Cardiovascular effects, antidepressant drugs

Vascular effects Cocaine causes increases in blood pressure and heart rate, which fall to normal levels between doses (Foltin et al. 1995). Tachyphylaxis develops to the cardiovascular effects, even within a single session. Concurrent use of ethanol, cannabis, and cocaine causes even greater cardiovascular effects than those of each drug alone. Interactions can also occur with antidepressant drugs like desipramine. 

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). 

There are few studies of pharmacodynamics that are analyzed by sex and even fewer that combine pharmacokinetics and pharmacodynamics. The most information to date has been provided on the cardiovascular effects of drugs, followed by pharmacodynamic studies of analgesics, immunosuppressants, and antidepressants. 

Bigger JT, Kantor SJ, Glassman AH, et al. Cardiovascular effects of tricyclic antidepressant drugs. In Lipton MA, Dimascio A, Killam KF, editors. Psychopharmacology a Generation of Progress. New York Raven Press, 1978 1033. 

Xylometazoline is contraindicated in patients with narrow-angle glaucoma, because the drug may increase intraocular pressure, and in patients receiving tricyclic antidepressants, because of the potential for adverse cardiovascular effects. 

Side Effects and Toxicity. Adverse effects to the tricyclic antidepressants, primarily the result of the actions of these compounds on either the autonomic, cardiovascular, or central nervous systems, are summarized in Table 3. The most serious side effects of the tricyclics concern the cardiovascular system. Arrhythmias, which are dose-dependent and rarely occur at therapeutic plasma levels, can be life-threatening. In order to prevent adverse effects, as well as to be certain that the patient has taken enough drug to be effective, the steady-state serum levels of tricyclic antidepressant drugs are monitored as a matter of good practice. A comprehensive review of structure—activity relationships among the tricyclic antidepressants is available (42). 

Bupropion appears to reduce nicotine withdrawal symptoms and may simulate the actions of nicotine on the brain reward system. The most common side-effects related to bupropion are insomnia (30-45% at a dose of 300 mg/day) and dry mouth. Other commonly reported adverse events include hypertension, headache, and nausea. Seizures are a known risk associated with the use of somewhat higher doses compared with other antidepressants (0.1-0.4%), especially for the immediate-release form of the drug and when given at dosages of 450 mg/day or higher. Bupropion, unlike the TCAs, is virtually free of adverse cardiovascular effects, which makes it quite attractive for specific populations. 

III. Clinical presentation. Tricyclic antidepressant poisoning may produce any of three major toxic syndromes anticholinergic effects, cardiovascular effects, and seizures. Depending on the dose and the drug, patients may experience some or... 

Marshall, J.B. and Forker, A.D., Cardiovascular effects of tricyclic antidepressant drugs therapecutic usages, overdose and management of complications. Am. Heart J., 103, 401-414, 1982. 

Taylor D. Antidepressant drugs and cardiovascular pathology a clinical overview of effectiveness and safety. Acta Psychiatr Scand 2008 118(6) 434- 2. 

Vohra, J., Burrows, G. D. and Sloman, G. (1975) Assessment of cardiovascular side effects of therapeutic doses of tricyclic antidepressant drugs. Aust. N.Z. J. Med., 5, 7. 

Many different drug classes have shown to cause hypotension and orthostatic reactions and drugs for cardiovascular conditions, psychoactive medicines and polypharmacy, can all have this side effect (Box 5.15). Among the most frequently used drugs in the elderly are diuretics, ACE-inhibitors, angiotensin II antagonists, calcium channel blockers and antidepressants. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Sudden death has occurred in patients with preexisting heart disease on antidepressant therapy. It may be difficult, however, to separate a causally related drug effect from a cardiovascular incident precipitated by other factors and only by chance coincident with drug therapy. Furthermore, Roose ( 418), who has summarized the literature, noted that major depressive disorder occurs frequently after a myocardial infarct and may adversely affect the recovery process. 

Sedation is uncommon and instead many patients will find that these drugs may impair sleep, which is why the dose is best taken in the morning. There is also little effect on psychomotor function. Occasional patients have a small reduction in heart rate but otherwise effects on the cardiovascular system are rare. Epileptic convulsions can occur but are rare and much less common than with tricyclic antidepressants. There is some evidence for potentiation of electroconvulsive therapy (ECT)-induced seizures. Sexual dysfunction is reported, principally delayed ejaculation and anorgasmia. 

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. 

A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects. Many of them have other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures tricyclic antidepressants, which have anticholinergic, quinidine-like, and a-blocking effects, can cause severe cardiovascular toxicity. 

Selective serotonin reuptake inhibitors (SSRIs) are a type of antidepressant that stimulates the pineal gland s ability to produce melatonin. Antipsychotic drugs also have this effect. Other medicines have the opposite effect. Certain types of medicines used to treat cardiovascular disease called beta blockers reduce the production of melatonin by the pineal gland. Nonsteroidal antiinflammatories, which are used to treat pain and/or fever,... 

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. 

---