Overview of congestive heart failureOverview of congestive heart failureCongestive heart failure (CHF) is a condition in which the heart is unablCongestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of body. CHF can be incree to pump sufficient blood to meet the needs of body. CHF can be increased workload imposed on the heart. CHF is accompanied by abnormal ased workload imposed on the heart. CHF is accompanied by abnormal increases in blood volume and interstitial fluid; the heart, veins, and capincreases in blood volume and interstitial fluid; the heart, veins, and capillaries are therefore generally dilated with blood. Hence the term “congillaries are therefore generally dilated with blood. Hence the term “congestive(estive( 充血性充血性 )” heart failure, since the symptoms include pulmonary co)” heart failure, since the symptoms include pulmonary congestion with life heart failure, and peripheral edema with right heart failngestion with life heart failure, and peripheral edema with right heart failure. Underlying causes of CHF include arteriosclerotic heart disease, hyure. Underlying causes of CHF include arteriosclerotic heart disease, hypertensive heart disease, valvular heart disease(pertensive heart disease, valvular heart disease( 心瓣膜病心瓣膜病 ), dilated car), dilated cardiomyopathy(diomyopathy( 扩张性心肌病扩张性心肌病 ), and congenital heart disease(), and congenital heart disease( 先天性心脏先天性心脏病病 ). ). Left systolic dysfunction secondary to coronaryartery disease is thLeft systolic dysfunction secondary to coronaryartery disease is the most common cause of heart failure.e most common cause of heart failure.

Treatment of congestive heart failureTreatment of congestive heart failure

Heart FailureHeart Failure

Final common pathway for many cardiovaFinal common pathway for many cardiovascular diseases whose natural history resuscular diseases whose natural history results in symptomatic or asymptomatic left vlts in symptomatic or asymptomatic left ventricular dysfunctionentricular dysfunction

Cardinal manifestations of heart failure inCardinal manifestations of heart failure include dyspnea, fatigue and fluid retentionclude dyspnea, fatigue and fluid retention

Risk of death is 5-10% annually in patients Risk of death is 5-10% annually in patients with mild symptoms and increases to as hiwith mild symptoms and increases to as high as 30-40% annually in patients with advgh as 30-40% annually in patients with advanced diseaseanced disease

Main causesMain causes

Coronary artery diseaseCoronary artery disease HypertensionHypertension Valvular heart disease Valvular heart disease (( 心瓣膜病心瓣膜病 )) Cardiomyopathy Cardiomyopathy (( 心肌病心肌病 )) Cor pulmonaleCor pulmonale

Compensatory Compensatory changes in heart changes in heart failurefailure Activation of SNSActivation of SNS Activation of RASActivation of RAS Increased heart rateIncreased heart rate Release of ADHRelease of ADH Release of atrial natriuretic peptideRelease of atrial natriuretic peptide 心钠素心钠素 Chamber enlargement Chamber enlargement 心室腔扩大心室腔扩大 Myocardial hypertrophy Myocardial hypertrophy 心室肥厚心室肥厚

Classification of heart Classification of heart failurefailure Class I: No limitation of physical Class I: No limitation of physical

activityactivity Class II: Slight limitation of physical Class II: Slight limitation of physical

activityactivity Class III: Marked limitation of Class III: Marked limitation of

physical activityphysical activity Class IV: Unable to carry out Class IV: Unable to carry out

physical activity without discomfortphysical activity without discomfort

New classification of New classification of heart failureheart failure Stage A: Asymptomatic with no heart Stage A: Asymptomatic with no heart

damage but have risk factors for heart damage but have risk factors for heart failurefailure

Stage B: Asymptomatic but have signs Stage B: Asymptomatic but have signs of structural heart damageof structural heart damage

Stage C: Have symptoms and heart Stage C: Have symptoms and heart damagedamage

Stage D: End stage diseaseStage D: End stage disease

ACC/AHA guidelines, 2001ACC/AHA guidelines, 2001

心功能障碍

收缩功能 舒张功能

输出量

神经激素 心肌 1 受体RAA

CA 心缩力

顺应性

心肌肥大、重构 钠水潴留

血容量

静脉淤血

血管收缩

阻抗顺应性后负荷

血管肥厚、重构

前负荷

抗 RAA 系统药

改善舒张功能药正性肌力药

受体阻断药

利尿药

减前负荷药

减后负荷药

恢复心血管病理形态的药

CHF 的病理生理过程及可能治疗的环节 CHF 的病理生理过程及可能治疗的环节

长期病情心率

Strategy of treatment of Strategy of treatment of CHFCHF

The therapeutic goal for CHF is to increase cardiac The therapeutic goal for CHF is to increase cardiac output.output.

1)1) Inotropic agents that increase the strength of conInotropic agents that increase the strength of contraction of cardiac muscletraction of cardiac muscle

2)2) PDEI (phosphodiesterase inhibitors) agents that iPDEI (phosphodiesterase inhibitors) agents that increase cAMP to induce systoles and vasodilatatincrease cAMP to induce systoles and vasodilatationon

3)3) Calcium sensitizers extracellular fluid volumeCalcium sensitizers extracellular fluid volume4)4) adrenergic agonistadrenergic agonist5)5) adrenergic antagonistadrenergic antagonist6)6) Vasodilators: Calcium channel blocker Vasodilators: Calcium channel blocker 7)7) Decreasing RAS activity: ACEI and AT1 antagonist Decreasing RAS activity: ACEI and AT1 antagonist 8)8) Diuretic agentsDiuretic agents

Treatment of congestive heart Treatment of congestive heart failurefailure

ClassificationClassification1 Positive inotropic drugs1 Positive inotropic drugs Cardiac glycosidesCardiac glycosides β-adrenergic agonists (New dopamine receptor agonβ-adrenergic agonists (New dopamine receptor agon

ist)ist) phosphodiesterase inhibitors phosphodiesterase inhibitors Calcium sensitizersCalcium sensitizers2 Diuretics2 Diuretics3 Vasodilators3 Vasodilators Calcium channel blocker Calcium channel blocker Nitryl-vasodilatorsNitryl-vasodilators HydralazineHydralazine4 RAAS inhibitors: antiotensin converting enzyme inhibi4 RAAS inhibitors: antiotensin converting enzyme inhibi

tor and AT1 antagonisttor and AT1 antagonist5 β-receptor blocker5 β-receptor blocker

Classification1 Positive inotropic druClassification1 Positive inotropic drugsgsCardiac glycosides/Cardiac glycosides/ 强心苷类强心苷类

structure-activity relationship structure-activity relationship A cardiac glycoside molecule consists A cardiac glycoside molecule consists

of an aglyconeof an aglycone 苷元 苷元 or geninor genin 配基配基 , w, which possesses the same pharmacolhich possesses the same pharmacologic activity as the whole molecule cogic activity as the whole molecule combined chemically with one or morombined chemically with one or more sugars.e sugars.

Cardiac glycosidesCardiac glycosides

O

OOHCH3

CH3

HOC18 H31O9

12

A

C

B

D17

3

DigitoxinDigoxin

= H at 12 C= OH at 12 C

Sugars- 3 mols. of digitoxose 3 分子洋地黄毒糖

Aglycones苷元

Unsaturated lactone不饱和内酯环

steroid nucleus甾核

Convey the pharmacological activity

Convey cardiotonic activity

Modulate potency and pharmacokinetic distribution

O

OOHCH3

CH3

HOC18 H31O9

12

A

C

B

D17

3

1. The relationship between structure and effects

The Indispensable parts of activity

C14

C

C

The number of -OH and glycose will decide water-solubility and lipid-solubility

活性基团活性基团 activity ：： C17 C17 不饱和内酯环不饱和内酯环 Unsaturated lactone 、、 C14C14 羟基羟基 OHOH 、、 C3 C3 洋地黄毒糖洋地黄毒糖 digitoxose

脂溶性脂溶性 lipid-solubility ： ： C3 C3 洋地黄毒糖；水溶性洋地黄毒糖；水溶性 water-solubility ：： C12C12 及其他位点的羟基数及其他位点的羟基数

Classification of cardiac glycosides

1. grade 1: in plant, cedilanide 2. grade 2: extract of digitalis Digitoxin （洋地黄毒苷） , Digoxin （地高辛） ,

Deslanoside （旋花毛地黄苷） , Strophanthin K（毒毛旋花子苷 K)

3.3. 地高辛和洋地黄毒苷地高辛和洋地黄毒苷 CC33 位均联结位均联结 33 个洋地黄毒糖，个洋地黄毒糖，地高辛地高辛 CC1212 位多一个羟基，毒毛花苷位多一个羟基，毒毛花苷 KK 的甾核上有的甾核上有多个羟基，所以多个羟基，所以脂溶性：洋地黄毒苷脂溶性：洋地黄毒苷 >> 地高辛地高辛 >>毒毛花苷毒毛花苷 KK 。。

Process of drug through bodyDrugDrug AbsorptioAbsorptio

n rate n rate (%)(%)

ProteiProtein-n-bindinbinding (%)g (%)

HeptoeHeptoenteral-nteral-circulatcirculation (%)ion (%)

BiotraBiotransformnsformation ation (%)(%)

Kidney Kidney excretioexcretion (%)n (%)

TT1/21/2

digitoxindigitoxin 90~10090~100 9797 2727 30~7030~70 1010 5~7 5~7 dayday

digoxindigoxin 60~8560~85 <30<30 6.86.8 5~105~10 60~9060~90 33~36 33~36 hh

CedilanideCedilanide 20~4020~40 55 Few Few Quite Quite fewfew

90~10090~100 33 h33 h

StrophanthiStrophanthin Kn K

2~52~5 55 Few Few 00 90~10090~100 12~19 12~19 hh

Pharmacologic actionPharmacologic action

I. Action of cardiac glycosides on the heartI. Action of cardiac glycosides on the heart

1.1.Positive inotropic actionPositive inotropic action ：： Increasing coIncreasing contractility of cardiac muscle in heart failurntractility of cardiac muscle in heart failure. e.

(1) characteristic:(1) characteristic:A.A.myocardiac quick contractionmyocardiac quick contraction, Q-T period, Q-T period

↓ ①rate of force ↑↓ ①rate of force ↑ ② ②time to peak tension ↓time to peak tension ↓

B. no increase oxygen consumptionB. no increase oxygen consumption ： ： the increase in output is not accompanithe increase in output is not accompanied by an equivalent increase in oxygen ed by an equivalent increase in oxygen consumptionconsumption

Factors of oxygen consumptionFactors of oxygen consumption ：： 11 ）） Myocardia contractilityMyocardia contractility 22 ）） Heart rate Heart rate 33 ）） Myocadiac fiber length and toneMyocadiac fiber length and tone

Factors affect consumption of oxygen

I. The force of cardiac contraction

II. Heart rate

III. Volume of ventricular

C. Effect of positive inotropic act

① cardiac output is increased ② compensatory sympathetic tone is reduced ③ cardiac preload and afterload is decreased ④ heart rate is reduced ⑤ myocardiac fiber tone and oxygen consumption is decreased

⑥ increasing stroke volume causes a decrease in end-systolic volume

(2) Machanism of cardiac glycoside on positive inotropic action

A. Inhibiting Na+-K+-ATPase in therapeutic dose:

B. Increasing of calcium inward and induce the releasing of calcium from sarcoplasmic reticulum ( internal stores, by CICR)

α β↓ ↓

↓

↓

↓

glycoside→

Structure changes

Enzyme activity ↓

Na+↑, K+↓ in cell

Ca2+Na+exchange↓ in cell)↓

Na+-K+-ATPase is a recetor of glycoside

Mechanism of pharmacological act

Na+-K+-ATPase is the receptor of cardiac glycosides , so cardiac glycosides act by inhibiting the membrane Na+-K+-ATPase pump → Na+ i

→ Na+ i

Bidirectional exchange

① Na+ enter ↓ → Ca2+ ↓ outer

② Na+ outer ↑→Ca2+ ↑ enter

→by Na ＋ /Ca 2+exchanger

→ Ca2+ i↑

Ca2+ -induced Ca2+ release

Sarcoplasmic reticulum release Ca 2+

Enhance the increased cytosolic calcium concentration

Sarcoplasmic reticulum

→ Ca 2+ i↑

2.Negative chronotropic 2.Negative chronotropic actionaction

A. Continuous effect of positive A. Continuous effect of positive inotropic action inotropic action

decreasing sinus ratedecreasing sinus rate

heart rate is decreasedheart rate is decreased

Heart rate is decreased,Atropine can antagonize (block)

B. Increasing sensibility of myocardia to vagus nerve (increasing of potassiu(increasing of potassium outward and resting potential,m outward and resting potential, redreducing of automaticity).ucing of automaticity).

3. Affects of glycosides 3. Affects of glycosides to conductive tissuesto conductive tissues

A. Increasing conduction of the atrial A. Increasing conduction of the atrial muscle fibers, because increasing muscle fibers, because increasing excitation of vagus nerve (increasing excitation of vagus nerve (increasing of potassium outward).of potassium outward).

Increasing resting potential.Increasing resting potential.

Elevating rate of phase-0 Elevating rate of phase-0 depolarization. Acceleration rate of depolarization. Acceleration rate of depolarization phase-0 and atrial depolarization phase-0 and atrial fibers conductionfibers conduction..

B. Slowing (depress) conduction at the atrioventricular (A-V) node (inhibiting Na-K-ATPase, reducing resting potresting potentialential), and increase effctive refractory period

atrial fibrillation, atrial flutter, paroxymal (and) or supraventricular tachycardia

C. Increasing automaticity of Purkinjie fibres ： toxicity

A.A. If If Na+-K+-ATPase was inhibited more tha was inhibited more than 30%, n 30%, cardiac glycosides cardiac glycosides would induce would induce toxicity by the overload of intercellular free calcium concentration in myocardiac. (decrmyocardiac. (decreasing easing inotropic action))

B.B. If intercellular potassium concentration waIf intercellular potassium concentration was lower level, s lower level, cardiac glycosides cardiac glycosides would eawould easily induce sily induce toxicity in myocardiac. (arrhythmyocardiac. (arrhythmia)mia)

Mechanism of toxicity act

4. Affects of cardiac glycasides to ECG (electrocardiography)

A. Therapeutic dose:T-wave can become low, flat, isoelectric

or invertedS-T segment falls below the isoelectric lineP-R interval is lengthened, which is

associated with slower or delayed A-V conduction

Q-T interval is shortened, ERP and APD is shortened in Purkenje fibers

B. Higher dose: arrhythmias

The affects on ECG

T wave

It is characterized by an descend ST segment on the ECG

P-R

Q-T

P-P

Directly inhibit or reflected decrease sympathetic activity

• Exciting increase the vagal activity

• Inhibit RAAS system, promote the excrete of ANP

• cause arrhythmias (toxic doses)

II. Action of cardiac glycosides onII. Action of cardiac glycosides on vascular and kidney • Vasoconstriction, increase in peripheral vascular resistance

• Diuretic ， increase the blood flow through kidney and inhibit Na+-K+-ATPase → Na ＋ decreased re-absorb

II. Action of cardiac glycosides on II. Action of cardiac glycosides on neural and hormone

Clinical uses

1. Cardiac glycosides are given for CHF

Effects ： Best go with atrial fibrillation

Better hypertension congenital heart disease

not good anaemia lack of vitamin B1 not useful pericarditis 心包炎

2. Some kinds of arrhythmias

Atrial fibrillation

Atrial flutter

Supraventricular Tachycardia

Toxic effects

1. Responses of stomach-intestines :

Anorexia 厌食 , nausea ， vomiting ,

Abdominal pain and diarrhoea

2. CNS: visual disturbaces

3. Arrhythmia: 1) Tachycardia 2)AV block 3)Bradycardia <60 beat/min

Prophylaxis and treatment of the toxicity

• Clear the signal of toxic and the indication of withdraw

• Inspect the concentration of digoxin (3ng/ml), digitoxin(45ng/ml)

• If necessary ,potassium supplements and antiarrhythmic drugs ( phenytoin ,lidocaine,atropine )administered

• For severe intoxication ,antibodies specific to cardiac glycosides are available

Method of administration

• Classical ： whole effect dose

quick or slow (have use digoxin within two weeks)

The suitable dose to the patients

• Maintain ： 4 ～ 5 t ½

Digoxin 0.25mg/day , 6 ～ 7 day ( t ½ 33 ～ 36 hours)

Classification1 Positive inotropic drugsClassification1 Positive inotropic drugs -Adrenoceptor agonists

They are used intravenously in CHF emergenciesExample of -Adrenoceptor agonists :

Dobutamine ( 多巴酚丁胺 )• Exciting β1 Adrenoceptor → positive inotropic action →the volume of output↑• Exciting β2 Adrenoceptor→dilate the vascular → afterload↓

have benefits within short time

Classification1 Positive inotropic drugsClassification1 Positive inotropic drugs Phosphodiesterase- inhibitorsⅢ

Inodilator / inodilating drugs

Inhibiting the activity of PDE Ⅲ → cAMP↑→ causes an increase in myocardial contractility and vasodilatation →total peripheral resistance →cardiac output ↑

Examples:

Armirinone （氨力农） : Inhibits the excess product of NO, TNF and affects the neurohormone, anti-the forming of thrombus

milrinone （米力农） : stronger 20 time

vesnarinone （维司力农） : myocardial contract element’s the sensitivity to calcium

Classification1 Positive inotropic drugsClassification1 Positive inotropic drugs Calcium sensitizers

Pimobendan 匹莫苯 :

Inhibit PDE ; increase TnC’s sensitivity to calciumⅢ

Tn troponin— 肌钙蛋白； myosin －肌球蛋白； tropomyosin －原 ； Actin 肌动蛋白

Classification 2Classification 2 Diuretics

Diuretics inhibit sodium and water retention, →reduce the volume of blood, →venous pressure and the thus cardiac preload are reduced↓, increasing the efficiency of the heart as a pump→ cardiac output ↑, so reduce oedema due to heart failure

Heart failure

• Low-grade : Thiazides hydrochlorothiazide 氢氯噻嗪

• Higher-grade : Acute left heart failure

loop diuretics --- furosemide 呋塞米（速尿）

Spironolacton 螺内酯

（ anti-aldosterone ,keep potassium and diuretics)

Antiotensin converting enzyme inAntiotensin converting enzyme inhibitor (ACEI) and AT1 antagonisthibitor (ACEI) and AT1 antagonist

Calcium channel blocker Calcium channel blocker Nitryl-vasodilatorsNitryl-vasodilators HydralazineHydralazine

Classification 3Classification 3 Vasodilators

bradykinin

aldosterone

ACEI and AT blocker

Classification 3Classification 3 VasodilatorsAngiotensin-converting-enzyme inhibitorinhibitor (ACEII )

Captopril Enalapril

Methanism of anti-CHF:

1) Humour: Inhibit ACE→angiotensin Ⅱ and aldosterone levels↓, reduce sodium retention, increase bradykinin levels , ANP 、 NO 、 PGI2↑, reduce the release of NA ET and renew the expression of βreceptor

2) This therefore causes vasodilatation (include coronary artery) →reduction in peripheral resistance→ increase the cardiac output, Increase the blood flow of kidney so Improve the function of kidney

3) Prevent the remodel of the heart

AT1 antiagonists

Losartan （氯沙坦）The function just like ACEⅠ

It dosen’t influence bradykinin levels

Clinical utilize:

• CHF

• Protection of kidney

Calcium-channel blockers

Amlodipine 氨氯地平

Dilate artery

Dilate the coronary

Alleviate the LV Wall Tension

Vessel

Dilatation of the veins→ decreases preload

Dilatation of the artery→ decreases afterload

Decrease the oxygen demand of the heart

mechanism

Others --- Vasodilators

Nitrate esters: nitroglycerin , nitroprusside sodium 硝普纳

Hydralazine 肼屈嗪 direct dilate the vascular

Prazosin 哌唑嗪 ɑ- receptor blocker

Classification 4Classification 4 receptor blocker

Carvedilol 卡维地洛

labetalol 拉贝洛尔

Bisoprolol 比索洛尔

Carvedilol 卡维地洛

mechanism

• Anti RAAS system • Anti-arrthymias• Anti-myocardial ischemia

Cardiomyopathy 心肌病

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二 other action of cardiac gylcosides 1. Nerve system Toxic concentration:enhancing sym

pathetic activity increasing sympathetic impulse of p

reganglial and afterganglial fibers, can cause atrial fibrillation and ventricular tachycardia.

Therapeutic dose: increasing parasympathetic center in brain stem excitation------slowing rate of heart,inhibiting conduction

2. Effect of cardiac glycosides to kidney

①increasing renal blood flow and filtering rate of glomerulus

②competitive antagonism with aldosterone in proximal tubule

Clinical uses

1. Congestive heart failure *Depends in part on the cause of

the failure *Depends in part on the severity

of cardiac damage

A. The best therapeutic effect is the chronic, low-output form

Such as: heart failure with atrial fibrillation an rapid heart rate

B. The better therapy is

heart failure caused by hypertension, heart disease caused by coronary atherosclerosis Valvular stenosis( 瓣膜狭窄） Rheumatic valvulitis （风湿性瓣膜炎）

C. No better

Thyrotoxicosis （甲状腺中毒症） Thyroidism （甲状腺功能亢进）

Serious anemia Vitamin B deficiency Advanced valvular stenosis

D. No use pulmonocardiac disease activity carditis serious myocardia injured

(1) Activity rheumatic (2) other forms of infectious or toxic m

yocarditis , pulmonocardiac disease(3) advanced cardiomyopathy 心肌病(4) badly damaged hearts cardiopericarditis 心包炎

E. Acute heart failure

iv.Use strophanthin K cedilanide

}

2. Atrial fibrillantion

Ventricular rate ↑

↓

↓

↓

Atrial rate :400~650/min

Circulative blood flow ↓

Heart failure

Cardiac gylcosides

ventricular rate ↓ (atrial fibrillation)

Circulative blood flow volume ↑

(relive) sysptoms of heart failure

↓

↓

↓

•In atrial fibrillation, the same vagomimetic action helps control ventricular rate, thereby improving ventricular filling and increasing cardiac output.•Slowing conduction in A-V node,increasing concealed conduction （隐匿性传导） ,slowing ventricular rate.

Concealed conductionConcealed conduction

The impulses arriving at the AV The impulses arriving at the AV node are rapid and random in node are rapid and random in time. Most of these impulses time. Most of these impulses either fail to enter the AV node either fail to enter the AV node because it is refractory or because it is refractory or propagate only partway through it propagate only partway through it and give rise to the phenomenon and give rise to the phenomenon of concealed conduction.of concealed conduction.

3. Atrial flutteratrial rate : 320~360 beats/min, rapid and

regular In atrial flutter, the depressant effect of the

drug on atrioventricular conduction will help control an excessively high ventricular rate. The effects of the drug on the atrial musculature may convert flutter to fibrillation, with a further decrease in ventricular rate

Therapeutic action:

(1)Increasing block and ERP in atrioventricular (AV) node

heart rate decrease (ventricular rate)

(2) Shortening ERP of atrium

(convert) atrial flutter →atrial fibrillation

(3) After withdrawal cardiac glycosides, sinus rhythm may return, ERP increase (prolong ERP of shortened ERP in atrium)(4) Quinidine may convert atrial flutter to sinus rhythm , but may increase the risk of cardiac glycosides toxicity.

3. Paroxysmal supraventricular tachycardiaIncreasing function of vagal nerveEnhance vagal activityDecrease excitation of atriumNo use: supraventricular

tachycardia caused by glycosides------intoxication

Toxicity of cardiac glycosides1. Gastrointestinal and centre nerve systom occasions sickness , vomiting , purging 泄泻 ,

giddiness 眩晕 , confused vision , green vision or yellow vision , anorexia 厌食 , nausea , diarrhea , abdominal discomfort or pain , headache , fatigue

the drugs may stimulate the chemoreceptor of trigger zone (CTZ) in the area postrema of the medulla( 延髓极后区，化学感受区）

2. Toxic effects on the heart(1)Tachycardiac rhythm

abnormalities (arrhythmia)Atrioventricular (AV) node

Artial

Ventricular fibrillation

Bigeminy 二联律 , trigeminy 三联律

}Tachycardia

death

machanism

Severe inhibiting Na+-K+-ATPase

Depletion of K+ in cell

Resting potential or maximal diastolic potential

Change small(negative value)

(1)Automaticity easy to depolarization

(2) Delaying after depolarization↑迟后去极化

↓

↓

↓

}

(2) AV block

★ the development of AV block is due in part to the vagal effect of glycosides Na+-K+-ATPase is strongly depressed Resting potential↓

Phase 0 depolarization rate ↓

Conduction slows

★

↓

↓

(3)Sinus bradycardia

Sinus atrial node is depressed

↓

Automaticity ↓

Prevention of cardiac intoxication

1.Intoxication symptoms and signsGastrointestinal effectsNeurological effectsDrug concentration in blood can be

measured

2. Pathological situations

Ion pH of blood Oxygen deficiencyAgeDrug interaction

Treatment of cardiac glycosides introxication1. Administration K+ , orally or iv2. Administration of phenytoin treats s

evere tachycardiac rhythm abnormalities

ventricular tachycardia bigeminy 二联律 recovering activity of enzyme

ventricular tachycardiaVentricular fibrillation

Lidocaine :

}severe

Atropine:

Sinus bradycardiaAV conduction block

AdministrationAdministration

1 Digitalization 1 Digitalization Slow approach to “ digitalization”Slow approach to “ digitalization” Is the safest dosing technique.Is the safest dosing technique. Rapid approach to “digitalization”Rapid approach to “digitalization” can be achieved quickly with a can be achieved quickly with a

large loading dose (divided into large loading dose (divided into three or four portions and given three or four portions and given over 24~36 hours) followed by over 24~36 hours) followed by maintenance dosemaintenance dose

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2 Maintenance doses2 Maintenance doses3 Therapeutic method of Digoxin3 Therapeutic method of Digoxin tt1/2 1/2 36 hours 0.25 mg/day36 hours 0.25 mg/day 4~6 t4~6 t1/21/2 (6~7 (6~7 days) to approach steaddays) to approach stead

y-state level (Cy-state level (Cssss))