1 drugs acting on cardiovascular system

Drugs acting on Cardiovascular system

The drugs acting on cardiovascular system are divided into four groups: Cardiotonic drugs Anti-hypertensive drugs Anti-arrhythmic drugs Anti-anginal drugs

Cardiotonic drugs

Drugs which increase the force of contraction of the heart, are called cardiotonic drugs.

Classification:

1. Cardiac glycosides 3. Anticholinergic drugs – Digoxin -Atropine– Digitoxin -Scopolamine

2. Sympathetic drug 4. Xanthines-Adrenaline -Theophylline

-Dopamine -Theobromine

-Isoprenaline

Cardiac glycosides

• Cardiac glycosides are those glycosides which have specific action to the failing heart.

• Increase the force of contraction of failing heart and lower the heart rate and thereby maintain an effective circulation.

• Classification of cardiac glycosides:Natural

A). Plant source– From leaves of foxgloves:

• Digitalis purpurea: Digoxin, Digitoxin• Digitalis lanata: Digoxin, Lanatoside-C

– From the seeds of foxgloves:• Strophanthus kombe: Cymarin, Cymarol• Strophanthus gratus: Ouabain squill

B) Animal source: Toad venom: BufotoxinSynthetic:

-Digitoxigenin

-Digoxigenin

-Gitoxigenin

Digitalis

• Digitalis is a powerful inhibitor of Na+/K+ ATPase. As a result they increase the efficiency of failing heart increasing Na+ concentration within cell membrane;which enhances Ca++ availability to the contractile apparatus and increase the contractility.

Mechanism of action: • It alters ion transport system by inhibiting membrane

bound enzyme Na+/K+ ATPase, which is associated with Na+ pump. So– It decreases active transport of Na+ out of the cell

increasing intracellular Na+ concentration; this in turn decreases Ca++ transport out of cell.

– Release of stored Ca++ from the sarcoplasmic reticulum increases.

– Permeability of Ca++ increases. The net effect is increased intracellular Ca++ ions which increases the force of contraction of the cardiac muscles.

• Pharmacological actions: Cardiac effects:

On normal heart– Direct positive inotropic action– Decrease heart rate so decrease cardiac output– Increase systolic and mean systemic arterial pressure

due to direct arteriolar contraction– Decrease central venous pressure

On failing heart– Direct action: Positive inotropic action– Indirect action: decrease sinus rate, so decrease

heart rate

• Extra-cardiac effects:1. Kidneys:

– Diuresis(due to increase renal perfusion)– oedema(due to aldosterone antagonism)

2. Eye: Xanthopsia (appearance of yellow-green tings cause visual disturbance

3. CNS: paraesthesia, toxic psychosis4. Blood vessels: vasoconstriction, venodilation5. GIT: anorexia, nausea, vomiting6. Gynaecomastia (due to prolonged use)

Indications of Digitalis:

1. Congestive heart failure due to ischemia, hypertensive or valvular heart disease.

2. Atrial fibrillation

3. Atrial flutter

4. Paroxysmal supraventricular tachycardia

5. Left ventricular failure

Contraindications – Digitalis toxicity– CVS

• Recent myocardial infarction• Heart block• Arrhythmia

– renal impairment – Hepatic failure– Electrolyte imbalance specially hypokalaemia

and hypocalcaemia

• Digitalisation: Subjection of a patient to the action of digitalis is called digitalisation.

• Cautions:– Therapeutic index of digitalis is low ( therapeutic

dose is very near to toxic dose)– The dose of digitalis should be individualized.– Danger signs of digitalis toxicity after initial dose

are: nausea, vomiting, sinus bradycardia (HR<60beats per min)

• Digitalisation is done by three ways:1. Emergency digitalisation2. Rapid digitalisation3. Slow digitalisation Total digitalisation dose (TDD):

It is the initial loading dose of digoxin.-Oral route: 0.75-1.25mg-i/v route: 0.5-1mg

• Maintenance dose: Oral route: 0.125-0.5mg i/v route: 0.25mg

Anti-hypertensive drugs

• Hypertension: Persistent rise of blood pressure above the upper limit of normal level according to the age and sex of the individual is called HYPERTENSION (HTN)

• Normal limits of blood pressure:– Systolic: 100-140 mm Hg(120±20)– Diastolic: 60-90 mm Hg (75±15)

Causes of hypertension:• Primary hypertension (90-95%):

– also called as essential hypertension– Unknown etiology or idiopathic

• Secondary hypertension(5-10%):– Renal disease– Endocrine diseases (Conn’s disease, acromegaly,

Phaeochromocytoma)– Cushing's disease– Vascular causes (renal artery stenosis, coarctation of aorta)– Drugs (sympathomimetics, NSAIDs, contraceptive pills, steroids

• Risk factors:– Age– Hereditary– Anxiety– Obesity and lack of

exercise– Alcohol consumption– Salt intake

• Special patient groups– Race– Elderly– Diabetes– Renal disease– Stroke– Pregnancy– Hormone replacement

therapy – Oral contraceptives

Management of hypertension

Non-pharmacologic approaches: Weight reduction in obese patients: reduces

about 2.5/1.5 mm Hg per kg wt. lost Restriction to salt intake: not more than 6 g NaCl Dietary considerations: legumes, fresh fruits and

vegetables, whole grains Regular exercise Restricted alcohol intake Smoking cessation to reduce cardiovascular risk

Pharmacologic approach: Classification: A. Diuretics:

– Carbonic anhydrase inhibitors : acetazolamide – Loop diuretics: Furosemide, ethacrynic acid , mercurials – Thiazide diuretics: Hydrochlorthiazide– Potassium sparing: amiloride , triamterene, spironolactone– Osmotic diuretics : mannitol

B. Sympatholytics:– Centrally acting: Methyl-dopa, Clonidine– Beta-blockers: Atenolol, Propranolol, Metoprolol– Alpha-blockers: Prazosin, Phentolamine– Adrenergic neuron blockers: Guanethidine, Reserpine

C. Direct vasodilators:• Arteriolar dilators

• Diazoxide• Hydralazine• Minoxidil• Prazosin

• Vasodilators (non-selective)• Nitroprusside• Prazosin

D. Calcium Channel blockers:– Nifedipine– Verapamil– Diltiazem

E. Angitensin converting enzyme (ACE) inhibitors:– Captopril– Enalapril– Lisinopril– Ramipril

α-Methyl dopa

• It is useful in treatment of mild to moderately severe hypertension.

• It reduces the BP chiefly by reducing peripheral vascular resistance.

• It inhibits noradrenaline synthesis: DOPA Dopamine DOPA decarboxylase α-methyl dopa methyldopamine α methyl- noradrenaline

• Remains inside the vesicles and released in the same way as noradrenaline.

Mechanism of Action

• α-Methyl dopa forms false neurotransmitter α-Methyl noradrenaline which combines with α-adrenoceptors present in the surface of the lower brain stem, inhibiting the neurons of nucleus of tractus solitarius of vagus which in turn decrease central and peripheral sympathetic activities resulting in decreased BP.

• It also inhibits the decarboxylation of DOPA and 5-HT, thus decreased sympathetic tone.

• It also directly reduces renin activity which is responsible for conversion of angiotensin-I to angiotensin-II thereby reducing BP.

• Pharmacokinetics:– Well absorbed from the GIT– Half-life: 1.5 hrs– Antihypertensive effects; 4-6 hrs– Effective twice daily– Dose: 1-2 g in divided doses

• Indications:– Moderate to severe hypertension– Hypertensive crisis– Pheochromocytoma– Malignant carcinoid

• Adverse effects:– Mental symptoms (sedation, lassitude, vertigo)– Electrolyte imbalance– Thrombocytopenia– Headache– Psychic depression– Lactation– Dryness of mouth– Oedema– Postural hypotension– Allergic reaction

Unique side effects:• Flushing of skin• Failure of ejaculation• Depression• Hemolytic anemia• Granulocytopenia• Hepatic disturbance

Clonidine

• It is centrally acting sympatholytic agent (α2 adrenoceptor agonist) and acts by decreasing central sympathetic activity.

• Mechanism of action: It combines with α2 –receptors of lower brainstem which in turn inhibits release of noradrenaline from the neurons. It decreases sympathetic activity which results in decreased cardiac output due to decrease heart rate and relaxation of capacitance vessels. Thus BP is decreased.

Pharmacological actions of Clonidine:1. CNS: suppress sympathetic outflow2. CVS: decrease heart rate; decrease CO3. Blood vessels: reduction in resistance and relaxation of

capacitance vessels

Indications:4. Hypertension5. Prophylaxis of migraine6. Diagnosis of pheochromocytoma

• Adverse effects:– Sedation– Dry mouth– Drowsiness– Rebound hypertension

• Pharmacokinetics of Clonidine:– Bioavailability: 75%– Half-life : 8-12 hours– Excretion: half of the drug excreted unchanged– Dose: 0.2 and 1.2 mg/day

• Sudden withdrawal effects: It can result in life threatening crisis. Patient exhibit

nervousness, tachycardia, headache and sweating if one or two dose is omitted.

Note: sudden withdrawal of the drug must be avoided. If required should be done gradually.

Calcium channel blockers

• Calcium is the chief ion required for– Cardiac contraction– Smooth muscle contraction– Propagation of cardiac impulse

• Classification of Ca++ channel blockers1. Dihydropyridine family:

– Nifedipine – Nicardipine– Nisoldipine– Amlodipine– isradipine

2. Miscellaneous:– Verapamil– Deltiazem– Bepridil

• General pharmacokinetics for Ca++ channel blockers – Orally administered– Highly protein bound– Hepatic first pass metabolism– Renal excretion

• Mechanism of action: Calcium channel blockers bind with voltage

dependent Ca++ channel (L-type) in depolarised membrane. The resultant effect is relaxation of the smooth muscles and negative ionotropic and chronotropic action in the heart.

• Pharmacological action of Calcium channel blockers1. CVS:

1. Dilates main coronary vessels: improves myocardial perfusion2. Negative chronotropic effect: cardiac slowing and AV block3. Negative ionotropic effect: decrease force of contraction 4. Vasodilation: decrease total peripheral resistance Smooth

muscles• Smooth muscles:

1. Vascular smooth muscle: generalized relaxation2. Coronary vasodilation: antianginal action3. Visceral smooth muscle: relaxation of biliary tract; uterus and

bladder.

• Indications: 1. Angina pectoris (variant)2. Hypertension3. Cardiac arrhythmias4. Prevention of ischemic neurological damage due

to subarachnoid damage5. Raynaud’s disease6. Migraine7. Premature labour

• Contraindication:– Heart failure– Bradycardia– Second or third degree AV block– Sick sinus syndrome– Wolf Parkinson-White syndrome

• Adverse effects:• Due to vasodilation:

– Postural hypotension, reflex tachycardia– Bradycardia, palpitation– Headache, flushing, dizziness, ankle edema

• Gastrointestinal– Constipation– Nausea, vomiting– Gum hypertrophy

ACE-Inhibitors

• Angiotensin converting enzyme (ACE) inhibitors are :– Captopril– Enalapril– Lisinopril– Ramipril

• ACE inhibitors act by inhibiting the conversion of angiotensin I to angiotensin II; which is a powerful vasoconstrictor. It acts preferably on angiotensin sensitive vascular bed of kidney, brain and brain.

Mechanism of Action

• It inhibits the conversion of angiotensin I to angiotensin II, thus vasoconstrcitive action of angiotensin II is inhibited.

• Also ACE causes inactivation of bradykinin (vasodilator peptides) but in presence of ACE inhibitors bradykinin is active and causes vasodilation which in turn decrease TPR and finally BP.

Pharmacological actions

1. Vasodilation (reduction of TPR)2. Reduce preload and afterload 3. Reduction in the secretion of aldosterone so

decreased salt and water retention.4. Increase in renal blood flow.

Indications

• Hypertension• Renovascular hypertension due to excess renin• Malignant hypertension• Hypertensive crisis of scleroderma• End stage renal disease

• Refractory heart failure• Ischemic heart disease

Adverse effects

• First dose hypotension• Dry cough• Angioneurotic oedema• Hyperkalaemia• Loss of appetite• Stomatitis• Abdominal pain• Neutropenia• Proteinuria• Blood disorders

Contraindications

• Systolic blood pressure < mm Hg• Bilateral renal artery stenosis• Second and third trimester of pregnancy• Renal failure

Angiotension receptor blockers

• These are the agents that act on the angiotensin type I (AT1) receptor.

• Drugs:– Losartan– Valsartan– Candesartan– Eprosartan– Irbesartan– Telmisartan

• Unique features of ARBs from ACE-inhibitors:– These agents are unique from ACE –inhibitors in

that they don’t have effect on bradykinin.– They cause more complete inhibition of

angiotensin action because besides ACE other enzymes are present which can angiotensin II.

Losartan:

Mechanism of action: It causes antagonism in the angiotensin receptor thus causing a complete blockade of angiotensin II activity.

Pharmacokinetics:– Orally administered– Extensively metabolized; metabolites retain

activity– Plasma half-life: 2 hrs– Dose: 50 mg/d; can range from 25-100 mg/d

• Indications:– Hypertension

• Adverse effects: similar to ACE-inhibitors except that no angioedema and cough is present; both of which are mediated via bradykinin.

• Contraindications: – pregnancy

• Saralasin is an analog and competitive inhibitor of angiotensin II at its receptors.

• It also blocks the pressor and aldosterone releasing effect of infused angiotensin II and reduce blood pressure in high renin activity state such as renal artery stenosis.

• It has been withdrawn from market due to its unpredictable pharmacological outcomes.

Vasodilators

• Drugs:1. Oral vasodilators:

• Hydralazine • Minoxidil

2. Parenteral vasodilators:• Nitroprusside• Diazoxide• Fenoldopam

• Mechanism of action : This class of compounds cause the dilation of arteries or both arteries and veins; thus reducing overall peripheral resistance and in turn decreases the blood pressure.

• Hydralazine: – It is a hydrazine derivative and is known to dilate arterioles only

but not veins.– It causes tachyphylaxis to hypertensive effects developed rapidly.– It can be used in combination.

• Pharmacokinetics:– Orally administered– Extensive 1st pass metabolism– Low bioavailability– Half-life 2-4hrs– Dose: 40-200mg/day.

• Adverse effects:– Headache– Nausea– Anorexia– Palpitations– Seating – Flushing– Systemic lupus erythrematosus (SLE)

• Minoxidil– Orally active; half life-4hrs; 5-10mg/d in two doses– Vasodilation results due to opening of K+ ions

which brings the membrane to hyperpolarized state, producing relaxation.

– It also dilates arterioles but not veins.– Headache, sweating and hypertrichosis,

tachycardia and angina and edema are side effects

• Fenoldopam: • It is indicated for severe hypertension and

postoperative hypertension.• Acts as Dopamine (D1 receptors) agonist

resulting dilation of peripheral ateries.• Given parenterally (i.v. infusion); extensively

metabolized and very short half-life of 5 mins.• Very small dose of 0.025-0.05µg/kg/min.

Individualised care approach Calcium channel blockers :

Suited for :1) Elderly 2) Isolated systolic

hypertension3) Asthma/COPD patients 4) Raynauds disease/

migraine5) Pregnant hypertensive

Avoid in :1) CHF2) Conduction defects 3) Patients receiving beta

blockers 4) IHD/ post MI5) Left ventricular hypertrophy6) Males with enlarged

prostate 7) GERD

ACE Inhibitors • Suited for :1) High renin cases or those on low

salt 2) Physically active 3) Diabetics/ with nephropathy 4) Co existing angina / post MI

cases5) Coexisting Left ventricular failure

/ left ventricular hypertrophy6) Gout/PVD?Dyslipidemic patients

• Avoided in :1) Bilateral renal artery

stenosis 2) Pregnancy 3) Hyperkalemia 4) Pre existing dry cough

Beta adrenergic blockers • Suited for :1) Angina or post MI cases 2) Coexisting anxiety or

techycardia 3) Non obese high renin

hypertensive 4) Pregnancy

• Avoided in :1) CHF2) Bradycardia , conduction

defects 3) Asthma / PVD 4) Diabetic or borderline

glucose tolerance 5) Abnormal lipid profile 6) Patient to remain physically

active

Diuretics :• Suited for :1) Elderly patients 2) Low renin hypertensive 3) Isolated systolic

hyeprtension 4) Obese with volume

overload 5) Renal disease with salt

retention 6) Low cost therapy

• Avoided in :1) Young active hypertensive 2) Diabetes 3) Gout 4) Abnormal lipid profile 5) Pregnancy induce

hypertension

Combination therapy

1) Drugs increasing renin activity ( diuretics . Vasodilators ,

CCBs, ACE inhibtors ) with drugs having low renin activity ( beta blockers , clonidine , methyl dopa )

2) Drugs causing fluid retention( adrenergic blockers except

beta blockers ) with diuretics3) Drugs causing tachycardia ( hydralazine , DHPs)

with non selective beta blockers 4) ACE inhibitors / AT1 blockers with diuretics 5) CCB with diuretics6) Beta blocker + prazosin

• Combinations to be avoided :1) Adrenergic blocker with clonidine 2) Hydralazine with prazosin3) Verapamil/diltiazem with beta blocker 4) Methyl dopa + clonidine

Hypertension in pregnancy

Suitable drugs 1) Methyl dopa 2) Hydralazine 3) Dihydropyridine CCBs4) Cardioselective adrenergic

blockers ( atenolol, pindolol, acebutolol)

5) Prazosin 6) Clonidine

Drugs to be avoided 1) Diuretics 2) ACE inhibitors 3) Reserpine 4) Non selective beta blockers 5) Sod nitroprusside

ABCD method of drug sequencing

Younger and non black • Step 1 : AOlder and black • Step 1: C or D • Step 2: A+ c or D • Step 3 : A+C+ D • Step 4 : Add alpha blocker or spironolactone

or Beta blocker

Diabetes

• First line therapy :Type 1 : monotherapy :ACE inhibitors / AT1 blockers Combination : + beta blockers / CCBs / thiazides/

alpha blockers Type 2 :ACE inhibitors / AT1 blockers / CCBs

Renal disease

• ACE inhibitors • Thiazide diuretics not used in severe renal

impairment, instead loop diuretics are used

Anti-anginal drugs

• Angina pectoris– It is a clinical syndrome characterized by pre-cardiac

pain or discomfort due to myocardial ischemia, which is precipitated by exercise and relief by rest or sublingual nitro-glycerine.

– It occurs when coronary blood flow is insufficient to meet the metabolic requirement of the heart muscle.

– Myocardial oxygen demand mainly depends on• Preload,• After load and • Heart rate

• atherosclerotic angina, classic angina(angina of effort)

• vasospastic or variant angina(Prinzmetal's angina)

• Unstable angina

Determinants of Myocardial Oxygen Consumption.

• Wall stress• Intraventricular pressure• Ventricular radius (volume)• Wall thickness• Heart rate• Contractility

Regulation of smooth muscle contraction and relaxation

1) Increasing cGMP: dephosphorylation of myosin light chains, nitric oxide

2) Decreasing intracellular Ca2+:3) Stabilizing or preventing depolarization of the

vascular smooth muscle cell membrane: increase the permeability of K+ channels,

4) Increasing cAMP in vascular smooth muscle cells: cAMP increases the rate of inactivation of myosin light chain kinase

• Drugs:Organic nitrites and nitrates:

– Nitrites: sodium nitrite, amy-nitrite, octyl-nitrite– Nitrates: glyceryl trinitrate, isosorbide dinitrate

and isosorbide mononitrateCalcium channel blockers:

– Nifedipine– Verapamil– deltiazem

Beta-adrenoceptor blockers– Atenolol– Propranolol– Oxaprenolol

Xanthines:– Theophylline– Aminophylline

Miscellaneous– Dipyradimol

Drugs or Drug Groups under Investigation for Use in Angina.

• Metabolic modulators:eg, ranolazine• Direct bradycardic agents, eg, ivabradine• Potassium channel activators, eg, nicorandil• Rho-kinase inhibitors, eg, fasudil• Sulfonylureas:eg, glibenclamide• Thiazolidinediones/glitazones• Nitric oxide donors: eg, L-arginine• Capsaicin• Amiloride

Organic nitrates

• Pharmacokinetics of organic nitrates:• Glyceryl trinitrate is a short-acting• Undergoes 1st pass metabolism if given orally• Given sublingually usually 500mg tab/day• Onset of action within 15-30 mins• Duration:20-30mins• Used mainly in acute attack.

• Isosorbide di-and mono-nitrates are long acting

• Orally given• Systemic availability more than GTN• Used in prophylaxis.

Mechanism of action:

Organic nitrates act by relaxing smooth muscles of blood vessels. It occurs in following steps:

1. Denitration of org. nitrates ( org nitrates into inorganic)

2. Inorganic nitrates converted to NO (like EDRF)3. Activation of guanylyl cyclase i.e. raised cGMP4. Reduces intracellular Calcium concentration5. Relaxation of vascular smooth muscles

• Pharmaclogical actions:• CVS:

– Reduces preload (due to venodilation)– Reduces afterload (due to generalized vasodilation)– Dilates coronary arteries and increase blood flow to

ischemic areas• Others:

– Relaxation of bronchial smooth muscle– Relaxation of GIT smooth muscle i.e. decreased motility– Relaxation of smooth muscle of biliary tract, urethra and

uterus.

• Indications:– Angina pectoris– Congestive heart failure– Myocardial infarction

• Adverse effects:– Flushing of face– Throbbing headache– Postural hypotension– Syncope– Nitrate tolerance

• Contraindication:– Organic nitrate intolerence– Angina due to severe anemia– High intra-cranial pressure– Glaucoma– Migraine

• Nitrate tolerance:• During long term use , the nitrate effects is

gradually lowered and finally resulting in partial or complete loss of its benefit.

• Mechanism is reduced production of cGMP in vascular smooth muscles.

• Nitrate free period of 1-2 hours every 24 hrs helps prevent development of tachyphylaxis.

Anti-arrhythmic drugs

• Cardiac arrhythmias: The disorder in rate and rhythm of cardiac

contraction due to myocardial damage is known as cardiac arrhythmias.

• Cardiac arrhythmias consist of cardiac depolarizations that deviate form the normal in one or more aspects;– Abnormality at site of origin of impulse– Its rate and regularity– Its conduction

• Vaughan Williams classificationClass-I: Na+ channel blocker

Group A: Quinidine Procainamide Disopyramide Pharmacological actions:– Membrane stabilizing action– Prolongs refractory period– Prolongs action potential

Group B: Lidocaine Mexiletine Tocainide PhenytoinMembrane stabilizing actionShortens refractory periodShortens action potential

Group C: Flecainide EncanideMembrane stabilizing actionNo effect on action potential

Class-II drugs: β-blockers (counteracts catecholamines)

Propranolol Atenolol Metoprolol SotalolAbolish SA firingDecrease contractilityIncrease AV refractoriness

Class-III drugs: Repolarization prolonging Amidarone BretyliumProlongs refractory periodProlongs action potentialPrevents re-entry rhythm

Class-IV drugs: Calcium channel blockers Verapamil Deltiazem Inhibits slow Calcium channelsDepress contractility of AV node.

Quinidine

• It is a class-I anti-arrhythmic drug. It is an optical isomer of quinine (anti-malarial drug).

Pharmacokinetics:– Orally active; i.v. in emergency; i.m. painful– 80% bound to plasma proteins– Half-life: 4-6 hrs– Metabolized by liver (75%)– Excretion: unchanged fraction by kidney

Pharmacological actions of quinidine:– Cardiac tissue:

• Reduce automaticity• Reduce excitability• Reduce conductivity• Prolong refractory period• Reflex tachycardia

– Other action:• Anti-malarial• Anti-pyretic• Decrease B.P (vasodilation)

• Adverse effects:– Heart block– Sinus arrest– Myocardial depression– Q-T prolongation– Ventricular fibrillation– Nausea – Vomiting– Diarrhoea – Rash – Oedema

• Indications:• As anti-arrhythmic used in,

– Atrial fibrillation and flutter– Ventricular fibrillation and flutter– Paroxysmal supra-ventricular tachycardia– Premature supra-ventricular tachycardia– Atrial, nodal and ventricular premature beats

• Also as anti-malarial• Anti-pyretic• During digitalis therapy

• Cinchonism:– Headache, vertigo– Blurred vision– Tinnitus

• Contraindications:– Quinidine intolerance– Digitalis intoxication– Heart failure– Hypotension– hypokalemia

• Propranolol as anti-arrhythmic drug:– It blocks β-receptors in heart, thereby exerts

• Negative inotropic effect• Negative chronotropic effect• Depress atrioventricular conduction• Depresses automaticity

– It has:• Anti-arrhythmic effect• Anti-hypertensive effect• Anti-anginal-effect in CVS.

Lidgnocaine

• It is a local-anesthetic agent.• Can terminate arrhythmia if quinidine fails• Parenteral administration: i.v./i.m

Indications:– As local anesthetic– As anti-arrhythmic

• Mechanism of anti-arrhythmic effect of lignocaine:– It has membrane stabilizing effect by blocking

both activated and inactivated sodium channels; which in turn supresses SA node and also ectopic beats.

– Shortens refractory period and action potential; make uniform rhythm

• Adverse effects:– Bradycardia– Hypotension– Dizziness– Blurred vision– Sleepiness– Confusion– Convulsion