Lines of Treatment

•  General measures e.g.  rest,  sedatives,  frequent  small meals with salt restriction. 

• Treatment of the cause.• Angiotensin coverting enzyme inhibitors.• Diuretics• Spironolactone. > potassium retaining Diuretics

• *Positive  inotropic  agents  e.g.  cardiac  glycosides,  dopamine, dobutamine, prenalterol, 2 agonist, and PDE inhibitors.

• Vasodilators. • Beta  blockers.( don’t use with H.failure ) contraindicated in

H.failure • ., بشكل بس الجاية بالساليدات ينذكر رح معين بيشنت مع واحد نوع نستخدم

نستخدم ما عام

• B.B + H.F

POSITIVE INOTROPIC DRUGS

•  1-CARDIAC GLYCOSIDES= Digitalis 

• The most important cardiac glycosides is   Digoxin

• Pharmacokinetics• Absorption: from duodenum• Distribution: all over the body concentrated n heart(15-30 times) البالزما من .اكثر concentrated in sk.m.(10-15 times). bound to pl.pr(25%).• Plasma concentration=0.5-2 ng/ml. > narrow therapeutic index

MOA• A) Positive Inotropic Action • ↑ force of contraction by ↑ intracellular Ca++ • B) Vagal effects. ANS -   القلب ضربات معدل بيقلل predominates n small dose. causes →↓ S,A.N., ↑ atrial Conductivity, ↓ A.V.N. conductivity

Pharmacological Effects

1.  Cardiovascular System•  Heart

• Contractility: It has a strong +ve inotropic effect , ↑ cardiac output

• Heart rate: It ↓ the heart rate due to:• Vagal causes

•  Extravagal causes

Heart• Excitability= ability of H to respond to stimulation: S.D.→↑

excitability, while L.D.→↓ excitability • Automaticity= ability of heart to initiate it own impulse : L.D.→↑

automaticity

•E.C.G.: ↓ H.R.• Long P-R interval> delay conduction in Av node • Short Q.R.S. and short Q-T interval> increased force of

contraction • Depressed S-T segment• Arrhythmia .= ↑ automaticity• Circulation

• COP: Increased in HF.• A.B.P: Normalization.• Venous pressure: ↓.• Blood volume : ↓ ( diuresis)

2. Effects on the Kidney:

•  In congestive heart failure, digitalis produces diuresis due to:

• ↑ renal plasma flow and glomerular filtration rate.

• ↓ of tubular Na reabsorption.

• 3.   Effects on the Gastrointestinal Tract• It causes nausea, vomiting anorexia and diarrhea.  4.   Effects on the CNS• Yellow + green vision.• Black dots with white hollows

•3+4 with toxic does

Therapeutic Uses

• A. Absolute Indications:• Chronic congestive heart failure associated with atrial

fibrillation.•B. Relative Indications:   شي استخدم او استخدمه

بداله ثاني

1. Treatment of heart failure failing to respond to

diuretics .

2. Atrial fibrillation.

3. Atrial flutter.

4. Paroxysmal atrial tachycardia .

Contraindications

•  A. Absolute Contraindications• Heart block.• Hypertrophic obstructive cardiomyopathy.• B. Relative Contraindications• Cardiopulmonary disease • Renal and hepatic insufficiency• In hypertensive heart failure:The first line is antihypertensive with the emphasis on vasodilators. 

Factors Modifying Response to Digitalisa•Renal failure. •Hepatic failure.•Chronic  pulmonary  diseases,  hypoxia,  Cardiac disorders:A.Acute  myocardial  infarction  leads  to  increase sensitivityB.Acute Rheumatic carditis increases the risk of heart block.

Dosage and Administration of Cardiac GlycosidesSlow digtitalization “Cumulative method”:• Digitalization started with 0.5 mg twice per day for

two days or 0.5 mg 3 times per day for one day • followed by the maintenance dose. :  0.25  mg  daily 

لقرص قرص نص• Rapid digitalization “ Rapid loading method”:• In emergency, we give a large initial loading dose “”. It

is given in 3 or 4 divided doses at 6 hours intervals. In 24 hrs

Assessment of Response to Digitalis•Relief of dyspnea and orthopnea= dyspnea on lying down.

•Disappearance of tachycardia.•Disappearance of edema, congested neck veins and basal lung crepitations.

Precautions for Digitalis Therapy• Never give I.V. digitalizing dose before being sure that

the patient has not received any digitalis during previous 14 days to avoid digitalis toxicity.

• Make sure that K+ level is normal. • What increase activity of digitalis ? = decrease K+ = diuretics  • What decrees effect of digitalis ? Pectin, kaolin, cholestyramine 

DIGITALIS TOXICITY•  Manifestation of digitalis toxicity•  I- Cardiac:• Variable degree of A.V. block• Sinus bradycardia; complete sinoatrial block.• atrial tachycardia.• II- Extracardiac:• Anorexia, nausea, vomiting• Neurological effects: headache, muscle weakness, malaise,

drowsiness and parasthesia disorientation, confusion, aphasia, delirium and hallucination “digitalis delirium”

• White borders or halos may appear on dark objects.• Yellow and green.

Management of digitalis toxicity

• Stop digitalis administration.• Hypokalaemia can be corrected by slow IV infusion of K.• Antiarrhythmic drugs:• Fab fragments of digitalis

2- OTHER +ve INOTROPIC DRUGS•DOPAMINE 

•DOBUTAMINE  • increase in cardiac output due to stimulation of 1 receptors. Given IV

•PRENALTEROL• Similar to dobutamine but has longer duration +given orally.

3-PHOSPHODIESTERASE INHIBITORS

• CARDIO-ACTIVE BIPYRIDINES Amrinone, Milrinone . 

• INHIBIT PHOSPHODIESTERASE = ↑level of cAMP ↑ Ca2+

•METHYLXANTHINESSame 

VASODILATORS

• effective in heart failure?•venodilators = nifedipine ↓in preload •Arteriodilators= nitrates ↓ in afterload •or both(Mixed) sodium nitroprusside, ACEIs

Vasodilators can be used in the Following Situations

•Pump failure-complicating AMI, valvular heart disease postoperative in cardiac surgery.

•Chronic congestive heart failure.

VASODILATORS

1. ACEIs. the, best, if not tolerated

2. ARBs Angiotensin II Receptor Blockers: Losartan ,valsartan.

3. Nitrates, the oral preparations for CHF, and I.V.

nitroglycerine for acute pulmonary edema.

DIURETICS• They are used in order to: (1) Prevent fluid retention. = decrees plasma volume(2) Relieve edema. (3) Decrease systemic pulmonary venous pressure.

• Thiazides: In mild and moderate heart failure.• Frusemide: In server heart failure.• Potassium retaining diuretics: Spironolactone : In-patient with heart failure with secondary hyperaldosteronism.

RATIONAL FOR USE OF BETA-BLOCKERS IN HEART FAILURE

• The potential benefits of therapy with B-blockers are due to the ability of these drugs to reduce excessive sympathetic stimulation which cause.

tachycardia and increased myocardial oxygen demand, cardiac hypertrophy,.

-blocker Carvedilol has considerable 1- vasodilator activityVasodilator cus it has alpha and beta blocking activity . 2-Antioxidant properties.

  3-Up-regulation of beta-receptors• فيلير للهارت استخدمه اللي الوحيد هذا

Mention 2 drugs used in treatment of ACUTE PULMONARY EDEMA\ Acute heart failure \ Cardiac asthma

• Hospitalization.• Semisitting or sitting position.• Treatment of the cause MI • Morphine: I.V. in low dose dose of 2-5 mg,

• Relieving pain.• Arteriolar dilatation.• Venodilatation.• Sedation.

•Oxygen•Diuretics•Vasodilators•Rapid digitalizationAminophylline