How do serotonin norepinephrine reuptake inhibitors (SNRIs)? work
SNRIs are the newest class of antidepressants. SNRIs work by increasing the levels of serotonin and norepinephrine that are active in the brain. Serotonin and norepinephrine are produced by nerves and released into the surrounding tissues where they can attach to nearby receptors on other nerves, thereby stimulating the other nerves. The released serotonin and norepinephrine then are taken up and released again by the nerves that produce them. SNRIs block the uptake ("reuptake") of the serotonin and norepinephrine so that more of the serotonin and norepinephrine are free in the tissues surrounding the nerves.
What are the side effects and drug interactions for SNRIs?
Drug interactions and side effects associated with SNRIs are similar to those seen with SSRIs.
SNRIs may increase blood pressure, especially at high doses. High blood pressure caused by SNRIs may be managed by reducing the dose of the SNRI.
What are examples of SNRIs?
- duloxetine (Cymbalta)
- venlafaxine (Effexor)
- desvenlafaxine (Pristiq, Khedezla)
- levomilnacipran (Fetzima)
What are examples and side effects of tricyclic antidepressant (TCA) medications?
- TCAs have been in use since the 1950s when imipramine (Tofranil) was shown to be effective for treating depression.
- TCAs primarily work by increasing the level of norepinephrine in the brain and to a lesser extent serotonin levels.
- Some TCAs also are antihistamines (block the action of histamine) or anticholinergic (block the action of acetylcholine, a neurotransmitter), and these additional actions allow for uses of TCAs other than for treating depression as well as additional side effects.
What are the side effects of tricyclic antidepressants (TCA) medications?
Serious side effects and adverse events of tricyclic antidepressants include:
- TCAs are associated with a number of cardiovascular (heart and blood vessels) effects such as orthostatic hypotension and abnormal heart rates and rhythms. Orthostatic hypotension may lead to dizziness, falls, and fractures. Orthostatic hypotension may be managed by reducing or discontinuing the TCA dose, increasing salt intake, or treatment with steroids.
- If abnormal heart rhythms develop, TCAs should be discontinued. TCAs are not a good choice for patients with cardiovascular conditions.
- TCAs have anticholinergic effects which manifest as dry mouth, constipation, urinary hesitation, sexual dysfunction, increased heart rate, and visual disturbance. Desipramine (Norpramin) and nortriptyline (Pamelor) cause less anticholinergic effects than other TCAs.
- TCAs should be avoided by individuals with prostatic hypertrophy, cognitive impairment, or narrow-angle glaucoma because drugs with anticholinergic side effects can worsen symptoms of these conditions.
Some side effects and treatments of tricyclic antidepressants include:
- Dry mouth relief: Sugarless gum or candy, or pilocarpine (Salagen) oral rinse may alleviate dry mouth.
- Constipation: Constipation may be relieved by bulk laxatives and increased drinking hydrating fluids.
- Urinary retention: Urinary hesitation may be treated with bethanechol (Urecholine).
- Visual disturbances: Visual disturbances may be treated with pilocarpine eye drops.
- Sexual dysfunction: Erectile dysfunction (ED, impotence) may be managed with sidenafil (Viagra), reducing the TCA dose or discontinuing the TCA. Yohimbine, ginkgo, bethanechol, and neostigmine have also been used for managing TCA induced sexual dysfunction in some patients.
More serious side effects include:
- TCAs also cause sedation. Amitriptyline (Elavil, Endep), doxepin (Sinequan), and trimipramine (Surmontil) are more sedating than amoxapine and desipramine (Norpramin). Sedation may improve after a few weeks of treatment. Sedating TCAs may be beneficial for depressed patients who have insomnia.
- Dose dependent and reversible weight gain may occur during TCA treatment. Amitriptyline (Elavil, Endep) causes weight gain more often than desipramine (Norpramin).
What drugs interact with TCAs?
- TCAs may inhibit the antihypertensive effect of clonidine (Catapres). Therefore, combining TCAs with clonidine may lead to dangerous elevations in blood pressure.
- TCAs may affect the heart's electrical conduction system. Combining TCAs with drugs that also affect the heart's conduction system (for example, disopyramide [Norpace], pimozide [Orap], procainamide [Pronestyl, Procan SR, Procanbid]) may increase the frequency and severity of an abnormal heart rate and rhythm.
- Combining TCAs with carbamazepine (Tegretol) may result in lower TCA blood levels because carbamazepine increases the break down of TCAs, potentially reducing their effect.
- TCAs may increase the blood pressure elevating effect of epinephrine, norepinephrine, dopamine, phenylephrine, and dobutamine.
- Cimetidine (Tagamet) may reduce the breakdown of some TCAs, for example, amitriptyline (Elavil, Endep), increasing the level of the TCA in the body and potentially leading to increased side effects. As mentioned previously, TCAs should not be combined with MAOIs.
What are examples of TCAs?
- amitriptyline (Elavil and Endep are discontinued brands in the US)
- clomipramine (Anafranil)
- desipramine (Norpramin)
- doxepin (Sinequan and Adapin are discontinued brands in the US)
- imipramine (Tofranil)
- nortriptyline (Pamelor; Aventyl is a discontinued brand in the US)
- protriptyline (Vivactil)
- trimipramine (Surmontil)
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