Cardiac Glycosides Cardiac Glycosides

Department of Department of Pharmacology NEIGRIHMSPharmacology NEIGRIHMS

Shillong, IndiaShillong, India

Cardiac Glycosides - IntroductionCardiac Glycosides - Introduction

Drugs having the cardiac ionotropic Drugs having the cardiac ionotropic property – increase in force of contractionproperty – increase in force of contraction– They increase the myocardial contractility and They increase the myocardial contractility and

improves cardiac output without proportionate improves cardiac output without proportionate increase in Oxygen consumptionincrease in Oxygen consumption

– Do not increase the heart rateDo not increase the heart rate Digitalis is the genus name for the family Digitalis is the genus name for the family

of the plants that provide most of the of the plants that provide most of the medically useful cardiac glycosides - medically useful cardiac glycosides - DigoxinDigoxin

Sources - Cardiac glycosidesSources - Cardiac glycosides

Cardenolides and BufadienolidesCardenolides and Bufadienolides Digitalis purpurea – Digitoxin, Gitoxin and Digitalis purpurea – Digitoxin, Gitoxin and

GitalinGitalin Digitalis lanata - Digitoxin, Gitoxin and Digitalis lanata - Digitoxin, Gitoxin and

DigoxinDigoxin Strophanthus gratus – OuabinStrophanthus gratus – Ouabin Thevetia nerifolia – ThevetinThevetia nerifolia – Thevetin Convallaria majalis – ConvallotoxinConvallaria majalis – Convallotoxin Bufo vulgris - BufotoxinBufo vulgris - Bufotoxin

Images of Cardiac GlycosidesImages of Cardiac Glycosides

Digitalis purpurea Digitalis lanata

Strophanthus gratus

Images of Cardiac GlycosidesImages of Cardiac Glycosides

Urginea maritima Thevetia nerifolia

Convallaria majalis

ChemistryChemistry All Cardiac glycosides All Cardiac glycosides

– aglycone aglycone (genin) part (genin) part (active (active pharmacologically)pharmacologically)

– sugar sugar (glucose or (glucose or digitoxose) attached at digitoxose) attached at Carbon 3 of nucleusCarbon 3 of nucleus

Aglycone – Steroid Aglycone – Steroid ring ring (cyclopentanoperhydr(cyclopentanoperhydrophenanthrene ring) ophenanthrene ring) and lactone ring and lactone ring attached at 17attached at 17thth position position

Cardiac glycosides - Cardiac glycosides - PharmacokineticsPharmacokinetics

Absorption and Distribution:Absorption and Distribution:– Cardiac glycosides vary in their absorption, distribution, metabolism Cardiac glycosides vary in their absorption, distribution, metabolism

and excretion characteristicsand excretion characteristics– Presence of food in stomach delays absorption of Digoxin and DigitoxinPresence of food in stomach delays absorption of Digoxin and Digitoxin– Digitoxin is the most lipid solubleDigitoxin is the most lipid soluble– Vd of Cardiac glycosides are very highVd of Cardiac glycosides are very high– All are concentrated in heart, skeletal muscles, liver and kidneyAll are concentrated in heart, skeletal muscles, liver and kidney

Metabolism:Metabolism:– DigitoxinDigitoxin is partly metabolized in liver and excreted in bile is partly metabolized in liver and excreted in bile– Cardioactive metabolite (digoxin) and other metabolites are Cardioactive metabolite (digoxin) and other metabolites are

reabsorbed in gut wall - reabsorbed in gut wall - enterohepatic circulation – long half lifeenterohepatic circulation – long half life– No relation with renal impairment No relation with renal impairment – DigoxinDigoxin is primarily excreted unchanged in urine and rate of excretion is primarily excreted unchanged in urine and rate of excretion

parallels creatinineparallels creatinine– So, renal impairment and elderly – long half lifeSo, renal impairment and elderly – long half life– All CGs are cumulative – steady state is attain after 4 half livesAll CGs are cumulative – steady state is attain after 4 half lives

Cardiac glycosides - Cardiac glycosides - PharmacokineticsPharmacokinetics

* Ouabain is administered parenterally and is excreted unchanged in urine

Pharmacological Actions on HeartPharmacological Actions on Heart

Acts on Failing Heart:Acts on Failing Heart: What is a failing Heart ??? What is a failing Heart ???

– Inability of the heart to pump sufficient Inability of the heart to pump sufficient blood to meet the metabolic demands of blood to meet the metabolic demands of the bodythe body

– Reduced efficiency of the heart as a Reduced efficiency of the heart as a pumppump

Contd. ---Contd. ---

•Starling`s law•Laplace`s law

Pharmacological actions on HeartPharmacological actions on Heart

Direct Effect on Myocardial contractility, and Direct Effect on Myocardial contractility, and electrophysiological properties and also has electrophysiological properties and also has vagomimetic effectvagomimetic effect

Force of contraction:Force of contraction:– Dose dependent increase in force of contraction in Dose dependent increase in force of contraction in

failing heart – positive ionotropic effectfailing heart – positive ionotropic effect– Systole is shortened and prolonged diastoleSystole is shortened and prolonged diastole– Contracts more forcefully when subjected to increased Contracts more forcefully when subjected to increased

resistanceresistance– Increase in cardiac output – complete emptying of failed Increase in cardiac output – complete emptying of failed

and dilated heartand dilated heart Tone:Tone:

– Decrease end diastolic size of failing ventricleDecrease end diastolic size of failing ventricle– Reduction in oxygen consumptionReduction in oxygen consumption

Contd. ---Contd. ---

Rate and Conduction: Rate and Conduction: 1.1. BradycardiaBradycardia2.2. Slowing of impulse generation (SAN)Slowing of impulse generation (SAN)3.3. Delay of conductivity of AVNDelay of conductivity of AVN

Direct depressant action on SA and AV Direct depressant action on SA and AV nodes (extravagal)nodes (extravagal)

Increase in vagal tone:Increase in vagal tone:– Is due to improvement in circulationIs due to improvement in circulation– Also due to direct stimulation in vagal center, Also due to direct stimulation in vagal center,

sensitization of baroreceptors and sensitization of baroreceptors and sensitization of SA node to Achsensitization of SA node to Ach

Contd. ---Contd. ---Str

oke

Volu

me

Preload

Normal

Digitalis

CHF

Contd. ----Contd. ----

Digitalis – Electrophysiological Digitalis – Electrophysiological actionsactions

Electrophysiological actions – Electrophysiological actions – contd.contd.

Mainly via 2 actions – autonomic and direct actionMainly via 2 actions – autonomic and direct action Direct action: Direct action:

– At therapeutic dosesAt therapeutic doses Early brief prolongation of action potentialEarly brief prolongation of action potential Followed by period of shortening of action potential – mainly platue Followed by period of shortening of action potential – mainly platue

phasephase Shortening of action potential contributes to shortening of Shortening of action potential contributes to shortening of

refractoriness of atria and ventricles – excitability increasesrefractoriness of atria and ventricles – excitability increases– At higher dosesAt higher doses

Reduced resting membrane potential – less negativeReduced resting membrane potential – less negative Extrasystoloes – oscillatory afterpotentials appear following normal Extrasystoloes – oscillatory afterpotentials appear following normal

action potentialsaction potentials In the event of below threshold action potentials (less negative) – In the event of below threshold action potentials (less negative) –

afterpotentials interfere with normal conductionafterpotentials interfere with normal conduction At further stage – after potentials themselves reach the threshold At further stage – after potentials themselves reach the threshold

to elicit action potential (ectopic beat) coupled with preceding to elicit action potential (ectopic beat) coupled with preceding normal onenormal one

Afterpolarization actions - ouabinAfterpolarization actions - ouabin

Digitalis – Electrophysiological Digitalis – Electrophysiological actionsactions

Autonomic actions:Autonomic actions:– Involves both Parasympathetic and Involves both Parasympathetic and

sympathetic systemssympathetic systems– At therapeutic doses – cardio selective At therapeutic doses – cardio selective

parasympathomimetic actionparasympathomimetic action– Sensitization of baroreceptors, central vagal Sensitization of baroreceptors, central vagal

stimulation and falicitation of muscarinic stimulation and falicitation of muscarinic transmission at cardiac muscle cellstransmission at cardiac muscle cells

– More prominent action in atria and AV nodal More prominent action in atria and AV nodal function than purkinje fibersfunction than purkinje fibers

– However sympathetic action is increased in However sympathetic action is increased in toxic dosestoxic doses

Digitalis – Electrophysiological Digitalis – Electrophysiological actionsactions

Digitalis action – Blood vesselsDigitalis action – Blood vessels

Mild vasoconstrictor in Normal individualsMild vasoconstrictor in Normal individuals In CHF – compensated by improvement of In CHF – compensated by improvement of

increased in cardiac outputincreased in cardiac output No prominent action in Systolic and No prominent action in Systolic and

diastolic BP – no contraindication in diastolic BP – no contraindication in hypertensiveshypertensives

No significant action on coronary vesels – No significant action on coronary vesels – not contraindicated in patient with not contraindicated in patient with coronary artery diseasecoronary artery disease

Digitalis – mechanism of actionDigitalis – mechanism of action

Inhibition of Na/K Inhibition of Na/K ATPaseATPase

blunting of Cablunting of Ca2+2+ extrusion extrusion

CaCa2+2+ sarcomere sarcomere

shorteningshortening

Digitalis action – other tissuesDigitalis action – other tissues Kidney: Kidney:

– Diuresis due to the improvement of circulationDiuresis due to the improvement of circulation– No diuresis in Normal personsNo diuresis in Normal persons

Other smooth muscles:Other smooth muscles:– Inhibition of Na+/K+ ATPase – increased spontaneous Inhibition of Na+/K+ ATPase – increased spontaneous

activity – anorexia, nausea, vomiting and diarrhoeaactivity – anorexia, nausea, vomiting and diarrhoea CNS:CNS:

– No major visible action in therapeutic dosesNo major visible action in therapeutic doses– High doses – stimulation of CTZ - nausea and vomitingHigh doses – stimulation of CTZ - nausea and vomiting– Toxic doses – central sympathetic stimulation, mental Toxic doses – central sympathetic stimulation, mental

confusion, disorientation and visual disturbanceconfusion, disorientation and visual disturbance

Digitalis – Adverse effectsDigitalis – Adverse effects Cardiac and Extracardiac:Cardiac and Extracardiac: Extracardiac:Extracardiac:

– GIT: nausea, vomiting and anorexia etc.GIT: nausea, vomiting and anorexia etc.– CNS: CTZ stimulation, headache, blurring of CNS: CTZ stimulation, headache, blurring of

vision (Flashing light, Altered color vision), vision (Flashing light, Altered color vision), mental confusion etc.mental confusion etc.

– Serum Electrolyte: KSerum Electrolyte: K++ : Digitalis competes for K : Digitalis competes for K binding at Na/K ATPasebinding at Na/K ATPase

Hypokalemia: increase toxicityHypokalemia: increase toxicity Hyperkalemia: decrease toxicityHyperkalemia: decrease toxicity

– MgMg2+2+ : Hypomagnesemia: increases toxicity : Hypomagnesemia: increases toxicity– CaCa2+2+ : Hypercalcemia: increases toxicity : Hypercalcemia: increases toxicity

Digitalis – Adverse effectsDigitalis – Adverse effects

Cardiac:Cardiac: PSVT: Proprnolol IV or oralPSVT: Proprnolol IV or oral AV block: Atropine - 0.6 to 1.2 mg IMAV block: Atropine - 0.6 to 1.2 mg IM Ventricular arrhythmia: Excessive Ventricular arrhythmia: Excessive

ventricular automaticity: Lidocaine IV (or ventricular automaticity: Lidocaine IV (or Phenyton)Phenyton)

Tachyarrythmias: Heart rate abnormally Tachyarrythmias: Heart rate abnormally increased due to prolong diuretic and increased due to prolong diuretic and digitalis therapy – Potassium chloride digitalis therapy – Potassium chloride 20m.mol IV20m.mol IV

Digitalis – Common Drug Digitalis – Common Drug interactionsinteractions

Diuretics: Hypokalaemia (K+ Diuretics: Hypokalaemia (K+ supplementation required)supplementation required)

Calcium: synergizes with digitalisCalcium: synergizes with digitalis Adrenergic drugs: arrhythmiaAdrenergic drugs: arrhythmia Propranolol and CaPropranolol and Ca++++ channel channel

blockers: depress AV conduction and blockers: depress AV conduction and oppose positive ionotropic effectsoppose positive ionotropic effects

Digitalis - contraindicationsDigitalis - contraindications

Hypokalemia: ToxicityHypokalemia: Toxicity WPW syndrome: VF may occurWPW syndrome: VF may occur Elderly, renal or severe hepatic Elderly, renal or severe hepatic

disease: more sensitive to digitalisdisease: more sensitive to digitalis Diastolic dysfunction of heartDiastolic dysfunction of heart Partial AV block: Complete blockPartial AV block: Complete block

Digitalis – therapeutic UsesDigitalis – therapeutic Uses

Congestive Heart FailureCongestive Heart Failure

&&

Cardiac ArrhythmiasCardiac Arrhythmias

DigitalisDigitalis - Congestive Heart Failure- Congestive Heart Failure

Systolic dysfunction: dilated ventricles and Systolic dysfunction: dilated ventricles and unable to develope sufficient wall tension – unable to develope sufficient wall tension – IHD, Valvular disease, Myocarditis etc.IHD, Valvular disease, Myocarditis etc.

Diastolic dysfunction: Thickened wall, Diastolic dysfunction: Thickened wall, filling is impaired and low output – filling is impaired and low output – prolonged hypertension, CHD, prolonged hypertension, CHD, hypertrophic myopathyhypertrophic myopathy

Long standing CHF patients have both the Long standing CHF patients have both the types of dysfunctionstypes of dysfunctions

Digitalis therapy improves the conditions Digitalis therapy improves the conditions in CHF, but neither arrest progression nor in CHF, but neither arrest progression nor reverse pathological changereverse pathological change

Enlarged Heart - Images

Digoxin DigitalizationDigoxin Digitalization Digoxin has low therapeutic window and margin of safety is Digoxin has low therapeutic window and margin of safety is

very lowvery low Therapeutic level of digoxin is 0.5 – 1.5 ng/mlTherapeutic level of digoxin is 0.5 – 1.5 ng/ml It is administered such a way that patient gets maximum It is administered such a way that patient gets maximum

benefits with minimal adverse effectsbenefits with minimal adverse effects Previously rapid digitalization was done but obsolete nowPreviously rapid digitalization was done but obsolete now Slow digitalization:Slow digitalization:

– Administer digoxin 0.25 mg (or even 0.125mg) daily in the Administer digoxin 0.25 mg (or even 0.125mg) daily in the evening – full response in 5-7 daysevening – full response in 5-7 days

– If no improvement administer administer 0.375 for 1 weekIf no improvement administer administer 0.375 for 1 week– If no, administer 0.5 mg in next weekIf no, administer 0.5 mg in next week– Monitor patient for blood levels, if no monitor in improvement Monitor patient for blood levels, if no monitor in improvement

of signs and symptomsof signs and symptoms– If bradycardia, stop the drugIf bradycardia, stop the drug

Digitalization – contd.Digitalization – contd.

Rapid digitalization (oral): Rapid digitalization (oral): – Administer 0.5 to 1 mg statAdminister 0.5 to 1 mg stat– 0.25 mg every 6 Hrly0.25 mg every 6 Hrly– Monitor for toxicityMonitor for toxicity– Patient is digitalized within 24 HrsPatient is digitalized within 24 Hrs

Rapid IV: Seldom used nowRapid IV: Seldom used now– As desperate measure in CHF and atrial As desperate measure in CHF and atrial

fibrillationfibrillation– 0.25 mg slow IV stat followed by 0.1 mg every 0.25 mg slow IV stat followed by 0.1 mg every

HrlyHrly

Digoxin - Cardiac ArrhythmiasDigoxin - Cardiac Arrhythmias Cardiac dysrhythmia (arrhythmia)Cardiac dysrhythmia (arrhythmia)

– Large and heterogeneous group of conditions in which there is Large and heterogeneous group of conditions in which there is abnormal electrical activity in the heartabnormal electrical activity in the heart

– The hearts too fast or too slow, and may be regular or irregularThe hearts too fast or too slow, and may be regular or irregular Atrial fibrillation is the most common type of arrhythmias Atrial fibrillation is the most common type of arrhythmias

although not life threateningalthough not life threatening– Often irregular and rapid atrial contractions originating in atrial Often irregular and rapid atrial contractions originating in atrial

musclesmuscles– Ultimately interferes with ventricular contractions (heart beat)Ultimately interferes with ventricular contractions (heart beat)– If treated, it is not life threateningIf treated, it is not life threatening– Generally occurs above 50 years of ageGenerally occurs above 50 years of age– Digitalis action:Digitalis action:

Acts by decreasing the number of impulses passing down the AV node – Acts by decreasing the number of impulses passing down the AV node – direct, vagomimetic and sympathetic actiondirect, vagomimetic and sympathetic action

Decreases average atrial ERP – increases fibrillation frequencyDecreases average atrial ERP – increases fibrillation frequency Decreases the ventricular rate and pulse deficit is abolishedDecreases the ventricular rate and pulse deficit is abolished Can bring down ventricular rate to 70-80/minCan bring down ventricular rate to 70-80/min

Digoxin - Cardiac ArrhythmiasDigoxin - Cardiac Arrhythmias

Atrial flutter:Atrial flutter:– Regular and synchronous contractionsRegular and synchronous contractions– Atrial rate is less than AF (200-350)Atrial rate is less than AF (200-350)– Digoxin enhances AV block and reduces ventricular rateDigoxin enhances AV block and reduces ventricular rate– Converts atrial flutter to fibrillation – reduction in atrial Converts atrial flutter to fibrillation – reduction in atrial

ERP ERP PSVT:PSVT:

– Heart rate is 150-200/minHeart rate is 150-200/min– A-V conduction is 1:1 due to reentry in SA or AV nodeA-V conduction is 1:1 due to reentry in SA or AV node– IV injection of Digoxin prevents this by increasing vagal IV injection of Digoxin prevents this by increasing vagal

tonetone

Pharmacotherapy of CHF – Pharmacotherapy of CHF – Goal Goal

Improvement of cardiac performanceImprovement of cardiac performance– Ionotropic drugs: digoxine, dopamine, Ionotropic drugs: digoxine, dopamine,

dobutamine and amrinonedobutamine and amrinone– Diuretics: frusemide and thiazidesDiuretics: frusemide and thiazides– Vasodilators: ACE inhibitors/AT1 antagonists, Vasodilators: ACE inhibitors/AT1 antagonists,

hydralazine or nitroprussidehydralazine or nitroprusside Arrest or reversal of disease progression:Arrest or reversal of disease progression:

– ACE inhibitors or AT1 antagonistsACE inhibitors or AT1 antagonists– Beta-blockersBeta-blockers– Aldosterone antagonistsAldosterone antagonists

Heart failure - classificationHeart failure - classification Class I (Mild): Class I (Mild): No limitation of physical activity. Ordinary No limitation of physical activity. Ordinary

physical activity does not cause undue fatigue, palpitation, or physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath).dyspnea (shortness of breath).

Class II (Mild): Class II (Mild): Slight limitation of physical activity. Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnoea.fatigue, palpitation, or dyspnoea.

Class III (Moderate): Class III (Moderate): Marked limitation of physical activity. Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnoea.fatigue, palpitation, or dyspnoea.

Class IV (Severe): Class IV (Severe): Unable to carry out any physical activity Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.If any physical activity is undertaken, discomfort is increased.

Pharmacotherapy of CHF – Pharmacotherapy of CHF – contd.contd.

Diuretics: FurosemideDiuretics: Furosemide– Decrease in preload and improvement of ventricular functionDecrease in preload and improvement of ventricular function– Removal of peripheral oedema and pulmonary congestionRemoval of peripheral oedema and pulmonary congestion

Vasodilators:Vasodilators:– Nitrates (GTN and IDN): reduce preload by pooling of blood in Nitrates (GTN and IDN): reduce preload by pooling of blood in

capacitance vesselscapacitance vessels– Arteriolar dilators (Hydralazine, Minoxidil, CCBs etc) decrease Arteriolar dilators (Hydralazine, Minoxidil, CCBs etc) decrease

in peripheral resistance and facilitates more blood pumping by in peripheral resistance and facilitates more blood pumping by weak heartweak heart

– Pre and afterload reductionPre and afterload reduction ACEIs/ARBs effectve orally and Nitroprusside IV dilatorACEIs/ARBs effectve orally and Nitroprusside IV dilator In severe decompensated patients: IV nitroprusside (titrated) + In severe decompensated patients: IV nitroprusside (titrated) +

loop diuretic + IV ionotropic drugs loop diuretic + IV ionotropic drugs For maintenance, Hydralazine + ACEIs/ASRBs are usedFor maintenance, Hydralazine + ACEIs/ASRBs are used ACEIs and ARBs are recmmended for all grades of failureACEIs and ARBs are recmmended for all grades of failure

ACE inhibitors/ARBs

Afterload reduction Preload reduction Reduction of facilitation of

sympathetic nervous system Reduction of cardiac hypertrophy Drugs of choice in heart failure (with

diuretics) Used in all class of CHF

CHF – Beta blockers, how?CHF – Beta blockers, how?

Beta Blockers: metoprolol & bisoprololBeta Blockers: metoprolol & bisoprolol1.1. Initially reduce cardiac contraction and stroke volume i.e., Initially reduce cardiac contraction and stroke volume i.e.,

ejection fraction - but slowly Ef increasesejection fraction - but slowly Ef increases

2.2. Prevention of ventricular wall stretching – prevent Prevention of ventricular wall stretching – prevent remodelingremodeling

3.3. Prevention of Renin-angiotensin systemPrevention of Renin-angiotensin system Used in mild and moderate cases of heart failure with Used in mild and moderate cases of heart failure with

dilated cardiomyopathy and systolic dysfunctiondilated cardiomyopathy and systolic dysfunction No use in severe decompensate heart, other drugs should No use in severe decompensate heart, other drugs should

be continuedbe continued Useful in class II and Class III failuresUseful in class II and Class III failures Dose: start as low dose, carvedilol – 3.125 mg/day, Dose: start as low dose, carvedilol – 3.125 mg/day,

metoprolol – 200 mg/daymetoprolol – 200 mg/day

CHF –CHF –Aldosterone antagonist (Spironolactone)

Rise in plasma aldosterone level in CHF leads to– Increase in preload due to ECF rise– Risk of arrhythmia due to hypokalaemia – sudden death– Pathological remodeling of myocardium– Enhancement of sympathomimetic activity

Spironolactone antagonizes all the above effects – mobilization of edema fluid, prevents hypokalaemia

Dose: low dose of 12.5 to 25 per day (to avoid hyperkalaemia)

Used as add on therapy to ACEI/ARBs in moderate to severe CHF

Prevents hypokalaemia induced by diuretics Serum K+ monitoring required – risk of hyperkalaemia

CHF – Phosphodiesterase III inhibitors

Amrinone: (amicor/inocor/iarditone)– Selective PDE III inhibitor– MOA: Prevents intracellular breakdown of cAMP by PDE

III – increases cAMP conc. And Ca++ influx– Clinically, positive ionotropy and vasodilatation– Dose: IV Bolus 0.5 mg/kg followed by 5-10 mcg/kg/min– Adverse Effects: Thrombocytopenia, hepatotoxicity,

arrhythmia, nausea, & vomiting– Uses: Only for short term therapy of CHF and not used

for maintenance although effective orally

CHF – Sympathomimetics (ionotropic)

Dobutamine:(2-8 mcg/kg/min)– Beta-1 agonist and acts via cAMP and increase

in Ca++ conc.– Relatively do not increase heart rate– Further Beta-2 effects – muscle vasodilatation– Less change in heart rate and BP– Cardiac workload decreases – low oxygen

demand– Uses: acute heart failure with MI, cardiac

surgery and advanced decompensate CHF– Adverse effects: Tachycardia (reflex action due

to beta-2 action), tolerance (down regulation of beta receptors after 72 Hrs)

CHF - Dopamine 3 – 10 mcg/kg/min IV Acts on pre-junctional D2 and post-

junctional D1 receptors Actions: Splanchnic and Renal

vasodilatation (D1) and suppression of NA release (D2 effect) – increase renal perfusion and increase g.f.r

Uses: Patient in shock, adjunct to frusemide in refractory cases (short term only)

Adverse effects : tachycardia, arrhythmias and peripheral vasoconstriction

Remember

Sources and names of Cardiac Glycosides Digoxin – Pharmacological actions in

failing heart, process of digitalization Digoxin – Drug interactions Role of Diuretics, Beta-blockers, ACE

inhibitors, Vasodilators, Aldosterone antagonists and PDE III inhibitors in Heart failure

Pharmacotherapy of Heart failure

Thank You

Big Hearted ?

Digitalis – mechanism of actionDigitalis – mechanism of action