Tricyclic antidepressants cardiac effects

Tricyclic antidepressants have effects on heart rate (HR), blood pressure (BP), and three distinct measures of the electrocardiogram (EKG). The EKG parameters affected are (1) the PR interval, which represents depolarization of the aorta (2) the QRS duration, which represents intraventricular conduction time and (3) the QTc, which represents the depolarization and subsequent repolarization of the ventricles, corrected for cardiac rate. 

The tricyclic antidepressants are effective in treating severe major depression. Some panic disorders also respond to TCAs. Imipr-amine has been used to control bed-wetting in children (older than 6 years) by causing contraction of the internal sphincter of the bladder. At present it is used cautiously, because of the inducement of cardiac arrhythmias and other serious cardiovascular problems. 

Clinical signs of toxicity most frequently seen include sedation, coma, seizures, extrapyramidal effects, and rarely hypotension and cardiac arrhythmias. Coma and seizures may develop rapidly following an exposure to loxapine. Cardiac effects include prolonged QRS, Q-T intervals, and mild hypotension however, the cardiac effects are less pronounced than those associated with tricyclic antidepressants. Anticholinergic effects, including dry mouth, blurred vision, and tachycardia, have been seen. Neuroleptic malignant syndrome has been reported after therapeutic use and acute intoxication. Hypokalemia has also been noted. 

Tricyclic antidepressants Antimuscarinic effects (see above). The three C s" of coma, convulsions, cardiac toxicity (QRS prolongation, arrhythmias, hypotension) Control seizures. Correct acidosis and cardiotoxicity with ventilation and bicarbonate. Control hyperthermia... 

Amantadine is used cautiously in patients with seizure disorders, psychiatric problems, renal impairment, and cardiac disease. Amantadine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. Concurrent use of antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase the anticholinergic effects (dry mouth, blurred vision, constipation) of amantadine... 

The answer is a. (Hardman, p 436J The most common side effects associated with tricyclic antidepressants are their anti muscarinic effects, which may be evident in over 50% of patients. Clinically, the anti muscarinic effects may manifest as dry mouth, blurred vision, constipation, tachycardia, dizziness, and urinary retention. At therapeutic plasma concentrations, these drugs usually do not cause changes in the EKG Direct cardiac effects of the tricyclic antidepressants are important in over dosage. 

Sodium bicarbonate administration for cardiac arrest is controversial because there are few clinical data supporting its use, and it may have some detrimental effects. Sodium bicarbonate can be used in special circumstances (i.e., underlying metabolic acidosis, hyperkalemia, salicylate overdose, or tricyclic antidepressant overdose). The dosage should be guided by laboratory analysis if possible. 

Tricyclic Antidepressants (TCAs). The TCAs have been nsed to treat ADHD for 30 or more years. Most often used are imipramine (Tofranil) and desipramine (Norpramin), mainly becanse they are the TCAs that most specihcally increase norepinephrine activity. Remember, boosting norepinephrine activity in the brain shonld improve attention. Other TCAs, namely, amitriptyline (Elavil, Endep) and nortriptyline (Pamelor), have been used, though they also increase norepinephrine activity. TCAs do offer a modest benefit for both the inattention and the hyperactivity of ADHD. In addition, they are often effective at doses mnch lower than those required to treat depression. However, their effectiveness nsnally falls short of the stimulant medications. In addition, TCAs have considerable side effects including dry mouth, constipation, drowsiness, weight gain, and adverse cardiac effects. 

Before the arrival of the new antidepressants, the older tricyclic antidepressants were widely used to treat depression and agitation in demented patients. They have now largely been abandoned in these patients as their prominent anticholinergic effects tend to worsen dementia and the increased risk for cardiac toxicity can be especially dangerous in geriatric patients. 

Serotonin-specific inhibitors (SSRI) include fluoxetine, paroxetine, sertraline, citalopram and others. They are not more effective than the tricyclic antidepressants but may suit some patients better and are generally safer in overdose (see Geddes et al., 1999). While the SSRIs are devoid of the cardiac effects (membrane stabilisation, inhibition of conduction) of the tricyclics in overdose, they increase the risk of hemorrhage into the gut or brain. 

A number of drugs in addition to atropine and scopolamine have antimuscarinic properties. Tbese include tricyclic antidepressants, phenothiazines, and antihistamines. Physostigmine has been used in the treatment of acute toxicity produced by these compounds. However, physostigmine can produce cardiac arrhythmias and other serious toxic effects of its own, and therefore, it should be considered as an antidote only in life-threatening cases of anticholinergic drug overdose. 

With the introduction of the SSRIs, the safety and tolerability of antidepressants improved remarkably. As a class, these medications have little or no affinity for cholinergic, (3-adrenergic or histamine receptors and do not interfere with cardiac conduction. They are well tolerated by patients with heart disease and by the elderly, who are especially sensitive to the anticholinergic and orthostatic effects of the tricyclic antidepressant agents (TCAs) and monoamine oxidase inhibitors (MAOIs). 

Equal efficacy as tricyclic antidepressants advantages include minimal anticholinergic effects, lack of orthostatic hypotension, no cardiac conduction problems, absence of weight gain, no sedation... 

Geriatric Considerations - Summary Bupropion has several advantages as an antidepressant agent for use in older adults. It has neither the anticholinergic or cardiac toxicities of the tricyclic antidepressants, and has fewer sexual side effects than selective serotonin reuptake inhibitors. Because this drug may lower seizure threshold, it should be used with caution in older adults with increased risk of seizures (e.g., previous stroke, early-onset Alzheimer s disease). 

Assessment of physical, as well as psychiatric status, is also critically important. The presence of intercurrent medical disorders, as well as any medication used to manage them, increases the likelihood of an adverse outcome with an otherwise appropriate medication. With a recent history of myocardial infarction, certain tricyclic antidepressants (TCAs) or low-potency antipsychotics might be contraindicated due to potential adverse effects on cardiac function. Another example is the avoidance of carbamazepine in a bipolar patient with a persistently low white blood cell count. Finally, b-blockers are typically contraindicated in a patient with asthma. 

Adverse effects of flumazenil include agitation, confusion, dizziness, and nausea. Flumazenil may cause a severe precipitated abstinence syndrome in patients who have developed physiologic benzodiazepine dependence. In patients who have ingested benzodiazepines with tricyclic antidepressants, seizures and cardiac arrhythmias may follow flumazenil administration. 

For many drugs, at least part of the toxic effect may be different from the therapeutic action. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures the body s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, 13 blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and any other drugs that may be given. 

Hoping to avoid such side effects as the sleep disruption and the occasional cardiac complications of the tricyclic antidepressants, and following the principle that clean drugs are theoretically preferable to dirty ones, the pharmaceutical industry has developed the selective serotonin reuptake blockers, a third generation of chemical agents to relieve depression. 

From the existing literature, St. John s wort appears to be a safe and effective alternative in the treatment of depression. Tricyclic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side effects, including dry mouth and constipation. St. John s wort has proved to be free of any cardiac, as well as anticholinergic, side effects normally seen with antidepressant medications. Based upon limited studies, St. John s wort appears to be an acceptable alternative to traditional antidepressant therapy. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Q9 Tricyclic antidepressants cause sedation and possess several other side effects. The antimuscarinic (atropine-like) effects of these agents include dry mouth, blurred vision, raised intraocular pressure, postural hypotension, impotence, changes in cardiac rhythm and muscle tremors. They can also cause obstruction of the bladder neck, followed by difficulty in initiating micturition. 

Sudden death, possibly related to cardiac effects in children and adolescents, has been discussed (SEDA-15, 13 SEDA-16, 9 SEDA-18, 18) it was concluded that children taking tricyclic antidepressants require careful monitoring of the electrocardiogram, even when relatively low doses are used (SEDA-18,18). 

The cardiac toxicity of tricyclic antidepressants in overdose has been a source of continued concern. Undesirable cardiovascular effects, besides representing a major therapeutic limitation for this category of drugs, delineate an area in which tricyclic compounds with novel structures, as well as second-generation antidepressants, may have significant advantages. The cardiovascular effects of tricyclic antidepressants and the new generation of antidepressants have been reviewed (SEDA-18,16) (16). 

To date there have been no prospective studies that clearly show increased mortality in cardiac patients who use tricyclic antidepressants. It has been suggested that overall mortality due to cardiac disease may be higher in depressed patients who remain untreated than in those who receive either an antidepressant or electroconvulsive therapy (33). Even in patients who have chronic heart disease, the risks of effective treatment with a tricyclic appear to be minimal (34). 

As many as 20% of patients taking adequate doses of a tricyclic antidepressant experience marked postural hypotension. This effect is not consistently correlated with plasma concentrations and tolerance does not develop during treatment (35-37). The mechanism for this effect is uncertain it has been attributed to a peripheral antiadrenergic action, to a myocardial depressant effect, and to an action mediated by alpha-adrenoceptors in the central nervous system (38). Studies of left ventricular function in man are conflicting. One study of systolic time intervals showed a decrement in left ventricular function with therapeutic doses (39), while two in which cardiac function was observed directly during cardiac catheterization after overdosage showed no evidence of impaired myocardial efficiency, whereas the hypotension persisted after left ventricular filling pressures and cardiac output had returned to normal (40,41). 

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