excitation, cardiac dysrhythmias. It
is a class I a antiarrhythmic drug. It also possesses some
anticholinergic and local anasthetic properties.
 Pharmacokinetics: It is completely absorbed. Protein binding
is 50-60%, metabolized in liver. The half life is 6.7hrs (range
4-10hrs), 50% unchanged drug is excreted in urine.
 Brand name: Norpace cap 150mg oral, Norpace CR 150mg.

21.  It is an antiarrhythmia agent used primarily for ventricular
rhythm disturbance.
 MOA: It works by inhibiting the rapid inward sodium current
across myocardial cell membranes.
 Indications: irregular heartbeat and maintain a normal heart
rate.
 Pharmacokinetic: It is well absorbed, absorption is complete
within 2-3 hrs, significant first pass metabolism results in an
absolute bioavailability of approximately 38%. Volume of
distribution is 300L, protein binding are approximately 95%,
metabolized in liver, excreted in urine.
 Brand name: Ethmozine 250mg

22.  Encainide:
 This compounds belongs to the class of organic compounds
known as benzanilides. These are aromatic compound
containing an anilide group in which carboxamide group is
substituted with benzene ring.
 It increases death rate in patients who had asymptomatic heart
rhythm abnormalities after a recent heart attack.
 MOA: It can blocks the voltage gated sodium channels. It
stabilizes the neuronal membrane by inhibiting the ionic fluxes
required for the initiation and conduction of impulses.
 Uses: antiarrhythmic agent in arterial fibrillation, atrial flutter,
ventricular tachycardia, ventricular fibrillation.
 Brand name: Encainide hydrochloride 25mg oral

23.  Flecainide:
 MOA: It acts on sodium channel on the neuronal cell
membrane, limiting the spread of seizure activity and reducing
seizure propagation. The antiarrhythmic action are mediated
through effects on sodium channels in purkinje fibers. It has
local anesthetic activity.
 Pharmacokinetics: it completely absorb orally, protein
binding is 40%, metabolized in liver, excreted in urine.
 Uses: antiarrhythmic agent specially used for the prevention of
paroxysmal supraventricular tachycardias (PSVT), including
atrioventricular nodal reentrant tachycardia, atrioventricular
reentrant tachycardia and other supraventricular tachycardias.
 Brand name: Flecainide Acetate tab. 100mg/1 oral, Tambocor
50mg. Oral.

24.  Indecainide:
 It is rarely used antidysrhythmic. It has local anaesthetic
activity and belongs to the membrane stabilizing (class1) group
of antiarrhythmic agent.
 It has electrophysiological effects characteristics of the IC class
of antiarrhythmic.
 It acts on sodium channel on the neuronal cell membrane,
limiting the spread of seizure activity and reducing seizure
propagation. The antiarrhythmic action are mediated through
effects on sodium channels in purkinje fibers.
 Uses: used for treatment of life threatening dysrhythmias and
sustained ventricular tachycardia.

25.  Lorcainide:
 It is a new type-1 antiarrhythmic drug that is well absorbed
orally, with bioavailability increasing with both dose and
continued administration.
 It is metabolised in liver, and patient with significant liver
disease will require dosage reduction.
 The drug has an active metabolite, norlorcainide, whose
activity is similar to lorcainide but whose half life is 26hrs
instead of 8 hrs for parent compound.
 The long half life of the metabolite and changing
bioavailability of lorcainide requires that a given dose
administered for 1 week for the maximum effect to be
demonstrated.

26.  Propafenone:
 MOA: It reduces fast inward current carried by sodium ions. It
reduces spontaneous automaticity and depresses triggered
activity.
 Pharmacokinetics: Completely absorbed through oral
administration (90%). Systemic bioavailability ranges from 5-
50%, due to significant first pass metabolism, volume of
distribution is 250L, protein binding is 97%, approximately
50% of drug metabolites are excreted in the urine.
 Uses: it prolongs the time to recurrence of proximal atrial
fibrillation/ fllutter (PAF), also used for life threatening
documented ventricular arrhythmias, such as sustained
ventricular tachycardia.

27.  Propranolol:
 It is colourless white powder with bitter taste. Mol. Formula is
C16H22ClNO2.
 MOA: It decreases heart rate, cardiac output and force of
contraction. BP is lowered in hypertensive, produce no effect on
normotensive.
 Indication: Hypertension, angina pectoris, migraine, anxiety,
tachycardia, fallot tetrology.
 Pharmacokinetics: Onset action 30min, peak conc. 1 to 1 1/2hrs,
duration of action 6-12hrs, plasma half life 3-5hrs, metabolized in
liver, crosses placenta, bbb, excreted in breast milk.
 Drug interaction: Propranolol with adrenaline develops
hypertension, bradycardia. Increased hypotension with quinidine,
haloperidol.

28.  Contraindications: Hypersensitivity, cardiac failure, sinus
bradycardia, CHF, with precautions in diabetes, pregnancy,
lactation, renal disease, hypotension, myasthenia gravis, hepatic
disease.
 Side effects: Swelling on face, skin rash, fever, hyperglycemia,
sore throat, dryness of eyes, blurred vision, decreased libido,
vomiting, diarrhoea, night mares, forgetfulness, muscle fatigue,
bad dreams, dry mouth, hepatomegaly.
 Dosge:
 Hypertension: Adult orally 40mg twice daily or 80mg once daily.
 Migranie: Adult 80 mg daily or in divided doses 40mg
 Angina: Adult orally 80mg to 320mg, 80 mg four time a day.
 Dysrhythrmias: Adult 10-30 mg t.i.d. Or four times a day.
 Band names: Propranolol: Tablet ciplar, prop, betacap, betabloc,
inderal, corbeta 10mg, 20mg, 40mg, 80mg.

29.  Acebutolol:
 It is cardioselective beta-adrenergic antagonist with little effect on
the brochial receptors.
 MOA: Activation of beta 1-receptor by epinephrine increases the
heart rate and bp, and heart consume more oxygen. It blocks theses
receptors, lowering the heart rate and bp. This drug has the reverse
effect of epinephrine. In addition beta blockers prevent the release of
renin.
 Indications: Hypertension, ventricular premature beats in adults.
 Pharmacokinetics: well absorbed from GI tract with an absolute
bioavailability of approximately 40%, protein binding is 28%,
elimination via renal excretion is approximately 30-40% and by non
renal mechanism 50-60%, which includes excretion into bile and
direct passage through intestinal wall.
 Brand name: Acebutolol 400mg oral, Monitan 100mg.

30.  Esmolol: is a short acting drug having quick action.
 MOA: It is similar to other bata-blockers.
 Indications: Supraventricular tachycardia,
hypertension.
 Contraindications: Hypersensitivity, cardiac failure,
with precautions in diabetes, pregnancy, lactation,
renal disease, hypotension, children.
 Side effects: Headache, confusion, anxiety,
depression, skin rash, vomiting, fatigue, dry skin,
hypotension, bronchospasm, nausea, heart burn, chest
pain, shortness of breath, alopecia, edema,
constipation, bloating.

31.  Pharmacokinetics: Onset action rapid, duration short,
plasma half life 9 min, metabolized by liver, excreted in
urine.
 Drug interaction: Increased effect with disopyramide,
increased level of esmolol with morphine.
 Dosage: for supraventricular tachycardia (SVT): Adult
initial dose, loading dose 500mcg/kg body weight per
minute, maintenance dose 50mcg/kg per minutes for
four minutes, maximum dose 300mcg/kg per minutes.
 Brand name: Esmolol: Injection Esocard, Netotach,
Miniblock 100mg, 250mg/10ml
 Treatment overdose: Discontinue drug therapy

32.  Amiodarone:
 It is long acting antiarrhythmic drug. It elongate duration of
action and effective refractory period of atria.
 Indications: severe ventricular tachycardia, atrial flutter, atrial
fibrillation.
 Pharmacokinetics: Orally, peak plasma conc. 2-10hrs, plasma
half life 3-8 weeks, metabolized by liver, excreted in urine.
 Contraindications: Hypersensitivity, lactation, pregnancy,
bradycardia, electrolyte imbalance, goitre, AV block.
 Drug interaction: Increased anticoagulant effect with
warfarin, bradycardia with beta blocker, calcium channel
lockers.

33.  Side effects: Headache, microdeposits in cornea, diarrhoea,
hepatotoxicity, tremors, ataxia, insomnia, skin rash, vomiting,
fatigue, skin rash, discolouration of skin (blue, gray), hypotension,
bradycardia, alopecia, edema, flusshing, leg pains, weakness.
 Dosage: 800-1600 mg/day for 1-3 weeks, then 600-800mg daily for
one month, then 200mg three times a day for one week, maintain
maximum effective dose 200mg daily. IV: initially 150mg over 10
min, slow IV.
 Brand name: Amiodarone: Tablet, injection, amiodar, duron,
panaron, tachyra, cardarone 100mg, 200mg tablet, injection
150mg/ml.
 Treatment overdose: Dopamine injection for circulatory
depression, diazepam for convulsion, oxygen respiration.
 Bretylium: this drug was induced in 1960 and used as
antihypertensive. Due to its adverse effect it is not put in use now a
days.

34.  The main action of this group of medicine is to inhibit calcium ion
mediated channel.
 Verapamil:
 MOA: It inhibits calcium ion flow across cell membrane during
cardiac depolarization, produces relaxation of coronary vascular
smooth muscle, dilate coronary arteries, decreases SA AV node
conduction.
 Indication: Chronic coronary insufficiency, angina pectoris,
hypertension, atrial flutter, atrial fibrillation.
 Contraindication: Sick sinus syndrome, cardiovascular shock,
pregnancy, hepatic injury, lactation, children with precautions in
CHF.
 Side effects: Headache, nausea, fatigue, flushing, ankle edema,
hypotension, constipation, anxiety, depression, insomnia, confusion,
weakness.

35.  Pharmacokinetics: Orally onset action variable, peak plasma conc.
3-4 hrs, half life IV 4 min, orally 3-7hrs, duration of action 18-24hrs.
 Drug interaction: Increase hypotension with prazosin, quinidine,
decreased effect of lithium, neurotoxicity is increased with
carbamazepine.
 Dosage: Adult orally 40-80mg three to four times a day maximum
dose 480mg/day, not to exceed 480mg/day. IV: 5mg initially, if
desired effect not obtained further 5mg after 5-10 min, child 1-5 yrs
2-3mg IV, age of child 6-14yrs 2.5-5mg only as onset dose.
 Brand name: Verapamil: Tablet, injection, calaptin, vasopten,
veramil, verap, 40mg, 80mg, 120mg, 240mg tablet, injection 5mg
per 2ml.
 Treatment of overdose: Administer atropine for AV block, for
hypotension give vasopressors.

36.  Diltiazem:
 It is potent coronary dilator.
 MOA: it inhibit calcium ion flow across cell membrane
during cardiac depolarization, produce effect of
relaxation of coronary artery smooth muscles, due to
which coronary arteries dilation occurs, also dilates
peripheral arteries.
 Indication: Hypertension, atrial flutter, atrial
fibrillation, angina pectoris due to coronary
insufficiency.
 Contraindications: children, pregnancy, bradycardia,
sick sinus syndrome. Use with precautions in
pregnancy, lactation, children, hypotension, CHF.

37.  Side effects: Headache, skin rash, ankle edema, flushing,
dizziness, depression, insomnia, weakness, tremors, drowsiness.
 Drug interaction: Elevate serum digoxin cyclosporin,
theophylline level.
 Pharmacokinetics: Orally onset action 30-60min, peak plasma
conc. 2-3 hrs, plasma half life 4-9 hrs, metabolized in liver,
excreted in urine, breast milk.
 Dosage: Adult orally 30mg 2-4 times a day, before meals, at bed
time before meals, slowly increase dose 60-120mg twice daily.
Adult IV 0.25mg/kg body weight over 2-3 min slowly.
 Brand name: Diltiazem: Tablet dicard, dilcor, cardem, angigem,
channel, dilgard, icidil 30mg, 60mg, 90mg tablet.
 Treatment overdose: Give atropine for AV block, for
hypotension gives vaspressor.

38. Thank you