Nortriptyline , sold under the Allegron , Aventyl , Noritren , Nortrilen trademarks, and Pamelor among others, is a tricyclic antidepressant (TCA) used to treat clinical depression. Another licensed use for him is in the care of bed-wetting children. The use of off-label including chronic pain and migraine and labile affects in some neurological disorders. Chemically, this is a secondary amine dibenzocyclohene and is pharmacologically classified as second generation TCA.
Nortriptyline has fewer anticholinergics (such as dry mouth, constipation, blurred vision, etc.), Antihistamines (such as sedation and possibly weight gain), antiadrenergic (such as orthostatic hypotension), and cardiotoxic (toxic hearts, ie the capacity of these drugs to interfering with normal heart rhythms) compared to older first generation TCAs.
Nortriptyline is the main active metabolite of amitriptyline, the first generation TCA. This is a metabolite N -desmethyl from amitriptyline. Like amitriptyline it works by inhibiting reuptake of serotonin and norepinephrine, thus increasing the synaptic signal through this neurotransmitter. In particular it inhibits the reuptake of norepinephrine through serotonin, which is opposite to amitriptyline.
Video Nortriptyline
Medical use
In the UK, it can also be used to treat nocturnal enuresis, with a treatment program lasting no more than three months. It is also used off-label for the treatment of panic disorder, irritable bowel syndrome, prophylactic migraine and chronic pain or neuralgia modification, especially temporomandibular joint disorders.
Neuropathic pain
Although not approved by the FDA for neuropathic pain, many randomized controlled trials have demonstrated the effectiveness of TCA for the treatment of this condition in both depressed and non-depressed individuals. In 2010, evidence-based guidelines sponsored by the International Association for Pain Study recommended nortriptyline as a first-line drug for neuropathic pain.
Maps Nortriptyline
Contraindications
Nortriptyline should not be used in the acute recovery phase after myocardial infarction (ie, heart attack). In contrast to TCA clomipramine and imipramine, concurrent use of nortriptyline with monoamine oxidase inhibitors poses no risk of serotonin syndrome, although there is still a risk of hypertensive crisis.
Close monitoring is needed for those with a history of cardiovascular disease, stroke, glaucoma, or seizures, as well as in people with hyperthyroidism or receiving thyroid hormone.
Side effects
The most common side effects include dry mouth, sedation, constipation, increased appetite, blurred vision and tinnitus. The occasional side effect is a rapid or irregular heartbeat. Alcohol can exacerbate some of its side effects.
Overdose
Overdose symptoms and treatment are generally similar to other TCAs, including serotonin syndrome and adverse cardiac effects. Because TCA has a relatively narrow therapeutic index, the possibility of a serious overdose (intentional and deliberate) is quite high. Overdose nortriptyline is considered a medical emergency and often leads to death.
Interactions
Excessive alcohol consumption in combination with nortriptyline therapy may have a potential effect, which may lead to an increased danger of suicide attempts or overdose, especially in patients with a history of emotional disturbance or suicidal ideation.
Pharmacology
Pharmacodynamics
Nortriptyline is an amitriptyline active metabolite by demethylation in the liver. The pharmacological profile is as a table to the right of the show (inhibition or antagonism of all sites).
This effect is responsible for some therapeutic actions as well as for most side effects such as sedation, hypotension, anticholinergic effects, etc. Nortriptyline can also have a sleep-boosting effect due to the antagonism of H 1 and 5 -HT 2A receptors. In the short term, however, nortriptyline can disrupt sleep due to its activation effect.
Like other TCAs, nortriptyline also blocks the sodium channel, perhaps partly accounting for its analgesic action.
In one study of long-term efficacy, nortriptyline showed a higher relapse rate compared to fenelzin in individuals treated for depression, possibly because of the 10-hydroxynortriptyline toxic metabolites produced. The review authors noted that nortriptyline groups had more episodes before treatment.
In one study, nortriptyline had the highest affinity for dopamine transporters among TCA (K D 1.140 nM) in addition to amineptine (a norepinephrine-dopamine reuptake inhibitor), although the affinity for this transporter was still 261- and 63-fold lower than for norepinephrine and serotonin transporters (K D = 4.37 and 18Ã, nM, respectively). Pharmacokinetics
Pharmacogenetic
Nortriptyline is metabolized in the liver by the CYP2D6 liver enzyme, and the genetic variation in genes encoding this enzyme may affect metabolism, leading to changes in drug concentrations in the body. Increased nortriptyline concentrations may increase the risk of side effects, including adverse effects of anticholinergic and nervous systems, while decreasing concentrations may reduce drug effectiveness.
Individuals can be categorized into different types of CYP2D6 metabolism depending on the genetic variation they carry. These types of metabolizers include poor, intermediate, extensive, and ultrarapid metabolites. Most individuals (about 77-92%) are large metabolites, and have "normal" nortriptyline metabolism. Poor and intermediate metabolism has reduced drug metabolism compared with broad metabolites; patients with this type of metabolizer may have an increased likelihood of having side effects. The metabolism of ultrarapidosis using nortriptyline is much faster than extensive metabolites; patients with this type of metabolizer may be more likely to experience pharmacological failure.
The Clinical Pharmacogenetics Implementation Consortium recommends avoiding nortriptyline in people who are ultraprite CYP2D6 or poor metabolism, due to the risk of lack of efficacy and side effects, respectively. Initial dose reduction is recommended for patients who are CYP2D6 intermediate metabolites. If the use of nortriptyline is justified, therapeutic drug monitoring is recommended to guide dose adjustment. The Dutch Pharmacogenetics Working Group recommends reducing the nortriptyline dose on CYP2D6 poor or intermediate metabolism, and choosing alternative medicine or increasing the dose in ultrarapid metabolism.
Chemistry
Nortriptyline is a tricyclic compound, especially dibenzocycloheptadiene, and has three rings attached to a side chain attached to its chemical structure. Other dibenzocycloheptadiene TCAs include amitriptyline ( N -methylnortriptyline), protriptyline, and butriptyline. Nortriptyline is a secondary TCA amine, with N -methylated parent amitriptyline being a tertiary amine. Other secondary amine TCAs include desipramine and protriptyline. The chemical name of nortriptyline is 3- (10,11-dihydro-5 h -dibenzo [ a , d ] cyclohepten-5-ylidene) - N -methyl-1-propanamine and its free base form have the chemical formula C 19 H 21 N 1 with weight molecule 263,384 g/mol. It is used commercially as a hydrochloride salt; free basic form is rarely used. The CAS Registration Number of free base is 72-69-5 and the hydrochloride is 894-71-3.
History
Nortriptyline was developed by Geigy. It first appeared in the literature in 1962 and was patented in the same year. The drug was first introduced for the treatment of depression in 1963.
Society and culture
Common names
Nortriptyline is the generic name of English and French from the drug and INN , BAN , and DCF , while nortriptyline hydrochloride is USAN , USP , BANM , and JAN . The generic names in Spanish and Italian and DCIT are nortriptilina , in German is nortriptylin and in Latin is nortriptylinum .
Brand name
The nortriptyline brand names include Allegron , Aventyl , Noritren , Norpress, Nortrilen , Norventyl, Norzepine, Pamelor , and Sensoval, among many others.
References
External links
- Nortriptyline - Drugs.com
Source of the article : Wikipedia
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