Tricyclic antidepressants causative agents

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. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

Altered homeostasis in older persons can lead to important and common adverse drug effects the less robust homeostatic milieu may be stressed by drugs, causing adverse effects. Examples include orthostatic hypotension due to antihypertensives and other agents that cause a-adrenergic blockade (e.g. terazosin, doxazosin, tricyclic antidepressants and phenothiazines) in those with barorecep-tor dysfunction. Diuretics can cause hyponatraemia or hypokalaemia in older patients, whereas ACE inhibitors and NSAIDs can cause hyperkalaemia. 

Tricyclic antidepressants potentiate the pressor effects of directly acting sympathomimetic amines, such as adrenaline (epinephrine) or noradrenaline (norepinephrine), to cause hypertension. Small amounts of these, such as may be present in local anaesthetic solutions, can be dangerous. Tricyclic antidepressants will inhibit the antihypertensive effects of the older anti hypertensive drugs, such as adrenergic neurone-blocking agents, e.g. guanethidine, a-methyl-DOPA, and clonidine. 

Imipramine, a tricyclic antidepressant drug with strong antimuscarinic actions, has long been used to reduce incontinence in institutionalized elderly patients. It is moderately effective but causes significant CNS toxicity. Propiverine, a newer antimuscarinic agent, has been approved for this purpose. 

Physostigmine Suggested for antimuscarinic anticholinergic agents not for tricyclic antidepressants Adult dose is 0.5-1 mg IV slowly. The effects are transient (30-60 minutes), and the lowest effective dose may be repeated when symptoms return. May cause bradycardia, increased bronchial secretions, seizures. Have atropine ready to reverse excess effects. Do not use for tricyclic antidepressant overdose. 

Some of the tricyclic antidepressants also have the ability to block serotonin 2A receptors, which may contribute to the therapeutic actions of those agents with this property. Blockade of serotonin 2A receptors is discussed in Chapter 7. Tricyclic antidepressants also block sodium channels in the heart and brain, which can cause cardiac arrhythmias and cardiac arrest in overdose, as well as seizures. 

The first-generation tricyclic antidepressants, the monoamine oxidase inhibitors, and the newer agents can cause sedation, insomnia, orthostatic hypotension, or nausea. Because of their anticholinergic properties, they may also produce cardiac toxicides (Table 43.2). 

Tragically, while the older antidepressant drugs cannot prevent suicide and can cause it, in relatively small amounts, they can become lethal instruments in the hands of suicidal patients. As little as 1 week s supply of most tricyclics can cause death, often due to cardiac dysfunction. In combination with other drugs, their lethality increases. Thus millions of depressed, suicidal patients are given the tool with which to kill themselves. By 1981, the tricyclics were overtaking the barbiturates as the medications most frequently involved in serious overdoses ( Tricyclics, 1981). The tricyclics remain a major public health problem as agents of suicide (Henry et al., 1995). 

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