Tricyclic antidepressants drug reaction

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

The word "tolerability" is perhaps a little clumsy but it describes accurately what is assessed, namely how well the drug is tolerated by those to whom it is administered. This last qualification is necessary because there are many instances in which a drug is better tolerated or less well tolerated by young healthy volunteers than by patients. For example, anxiolytics and tricyclic antidepressants are usually far better tolerated by patients with depression than by healthy volunteers. However, healthy volunteer studies generally provide useful information about tolerability even if it may under- or overestimate tolerability in patients. Many adverse reactions wiU be directly related to the known pharmacological activity of the drug and are therefore predictable. 

Iprindol (25) is yet another antidepressant drug that differs structurally from the classical tricyclic antidepressants. Condensation of phenylhydrazine and cyclooctanone by the Rogers-Corson modification of the Fischer indole synthesis affords the tricyclic intermediate, 24. The active hydrogen of 6,7,8,9,10-hexahydro-5H-cyclooct[b]indole (24) is removed by reaction with sodium metal in DMF and the resulting salt condensed with 3-dimethylaminopropyl chloride. There is thus obtained iprindol (25). ... 

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

Selegiline should not be coadministered with tricyclic antidepressants or selective serotonin uptake inhibitors because of the possibility of a severe adverse drug reaction (e.g., hyperpyrexia, agitation, delirium, coma). 

Although the tricyclic and MAOI antidepressants cause an immediate pharmacologic action (drug reaction in the body), their clinical action (observable reaction) is delayed. This delay can last weeks or even months. This makes it difficult to use these antidepressants to treat severe depression when an immediate response is desired. The more severe cases of depression and other psychiatric and emotional problems may require other treatments in addition to the drug therapy. 

Abbreviations NAT2, N-acetyltransferase 2 TPMT, thiopurine S-methyltransferase UGT1A1, UDP-glucuronosyltransferase 1A1 HER2, human epidermal growth factor receptor 2 (ErbB2) EICV, hepatitis C virus TCAs, tricyclic antidepressants ADRs, adverse drug reactions. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Tricyclic antidepressants rarely cause cholestatic jaundice and agranulocytosis due to hypersensitivity reactions. The rare liver necrosis may reflect severe hypersensitivity. Two fatal cases of hypersensitivity myocarditis and hepatitis have been described (1). A variety of dermatological manifestations have been reported (rash, urticaria, vasculitis), but their relation to drug ingestion is often uncertain. A single case of pulmonary hypersensitivity with... 

There is a more clear-cut cause-and-effect relation in the parkinsonian symptoms that occasionally occur with high-dosage tricyclic therapy in susceptible individuals (particularly elderly women). Because of its piperazine side-chain and structural resemblance to the phenothia-zines, amoxapine has antidopaminergic properties that appear to produce typical dystonic reactions (88), but other tricyclic antidepressants may also be implicated in producing the full range of so-called extrapyramidal syndromes, including akathisia, dystonic reactions, parkinsonism, and tardive dyskinesia. Case reports have been described before (SEDA-16, 9 SEDA-17, 18 SEDA-18, 18). In the reports of tardive dyskinesia the problem is often that these patients have taken many different drugs. 

Drug-induced photosensitivity reactions are divided into phototoxicity (a nonimmunologic reaction) and photoallergic reactions (an immunologic reaction). The latter form is far less common. Medications associated with photosensitivity reactions include fluoroquinolones, nonsteroidal antiinflammatory drugs, phenothiazines, antihistamines, estrogens, progestins, sulfonamides, sulfonylureas, thiazide diuretics, and tricyclic antidepressants. 

Adverse drug reactions can result from combining MAO inhibitors with tricyclic/tetracyclic antidepressants and related compounds, including carbamazepine, cyclobenzaprine, and mirtazapine, and should be avoided except by experts to treat difficult cases... 

Affective and Mental Disorders. Anxiety and emotional instability can be associated with psychogenic reactions, such as vasovagal syncope, that may appear to be drug related. Medications used to treat these disorders may potentiate the activity of ophthalmic medications. The use of monoamine oxidase inhibitors or tricyclic antidepressants can enhance the systemic effects of topically applied phenylephrine and a2-adrenergic agonists. 

MAO Inhibitors and Other Antidepressants. Product literature and case reports caution against concurrent use of MAO inhibitors with tricyclic antidepressants (e.g., amitriptyline, imipramine) because severe atropinelike reactions, tremors, convulsions, hypothermia, and vascular collapse can occur. The labeling for most of these products warns that therapy with a MAO inhibitor or a tricyclic antidepressant should not be initiated until at least 7-14 days after therapy with the other drug has been discontinued. 

Abbreviations ADR, adverse drug reaction TCA, tricyclic antidepressant. 

Administered as a single, daily dose on an empty stomach Monoamine oxidase inhibitors drug-food interactions with tyramine-rich foods such as red wines, dark beers, aged cheeses, yogurt may precipitate hypertensive crisis drug interactions tricyclic antidepressants and SSRIs, sympathomimetics disulfiram-like reaction with alcohol... 

Cyclobenzaprine is structurally closely related to the tricyclic antidepressants (see later) and therefore shares many of their adverse reactions. These include drowsiness (CNS effects), dry mouth (anticholinergic effects), and dizziness. The potential for serious interactions with MAO inhibitors also exists. Nevertheless, the drug s centrally acting skeletal muscle relaxation is useful for short-term treatment of local muscle spasms. 

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