cardiovascular pharmacology
DESCRIPTION
Cardiovascular pharmacology. - Antiarrhythmic drugs - Drugs in heart failure - Antihypertensive drugs - Antianginal drugs - Antihyperlipidemic drugs. Antiarrhythmic Drugs. CARDIAC CONDUCTION SYSTEM - S.A. node - Inter-nodal pathways - A.V. node - PowerPoint PPT PresentationTRANSCRIPT
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Cardiovascular pharmacology
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- Antiarrhythmic drugs- Drugs in heart failure- Antihypertensive drugs- Antianginal drugs- Antihyperlipidemic drugs
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Antiarrhythmic Drugs
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CARDIAC CONDUCTION SYSTEM
- S.A. node - Inter-nodal pathways - A.V. node - Bundle of His and branches - Purkinje fibres
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CARDIAC ACTION POTENTIAL
DEFENITIONS
- Depolarization- Repolarization- Resting membrane potential- Inward current- Outward current
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Action Potential
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T-Ca2+ kanál
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WHAT IS ARRHYTHMIA?
An Abnormality in the : ■ rate ............... high= tachycardia
low = bradycardia ■ regularity ..... extrasystoles ■ site of origin ... ectopic pacemakers ■ or disturbance in conduction
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Circus Movement
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Therapeutic use & Rationale of antiarrhythmic drugs
The ultimate goal of antiarrhythmic drugs therapy is to restore normal rhythm & conductionWhen it is possible to revert to normal sinus rhythm , drugs are used to prevent more serious & lethal arrhythmias.
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ContinueAntiarrhythmic drugs are used to :
or conduction velocity
Alter the excitability of cardiac cells by changing the effective refractory period
Suppress abnormal automaticity
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CLASSIFICATION OF ANTIARRHYTHMIC DRUGS
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Vaughn Williams classificatinCLASS 1 Na+ channel blockers ( membrane
stabilizing drugs)CLASS II:
β- adrenoceptor blockersCLASS III:
drugs that prolong action potential duration CLASS IV: calcium channel blockers
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CLASS 1
Blocking the rapid inflow of Na+ ions ,decreasing the rate of rise of depolarization ( slope of
Phase O ) Suppress abnormal
automaticity by decreasing the slope of phase 4 , which is generated by pacemaker currents
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CLASS 1
At high concentration they have local anaesthetic effect
-Ve inotropic effect
( cardiac depression )
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CLASS 1
SUBCLASSIFIED INTO : {1A } : Block potassium channels
leading to prolongation of action potential duration & refractory period of both atrial & ventricular tissues
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QUINIDINE
Isomer of quinine
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QUINIDINE ( other actions ) Anticholinergic effect. - Increase conduction through the
A.V. node May lead to high ventricular rate in atrial flutter. Can be prevented by
administration of a drug that slow A.V. conduction such as digoxin, β blocker
calcium channel blockers.
Depress cardiac contractility
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QUINIDINE
ECG changes: - prolongation of P-R and Q-T interval - widens QRS complex
Has α-adrenergic blocking effect which cause vasodilatation and reflex sinus tachycardia This effect is seen more after i.v. dose
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Clinical uses of quinidine
In almost all types of arrhythmias Common uses: atrial flutter & fibrillation Can be used for ventricular tachycardia
To maintain sinus rhythm after D.Ccardioversion
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Adverse effects of quinidine
GIT: anorexia, nausea, vomiting, diarrhea CARDIAC:
quinidine syncope:- episodes of fainting - (due to torsades de pointes developing at
therapeutic plasma levels )- may terminate spontaneously or lead to fatal ventricular fibrillation
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Torsades de pointes
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Adverse effects ( continue) Anticholinergic adverse effects
Cinchonism
( tinnitus , headache & dizziness)
Hypotension
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Adverse effects ( continue)
- At toxic concentrations, can precipitate arrhythmia and produce asystole ( cardiac arrest ) if serum concentrations exceed 5 µg/ml or in high potassium levels ( > 5mmol/L).
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QUINIDINE Drug interactions:- Increase concentration of digoxin: - Displace digoxin from plasma proteins - Decrease digoxin renal excretion
GIVEN ORALLY ....rarely given I.V.
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PROCAINAMIDE
AS compared to quinidine less toxic on the heart... can be given I.V. more effective in ventricular than in atrial arrhythmias Weak anticholinergic No α-blocking actions
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PROCAINAMIDE
Therapeutic uses:- In atrial and ventricular arrhythmias
-Second choice ( after lidocaine ) in ventricular arrhythmias after acute myocardial infarction
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ADVERSE EFFECTS In long term therapy causes systemic lupus erythematosus (in 5-15% )
Hypotension
Torsades de pointes
Hallucination & psychosis
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CLASS 1 B
Shorten action potential duration e.g. lidocaine mexiletine
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LIDOCAINE
USES :Drug of choice for treatment of ventricular arrhythmias in emergency as in : cardiac surgery , acute myocardial infarction- NOT effective in atrial arrhythmias- NOT effective orally (3% bioavailability) - GIVEN I.V. bolus or slow infusion
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ADVERSE EFFECTS : hypotension
Neurological adverse effects (paresthesia, tremor, dysarthria (slurred
speech), hearing disturbances, confusion and convulsions )
T1/2 = 2hrs
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MEXILETINE - Given ORALLYUSES :1- ventricular arrhythmia 2- digitalis-induced arrhythmias3- chronic pain e.g. diabetic neuropathy and
nerve injuryADVERSE EFFECTS :1- nausea , vomiting2- neurological 3- arrhythmias & hypotensiont1/2 = 10 hr
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CLASS 1C
have no or little effect on action potential duration
e.g. flecainide propafenone
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FLECAINIDEUSES :- Supraventricular arrhythmias in patients with normal hearts - Wolff-Parkinson-White syndrome
- Ventricular arrhythmias { very high risk of proarrhythmia }
- Reserved for resistant arrhythmias
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Wolff-Parkinson-White syndrome
Pre-excitation of the ventricles due to an accessory pathway known as the Bundle of Kent. This accessory pathway is an abnormal electrical communication from the atria to the ventricles
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ADVERSE EFFECTS :
1- CNS : dizziness, tremor, blurred vision, abnormal taste sensations,
paresthesia
2- Arrhythmias
3- heart failure due to -ve inotropic effect
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OTHER CLASS 1C DRUGS:
PROPAFENONE: - Chemical structure similar to propranolol- has weak beta-blocking action- cause metallic taste and constipation
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CLASS 11 DRUGS β- ADRENOCEPTOR BLOCKERS
PHARMACOLOGICAL ACTIONS : block β1- receptors in the heart → reduce the
sympathetic effect on the heart causing : - decrease automaticity of S.A. node and ectopic pacemakers - prolong refractory period ( slow
conduction ) of the A.V node this help prevent re-entry arrhythmias
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CLINICAL USES : Atrial arrhythmias ( with emotion, exercise thyrotoxicosis ) WPW digitalis-induced arrhythmias To reduce the incidence of post
myocardial infarction arrhythmias
Propranolol Atenolol
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Prolong the action potential duration & refractory period .
{Prolong phase 3 }
Class III
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CLASS IIIAMIODARONE
- Prolong action potential duration and effective refractory period
- Has an additional action of classes- ( 1, 2 and 4 ) - Vasodilating effect ( α- and β-adrenoceptor &calcium channel
blocking effects )
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AMIODARONE
Clinical uses Serious ,resistant ventricular
arrhythmias, Maintenance of sinus rhythm after D.C.
cardioversion of atrial flutter and fibrillation
Resistant supraventricular arrhythmias e.g. WPW
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ADVERSE EFFECTS
1-bradycardia & heart block, heart failure
2- pulmonary fibrosis
3- hyper- or hypothyroidism 4- photodermatitis ( in 25%) and skin deposits 5- Bluish discoloration of the skin
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(CONTiNUE)
5- tremor, headache, ataxia, paresthesia6- constipation 7- corneal microdeposits8- hepatocellular necrosis9- peripheral neuropathy
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AMIODARONE
Pharmacokinetics: extremely long t1/2 = 13 - 103 DAYS
Drug Interactions: reduce clearance of several drugs e.g.
quinidine, warfarin, procaiamide, flecainide
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Given by a rapid I.V. infusion
Acute conversion of atrial flutter or atrial fibrillation to normal sinus rhythm. Causes QT interval prolongation , so it precipitates torsades de pointes.
PURE CLASS III Ibutilide
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Verapamil , Diltiazem
Main site of action ( A.V.N & S.A.N )
(causing slow conduction & prolong effective refractory period ).
Class 1V calcium channel blockers
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CALCIUM-CHANNEL BLOCKERS
USES
1- atrial arrhythmias
2- supraventricular arrhythmias e.g. WPW
NOT effective in ventricular arrhythmias
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MISCELLENIOUS ANTIARRHYTHMIC DRUGS
ADENOSINE
DIGITALIS
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ADENOSINE
- naturally occurring nucleoside-half-life= less than 10 sec.Mechanism: In cardiac tissues Binds to type 1 (A1) receptors which are coupled to Gi- proteins , activation of this pathway cause : Opening of potassium channels (hyperpolarization) Decrease cAMP which inhibits L-type calcium channels ( calcium influx ) causing
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Continue….
decrease in conduction velocity (negative dromotropic effect ) mainly at AVN.
In cardiac pacemaker cells ( SAN) , inhibits pacemaker current, which the slope of phase 4 of pacemaker action potential ( spontaneous firing rate {negative chronotropic effect})
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ADENOSINE ■ First drug of choice in paroxysmal supraventricular tachycardia
■ preferred over verapamil ( safer and does not depress contractility )■ given 6 mg I.V. bolus followed by 12 mg if necessary
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ADENOSINE
Adverse effects:■ Flushing in about 20% of patients■ Shortness of breath and chest burning in
10% of patients ( bronchospasm)
■ AV block ( contraindicated in heart block)
■ Rarely: hypotension, nausea, paresthesias,
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BRADYARRHYTHMIAS
ATROPINE
■ can be used in sinus bradycardia after myocardial infarction and in heart block
■ in emergency heart block isoprenaline
may be combined with atropine
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NONPHARMACOLOGIC THERAPY OF
ARRHYTHMIAS
Implantable Cardiac Defibrillator (ICD) can automatically detect and treat fatal arrhythmias such as ventricular fibrillation
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Thank you