Urinary retention, norepinephrine

The TCA drugs have lost their place as first-line therapy for depression because of their bothersome side effects (Table 33.2) at therapeutic doses and lethal effects in toxic doses. In addition to their presynaptic effects on the neuronal uptake of norepinephrine and serotonin, they block several postsynaptic receptors. They are potent cholinergic muscarinic receptor antagonists, resulting in symptoms such as dry mouth, constipation, tachycardia, blurred vision and urinary retention. Blockade of histamine receptors (Hi) often results in sedation and weight gain. Antagonism of aj-adrenoceptors in the vasculature can cause orthostatic hypotension. 

Atomoxetine increases the brain concentrations of norepinephrine. Adverse effects (constipation, dry mouth, nausea, fatigue, decreased appetite, insomnia, chest pain, palpitations, anxiety, erectile dysfunction, mood swings, nervousness and urinary retention) are more common in poor metabolizers of CYP2D6, as atomoxetine is metabolized through the cytochrome CYP2D6 pathway. 

Norepinephrine increases in parts of fhe brain and body and at receptors other than those that cause therapeutic actions (e.g., unwanted actions of norepinephrine on acefyichoiine reiease causing decreased appefife, increased heart rate and biood pressure, dry mouth, urinary retention, etc.)... 

Urinary retention in men over 50 with borderline urine flow has been observed with other agents with potent norepinephrine reuptake blocking properties (e.g., reboxetine, milnacipran), so administer atomoxetine with caution to these patients... 

Reboxetine. Reboxetine (21) is a norepinephrine-selective reuptake inhibitor that lacks affinity for most of the monoamine receptors. It thus does not exhibit the typical side-effect profile of the tricyclics. Nevertheless, side effects include increased sweating, postural hypotension (leading to dizziness), dry mouth, constipation, blurred vision, impotence, and dysuria. Tachycardia and urinary retention have also been reported (59). There is no evidence of cardiotoxicity and sexual dysfunction seems to be rare. In contrast to some of the earlier tricyclics that are sedative, reboxetine is nonsedating and can cause insomnia (60,61).. 

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