Drugs that causes Long QT Syndrome

LQTS is the most common and best understood type of channelopathy. It occurs in about 1 in 5,000 people. In 7 in every 10 people with LQTS, the ion channels involved have been identified. In most cases two of the potassium channels that regulate the movement of potassium ions from the inside to the outside of the cell are affected. In a small proportion of people with LQTS, a sodium channel that regulates the flow of sodium ions from the outside to the inside of cells is affected.

In people with potassium channel associated LQTS, the channels do not behave as efficiently as normal. They let potassium ions into the cell too slowly. If the sodium channel is affected, too many sodium ions are allowed into the cell. (See the LQTS diagram - figure 2B - below.) This results in an electrical disturbance in the cells of the heart called 'prolonged repolarisation'. This can be seen on an ECG recording as a lengthening of the time period known as the 'QT interval'.  This is where the name Long QT Syndrome comes from.

Rare forms of LQTS known as Andersen's and Timothy Syndromes have been associated with potassium and calcium channel abnormalities respectively.

What are the symptoms?

LQTS varies greatly in severity. Symptoms vary according to the type of channel involved, whether the person is male or female, their age, and the length of the QT interval on the ECG. Males are more likely to have symptoms before puberty, while females are more likely to have them in adolescence and early adulthood. Relatives from the same family who have inherited the same mutation may have very different experiences. For example, some may have a normal QT interval and not have any symptoms; some may have a very abnormal QT interval but no symptoms; and some may have a very abnormal QT interval and have many events that put them at risk.

The most common symptom of LQTS is blackouts. Sometimes palpitations due to extra or 'ectopic' heartbeats can be a problem.

Potassium channel LQTS is associated with sudden death which is related to exercise or when the person has been startled or awoken suddenly ('sudden arousal'). The sodium channel form is associated with death while asleep.

Are there any physical signs?

There are no physical signs of LQTS. However, people with Andersen's Syndrome may also have muscle weakness or minor abnormalities of the skull, chin, fingers and toes.

How is it diagnosed? 

Diagnosis involves having an ECG. Sometimes it is possible to tell which ion channel has been affected just by looking at the ECG recording. Unfortunately, in many people who might be carriers, the ECG does not show any sign of the condition. Repeated ECGs, exercise tests and 24-48 hour tape monitoring may be needed before any hint of the condition is seen, and even then there may be no sign of it (we describe all these tests in cardiac tests).

Genetic testing can sometimes identify carriers of LQTS. Unfortunately, this form of testing is limited at the moment, as 3 in every 10 people who are known to have LQTS do not have mutations of the genes known to be associated with LQTS. An additional problem is that most families who do have the mutations appear to have a specific change to the DNA code which is not found in other families (known as a 'private’ mutation). This sometimes makes it difficult to decide whether a mutation is causing the disease or not. Things are further complicated by the fact that people with the same mutation can have effects that vary greatly in severity. All of this makes it very difficult for doctors to decide on the best way to treat people with this condition.

Treatment and advice

If you have LQTS, your doctor will advise you to avoid excessive exercise or strenuous athletic activities. He or she will also advise you to avoid certain drugs that can make the condition worse and which could increase the risk of blackouts and sudden cardiac death.

1) In Normal Heart potassium flows out of the cell to 'repolarise' the heart, and sodium flows into the cells to activate the heart.

2) In people with LQTS: The flow of potassium is usually reduced. In some people with LQTS, the flow of sodium may be increased.

In people with Brugada Syndrome or PCCD. The flow of sodium into the heart cells is reduced.

The level of risk of sudden death helps decide on the need for treatment. Those who are statistically at greatest risk of sudden death are people with one or more of the following features: 

• A previous cardiac arrest
• Blackouts
• A very long QT interval on the ECG
• Sodium channel mutations
• Young adult women.

Children who are most at risk tend to be young boys before puberty, and girls who are passing into puberty.

Drugs

The first line of treatment is with drugs. The most commonly used drugs are betablockers. These block the effects of adrenaline and associated natural chemicals in the body that make the heart pump harder and faster. They therefore also block the effects of exercise on the heart. They are effective in the most common forms of LQTS as they reduce symptoms and the risk of sudden death. However, they are less effective in people with the sodium channel form of LQTS. 

There are other more recent trends in drug treatment that look promising, but their long-term benefits are unknown. These involve using antiarrhythmic drugs. These drugs block disturbances in the heart rhythm that can cause sudden death. Potassium supplement pills have also been tried with occasional success.

Antiarrhythmics

Class 1: ajmaline*, cibenzoline*, dihydroquinidine*, disopyramide, encainide*, flecainide, mexiletine, pirmenol*, procainamide, propafenone quinidine*

Class 3: almokalant*, amiodarone, azimilide*, bretylium, dofetilide*, dronedarone*, d-sotalol*, ersentilide*, ibutilide*, nifekalant*, sematilide*, sotalol, terikalant*

Anti-anginals/vasodilators

bepridil*, lidoflazine*, prenylamine*, ranolazine, terodiline*, vardenafil

Anti-hypertensives

indapamide, isradipine, moexipril/hydrochlorthiazide, nicardipine

Antihistamines

astemizole*, azelastine, diphenhydramine, ebastine*, hydroxyzine, terfenadine*

Serotonin agonists and antagonists

cisapride*, dolasetron, granisetron, ketanserin*, ondansetron

Antimicrobials

Macrolide antibiotics: azithromycin, clarithromycin, erythromycin, roxithromycin*, spiramycin, telithromycin

Quinolone antibiotics: ciprofloxacin, gatifloxacin*, gemifloxacin*, grepafloxacin*, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin*

Antifungals: cotrimoxazole, fluconazole (caution with itraconazole), ketoconazole, voriconazole

Others: pentamidine, trimethoprim sulfa (bactrim)

Antiviral: foscarnet (HIV)

Antimalarials

amantidine, chloroquine, halofantrine*, quinine

Psychiatric drugs

Tricyclic antidepressants: amitriptyline, amoxapine*, clomipramine, desipramine*, doxepin, imipramine, nortriptyline, protriptyline*, trimipramine

Phenothiazines: chlorpromazine, fluphenazine, prochlorperazine, thioridazine*, trifluoperazine

Others: atomoxetine, citalopram, clozapine, droperidol*, fluoxetine, haloperidol, levomethadyl*, lithium, maprotiline, mesoridazine, methadone, paroxetine, pericycline, pimozide, quetiapine, risperidone, sertindole, sertraline, trazodone, venlafaxine, zimeldine*, ziprasidone

Anticonvulsant

felbamate*, fosphenytoin (prodrug of phenytoin)

Anti-migraine

naratriptan, sumatriptan, zolmitriptan

Anti-cancer

arsenic trioxide, geldanamycin*, sunitib, tacrolimus, tamoxifen

Others

alfuzosin, chloral hydrate, clobutinol*, domperidone, galantamine, octreotide, organophosphates*, perflutren lipid microspheres, probucol, solifenacin, tizanidine, tolterodine, vasopressin

Stimulant drugs

Some cold remedies contain these drugs so it is important always to check the label.

adrenaline (epinephrine), amphetamine, cocaine, dexmethylphenidate, dobutamine, dopamine, ephedrine, fenfluramine, isoprenaline (isoproterenol), levalbuterol, metaproterenol, methylphenidate, midodrine, norepinephrine (noradrenaline), phentermine, phenylephrine, phenylpropanolamine, pseudoephidrine, ritodrine, salbutamol (albuterol), salmeterol, sibutramine, terbutaline.

* = Drugs which are unlicensed, withdrawn or suspended in the international market.

Source: FDA

by

AKSHAYA SRIKANTH

Pharm.D Resident

India

ATAXIA: What Does it Mean

 Ataxia is a Poor coordination and unsteadiness due to the brain's failure to regulate the body's posture and regulate the strength and direction of limb movements. Ataxia is usually due to disease in the cerebellum of the brain, which lies beneath the back part of the cerebrum.

General analysis of the case:

A) Patient complains:

1. Instability of walking and repeated falling down (poor balance or decreased equilibrium)
2. Shaking of the hand at the start of the action( intention tremor)

B) Signs which has been seen by the physician:

1. Slurred speech (dysarthria)

C) Other condition of the patient:

1. He is known hypertensive case for 10 years; his BP is 190/90 with medication.

D) Important negative data:

1. No alcohol consumption, because alcohol can produce the same clinical picture.

E) Provisional diagnosis:

All symptoms and signs indicating cerebellar disease because:

1. Instability of walking and repeated falling down --> poor balance ---> balance is the function of vestibulocerebellum.
2. Intention tremors ---> loss of damping function which is a function of the spinocerebellum.
3. Dysarthria ----> loss of timing function which is a function of the cerebrocerebellum.

Tasks:

Tasks 1 & 2:

• Head region tests:
• Eye examination Nystagmus
• Hypotonia of the face and neck muscles and this result in pulling of the face toward the normal side ((defective attitude))
• Dysarthria broken speech because cerebellum controls the vocal cords.
• Upper limbs teat:
• Finger – nose – finger test. Overshooting and missing of the wanted point. Dysmetria or post-pointing or intention tremors.
• Fast alternative movements ((Dysdiadochokinesia))
• Rebound phenomena. The patient hand will slip to hit his face.
• Lower limbs test:
• Straight line test. The patient is unable to walk in a straight line and he has a drunken gait.
• Heel-shin test. The heel wavers away from the line of the shin.
• Reflexes:
• Cerebellar damage --> muscle Hypotonia.
• Deep tendon reflexes (knee reflex) --> pendular and weak (hyporeflexia)
• Superficial reflexes (plantar reflex) --> weakened.

Task3:

C.T. or MRI.

Task 4:

By executing a Romberg’s test we can identify the site of the lesion 

1. Positive Romberg’s test suggest a dorsal column lesion (( sensory ataxia))
2. Negative Romberg’s test suggests lesion to the midline and adjacent structures of the cerebellum.

The lesion could be:

• Tumors.
• Hemorrhage.
• Infarction.
• Abscesses.
• Multiple sclerosis.

Task 5:

The loss of the damping function of the cerebellum ---> overshooting ---> correction ---> repeated overshooting and correction leads to the shaking of the hands. (Intention tremors).

Task 6:

Because the equilibrium function (controlling the contraction of the agonist and antagonist muscle groups) of the cerebellum is disturbed. 

Task 7:

Dr.Wajid said that we should cross this question because it is unreasonable.

Task 8:

He has this problem because the formation of words depends on rapid and orderly succession of individual muscle movements in the larynx, mouth, and respiratory system. Lack of coordination among these and inability to adjust in advance either the intensity of sound or duration of each successive sound causes jumbled vocalization, with some syllables loud, some weak, some held for long intervals, some held for short intervals, and resultant speech that is often unintelligible. This is called dysarthria.

Task 9:

They are the Anterior and posterior spinocerebellar tracts.

You need to know these facts about these tracts:

• Course.
• Contra or ipsilateral tract.
• Number of synapses.
• Type of information transmitted.

These information can be found in neuroanatomy by Snell pages 147-150  and figure 4-13 page 149 and the table 4-3 page 150

by

Akshaya Srikanth

Pharm.D Resident

Hyderabad, India

BREATHING NEW LIFE INTO OLD MEDICINES

Discovering and developing new treatments for disease is a challenging, time-consuming, and expensive endeavor. For every drug that eventually makes it to the pharmacy, hundreds of compounds fail to deliver results and millions of dollars are spent without a direct return on investment. However, in these economically challenging times, existing drugs and compounds—whether in development, already on the market, or even ones that have failed clinical trials due to lack of efficacy—are being re-examined by pharmaceutical companies and research institutions. The goal of this approach—called drug repurposing— is to find potential new uses for these drugs.

High-throughput drug screening platforms in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics will be used to screen existing drugs for new applications.

There are three main benefits to drug repurposing—it’s safer, faster, and cheaper. Since a repurposed drug has already passed a significant number of toxicity and other tests, its risks are better known and the chance of failure is reduced. More than 90 percent of new drugs fail during development, contributing to the high cost of pharmaceutical research and development. A new therapy based on a repurposed drug could benefit patients sooner—ultimately saving and improving more lives.

In the past, drug repurposing efforts were hampered by the lack of a complete drug collection. Fortunately, a comprehensive listing of clinically approved drugs was recently made available by the NIH. Now, in order to make the promise of drug repurposing a reality, Sanford-Burnham researchers are building the world’s most comprehensive library (collection) of repurposed drugs, which can be leveraged against our strengths in stem cell biology, phenotypic cell-based screening, and high-throughput drug screening. Moreover, this library will be made available to other non-profit research institutions to advance translational medicine.

Despite the promise of drug repurposing, serendipitous discovery of new applications for existing drugs happens rarely, and only at the point when people are actually taking them. With the advent of stem cell-based human disease models—called disease in a dish—researchers can now test large numbers of approved drugs for their efficacy against a number of diseases before they reach clinical testing in humans. In this technique, researchers at Sanford-Burnham and elsewhere take skin samples from a patient or healthy volunteer, dial them back developmentally to stem cells, and induce their differentiation into the desired cell type (neurons, for example, if studying Alzheimer’s disease). The advantage to disease-in-a-dish modeling is that it generates large numbers of otherwise hard-to-access cell types, complete with an individual’s genetic and epigenetic make-up—making it a valuable tool for discovering and developing therapies that are more personalized to the individual.

Using cells from a patient with muscular dystrophy and a small library of FDA-approved drugs, Sanford-Burnham scientists have already identified a series of agents that reverse the functional defect causing the disease, providing an initial proof-of-concept for this approach. Spurred on by this exciting data, the team is now developing disease-in-a-dish screens for other genetic diseases.

While we are making substantial progress, one challenge is the incompleteness of the current drug repurposing library available to us. The more complete this library, the greater the chance we will find a drug that can potentially be repurposed to treat a child with a genetic condition like muscular dystrophy or other diseases.

“Regrettably, pharmaceutical companies are not likely to engage in drug repurposing efforts for rare childhood diseases,” Sanford-Burnham’s Layton Smith told Drug Discovery News. “This is in part due to the smaller patient populations and challenges in running clinical trials in these indications. In addition, competition with generic drugs makes this effort commercially unviable, in spite of its great potential to benefit human health. Even if companies were motivated to engage in these efforts, it is very difficult for the pharmaceutical industry to perform the type of screens Sanford-Burnham is doing because of their limited access to patient samples.”

Non-profit research institutes such as Sanford-Burnham, on the other hand, are well positioned to respond to this market and research opportunity.

Source: Drug News

by

AKSHAYA SRIKANTH

Pharm.D

India

ADVERSE DRUG REACTION CASE REPORTS IN ELDERS

Ciprofloxacin Delirium and myoclonus in an elderly patient: case report

An 85 year old man received oral ciprofloxacin 500mg daily for an infected right hip joint. On the seventh day he experienced generalized myoclonic jerks, hallucination and delirium which improved with a small dose of clonazepam. Ciprofloxacin was permanently withdrawn after his symptoms recurred twice following re-administration. No further episodes of delirium myoclonic jerks occurred.

Jayathissa S. Eet al. Myoclonus and delirium associated with ciprofloxacin. Age and Ageing 39: 762, No. 6, Nov 2010.

Metformin Lactic acidiosis and vision loss in an elderly patient: case report 

A 67 year old woman developed lactic acidiosis and transient vision loss during treatment with metformin for type 2 diabetes mellitus. The woman, who had a history of coronary disease, hypertension and osteoarthritis, and who had been receiving metformin (dosage, route and duration of treatment not stated), presented to an emergency department with acute bilateral vision loss. Her vision loss had started the previous afternoon. Examination revealed a rectal temperature of 32.3o, a HR 55 beats/min, a BP of 117/94mm Hg, a respiratory rate of 34 breaths/min and a pulse oximeter reading of 98%. She was awake and alert but her visual acuity and fields were not intact and she had mid-sized pupils that were slow to react. Laboratory tests showed a pH OF 6.65 and a lactate level of 10.9mmol/L. Her creatinine level was 7.0 mg/dL from a baseline of 1.3 mg/dL and her serum metformin concentration was 28 microgram/mL. She also had hyperkalaemia with a potassium level of 7.1mmol/L. The woman was treated with calcium gluconate, insulin and glucose for hyperkalaemia and sodium bicarbonate for her metabolic acidiosis. Following a lack of response, emergency haemodialysis was initiated. Her vision returned 10 hours after admission with an acuity of 20/30 bilaterally. Her blood pH increased to 7.48, her hypothermia resolved and her laboratory values normalized. She was discharged without metformin therapy. Author comment: ‘’This patient’s metabolic acidiosis resulted from long-term metformin use in the setting of an elevated creatinine, which ultimately caused decreased excretion of the drug. Her presenting complaint was vision loss’’.

Kreshak AA, et al. Transient vision loss in a patient with metformin-associated lactic acidiosis. American Journal of Emergency Medicines 28: 1059e5-1059e7, No.9, Nov 2010.

Corticosteroids/methotrexate Kaposi’s sarcoma in an elderly patient: case report

A 65-year old man developed kaposi’s sarcoma with colonic and skin lesions, following treatment with methotrexate and corticosteroids, including prednisone for ulcerative colitis(UC).

Following a diagnosis of left sided UC and spondyloarthropathy in November 1993, immunomodulatory therapy with mercaptopurine and azathioprine was initiated; treatment was subsequently withdrawn due to gastrointestinal intolerance. In June 2001, methotrexate (dosage and route not stated) was introduced but was suspended in November 2007 to prevent potential drug-related toxicities; prednisone 5mg/day (route not stated) was administered continuously throughout this period. In August 2008, he was admitted for IV steroid therapy (details not stated) following an acute disease episode. During admission he developed violaceous reddish-brown nodules on both legs (time to reaction onset not clearly stated). Investigation revealed active UC with multiple reddish elevated lesions in the last 25cm of the colon, and thickening of the rectum and sigmoid colon walls. Skin histology showed a small, non-encapsulated dermal lesion composed of dilated, irregular and spiculated blood vessels, lined by few prominent endothelial cells; lymphocytes and macrophages comprised an associated infiltrate. Immunohistochemistry with CD34 and CD31 were positive; staining for human herpes virus 8 (HHV-8) showed moderate and focal nuclear positivity. Colonic kaposi’s sarcoma was the preliminary diagnosis. Anti-HHV-8 serology demonstrated an IgG antibody titre of 1/40. A protocolectomy was performed, confirming the presence of multiple nodular lesions of the sigmoid colon and rectum. Labelling for HHV-8 was positive. Multifocal kaposi’s sarcoma of the colon was the final diagnosis. The man’s skin lesions resolved after surgery and steroid withdrawal. At 12 months follow-up, he had no symptoms and no recurrence of skin lesions.
Rodriguez-Pelaez M, et al. kaposi’s sarcoma: An opportunistic infection by human herpesvirus-8 in ulcerative colitis. Journal of Crohn’s and colitis 4: 586-590, No.5, Nov 2010.

Influenza virus vaccine/influenza A virus vaccine H1N1 Guillain-Barre syndrome in an elderly patient: case report

A 75 year old man, with severe chronic obstructive pulmonary disease and dyspnoea, was hospitalized with worsening dyspnoea, cough and purulent expectoration. He reported a progressive debility in his lower limbs for the past week. Neurological examinations revealed grade 4/5 debility in his lower limbs and loss of osteotendinous reflexes. He had received a seasonal influenza virus vaccine 8 weeks earlier and an influenza A viral vaccine, H1N1 vaccine 2 weeks before the onset of the symptoms (route and doses not stated ). A lumber puncture and an electromyogram revealed albumino-cytological dissociation and acute demyelinating neuropathy affecting his lower limbs, respectively. Guillain-Barre syndrome secondary to influenza vaccine was suspected. He received immunoglobulins and rehabilitation. The weakness in his extremities and his respiratory process improved markedly; he was discharged and monitored. Author comment: There was casual effect between the vaccinations and Guillain-Barre syndrome, although it was not possible to determine which of the two was supposed to be responsible, whether it was the result of a sum of probabilities or a cumulative effect of antigen stimulation. Nieto ML, et al. Gullain-Barre syndrome secondary to H1N1 influenza vaccine.

Revista Clinica Espanola 210: 485-486, No. 9, Oct 2010.

by

Akshaya Srikanth

Pharm.D Resident

Hyderabad, India

HEART DISEASE PASSES FROM FATHER TO SON

Coronary artery disease, which kills tens of thousands each year, may be passed genetically from father to son, according to a new study.

The study, led by the University of Leicester, shows that the Y chromosome - a part of DNA only present in men - plays a role in the inheritance of the disease.

Coronary artery disease involves the narrowing of blood vessels delivering blood to the heart, and can lead to angina symptoms, such as constriction of the chest, and heart attacks.

Scientists analysed DNA from over 3,000 men enrolled in a heart health study and found that 90 per cent of British Y chromosomes belong to one of two major groups.  

The risk of coronary artery disease among men who carry a Y chromosome in one of the two groups is 50 per cent higher than for other men, and is independent of traditional risk factors such as high cholesterol, high blood pressure and smoking.  

The researchers believe the increased risk is down to the specific group's influence on the immune system and inflammation.  

Principal investigator Dr Maciej Tomaszewski said:

“We are very excited about these findings as they put the Y chromosome on the map of genetic susceptibility to coronary artery disease. We wish to further analyse the human Y chromosome to find specific genes and variants that drive this association.

“The major novelty of these findings is that the human Y chromosome appears to play a role in the cardiovascular system beyond its traditionally perceived determination of male sex.

Dr Hélène Wilson, research advisor at the British Heart Foundation (BHF), which was the main funder of the study, said:

“Lifestyle choices such as poor diet and smoking are major causes, but inherited factors carried in DNA are also part of the picture.

"The next step is to identify specifically which genes are responsible and how they might increase heart attack risk."

“This discovery could help lead to new treatments for heart disease in men, or tests that could tell men if they are at particularly high risk of a heart attack.

The study is published in The Lancet in February 2012 . LINK: LANCET

by

AKSHAYA SRIKANTH

Pharm.D Resident

Hyderabad, India

A Sense of Urgency

Bladder issues such as urinary tract infections, overactive bladder, interstitial cystitis, and incontinence are the top healthcare problems in the United States today. The best-selling items in pharmacies are now adult diapers, reaching 2.2 billion dollars in sales per year.

As men and women age, the incidence of bladder problems and urinary incontinence increases for both sexes. These problems are far more common in women, but many women just ignore them, thinking that leaking small amounts of urine when sneezing or laughing are not a real medical problem. They may feel too embarrassed to seek assistance, or they may look at it as just another normal part of aging.

Incontinence is defined as the involuntary release of urine and, while it often accompanies aging, it can be caused by many factors. For example, removal of the uterus can lead to weakening or prolapse of the bladder, resulting in incontinence, simply due to the lack of physical support from that organ. Incontinence can also result from a lack of estrogen, which weakens the bladder and urinary tract structures. Diseases like diabetes or the aftermath of stroke can cause incontinence. Constipation can also be a source of incontinence, as a result of straining. Men with benign prostatitis can develop incontinence. And, people with a history of bedwetting during childhood are more likely to experience some incontinence as an adult.

As incontinence becomes more frequent or worsens, coping behaviors increase. Using sanitary napkins or other feminine hygiene products, refusing to travel, mapping out the location of toilets, urinating again (just in case), avoiding fluid intake, stopping exercise, and wearing dark clothes can all be indicators of a problem with incontinence.

So, what can be done to help control incontinence, or at least deal with it better?

Some women try using feminine pads to catch the urine released unexpectedly with incontinence. However, those pads are not designed to capture the amount of fluid that may be present. The adult incontinence pads are a much better choice because they are designed like kitty litter, to form a gel when in contact with fluid, and they can also help control odor.

For women who are overweight, losing even just 5 to 10 pounds can dramatically reduce incontinence. Dietary changes, such as eliminating caffeine and avoiding spicy foods that can irritate the bladder, may help some people reduce incontinence. Fluid management throughout the day, and especially within 3 to 4 hours before bedtime, may be necessary to control “urge incontinence” (another name for overactive bladder). Avoiding alcoholic beverages may be essential for some people because it contributes to the loss of muscle control.

Many healthcare practitioners recommend Kegel exercises, which strengthen the pelvic floor muscles, for reducing incontinence. Dr. Michael Platt of the Platt Wellness Center suggests adding testosterone, applied vaginally daily, because it helps rebuild the muscles that have atrophied. He also believes that adrenaline may be part of the equation when it comes to understanding the causes for incontinence, and suggests that progesterone (as the natural balancer of adrenaline) may be used to reduce it. In addition to bioidentical hormone therapies, prescription drugs and surgeries are also options that may provide relief for some people.

If you are experiencing incontinence (or are close to someone who is), it is best to speak with a healthcare practitioner about it early on, so they can help you explore remedies before the problem escalates.

Source: WIP

by

AKSHAYA SRIKANTH

Pharm.D Resident

Hyderabad, India

How the heart works, and how it can cause sudden death

The heart is a specialised muscle that contracts regularly and continuously, pumping blood to the body and the lungs. The pumping action is caused by a flow of electricity through the heart that repeats itself in a cycle. If this electrical activity is disrupted - for example by a disturbance in the heart's rhythm known as an 'arrhythmia' - it can affect the heart's ability to pump properly. 

The heart has four chambers - two at the top (the atria) and two at the bottom (the ventricles). The normal trigger for the heart to contract arises from the heart's natural pacemaker, the SA node, which is in the top chamber.

The heart's natural pacemaker - the SA node - sends out regular electrical impulses from the top chamber (the atrium) causing it to contract and pump blood into the bottom chamber (the ventricle). The electrical impulse is then conducted to the ventricles through a form of 'junction box' called the AV node. The impulse spreads into the ventricles, causing the muscle to contract and to pump out the blood. The blood from the right ventricle goes to the lungs, and the blood from the left ventricle goes to the body.

The SA node sends out regular electrical impulses causing the atrium to contract and to pump blood into the bottom chamber (the ventricle). The electrical impulse then passes to the ventricles through a form of 'junction box' called the AV node (atrio-ventricular node). This electrical impulse spreads into the ventricles, causing the muscle to contract and to pump blood to the lungs and the body. Chemicals which circulate in the blood, and which are released by the nerves that regulate the heart, alter the speed of the pacemaker and the force of the pumping action of the ventricles. For example, adrenaline increases the heart rate and the volume of blood pumped by the heart.

The electrical activity of the heart can be detected by doing an 'electrocardiogram' (also called an ECG).

A death is described as sudden when it occurs unexpectedly, spontaneously and/or even dramatically. Some will be unwitnessed; some may occur during sleep or during or just after exercise. Most sudden deaths are due to a heart condition and are then called sudden cardiac death (SCD). Up to 95 in every 100 sudden cardiac deaths are due to disease that causes abnormality of the structure of the heart. The actual mechanism of death is most commonly a serious disturbance of the heart's rhythm known as a 'ventricular arrhythmia' (a disturbance in the heart rhythm in the ventricles) or 'ventricular tachycardia' (a rapid heart rate in the ventricles). This can disrupt the ability of the ventricles to pump blood effectively to the body and can cause a loss of all blood pressure. This is known as a cardiac arrest. If this problem is not resolved in about two minutes, and if no-one is available to begin resuscitation, the brain and heart become significantly damaged and death follows quickly.

by

Akshaya Srikanth*, Dr.Chandra Babu

RIMS Medical College, Kadapa

A.P, India