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More than 10,000 cases of potential calcium channel blocker toxicity occurred in the United States in 2010. When death occurs in medicine overdose, heart medications are the cause more than 10% of time. The three most common types of heart medications that result in this outcome are calcium channel blockers along with beta blockers and digoxin.
The level of digoxin for treatment is typically 0.5-2 ng/mL. Since this is a narrow therapeutic index, digoxin overdose can happen. A serum digoxin concentration of 0.5-0.9 ng/mL among those with heart failure is associated with reduced heart failure deaths and hospitalizations. It is therefore recommended that digoxin concentration be maintained in approximately this range if it is used in heart failure patients.
High amounts of the electrolyte potassium (K+) in the blood (hyperkalemia) is characteristic of digoxin toxicity. Digoxin toxicity increases in individuals who have kidney impairment. This is most often seen in elderly or those with chronic renal insufficiency or end-stage kidney disease.
Calcium channel blockers, also known as calcium channel antagonists, are widely used for a number of health conditions. Thus they are commonly present in many people's homes. In young children one pill may cause serious health problems and potentially death. The calcium channel blocker that caused the greatest number of deaths in 2010 in the United States was verapamil. This agent is believed to cause more heart problems than many of the others.
Studies in the 1990s in Australia and the United Kingdom showed that between 8 and 12% of drug overdoses were following TCA ingestion. TCAs may be involved in up to 33% of all fatal poisonings, second only to analgesics. Another study reported 95% of deaths from antidepressants in England and Wales between 1993 and 1997 were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. It was determined there were 5.3 deaths per 100,000 prescriptions.
Sodium channel blockers such as Dilantin should not be used in the treatment of TCA overdose as the Na+ blockade will increase the QTI.
Tricyclics have a narrow therapeutic index, "i.e.", the therapeutic dose is close to the toxic dose. Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs. However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.
In digoxin toxicity, the finding of frequent premature ventricular beats (PVCs) is the most common and the earliest dysrhythmia. Sinus bradycardia is also very common. In addition, depressed conduction is a predominant feature of digoxin toxicity. Other ECG changes that suggest digoxin toxicity include bigeminal and trigeminal rhythms, venticular bigeminy, and bidirectional ventricular tachycardia.
Symptoms are typically precipitated ("triggered") by exercise-induced ventricular arrhythmias during periods of physical activity or acute emotional stress.
Hypermagnesemia is an electrolyte disturbance in which there is a high level of magnesium in the blood. It is defined as a level greater than 1.1 mmol/L. Symptoms include weakness, confusion, decreased breathing rate, and cardiac arrest.
Hypermagnesemia can occur in kidney failure and those who are given magnesium salts or who take drugs that contain magnesium (e.g. some antacids and laxatives). It is usually concurrent with other electrolyte disturbances such as a low blood calcium and/or high blood potassium level. Specific electrocardiogram (ECG) changes may be present.
Treatment when levels are very high include calcium chloride, intravenous normal saline with furosemide, and hemodialysis.
Hypermagnesemia occurs rarely because the kidney is very effective in excreting excess magnesium.
This cardiac arrhythmia can be underlain by several causes, which are best divided into cardiac and noncardiac causes.
Noncardiac causes are usually secondary, and can involve recreational drug use or abuse; metabolic or endocrine issues, especially in the thyroid; an electrolyte imbalance; factors; autonomic reflexes; situational factors such as prolonged bed rest; and autoimmunity.
Cardiac causes include acute or chronic ischemic heart disease, vascular heart disease, valvular heart disease, or degenerative primary electrical disease. Ultimately, the causes act by three mechanisms: depressed automaticity of the heart, conduction block, or escape pacemakers and rhythms.
In general, two types of problems result in bradycardias: disorders of the sinoatrial node (SA node), and disorders of the atrioventricular node (AV node).
With sinus node dysfunction (sometimes called sick sinus syndrome), there may be disordered automaticity or impaired conduction of the impulse from the sinus node into the surrounding atrial tissue (an "exit block"). Second-degree sinoatrial blocks can be detected only by use of a 12-lead EKG. It is difficult and sometimes impossible to assign a mechanism to any particular bradycardia, but the underlying mechanism is not clinically relevant to treatment, which is the same in both cases of sick sinus syndrome: a permanent pacemaker.
Atrioventricular conduction disturbances (AV block; primary AV block, secondary type I AV block, secondary type II AV block, tertiary AV block) may result from impaired conduction in the AV node, or anywhere below it, such as in the bundle of His. The clinical relevance pertaining to AV blocks is greater than that of sinoatrial blocks.
Patients with bradycardia have likely acquired it, as opposed to having it congenitally. Bradycardia is more common in older patients.
Beta-blocker medicines also can slow the heart rate and decrease how forcefully the heart contracts. Beta blockers may slow the heart rate to a dangerous level if prescribed with calcium channel blocker-type medications.
Bradycardia is also part of the mammalian diving reflex.
Risk factors for long QT syndrome include the following:
- female sex
- increasing age
- liver or renal impairment
- family history of congenital long QT syndrome
- pre-existing cardiovascular disease
- electrolyte imbalance: especially hypokalemia, hypocalcemia, hypomagnesemia
- concurrent administration of interacting drugs
Anorexia nervosa has been associated with sudden death, possibly due to QT prolongation. It can lead a person to have dangerous electrolyte imbalances, leading to acquired long QT syndrome and can in turn result in sudden cardiac death. This can develop over a prolonged period of time, and the risk is further heightened when feeding resumes after a period of abstaining from consumption. Care must be taken under such circumstances to avoid complications of refeeding syndrome.
Abnormal heart rhythms and asystole are possible complications of hypermagnesemia related to the heart. Magnesium acts as a physiologic calcium blocker, which results in electrical conduction abnormalities within the heart.
Clinical consequences related to serum concentration:
- 4.0 mEq/l decreased reflexes
- >5.0 mEq/l Prolonged atrioventricular conduction
- >10.0 mEq/l Complete heart block
- >13.0 mEq/l Cardiac arrest
Note that the therapeutic range for the prevention of the pre-eclampsic uterine contractions is: 4.0-7.0 mEq/L. As per Lu and Nightingale, serum Mg concentrations associated with maternal toxicity (also neonate depression - hypotonia and low Apgar scores) are:
- 7.0-10.0 mEq/L - loss of patellar reflex
- 10.0-13.0 mEq/L - respiratory depression
- 15.0-25.0 mEq/L - altered atrioventricular conduction and (further) complete heart block
- >25.0 mEq/L - cardiac arrest
Atrial bradycardias are divided into three types. The first, respiratory sinus arrhythmia, is usually found in young and healthy adults. Heart rate increases during inhalation and decreases during exhalation. This is thought to be caused by changes in the vagal tone during respiration. If the decrease during exhalation drops the heart rate below 60 bpm on each breath, this type of bradycardia is usually deemed benign and a sign of good autonomic tone.
The second, sinus bradycardia, is a sinus rhythm of less than 60 BPM. It is a common condition found in both healthy individuals and those considered well-conditioned athletes. Studies have found that 50–85% of conditioned athletes have benign sinus bradycardia, as compared to 23% of the general population studied. The heart muscle of athletes has become conditioned to have a higher stroke volume, so requires fewer contractions to circulate the same volume of blood.
The third, sick sinus syndrome, covers conditions that include severe sinus bradycardia, sinoatrial block, sinus arrest, and bradycardia-tachycardia syndrome (atrial fibrillation, flutter, and paroxysmal supraventricular tachycardia).
The most common symptom is dizziness or syncope which often occurs during exercise or as a response to emotional stress.
MAT usually arises because of an underlying medical condition. Its prevalence has been estimated at about 3 per 1000 in adult hospital inpatients and is much rarer in paediatric practice; it is more common in the elderly, and its management and prognosis are both those of the underlying diagnosis.
It is mostly common in patients with lung disorders, but it can occur after acute myocardial infarction and can also occur in the setting of low blood potassium or low blood magnesium.
It is sometimes associated with digitalis toxicity in patients with heart disease.
It is most commonly associated with hypoxia and COPD. Additionally, it can be caused by theophylline toxicity, a drug with a narrow therapeutic index commonly used to treat COPD. Theophylline can cause a number of different abnormal heart rhythms when in excess, and thus further predisposes COPD patients to MAT. Theophylline toxicity often occurs following acute or chronic overtreatment or factors lowering its clearance from the body.
Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes tachyarrhythmias and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, respiratory failure, stroke, cerebral hemorrhage, or heart failure. Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in renal failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 5000 deaths occur annually in the US due to cocaine overdose.
Inappropriate Sinus Tachycardia (IST) is a rare type of cardiac arrhythmia, within the category of supraventricular tachycardia (SVT). IST may be caused by the sinus node itself having an abnormal structure or function, or it may be part of a problem called dysautonomia, a disturbance and/or failure of the autonomic nervous system. Research into the mechanism and etiology (cause) of Inappropriate Sinus Tachycardia is ongoing.
IST is viewed by most to be a benign condition in the long-term. Symptoms of IST however, may be distracting and warrant treatment. The heart is a strong muscle and typically can sustain the higher-than-normal heart rhythm, though monitoring the condition is generally recommended.
The mechanism and primary etiology of Inappropriate Sinus Tachycardia has not been fully elucidated. An autoimmune mechanism has been suggested as several studies have detected autoantibodies that activate beta adrenoreceptors in a portion of patients. The mechanism of the arrhythmia primarily involves the sinus node and peri-nodal tissue and does not require the AV node for maintenance. Treatments in the form of pharmacological therapy or catheter ablation are available, although it is currently difficult to treat successfully.
Afterdepolarizations are abnormal depolarizations of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the cardiac action potential in the electrical conduction system of the heart. Afterdepolarizations may lead to cardiac arrhythmias.
Cocaine intoxication refers to the immediate and deleterious effects of cocaine on the body. Although cocaine intoxication and cocaine dependence can be present in the same individual, these syndromes present with different symptoms.
Ventricular tachycardia can occur due to coronary heart disease, aortic stenosis, cardiomyopathy, electrolyte problems (e.g., low blood levels of magnesium or potassium), inherited channelopathies (e.g., long-QT syndrome), catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, or a heart attack.
If the person is hemodynamically unstable or other treatments have not been effective, synchronized electrical cardioversion may be used. In children this is often done with a dose of 0.5 to 1 J/Kg.
The risk for untreated LQTS patients having events (syncopes or cardiac arrest) can be predicted from their genotype (LQT1-8), gender, and corrected QT interval.
- High risk (> 50%) - QTc > 500 ms, LQT1, LQT2, and LQT3 (males)
- Intermediate risk (30-50%) - QTc > 500 ms, LQT3 (females) or QTc < 500 ms, LQT2 (females) and LQT3
- Low risk (< 30%) - QTc < 500 ms, LQT1 and LQT2 (males)
A 1992 study reported that mortality for symptomatic, untreated patients was 20% within the first year and 50% within the first 10 years after the initial syncope.
Sick sinus syndrome is a relatively uncommon syndrome in the young and middle age population. Sick sinus syndrome is more common in elderly adults, where the cause is often a non-specific, scar-like degeneration of the cardiac conduction system. Cardiac surgery, especially to the atria, is a common cause of sick sinus syndrome in children.
Paroxysmal supraventricular tachycardia (PSVT) is a type of supraventricular tachycardia. Often people have no symptoms. Otherwise symptoms may include palpitations, feeling lightheaded, sweating, shortness of breath, and chest pain. Episodes start and end suddenly.
The cause is not known. Risk factors include alcohol, caffeine, nicotine, psychological stress, and Wolff-Parkinson-White syndrome which often is inherited from a person's parents. The underlying mechanism typically involves an accessory pathway that results in re-entry. Diagnosis is typically by an electrocardiogram (ECG) which shows narrow QRS complexes and a fast heart rhythm typically between 150 and 240 beats per minute.
Vagal maneuvers, such as the valsalva maneuver, are often used as the initial treatment. If not effective and the person has a normal blood pressure the medication adenosine may be tried. If adenosine is not effective a calcium channel blockers or beta blocker may be used. Otherwise synchronized cardioversion is the treatment. Future episodes can be prevented by catheter ablation.
About 2.3 per 1000 people have paroxysmal supraventricular tachycardia. Problems typically begin in those 12 to 45 years old. Women are more often affected than men. Outcomes in those who otherwise have a normal heart are generally good. An ultrasound of the heart may be done to rule out underlying heart problems.
It can result in many abnormal heart rhythms (arrhythmias), including sinus arrest, sinus node exit block, sinus bradycardia, and other types of bradycardia (slow heart rate).
Sick sinus syndrome may also be associated with tachycardias (fast heart rate) such as atrial tachycardia (PAT) and atrial fibrillation. Tachycardias that occur with sick sinus syndrome are characterized by a long pause after the tachycardia. Sick sinus syndrome is also associated with azygos continuation of interrupted inferior vena cava.
Symptoms reported by patients vary in frequency and severity.
Symptoms associated with IST include:
- Frequent or sustained palpitations
- Dyspnea (shortness of breath) and palpitations on exertion
- Pre-syncope (feeling as if about to faint)
- Fatigue (physical)
- Dizziness
- Exercise intolerance
- Occasional paresthesia and cramping
- Symptoms associated with autonomic nervous system disturbance, including GI disturbance