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Treatment of Heart failure

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Treatment of Heart failure Powered By Docstoc
					      Ionic movement



Na+ 145 m mol     Ca++
                            K+ 4 m mol
       ++++
       ____

   Na+ 10 m mol          K+ 140 m mol




                                         1
            Ionic movement
            Ca++
Na+   Cl-




                                   K+

                        Na+       ATPase
                   K+
  0    1     2



                    3         4




                                           2
    Phases of the action potential:
                    Phase 1              Phase 2
                    Cl- in               Ca+ + in
          + 30
          0 mV

Phase 0
Na+ in


            - 50
                     Phase 3
                     K+ OUT
                                                    Phase 4

      - 90 mV

                   Absolute refractory
                   period
                                                              3
        Pacemaker potential (automatic cells)


       Gradual decrease of K+ current    Prepotential
       Gradual increase of Na+ current
                                            Spontaneous diastolic
                                            depolarization

                                               Progressive diastolic
                                               depolarization

-75

- 80
                                                   prepotential
                                                                       4
                 E.C.G.
             R


                              Amplitude

P
                          T
          Q      S
           Q-R-S


    P-R
                     QT
                                          5
Causes of cardiac Dysrhythmia.
1- Abnormal pace-maker activity:
  Predisposing factors:
A- Catecholamines.
B- Partial depolarization resulting from
 ischemia may produce a slow wave of
 depolarization in phase 4 and start discharge
 impulses to the heart.
                                            6
Causes of cardiac Dysrhythmia.
- Delayed after depolarization:
  Due to increased intracellular Ca++
 concentration causing depolarization
 triggering off a set of action potential.
Drugs e.g. adrenaline or cardiac glycoside tend
 to intracellular Ca++ induce this effect


                                             7
8
Causes of cardiac Dysrhythmia.
2- Abnormal conduction (Re-entry)

                                   Unidirection
                                   Block



      Normal               Re-Entry
                           Circus movement
                           Ectopic beat
                                             9
               Sodium Channels
 Resting          Activated Inactivated
   Na+   Na+         Na+
                                    Na+


                              Na+




Sodium channel-blocking drugs bind to their
 receptors more when the channels are
 activated (open) or inactivated than when it is
 resting (fully repolarized).
                                            10
                              Phase 1
                              Cl- in
              + 30
              0 mV
                                                       Phase 3
   Phase 0
                                                       K+ OUT
   Na+ in
                           Phase 2
                - 50       Ca+ + in

                                                                 Phase 4    pacemaker


        - 90 mV            Absolute refractory                                         non
                           period
    outside          Na+                                               Na+ Ca++
                               Ca++

Cell membrane                                    Na+      K+


     Inside                           K+   K+                     K+
                                                   ATPase                         11
     cell              Action potential current                    Diastolic current
     Phases of the action potential
-Phase 0 : Activation of Na+ channels
           rapid Na+ influx
            (excitability & conductivity)
- Phase 1: Inactivation of Na+ & Cl- influx.
- Phase 2: Activation of slow Ca++ channels
          Slow Ca++ influx.




                                               12
                  Phase 3:
-Phase 3: Inactivation of Ca++ channels

  Activation channelsof K+

       Rapid K
               + Efflux.
     Action potential duration (APD)
     Effective refractory period (ERP)


                                          13
                  Phase 4:
a) Normal cardiac muscle fiber      resting
  potential. Activation of A.T.Pase        Na+/
  K+ pump        Restore electrolyte balance.
b) SAN, AVN, ectopic focus     slow Ca++, Na+
  influx    Slow diastolic depolarization =
  prepotential = Automaticity.

                                            14
      Drugs blocking ion channels:
1- Activated Na+ channels         phase 0
        Excitability and      Conductivity.
2- Inactivated Na+ channels        phase 4
        Automaticity.
3- Slow Ca++ channels            phase 4
        Automaticity.
4- K+ channels        long phase 3
      long APD & long ERP


                                              15
      Classification of Antiarrhythmic drugs:
                 Vaughan Williams:
                  Class I, II, III, IV, V.
Class I: Block Sodium channels.
Class II: Block sympathetic drive to the heart.
Class III: Block potassium channels.
Class IV: Block calcium channels.




                                                  16
    Classification of Antiarrhythmic drugs:
               Vaughan Williams:
             Class I, II, III, IV, V.
Class I  : Ia, Ib, Ic.
 Hyperkalemia exacerbates cardiac toxicity
Group Ia:        - Quinidine, procainamide &
 Disopyramide.




                                               17
  Classification of Antiarrhythmic drugs
Group Ib:
 - Lidocaine, Phenytoin, Tocainide &
     Mexiletine.
 - Shorten the APD.
 - Minimal slowing of conduction.
 - Minimal phase 0 depression.



                                       18
     Classification of Antiarrhythmic drugs

Group Ic:
 - Flecainide, encainide, Moricizine &   propafenone.
 -   No effect on APD & ERP.
 - Marked slowing of conduction.
 - Marked phase 0 depression.




                                                        19
    Classification of Antiarrhythmic drugs:
                Class I, II, III, IV, V.
Class II:
 - Beta-adrenergic blockers e.g. Propranolol.
 - Block the sympathetic drive to heart.
 - ERP in the A.V. node        slow conduction
 .
 - Cause slowing of the spontaneous diastolic
 depolarization       slowing of the pacemaker
 rate.

                                              20
    Classification of Antiarrhythmic drugs:
                Class I, II, III, IV, V.


Class III:
 - Potassium channel blockers.
 - Amiodarone, sotalol, bretylium & ibutilide.
 - Prolongation of APD & ERP.



                                              21
    Classification of Antiarrhythmic drugs:
                Class I, II, III, IV, V.

Class IV:
 - Calcium channel       blockers:
    Verapamil & diltiazem.
 - Depress phase 4      depress automaticity.
 - A.V. node    depress conductivity.


                                                22
     Classification of Antiarrhythmic drugs:
                 Class I, II, III, IV, V.
Class V: Miscellaneous.
- Potassium channel openers (activator) e.g.
   Adenosine             Hyperpolarization.
- Digitalis: by its parasympathomymetic action.
- Potassium ion: hypokalemia cause arrhythmia
  and hyperkalemia depress conduction.
     Normalize.
- Magnesium ion: Normalize.
                                               23
Quinidine
An alkaloid found with quinine in cinchona
 bark .
As quinine it has: analgesic, antipyretic,
 antimalarial, oxytocic & skeletal muscle
 relaxant.



                                             24
 Quinidine
Absorption and fate:
 Completely absorbed from GIT.
 50% bound to albumin.
 50% metabolized in liver.
 50% excreted by kidney.


                                 25
 Pharmacological actions:
A- Heart:
  I- Direct myocardial depressant –ve inotropic
  II- Vagal blocking action ( Antimuscarinic,
      Atropine-like )
1- Automaticity : Inhibit S.A node as well
  as ectopic pacemaker ( decrease the slope of
  phase 4 depolarization).
                                             26
2- Conductivity :
  I- Direct effect:
   A- Slow conduction in atria & ventricle.
   B- prolong action potential duration (increase QT
        interval) & prolong E.R.P.
   II- Vagal block Enhance conductivity in A.V.
        node & bundle of Hiss.
3- Contractility: Is depressed –ve inotopic.
4- Excitability: Is depressed.

                                                  27
            Group: IA, Quinidine:
                                          Phase 3
                                          K+ OUT


Phase 0
Na+ in
                                                    Phase 4




                  Absolute refractory
                  period
            Na+    Ca++                              Na+ Ca++
  outside
                                               K+
                                        Na+


inside                    K+   K+                   K+
                                          ATPase
                                                                   28
                                                    Diastolic current
  5- E.C.G:
                          4- QRS widened
1- Amplitude decreased

             P                       5- T-wave inverted


                 2- P-R


                           3- Q-T


     Prolongation of: 2, 3.
                                                     29
B- Arterial pressure:
  V.D ( Alpha adrenergic blocking action)
     hypotension especially if give I.V.




                                            30
 Side effects of quinidine
1- Slow A-V conduction
  heart block.
2- Hypotension:
  particularly in given I.V.
3- Hypersensitivity:
  Fever, skin rash, angioneurotic edema &
  vascular collapse.

                                            31
4- Paradoxical Tachycardia:
  Sudden increase of the ventricular rate due
  to reduction of the degree of A.V. block due
  to predominance of atropine-like effect of
  quinidine on the A.V. node causing
  enhancement of conduction.


                                             32
5- Embolism:
  After quinidine restore the normal sinus
  rhythm & complete contraction of atria,
  the thrombi formed due to chronic
  fibrillation may dislodge leading to
  Embolism.
6- My cause new arrhythmias (torsade de
  pointes).

                                         33
7- Cinchonism:
  Large doses of quinidine may produce
  (cinchonism) which involve:
  ringing of ears, blurred vision, headache,
  nausea & vomiting.
  These symptoms are similar to those of
  salicylism.

8- G.I.T.: Nausea, Vomiting & Diarrhea.
                                               34
 Contraindication of quinidine:
1- Complete A-V block with an A-V nodal or
 idioventricular pacemaker is an Absolute
 contraindication as quinidine would
 depress this focus  Cardiac arrest.


                                             35
2- Old standing atrial fibrillation ( more than 6
  months        Embolism.
3- Subacute bacterial endocarditis
     Embolism.
4- Hypersensitivity.
5- Heart failure.
6- Arrhythmia due to digitalis intoxication.


                                                36
Therapeutic uses of quinidine:
1- Atrial Fibrillation :
  ( Less than 6 months duration)
  Patients should be digitalized before quinidine to
  prevent “Paradoxical tachycardia”.
2- Atrial flutter: E.R.P. &         Excitability.
3- Paroxysmal atrial tachycardia.
4- Atrial & Ventricular extrasystole.
5- ventricular tachycardia.

                                                  37
Preparation & Dosage:
1- Oral: Quinidine sulfate 0.2 gm tab
  Test dose: one tablet to hypersensitivity.
  Then 1 tablet every 2 hour for 5 dose
If failed
2 tablet every 2 hour for 5 dose on second
  day
Maintenance 1 tab T.D.S.
2- Parental: I.M. or I.V. 5% glucose
                                               38
Procainamide (Pronestyl)
Pharmacological actions:
a) Has local anesthetic action similar to
   procaine however not effective in blocking
   nerve trunk because of the amide group.




                                            39
d) Heart: Similar to quinidine but the
   atropine like effect is less than
   quinidine.
e) Blood pressure: V.D.         Hypotension
   especially after rapid I.V.I. But less than
   with quinidine.
e) C.N.S. May cause confusion &
   hallucination
                                            40
Toxicity of Procainamide.
1- Systemic lupus erythematosis-like syndrome
  (hydrallazin, alph-methyldoa, isoniazide &
  carbamazepine.
2- Hypersensitivity.
3- Hypotension with large I.V. dose.
4- G.I.T.: N, V, D.


                                           41
Uses:
 Supraventricular & Ventricular extrasystol or
 tachycardia.




                                            42
Disopyramide (Rhytmodan, Norpace).
Pharmacological Action:
 1- Quinidine-like.
 2- Anticholinergic ( Atropine-like) +++.
 3- Local anesthetic action.




                                            43
Side Effects of Disopyramie:
 1- Atropine side effects:
    a- Dry mouth.         B- blurred vision.
    c- glaucoma.          D- Urinary retention.
 2- Heart failure (-ve inotropic).
 3- Hypotension.



                                              44
Contraindication of Disopyramide.
 1- Heart block.
 2- Heart failure.
 3- Glaucoma.
 4- Enlarged prostate.




                                    45
Therapeutic uses:
 1- Supraventricular & ventricular arrhythmia.
 2- Arrhythmia after myocardial infarction.




                                            46
Class Ib:
  Lidocain, I.V.
  phenytoin, I.V.
  Mexiletine, Can be used orally.
  tocainide Can be used orally.




                                    47
Lidocaine: (Lignocaine, Xylocaine)
 - Local anesthetic.
Mechanism of action:
1- Decrease automaticity: Depress rate of
  phase 4 depolarization in purkinje fibre.
2- Shorten APD . in His-purkinje system.
3- Slows recovery of sodium channels from
  inactivation.
                                              48
                 Class: IB, Lidocaine:
                                           Phase 3
                                           K+ OUT


Phase 0
Na+ in
                                                     Phase 4




                      Action potential
                      duration
               Na+     Ca++                           Na+ Ca++
                                                K+
                                         Na+

                              K+   K+                K+
                                           ATPase
                                                                    49
          Action potential current                   Diastolic current
Therapeutic uses of Lidocaine:
Emergency Ventricular Arrhythmia as in:
1- Myocardial infarction.
2- Digitalis toxicity.
3- During cardiac surgery.
4- During general anesthesia.

Not recommended for supraventricular
 arrhythmia.
                                          50
Lidocaine:
1- Rapid onset & Short duration.
2- Rapidly absorbed orally But undergoes
 extensive First pass metabolism
  therefore Only used I.V. Infusion.
3- No Atropine-like effect.
4- Less hypotensive action.
5- Less cardiac depressive action.
                                           51
Lidocaine:
Dose:
    1-2 mg / kg i.v. bolus.
Then 2-4 mg / minute infusion
With continuous ECG supervision.


                                   52
Lidocaine:
Side effects:
1- Mainly on C.N.S.
    Drowsiness, Sedation,
    Convulsion.
2- Allergy.
                            53
Phenytoin: (diphenylhydantoin, dilantin)
 - Antiepileptic drug.
 - Used for ventricular arrhythmia due to
    digitalis toxicity.
 - Not for supraventricular arrhythmia.
 - Similar to lidocaine.
Dose : 50-100 mg slowly I.V.
                                            54
Group IC:
Flicainide, Proarrhythmic effect (last resort).
, Moricizine & Propafenone :
1- Markedly slow conduction velocity
  in atrial and ventricular cells.
2- No effect on ventricular action
  potential duration or the QT interval.

                                                  55
Class II : Beta-Adrenergic Blocker
1- cardiac Beta-Adrenergic Blocker
 and reduction of cAMP, which results in the
 reduction of both Na+ & Ca++ current and
 suppression of abnormal pacemaker.
2- Increase ERP of A-V node.



                                          56
Class II : Beta-Adrenergic Blocker
3- Used in supraventricular
 arrhythmia ( A.F, A.Fl, & P.A.T.).
4- Also used in ventricular arrhythmia
 without heart block.



                                     57
Class III: Potassium channel blocker
Amiodarone, Sotalol, bretylium & Ibutilide.
Amiodarone: (Cordarone):
 1- Antiarrhythmic & Antianginal .
 2- Prolong duration of Action potential.
 3- Increase ERP.
 4- Half   life 60 days.
 5- Block Na+, Ca++, K+ channels.
                                              58
   Class III: Amiodarone: K+ blocker
                                        Phase 3
                                        K+ OUT

Phase 0
Na+ in
                                                  Phase 4




                Absolute refractory
                period

          Na+    Ca++                              Na+ Ca++
                                             K+
                                      Na+

                        K+   K+                   K+
                                        ATPase
                                                                 59
                                                  Diastolic current
Side effects of Amiodarone:
1- Cutaneous photosensitivity (gray man
  syndrome).
2- Corneal micro-deposition.
3- Thyroid dysfunction.
4- pulmonary fibrosis.
5- Liver damage.
                                          60
Therapeutic uses of Amiodarone.
 1-Effective in most types of
    arrhythmia.
 2- Refractory supraventricular &
   ventricular Tachyarrhythmia.

                                  61
Class IV: Calcium channel blocker.
Verapamil & Diltiazem
 are the only Ca++ channel blockers used as
 antiarrhythmic.




                                          62
  Group IV: verapamil: Ca++ blocker
                                        Phase 3
                                        K+ OUT

Phase 0
Na+ in
                                                    Phase 4



                Absolute refractory
                period

                                             Ca++
          Na+    Ca++                                 Na+

                                      Na+   K+

                        K+   K+                     K+
                                        ATPase
                                                                      63
                                                  Diastolic current
Verapamil & Diltiazem Uses:
A- Prophylaxis of angina pectoris.
B- Hpertension.
C- Supraventricular tachycardia (AF, AFL, PAT.)
 a- Depress automaticity.
 b- Slow ventricular rate (delay
 conduction in A-V node)
                                                  64
Adenosine:
6-12 mg intravenous bolus,
The drug slows conduction in the atrioventricular
  node, probably by hyperpolarizing this
  tissue and by reducing calcium current.
Drug of choice for AV nodal arrhythmia, PAT.
Short duration of action 15 seconds.
Flushing and bronchospasm are the side effects.
                                                    65
    Phases of the action potential:
                    Phase 1          Phase 2
                    Cl- in           Ca+ + in
          + 30
          0 mV

Phase 0
Na+ in


            - 50
                     Phase 3
                     K+ OUT
                                                Phase 4

     - 90 mV

                   Absolute refractory
                   period

                                                          66
Treatment of heart Block:
1- Atropine .
2- Isoprenaline.
3- Hydrocortison (after myocardial
  infarction due to its anti-inflammatory
  reaction.


                                            67
Electric Cardio-version:
  (Direct current electric shock)
Treatment of choice in:
1- Atrial Fibrillation.
2- Atrial Flutter.
3- Ventricular Fibrillation.

                                    68