Phenothiazines Amitriptyline

The tricyclic antidepressants (e.g., desipramine and amitriptyline) and some phenothiazines block the sympathetic neuronal amine uptake system they thereby would also block the uptake of guanethidine and thus reduce its hypotensive effectiveness. Conversely, guanethidine competitively inhibits the uptake of drugs that are substrates for neuronal uptake, such as the indirectly acting adrenomimetics, or sympathomimetics (see Chapter 10). 

Tricyclic antidepressants, like some of the phenothiazine derivatives, are sedative in nature. Those compounds containing a tertiary amine (imipramine, amitriptyline, and doxepin) are the most sedative. Those compounds containing a secondary amine (nortriptyline and desipramine) are less so, and protriptyline has no sedative effect. 

Tricyclic antidepressants—so called because of the characteristic three-ring nucleus—have been used clinically for four decades (Figure 30-1). They closely resemble the phenothiazines chemically and, to a lesser extent, pharmacologically. Like the latter drugs, they were first thought to be useful as antihistamines with sedative properties and later as antipsychotics. The discovery of their antidepressant properties was a fortuitous clinical observation. Imipramine and amitriptyline are the prototypical drugs of the class as mixed norepinephrine and serotonin uptake inhibitors though they also have several other properties. 

Amitriptyline hydrochloride and imipramine hydrochloride are similar in structure, with the exception of the nitrogen in the center ring, and belong to the family of phenothiazine compounds. Finally, the two-carbon bridge linking the aromatic rings may be ethyl (-CH2CH2-) or ethylene (-CH=CH-). 

Phenothiazines and related drugs, e.g., chlorpromazine (Largactil/ Thorazine). Some tricyclic antidepressants, e.g., amitriptyline Dibenzodiazepine derivatives and thienobenzodiazepines, e.g., clozapine, olanzapine Benzodiazepines, e.g., diazepam (Valium), nitrezepam (Librium) and lorazepam Barbiturates Opiates... 

Molnar et al. [69] studied antibacterial effect and plasmid curing property of several phenothaizines and tried to correlate these functions with respect to their chemical structure. They observed that diethazine, amitriptyline, and impipramine showed bacteriostatic and bactericidal effect on different bacteria. Chlorpromazine sulfoxide and fluorescein were ineffective even at 1000 Ag/ml. The antibacterial compounds deleted at 40-70% frequency the F lac-t- plasmid of Escherichia coli K12 Le-140. Similar plasmid elimination potentiality by phenothiazines was reported by the same group of authors in 1982 [72],... 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

At about the same time, the drug imipramine was first produced. It was originally developed as a phenothiazine (antipsychotic), but was found to have antidepressant properties. Soon came amitriptyline, followed later by other "tricyclic" and "heterocyclic" antidepressants. 

CYP1A2 Antidepressants amitriptyline, clomipramine, imipramine, fluvoxamine Neuroleptics haloperidol, phenothiazines, thiothixene, clozapine, olanzapine Others tacrine, caffeine, theophylline, acetaminophen, phenacetin No report of polymorphism until 1999 significance of following findings remains unclear 1C reduced activity 23% in Japanese 1F higher inducibility 32% in Caucasians... 

Clinically important, potentially hazardous interactions with amiodarone, amisulpride, amitriptyline, amoxapine, arsenic, bepridil, bretylium, calcium, chlorpromazine, clomipramine, desipramine, disopyramide, doxepin, erythromycin, fluphenazine, imipramine, iron salts, magnesium, mesoridazine, nortriptyline, pentamidine, perphenazine, phenothiazines, pimozide, procainamide, prochlorperazine, promazine, promethazine, protriptyline, quinidine, sotalol, sucralfate, thioridazine, tricyclic antidepressants, trifluoperazine, trimipramine, zinc salts... 

Phenothiazines Buterophenones Rauwolfia alkaloids Benzodiazepines MAO inhibitors Imipramine Amitriptyline Lithium salts... 

Tricyclic antidepressants resemble the phenothiazine antipsychotics such as chlorpromazine in structure and function. Like the phenothiazine derivatives (e.g., chlorpromazine), tricyclic antidepressants (e.g., amitriptyline) may reduce the seizure threshold and precipitate seizures in epileptic patients, cause cholestatic jaundice, movement disorders, and hematologic side effects. Unlike the phenothiazine derivatives, the tricyclic antidepressants may increase motor activity, have a very slow onset and long duration of action, a relatively narrow margin of safety, and a strong anticholinergic effect. In fact, dry mouth is the most common side effect, and other anticholinergic effects such as tachycardia, loss of accommodation, constipation, urinary retention, and paralytic ileus have been reported following amitriptyline. 

ACETOPHENAZINE, see Phenothiazines, piperazine ALPRAZOLAM, see Benzodiazepines AMITRIPTYLINE, see Tricyclic antidepressants AMOXAPINE, see Tricyclic antidepressants BENZODIAZEPINES (alprazolam, chlordiazepoxide, clorazepate, diazepam, halazepam, lorazepam, oxazepam, prazepam, temazepam)... 

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