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What are the classess of antiarrhythmic drugs?
- Ia - intermediate Na channel blockers. Prolong APD.
- Ib - fast Na channel blockers. Shorten APD.
- Ic - slow Na channel blockers. Minimal effect on APD.
- II - beta-blockers
- III - K channel blockers
- IV - Calcium channel blockers
What is the mnemonic for the classess of antiarrhythmic drugs?
- Some - Sodium channel blockers
- Block - Beta-blockers
- Potassium - Potassium channel blockers
- Channels - Calcium channel blockers
What is procainamide?
- Ia class antiarrhythmic drug.
- It blocks Na current in stage 0 of cardiac cycle (upstroke), thus proloonging APD.
What action does Procainamide have on K channels?
It has non-specific K channel blocking activity. This causes prolongation of APD.
Does Procainamide affect SAN and or AVN?
It has direct depressant action on SAN and AVN.
Does Procainamide have extracardiac effects?
- Procainamide has gangliobloking effect which causes vasodilation.
- This is more pronounced in quick IV push or severe LV dysfunction.
What is the danger of use of Procainamide in renal failure?
- Procainamide is metabolised in the liver with formation of NAPA - a class III substance. NAPA has been implicated in causing TDP.
- NAPA is secreted by kidneys.
How are Quinidine and Procainamide similar?
- Both belong to Class Ia drugs;
- Both work by causing Na channles blokade;
- Both slow upstroke (phase 0) and increase APD;
- Both cause QT prolongation;
- Both cause K channel bloakde as well;
- Both can induce TDP.
What is the specific toxic syndrome is observed in Quinidine poisoning/overdose?
Cinhonism: headache, tinnitus and dizziness.
Disopyramide belongs to Class III antiarrhythmic agents. True of False?
- Dysapiramide belongs to Na channel blockers (Class Ia).
- It is much more potent than Quinidine.
Disopyramde is the first line agent in heart failure. True or False?
- Disoyramide is contraindicated in severe heart failure due to the fact that it slows the upstroke speed and increases APD.
- It can also cause HF de novo.
How to memorize Class Ia drugs?
- Double - Disopyramide
- Quarter - Quinidine
- Pounder - Procainamide
What is the mnemonic for Class Ib agents?
- Lettuce - Lidocaine
- Tomato - Tocainide
- Mayo - Mexilitine
- Pickles - Phenytoin
What is bioavailability of Lidocaine following oral administration?
Lidocaine is extensively metabolised in the liver as first pass clearance. PO bioavailability of Lidocaine is ~3%.
What is T1/2 of Lidocaine?
T1/2 of Lidocaine is 1-2hrs.
Why there is increased tolerance to Lidocaine in patients in acute phase of illness (e.g. AMI)?
Lignocaine is bound by alpha1-gycoprotein - an acute phase substance which makes it less available for pharmacological interaction.
How Lidoacaine exerts its action?
Lidocaine blocks both activated and inactivated Na channels.Blocade of inactivated Na channels leads to greater degree of action especially in the Purkinje fibres and ventricular cells. This makes Lidocaine most valuable in ventricular arrhythmias.
What is the mnemonic for Class Ic antiarrhythmic agents?
- More - Moricizine
- Fries - Flecainide
- Please - Propaphenon
- All class Ic drugs act on both Na and K channels.
- They have slow unblocking kinetics.
What are the actioins of Flecainide?
- Blocks both Na and some K channels;
- Slow unblocking kinetics;
- Does not prolong QT and APD.
Flecainide has mild muscarinic effect. True or False?
False. Flecainide has no muscarinic effect.
What Flecainide is used for?
Flecainide is used for supraventricular arrhythmias in otherwise normal heart.
What are the similarities between Propranolol and Propaphenon?
Propaphenon has structural similarities with Propranolol and exerts weak beta-blockig activities.
What are the uses of Propaphenon?
- Propaphenon is used for management of supraventricular arrhythmias.
- The average daily dose is 450-900mg. T1/2 5-7hrs.
What are Class III antiarrhythmic agents?
- Class III antiarrhythmic agents prolong action potential by way of
- - blocking K channels or
- - enchancing inward curent (e.g. through Na channels)
Is there a mnemonic for class III agents?
- A - Amiodarone
- Big - Brytelium
- Dog - Dofetilde
- Is - Ibutilide
- Scary - Sotalol
What are the results of action of Class III drugs on the cardiac cycle?
- Ther results of the action are:
- - QT prolongation;
- - Depression of repolarisation;
- - Reverse-use dependence;
- - Action potential stability.
What does reverse use dependence denote?
Reverse use dependence is the effect where the Class III agents cause APD prolongation more at slow heart rates, NOT at fast heart rates.
What are the advantages in QT prologation caused by antiarrhythmic agents?
QT prolongation leads to increase in APD => increase in reafractory period. This mechanism underlies the use of the medication in treament of re-entry arrhythmia.
What are the effects of Amiodarone on cardiac muscle?
- Amiodarone blocks inward K curent in repolarisation thus leading to marked prolongation of QT interval.
- It does it across wider range of heart rates, therefore it does not have the reverse-dose dependence effect.
- Amiodarone also block inactivated Na channels.
- It exerts weak adrenergic action and Ca channel blockade.The upshot of the actions is slowing of AV conduction and slowing of the heart rate.
What are important adverse effecs of Amiodarone?
- Amiodarone blocks conversion of T4 to T3 and may cause hypo- and hyperthyroidism;
- Amiodarone causes pulmonary fibrosis in ~1% of patients;
- It can cause corneal deposits, blurred visions and occasinally optical neuritis;
- Amiodrone causes abnormal LFT;
- People taking Amiodarone develop gray-blue skin dyscolorations on sun exposed areas.
What are more common adverse exracardiac effects of Verapamil?
- - Nervousness
- - Lassitude
- - Constipation
- - Pretibial oedema
Which group of antiarrhythmic agents does Verapamil belong to?
Verapamil is a Class III agent. It is a Ca channel blocking drug.
What action does Verapamil have in the heart?
- - Verapamil block both actvated and inactivated Ca channels in the heart;
- -It affects the tissues that fire more frequently, incompletely depolarized tissues and tissues that depend exclusively on Ca current;
- - It always slows conduction in SAN and AVN;
What paradoxical effecct can Verapamil occasionally have on the SAN?
Vasodilatory effect can sometimes lead to a small increase in the firing rate (e.g. tachycardia).
What is the main site of metabolism of Verapamil?
Verapamil is extensively metabolised in the liver. Therefore the dose must be adjusted in liver disease.
What is bioavailability ond T1/2 oof Verapamil?
The bioavailability and T1/2 of Verapamil is 20% and 7hr respectively.
What is the more fearsome adverse effect of Verapamil on the cardiac conducting system and how it can be negated?
Verapamil can cause AVB if used in WPW. This can be treated with Atropine or a beta-blocker.
Effective oral doses of Verapamil are lower that those of IV. True or False?
Verapamil undergoes extensive first pass metabolism in the liver. Its bioavailability in oral administratin is only 20%. Therefore the effective doses for oral administration are higher than IV doses.
Why use of Verapamil in sustained ventricular tachycardia can lead to haemodynamic collapse?
Verapamil invariaby affects SAN and AVN. In the case of a sustained VT, it blocks AVN causing the collapse.
What are Class II agents? Give some examples.
- Class II agents are beta-blockers. The examples are:
What is the mechanism of action of Class II drugs?
- These drugs cause their action through the direct membrane effect via Na channel block;
- They decrease SAN firing rate (automaticity) and AVN conduction velocity.
Na current is not he main determinant in of ion current the phase 0 of the cardiac cycle for all paaarts of the heart. True or False.
True. While Na current is the main determinant of the upstroke in most parts of the heart - upstroke in AVN is Ca dependent.
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