Comprehensive Guide to Drug Effects on ECG Patterns and Cardiac Safety

I welcome you all for the session on Drug  Effects on ECG. This is one of the topics   that we have in our programme on Interpretation  and Application of ECG in Clinical Practice. We   know pretty well that ECG is one of the crucial  investigative parameters. We usually take it for  

patients who have cardiac disease or people who  complain of chest pain or, you know, angina. There   are few things when a patient is complaining,  then we will be interested to take ECG. And based on the findings in the ECG, we will try  to, you know, uh arrive at uh uh diagnosis um or,  

you know, that will indicate us to guess few,  you know, disorders which are related to heart.   Now, in this session, we are  going to see uh the drugs,   the various drugs which can cause changes  in ECG, uhm so that by by, you know,  

getting into, oh you know, the clinical  spectrum of problems that the patients are   having, we will arrive at a proper diagnosis, and  we can also, you know, oh treat them accordingly. Now, for the sake of this presentation, I  have actually categorised the drugs into 4.  

The reason is that, there are few drugs which  affect, uhm you know, heart straight away, and   they change the electrophysiology and they modify  the ECG pattern. They are directly acting drugs.   We have other drugs, let us say drugs which  uh, you know, do not actually act on heart,  

but still they produce changes in  the ECG through reflex mechanisms,   or, you know, we we call them as indirectly  acting drugs uh which affect ECG. Then we have non-cardiac medications. You  see here, uhm non-cardiac medications,  

uh they may be antimicrobials, they may  be antidepressants or antipsychotic drugs.   They also, you know, act through some non-specific  mechanisms, and they change the ECG pattern.   And then, finally we have uh drugs of abuse, uh  you know, drugs we use for recreational purpose  

or non-medical purpose, they also affect  heart, and then we get changes in the ECG. So, these are, you know, broadly I have classified  the drugs that affect ECG into 4. Now, we are into   the drugs that act directly on heart. Heart, let  us say myocardial muscle or conducting system, you  

know, they have various uh, you know, receptors  and channels. uhm And we have drugs which could,   you know, uhm stimulate, renovate these  receptors and, you know, channels, and thereby,   we get a lot of changes in the electrophysiology,  and then we ultimately see changes in the ECG.

The crucial receptors and channels, I have listed  here. uh We have sympathetic receptors, uhm   you know, we have uh adrenergic and, you know,  non-adrenergic and system, and we have alpha   and beta receptors in it; beta 1, beta 2, beta 3,  and then alpha 1 and alpha 2. In in, uhm you know,  

myocardium we have predominantly beta 1 receptor  located. We also have parasympathetic receptors,   cholinergic receptors. Basically, we classify  cholinergic receptors into muscarinic and   nicotinic; but in heart, what we see is, you  know, M2, muscarinic 2 type receptor uh which is  

predominantly seen in heart, both in myocardial  muscle and in in the conducting system. Then we have calcium channels, L type calcium  channels; and then, sodium channels; and then,   potassium channels; and then, myocardial  membrane has got sodium potassium ATPase,  

which is an enzyme. So, these are the potential  targets for drugs. And these drugs acting on   various receptors and channels in the heart, they,  you know, facilitate changes in the myocardium.   Sometimes, you know, these changes may be inert.  We may not have significant clinical, you know,  

outcomes of it; but sometimes, these these changes  may be dangerous and maybe, you know, serious and   which can give, you know, significant  cardiovascular morbidity and mortality. Now, we are into the drugs which could affect ECG  based on, you know, their action somewhere else,  

mostly; let us say blood vessels, arteries  and veins. And, you know, by acting on those   arteries and veins, we could get changes in the  ECG. uh These drugs may not straightaway act on   myocardium to bring in changes in the ECG. Okay.  That is why we put them as, you know, indirectly  

acting drugs or, you know, uh drugs through reflex  mechanisms, they they produce changes in the ECG. Ganglion stimulants; I am going to the last  one; you know, we have autonomic ganglia.   Drugs acting on those ganglia will will release  catecholamines. And these catecholamines, you  

know, through reflex mechanisms, act on in heart,  and they bring in changes, ganglionic stimulants.   And then, we have lot of vasodilators. See here,  vasodilators; many of them are going to act on   arteries, and a few of them will be acting  on, uh you know, veins. And then, uhm you  

know, we will have vasodilatation, maybe  arterial dilatation or venodilation. And then, through reflex mechanisms, you know,  catecholamines may be released, and they may   produce changes in the ECG. uh Most importantly,  we have calcium channel blockers, uh and then  

alpha blockers, again sympathetic; uh we were, we  have seen sympathetic receptors, alpha and beta.   Here alpha uh 1 receptor blockers, uhm they  they produce significant vasodilatation,   reduction in the blood pressure and  they may change uh the ECG pattern.

Then nitrates are venodilators; potassium  channel openers; and ACE inhibitors,   angiotensin converting enzyme inhibitors  and angiotensin receptor blockers.   uhm ACE inhibitors are good to heart. uh  They do not significantly change the ECG,  

but sometimes, in the peripheral vasodilatation,  through refle reflex mechanisms, we may have,   you know, changes in the ECG. The third category  drugs, I have already told that uh they are   mostly non-cardiac medications,  maybe antibiotics, maybe, you know,  

antipsychotics, uh maybe antifungal drugs,  okay, or drugs acting in the GI tract. uh They are non-cardiac drugs. And most of these  drugs may increase uh QT interval, you know, and   they may cause sometimes polymorphic ventricular  tachycardia. Now, these category of drugs,  

they they bring in changes through non-specific  mechanisms. And then, uh the fourth category,   we have drugs of abuse. You know, we use  drugs, uh not; you know, sometimes people are,   you know, getting tempted to use drugs for  recreational purposes, uhm non-medical purposes.

They get habituated and they started using,  you know, amphetamines, opioids, cocaine and   cannabis. And they may also cause, you know,  serious uh electrophysiological changes in the   heart. And ultimately, you know, the pe people who  are using it may suffer with significant cardiac  

morbidity. Now, we are actually going ahead  with uhm the individual drugs, uh how they   affect uh the ECG, and what are the exact changes  we will get to see in ECG if we are using those   medications, and the mechanisms by which these  drugs are going to cause, you know, ECG changes.

We have beta 1 receptor, and we know pretty well  that beta 1 receptors are located everywhere in   heart, let us say uhm endocardium, it  is there; and, you know, uh myocardium,   it is there; and conducting system, everywhere it  is present, beta 1 receptors. And it is basically  

a stimulatory receptor; that is why we call  them as Gs uhm, you know, receptor. And there   are drugs, there are uh neurotransmitters that  will stimulate beta 1 receptors and similarly,   there are drugs and neurotransmitters  that will inhibit the beta 1 receptors.

If if something is stimulating beta 1  receptor, it it increases force of contraction,   it increases rate of contraction, and you see  increased cardiac output and increased heart rate.   And similarly, if if you have something  which is inhibiting beta 1 receptors,  

uhm you know, uhm it it causes reduction in  the heart rate and reduction in the force of   contraction, conductivity, and then reduction in  the cardiac output. We have drugs that stimulate   beta 1 receptors, uh like adrenaline,  noradrenaline, isoprenoline and dobutamine.

Isoprenoline and dobutamine, they are cardiac  stimulants. We use them in case we have shock,   we have, you know, cardiogenic shock; and  cardiogenic failure, sometimes we use them.   Noradrenaline, again, in severe hypotension,  cardiogenic shock, we are using. Adrenaline,  

we use it for anaphylaxis; and then, we use it  again in, you know, cardiac arrest and cardiogenic   shock. They are life-saving medications. And  without proper reason, if you are using them,   they may be dangerous also, because, uhm  you know, they are going to stimulate heart.

And for no reason, if you are stimulating heart  with these powerful pharmacological agents, uh you   know, we may even have, you know, uh myocardial  infarction. We have seen patients, you know,   getting treated for allergy with adrenaline going  for, uh you know, acute myocardial infarction.  

Basically, these drugs cause tachycardia. You see,  the heart rate is increased more than 100. The   normal heart rate is about 60 to 100, and all  these medications that are stimulating beta 1   receptor may cause increased heart rate that  we call it a tachycardia, and ECG will give  

us the heart rate of 100 and more; 120, 140 or  even 200 we can get the heart rate in the ECG. And sometimes, they also cause a reduction in  the T wave amplitude and they also, you know,   increase QT interval. These are the ECG changes  that we commonly encounter when we are using  

drugs that stimulate beta 1 receptors. And we have  drugs that block beta 1 receptors. uh You know,   uhm we have non-selective blockers, uh you know,  you have beta 1, beta 2 and beta 3 receptors. And   from pharmacological action point of view, we  mainly use drugs that modulate beta 1 and beta 2.

And we have non-selective beta blockers, like they  block both beta 1 and beta 2. Drugs like sotelol,   pindolol and nadolol, they blocked both beta 1 and  beta 2. And we have selective beta 1 blockers like   metoprolol, atenolol, celiprolol, esmolol and  acebutolol. They do not have significant action  

on beta 2 receptor, they only act on beta 1  receptors and they block beta 1 receptors.   And what are the changes beta 1 inhibition  brings in ECG? uh We know, uh you know, uh beta   1 stimulation is stimulating heart, and  beta 1 inhibition is inhibiting heart.

So, the heart rate is going to come down,  force of contraction is going to come down,   cardiac output is going to come down. And  hence, what we see in ECG is bradycardia   and AV block. AV node uh is located between  atria and ventricle, and the impulses are  

transmitted from SA node through, uhm you know,  AV node to uh the ventricles and all other zones   in the myocardium. So, if if we are using  beta 1 blockers, they they bring in AV block   and they also reduce heart  rate, and we get bradycardia.

And sometimes, they also cause prolongation of PR  interval, QRS widening they cause, and, you know,   prolongation of QTC interval. Okay. So, whenever  a patient is receiving beta 1 blockers, these   ECG ECG changes may happen. Okay. Now, we are uh  going to uh M2 receptor, you know, muscarinic 2  

type receptor. uh You know, the neurotransmitter  uh endogenously present to modulate muscarinic   activity is acetylcholine, which is secreted  from the parasympathetic or cholinergic neurons. And these receptors are located in  myocardial muscle and conducting system.  

It is basically inhibitory in  nature, so, it goes with GI receptor.   And again, we have drugs and uh, you know,  mediators that stimulate M2 receptors;   and then, that inhibits, you know, M2 receptors.  And if we stimulate M2 receptor, uhm you know, we  

get reduction in the heart rate, we get reduction  in the force of contraction and conductivity.   And similarly, if we inhibit muscarinic  receptors, M2 receptors to be, uh you know;   more precisely putting it here; if we inhibit M2  receptors, we get increased heart rate, meaning  

that we can have tachycardia and we may also have  increased force of contraction and conductivity. Now, what are the drugs that stimulate  M2 receptors? We have directly acting   cholinomimetics like pilocarpine, and these  drugs stimulate M2 receptor straightaway.  

Whereas, we have other drugs which indirectly,  you know, stimulate M2 receptors. They are   indirectly acting cholinomimetics.  They do not act on the receptors,   uh rather they, you know, uhm you know,  inhibit an enzyme called acetylcholinesterase.  

This is enzyme that metabolises acetylcholine.  Acetylcholine is the cholinergic neurotransmitter. And if you could inhibit the enzyme that  destroys acetylcholine, what happens is that,   uhm you know, uh the levels of acetylcholine  in the synapse will be more, will be  

increased. And this enhanced acetylcholine will  will be stimulating too much these M2 receptors,   and then you will have all cholinergic activity.  That is why these drugs like physostigmine,   neostigmine, pyridostigmine, donepezil, uh  rivastigmine and galantamine, these drugs,  

they are called as indirectly acting  cholinomimetics, because they are   not acting on receptors as such; they  only block acetylcholinesterase inside. And here if you see, uh galantamine  and rivastigmine, they are used in  

Alzheimer's disease. Again, in donepezil is used  in Alzheimer's disease, you know, memory loss and   old age, senile dementia we get na. And the  physostigmine, neostigmine, pyridostigmine,   there were lot of therapeutic potential in various  conditions. Now, what are the ECG changes we get  

when we are stimulating M2 receptor? Like we  have already discussed that it is going to be   inhibitory in nature, we get bradycardia, we get  AV nodal block, most commonly, first degree AV   nodal block. And then, we also get prolongation  of PR interval, RR interval and QTc interval.

So, if a patient is receiving uh drugs for  Alzheimer's disease, his ECG may go for   these changes. M2 inhibition? Anticholinergics,  they are called, we have atropine;   we have hyoscine; ipratropium: ipratropium  is an anticholinergic drug that we use for  

bronchial asthma; and then we have tropicamide,  it it is used as eyedrops, you know, for   when we check the vision refraction, you know,  we use tropicamide to dilate the pupils. And   then pirenzepine is an anticholinergics that,  anticholinergic that is used for peptic ulcer.

These anticholinergics may also affect, you know,  heart, because we have M2 receptor, and these   drugs may sometimes have, you know, minimal effect  on M2 receptors, and they inhibit M2 receptors.   And what ultimately we have is that, you know,  cardiac stimulation. We have tachycardia. The  

heart rate is increased and we have sometimes  AV nodal block and, you know, reduction in the,   uh you know, duration of PR interval, and  sometimes you will also have flattening of T wave. Then I think we have calcium channels. Calcium  channels are seen everywhere in muscles,  

wherever we have contraction, maybe intestinal  smooth muscle, maybe skeletal muscle or maybe in   myocardium; everywhere we have calcium channels.  In myocardium, we have L type calcium channel.   It is present in myocardial muscle and also in  conducting system we have L type calcium channel.  

What it does is that, it increases. Whenever we stimulate these calcium channels,  whenever we have more entry of calcium into the   muscle, it causes increased muscle contraction.  And we have drugs that block these calcium  

channels, specifically in myocardium. We  have drugs like verapamil and diltiazem. uhm   You know uh, it it leads to inhibition of  cardiac contractility. So, what happens is that,   the heart rate is coming down. uhm It causes  bradycardia, AV block, a widening of QRS complex,  

and then cardiac asystole which is very dangerous,  the patient may even die out of it. Okay. And these drugs are antiarrhythmic drugs,  verapamil and diltiazem. And many of the   antiarrhythmic drugs, you know, they, by nature,  you know, they are going to bring in lot of  

changes in the ECG, plus their site of action  is heart, and hence, naturally they are going   to affect the cardiac electrophysiology, and we  will have lot of ECG changes. Sodium channel,   uhm you know, these channels are present in  the myocardial muscle and conducting system.

uh What it does is that, it causes a  rapid upstroke of cardiac action potential   and impulse conduction. And uh we have  drugs that block sodium channels. uh   You know, they are called sodium channel blockers.  And we actually sub-categorise them into 3 types,  

you know, sodium channel blockers, class  1A, 1B, and then 1C. They are basically,   you know, antiarrhythmic drugs. When when  the rhythm of the heart is already, you know,   uh uh you know, affected, and there is  dysrhythmia or there is abnormal rhythm  

of the myocardium, we will be using several, you  know, antiarrhythmic drugs to set the rhythm, to   bring back, uh you know, to a normal  rhythm, you know, regularly regular. Whenever this regularly regular  rhythm is altered due to some  

reasons, we will be using drugs to  bring the rhythm back, you know.   uh For that purpose, we may be using sodium  channel blockers. Class 1A drugs, they block   the sodium channel in open state and they also  produce prolongation of action potential. They  

are associated with prolongation of action  potential. We have class 1B drugs. You know,   they are sodium channel blockers. They block  the sodium channel in inactivated state. At the same time, they also reduce  or shorten the action potential.  

We have class 1C drugs. They block the sodium  channel in open state like class 1A drugs,   but they do not have significant effect on  the action potential. Okay. Now, what are the   drugs we have uhm as sodium channel blockers  and what is the effect these drugs bring in,  

uh you know, uh in the electrophysiology and  ultimately in the ECG tracings. Class 1A drugs:   We have drugs like quinidine, uhm you know,  of course, like antimalarial drug quinine, uhm   it is an iso isomer or a stereomer,  uh isomer of uh quinine, quinidine.

And then, procainamide, disopyramide; these  drugs are used in ventricular tachyarrhythmias,   like ventricular tachycardia and  other ventricular arrhythmias.   And uh these drugs produce prolonged PR interval,  QT interval, and they also widen the QRS complex.  

Class 1B drugs: Lidocaine, the same  local anaesthetic that we are using it.   Okay. And then, mexiletine. They are used  in again ventricular tachyarrhythmias. All   sodium channel blockers are useful in ventricular  tachyarrhythmias, uh either class 1A or 1B or 1C.

And the ECG changes also are pretty similar for  all the classes of sodium channel blockers, 1A,   1B and 1C. Here again, they  produce a prolonged PR interval,   widening of QRS complex and shortening  of RR interval. Then we have 1C drugs,  

flecainide and propafenone. A very many  drugs; for this presentation purpose, I   have actually restricted the number of drugs that  I am going to quote here. They are again used in,   you know, ventricular tachyarrhythmias and they  produce bradycardia, first degree AV block,  

widening of QRS complex and asystole, and  which is a very significant cardiac morbidity. In case if you are using these drugs and we need  to be aware of the fact that these drugs may also   produce cardiac asystole. Now, we are moving to  potassium channels. They are presenting, they are  

present in uh, you know, conducting system of  the heart mainly. And these potassium channels   regulate resting membrane potential. And also they  they try to regulate the frequency of SA node, and   indirectly, you know, that means  that it can control the heart rate.

Potassium channel blockers: We have drugs like  amiodarone, bretylium and dofetilide. They are   again used as antiarrhythmic drugs. Amiodarone is  one of the broadest spectrum antiarrhythmic, which   can be used in any type of arrhythmia, and it is  used predominantly in ventricular tachycardia,  

paroxysmal supraventricular tachycardia and atrial  fibrillation. And what these drugs uh produce in   ECG is that, they usually prolong, uh  you know, QT interval or QTC interval. And this can sometimes lead to polymorphic  ventricular tachycardia or which is also known as  

Torsades de Pointes. Sodium potassium  ATPase: It is present in the membrane   of the myocardial muscle and uh, you  know, uhm it is a target for a drug,   you know, age old medication that  is used in cardiac failure, digoxin.  

And it is also present in the conducting system  AV node, SA node, everywhere it is present.   What it does is that, it tries to maintain  low sodium and high potassium in the cell. And also it maintains the  resting membrane potential.  

And when we block this enzyme, you know,  sodium potassium ATPase, digoxin does it.   We have lots of digoxin like drugs. And  many of these drugs, what they do is that,   they increase the force of contraction. At the  same time, they produce AV nodal block and they  

reduce the heart rate. So, digoxin like drugs  are, you know, so unique, you know. They increase   the heart; I mean, they increase the cardiac  output. They increase the force of contraction. At the same time, they reduce heart rate, they  they reduce uh, you know, uh the conductivity of  

the impulses and they produce bradycardia, okay,  which is very unusual for a drug, okay; increased   cardiac output, at the same time bradycardia.  They, they also produce significant ECG changes.   For example, you take digoxin like drugs,  practically, they ca they can cause any any any  

change in the ECG. They can cause atrial, uh  premature beats, you know, functional premature   beats, atrial tachycardia, AB block, premature  ventricular beats and ventricular bigemini. Now, I think we are moving towards indirectly  acting drugs. What we have seen so far is,  

you know, the drugs that were acting directly  on heart on various receptors and channels and   bringing in changes in the ECG. Now, we are going  to talk about drugs that act in the periphery, uh   vasodilators, at the same time producing changes  in the ECG. If you see here, calcium channel  

blockers, we are taking first. uh They act, uhm  you know, uhm in the arteries, smooth muscles. uh They are L type calcium channel  blockers. Drugs like nifidipine,   amlodipine, nicardipine and felodipine. They  are used in hypertension; uh very popular in  

the treatment of hypertension, calcium channel  blockers. They do not have significant direct   cardiac activity. They only have very  minimal uh cardiac activity, as such,   these calcium channel blockers. But what they do  is that, because of the peripheral vasodilatation,  

there will be reflex uh, you know, secretion of  uh uh catecholamines from the autonomic ganglia. And these catecholamines act on myocardium and  they cause reflex tachycardia. And occasionally,   minimal bradycardia, you know, is associated with  nifidipine like drugs. And they also produce AV  

block, non-specific ST and T wave changes; calcium  channel blockers, they are vasodilators. And then,   we have alpha blockers; alpha 1 blockers.  Because we know that there are receptors alpha 1   and alpha 2; and alpha 1 receptor is  present in the arterial smooth muscle,  

uh drugs like prazosin, terazosin,  doxazosin and tamsulosin. They are used in benign prostatic hypertrophy  also, especially, tamsulosin and doxazosin.   Whereas, prazosin is mainly used in  systemic hypertension. When there is a,  

you know, very severe elevation of uh blood  pressure, and uh, you know, when we find it   difficult to handle uh systemic hypertension  with routinely used drugs, we go for these alpha   1 blockers. They are very significant, you know,  in reducing the blood pressure. And what they do  

in uh the ECG is that, they produce ventricular  brady and tachyarrhythmia, first degree AV block. Then we have nitrates. Unlike, you know, calcium  channel blockers and uh, you know, uh alpha   1 blockers, nitrates, they predominantly  are venodilators; they dilate the veins,  

larger veins and also smaller veins. They act  by releasing nitric oxide. And they are used   in angina pectoris. uhm See, when when patients  have a cardiac chest pain and we want to relieve   the chest pain immediately, you know, we give  nitrates sublingually, and then, you know,  

it releases nitric oxide, produces venodilatation  and reducing, you know, venous return. They reduce the cardiac workload and they reduce  anginal chest pain. And what nitrates produce here   in ECG is that, you know, they cause tachycardia.  And otherwise, I mean, they are pretty safe,  

there is no significant uh uh, you know, uh  electrophysiological changes that we encounter   with nitrates. Potassium channel openers: We have  drugs like nicorandil and minoxidil. Minoxidil is   a potassium channel opener, uh you know, rarely  used in hypertension nowadays, but uh it is found  

to be associated with increased hair growth and  hence minoxidil uhm as a lotion or, you know,   as a liquid preparation, it is used in alopecia,  you know, baldness, we are using minoxidil. But then, it is a, you know, vascular smooth  muscle uh relaxant. Okay. And uh, you know,  

it it causes increased intracellular potassium  and muscle relaxation. And what it does is that,   it causes a T wave changes and also shortening  of QT interval, potassium channel openers.   Then we have vasodilators. ACE inhibitors,  angiotensin converting enzyme inhibitors;  

drugs like captopril, enalapril  and lisinopril. And then, ARBs,   angiotensin receptor blockers, like  valsartan, telmisartan, irbesartan. You know, there are very many drugs that are  used. And now, this is the class of drugs,  

both ACE inhibitors and ARBs are  very commonly used in hypertension.   They are antihypertensives. They also have cardiac  protective activity, okay, but then they do not   have much or significant electrophysiological  changes. So, rarely they produce Qt prolongation,  

AV nodal block and then ST depression. uh  They are considered to be pretty safe as far   as heart is concerned. ACE inhibitors  and angiotensin receptor blockers. Now, we have uh the last uh category of drugs uh  in the indirectly acting or the drugs that act  

through reflex mechanisms producing ECG changes.  We have ganglionic stimulants. Autonomic ganglia,   you know, they have uh parasympathetic uh  nerve supply and they act uh by releasing   acetylcholine. And this acetylcholine will  stimulate nicotinic receptor here. uh Basically,  

nicotinic receptors, there  are 2 classes uh NN type,   they act on neurons; and then, NM  type, they act on skeletal muscles. And here we are talking about, you know,  nicotinic receptors present in the neurons,  

in the autonomic ganglia. And stimulation of these  ganglia will cause release of catecholamines,   adrenaline and noradrenaline, and they will  stimulate myocardium to cause, you know,   increased force of contraction and rate  of contraction. Drugs like nicotine and  

lobeline, you know, they cause sometimes  uh release of catecholamines and   they produce ECG changes like sinus  tachycardia and ventricular tachycardia. We have now, you know, non-specific mechanisms,  non-cardiac medications. You know, we use uh,  

like I I was saying, you know, drugs for  other purposes, like, you know, antibacterial,   antiviral, antifungal, antipsychotics,  antidepressants, antihistamines or prokinetic   drugs; all these drugs, sometimes, you know,  they are associated with uh cardiac issues.  

They cause prolongation of QT intervals and they  may produce ventricular arrhythmias. How they   produce the mechanisms are not very clear, but  still uh they mediate through multiple receptors. They they produce interactions among various  receptors, and they may also be associated with  

electrolyte abnormalities and other unknown  mechanisms. They cause these electrolyte,   I mean, electrophysiological changes in  the heart, and they produce changes in   the ECG. And there are drugs which were  banned for their cardiovascular effects.  

You know, they were approved for some  other indications, they were in the market,   but later they have realised that they are  associated with electrophysiological changes   and significant cardiovascular morbidity  and mortality, and these drugs were banned.

Drugs like terfenadine, uhm it was used uh for  itching, for running nose, okay; astemizole,   again for allergy and hypersensitivity reactions;  cisapride, a prokinetic drug for gastrointestinal   problems. They were all approved for their  indications, but then later, uh you know, the  

scientists have realised that they were associated  with significant cardiovascular problems and they   were all banned from the market. And these are the  drugs which are already available in the market,   but still they are associated with  uh, you know, uh cardiac issues.

Antibacterials: Levofloxacin; even azithromycin  has it; clarithromycin; erythromycin; many of the   macrolide antibiotics have got this problem. And  antifungals like itraconazole or ketoconazole;   antivirals: nelfinavir; they increase the QT  interval; they are associated with significant  

cardio cardiovascular problems. In case if the  patient is already having a cardiac problem,   then we need to be very careful when  you are using these medications.   Antidepressants like amitriptyline, imipramine  and doxepin, they cause QT prolongation.

And antipsychotics like haloperidol, risperidone  and quitiapine, they cause, you know, this problem   polymorphic ventricular tachycardia in susceptible  patients. Antiemetics like even ondansetron   supposed to be a very safe drug has got  this issue. And domperidone, you know,  

they they they may cause QT prolongation  and polymorphic ventricular tachycardia.   Now, the point is that, why we need  to know these things is that, when   when we are using these medications in any  other individual, you know, who is normal,  

whose cardiac function is fine, he does not  have any morbidity, then the the issue that   these drugs are, you know, predisposing  the patients may be very, very minimal. But if the patients after 50  years, knowingly or unknowingly,  

they may be having cardiovascular problems,  and if you are using these medications and,   you know, we may predispose the patients to  get into this, uh you know, arrhythmias and,   you know, we may unknowingly, you  know, predispose them to get into this  

cardiovascular morbidity and mortality. Okay.  Now, what uh finally we have is drugs of abuse,   illicit drugs, uhm you know, opioids, for  unapproved indications we are using it. And people who are mixing these  medications in liquor and they  

are drinking it. And without knowing  that these drugs have got significant   cardiovascular, uh you know, uhm interactions.  Opioids, they may produce bradycardia.   And heroin is an opioid, which can  cause cardiac conduction abnormality.  

And many of these drugs are associated with,  you know, long QTc syndrome, widening of the   QRS complex. Hallucinogens like lysergic acid,  diethylamide, they may produce tachycardia. Cocaine: It can cause sinus bradycardia,  complete heart block. We have seen patients  

who have abused cocaine, you know,  getting into complete heart block.   Then, marijuana, cannabis, ganja,  you know; tachycardia, non-specific   ST and T wave changes. And amphetamines,  ecstasy like drugs; sinus tachycardia,  

supraventricular tachyarrhythmia. So, uh without,  you know, uh understanding the implications of,   you know, interaction of these drugs in the  cardiovascular system, people are abusing it. We need to strongly, you know, disagree with  the practice of using these medications. Okay.  

For that, it also makes them to get into lot of  uh psychological issues, central nervous system   issues, and also cardiovascular problems. Okay.  Now, uh we have almost come to the end of uh this   session. What we have seen is that, mm you know,  the drugs, we have categorised into 4 types;  

directly acting drugs, indirectly acting drugs,  and then drugs through non-specific mechanisms,   non-cardiac medications affecting ECG, and  then drugs of abuse producing ECG changes. Why we need to know this is that,  number 1, uhm which is very important,  

you will have a drug which does not have this,  you know, uhm you know, changes in the ECGs; so,   you can always go back and then use an antibiotic.  In case if you are treating a cardiac patient   who has got a respiratory infection, instead  of choosing azithromycin and levofloxacin,  

we can use amoxicillin, because  amoxicillin is an antibiotic,   which is useful in respiratory infection,  but does not have significant ECG changes. So, the idea of giving this session is that,  we can we can choose drugs which are not having  

significant, you know, interaction with, you know,  cardiac receptors. They they do not have, you   know, uh significant, uh you know, uh interaction  with alpha, beta or muscarinic receptors. So,   they can be safely prescribed in a condition in  which you can also, you know, prescribe a drug  

which has got significant ECG changes. That is  the point. We would like to impress here that,   always try to choose a drug which does not  have cardiovascular, you know, interactions. In that way, giving you an overview of drugs which  have got changes uh, you know, in the ECG is to  

guide you in choosing a drug which will not hit  the ECG. This is point number 1. Point number 2,   if at all you want to use the same medicines which  have got significant ECG changes, you can be,   you know, preparing the patient, and also the  physician can prepare himself in in handling  

an eventuality. Okay. Azithromycin can lead to  increased uh or prolongation of QT interval. And if you are knowing the fact,  then you can prepare the patient,   and the physician also will prepare himself  in handling the cardiovascular problems.  

So, these are the 2 points I think, as as a  medical student or as a treating physician,   we need to know. One is that, choose  a drug which does not affect ECG;   number 1. Number 2, if at all we are choosing  a medication which can cause ECG changes,  

be prepare yourself in handling the eventuality.  That is the idea of having this session in this,   you know, programme, Interpretation and  Application of ECG in Clinical Practice. Now, before concluding, I thought I will make  a small remark on regulatory requirement of  

developing a drug. If we develop a drug for a  non-cardiac purpose, non-arrhythmic purpose,   okay, maybe an antibiotic, maybe an  analgesic, maybe an antihistamine,   maybe uh an antihypertensive medication  uh which is not indicated for arrhythmia,  

if you have the idea of developing a drug, now,  there is a guideline which which talks about   every drug has to be evaluated for  its action on QT interval, because,   you know, we have seen many of the non-cardiac  medications are affecting QT interval. Okay.

And hence, this ICH; ICH is the agency, like  International Conference on Harmonisation;   this agency is giving guidelines on development  of drug products. Okay. They have given this   guideline on efficacy 14, E14 guideline, which is  titled like, you know, clinical evaluation of QT  

interval prolongation and proarrhythmic  potential for non-arrhyth antiarrhythmic   medications. Like any other medication, which is  not meant for arrhythmia if you are developing,   it is not just enough we are we are evaluating the  efficacy and safety in that particular indication,  

it is also very important that we need to test the  drug for its potential to increase QT interval. So, we have to do a thorough QT uh study and also  we need to have endpoints in the clinical trial,   so that, whatever drug that we  are getting fa for the market  

is not having significant cardiovascular action,  significant effect on the QT interval. Okay.   Why we are concerned about the cardiovascular  uh effects? Because many of the non-cardiac   drugs may also be associated with,  you know, significant morbidity like,  

you know, polymorphic ventricular  tachycardia or Torsades de Pointes. A sudden cardiac death can happen in  case if you are using those medications,   if they are associated with significant, you know,  interaction in the ECG or, you know, QT interval,  

cardiac electrophysiology. And they may,  you know, produce or they may predispose   patients to get into ventricular tachycardia,  ventricular fibrillation and flutter. They may   produce syncopal attacks or sometimes seizures.  In order to avoid all these complications,  

whenever we develop a drug, I think we need to  make sure that the drugs are not having their   actions on, you know, QT interval and also in the  myocardial muscle and conducting system. Okay. I think, with this, we have come to the end of uh  the presentation. uh This session was about drugs,  

drug effects on ECG. Okay. I hope this  session was useful to the beginners,   especially the medical students and practicing  physicians, uhm you know, in in giving, uhm you   know, a thought. Whenever they are choosing a  medication, like I have already highlighted,  

try to choose a medication which is not having,  uh you know, any cardiovascular interaction,   or if at all we are forced to choose a medication  which is having all these changes in the ECGs or   interactions in the myocardial muscle  and, uhm you know, conducting system,  

please be ready to handle any eventuality.  Okay. Thank you very much for patient listening.