Imipramine interaction

Shad MU, Preskom SH. A possible bupropion and imipramine interaction. JC/iw macol 991) 17, 118-19. 

Shapiro PA. Cimetidine-imipramine interaction case report and comments. Am J Psychiatry (1984) 141, 152. 

Miller DD, Macklin M. Cimetidine-imipramine interaction a case report. Am J Psychiatry (1983) 140, 351-2. 

Somani SM, Khurana RC, Mechanism of estrogen-imipramine interaction. JAMA (1973) 223, 560,... 

The idea that indole hallucinogens might increase startle by interacting with presynaptic autoreceptors has received some experimental support. Davis and Sheard (49) found that lesions of the dorsal and median raphe nuclei blocked the usual excitatory effect of a low dose (40 jtg/kg) of LSD on acoustic startle. Moreover, other treatments that decreased raphe cell firing rates also blocked the excitatory effects of LSD on startle. For example, pretreatment with chlor-imipramine (CIMI), which decreases raphe cell firing indirectly by blocking 5-HT reuptake (153), blocked the usual excitatory effect of LSD on startle without preventing the entry of LSD into the brain (47). These data were consistent with the disinhibition hypothesis. 

Additional ADRs linked to diet pills include psychosis myocardial ischemia drug interactions, such as the interaction of fenfluramine with imipramine, fenfluramine with amitriptyline or desipramine, or the toxic reaction between fluoxetine and phentermine and the release of serotonin while inhibiting its reuptake, contributing to hyperserotonin reactions. When the next craze takes hold of patients and their physicians, hopefully physicians and pharmacists will take a more vocal position and recommend restraint, xmtil some proof of efficacy and lack of toxicity is shown for new faddish off-label combinations. 

All were double-blind controlled evaluations and established iprindole as at least as effective as imipramine, and one study [195] included an examination of the doctor-patient interaction as a factor in such work (a similar discussion was felt necessary, as noted above [179] in the evaluation of oxpertine). In only two [192, 194] of the above reports is it possible to estimate the frequency and severity of anticholinergic side effects, thou in the one case [192] the care taken in the experimental design and the number of patients observed leaves little doubt that the dry mouth, constipation, etc. characteristic of imipramine therapy is either greatly reduced or even absent during iprindole treatment. This point is confirmed in an extension of this team s work to include a 12 month toxicity study [197] which, in addition, failed to produce evidence of haemopoitic, hepatic, cardiac, ocular or renal damage. Similar results followed other work. 

Amitriptyline Amitriptyline, 5-(3-dimethylaminopropyliden)-10,ll-dihydrodibenzocy-cloheptene (7.1.4), differs from imipramine in that the nitrogen atom in the central part of the tricyclic system is replaced by a carbon, which is bound to a side chain by a double bond. Amitriptyline (7.1.4) is synthesized by interaction of 10,ll-dihydro-A,iV-dimethyl-57f-dibenzo[a,d]cyclohepten-5-one with 3-dimethylaminopropyhnagnesium bromide and the subsequent dehydration of the resulting tertiary alcohol (7.1.3) using hydrochloric acid [ 11]. 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Mannitol (OsmitroL others) [Osmotic Diuretic] Uses Cerebral edema, T lOP/ICP, renal impair, poisonings Action Osmotic diuretic Dose Test dose 0.2 g/kg/dose IV over 3-5 min if no diuresis w/in 2 h, D/C Oliguria 50-100 g IV over 90 min T lOP 0.5-2 g/kg IV over 30 min Cerebral edema 0.25-1.5 g/kg/dose IV >30 min Caution [C, ] w/ CHF or volume overload Contra Anuria, dehydration, HE, PE Disp Inj SE May exacerbate CHF, N/V/D Interactions t Effects OF cardiac glycosides X effects OF barbiturates, imipramine, Li, salicylates EMS Monitor ECG for hypo-/hyperkalemia (T wave changes) OD May cause dehydration, t urine frequency/amount hypotension and CV collapse symptomatic and supportive... 

Zaleplon (Sonata) [C IV] [Sedotive/Hypnotic] Uses Insomnia Action A nonbenzodiazepine sedative/hypnotic, a pyrazolopyrimidine Dose 5-20 mg hs PRN -1- w/ renal/hepatic insuff, elderly Caution [C, /-] w/ mental/ psychological conditions Contra Component allergy Disp Caps SE HA, edema, amnesia, somnolence, photosens Interactions t CNS depression W/ CNS d es-sants, imipramine, thioridazine, EtOH X effects W/ carbamazepine, phenobarbital, phenytoin, rifampin EMS Concurrent EtOH can t adverse CNS effects OD May cause profound CNS depression symptomatic and supportive Zanamivir (Relenza) [Antiviral/Neuramidase Inhibitor] Uses Influenza A (including HlNl swine flu) B Action X Viral neuraminidase Dose Adults Feds > 7 y.2 inhal (10 mg) bid for 5 d initiate w/in 48 h of Sxs Caution [C, M] Contra Pulm Dz Disp Powder for inhal SE Bron-chospasm, HA, GI upset EMS Does not reduce risk of transmitting virus monitor for bronchospasm or other severe resp events OD May cause resp problems s5rmptomatic and supportive... 

The prevalence of concurrent prescriptions raises concern regarding drug interactions with stimulants. Stimulants, especially MPH, have been used to augment the effects of tricyclic antidepressants in the treatment of refractory depression. Although one early report claimed that circulating levels of imipramine can rise seven fold when taken concurrently with MPH (Wharton et al., 1971), a more recent study found that combining stimulants with desipramine (DMI) did not increase the plasma level of DMI relative to children treated with DMI alone (Cohen et al., 1999). 

This chapter describes the structure and neurochemical function of TCAs, metabolism and significant interactions with other medications, side effects, and specific recommendations for monitoring of side effects in children and adolescents. Because of the recent concern regarding the sudden deaths of children stabilized on TCAs, particular attention will be paid to the potential cardiovascular effects of these medications. The chapter will focus on the five TCA medications that have been most widely used in children amitriptyline (AMI), nortriptyline (NT), imipramine (IMI), desipratnine (DMI), and clomipramine (CMI). 

Henauer, S.A. and Hollister, T.E. (1984) Cimetidine interaction with imipramine and nortriptyline. Clin Pharmacol Ther 35 183—187. 

Clinicians should be aware of a few drug interactions with Zolpidem. Flumazenil acts as an antagonist to the hypnotic effects of zolpidem. There is decreased alertness when zolpidem is combined with cimetidine. There is an increase in anterograde amnesia in volunteers treated with a combination of imipramine and zolpidem. Haloperidol, ranitidine, chlorpromazine, warfarin, and digoxin, along with cimetidine and flumazenil, do not alter the pharmacokinetics of zolpidem (Salva and Costa, 1995). 

Reifler BV, Teri L, Raskind M, et al Double-bhnd trial of imipramine in Alzheimer s disease patients with and without depression. Am J Psychiatry 146 45-49, 1989 Reisberg B, Ferris SH, DeLean MJ, et al The Global Deterioration Scale for Assessment of Primary Degenerative Dementia. Am J Psychiatry 139 1136-1139, 1982 Reisine T, Zatz M Interactions between lithium, calcium, diacylglycerides and phorbol esters in the regulation of ACTEl release from AtT-20 cells. J Neurochem 49 884-889, 1987... 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

Imipramine Mixed and variable blockade of NET and SERT Like SNRIs plus significant blockade of autonomic nervous system and histamine receptors Major depression not responsive to other drugs chronic pain disorders incontinence obsessive-compulsive disorder (clomipramine) Long half-lives CYP substrates active metabolites Toxicity Anticholinergic, G.-blocking effects, sedation, weight gain, arrhythmias, and seizures in overdose Interactions CYP inducers and inhibitors... 

I.R. Coyle and G. Singer, The interactive effects of prenatal imipramine... 

The coat state assessment is a fast and simple qualitative method of assessing mouse depression-like states through observation of the condition of an animal s fur. In rodents, coat state tends to decline with increased depression, similar to depressed patients who frequently exhibit poor hygiene (29-31). Antidepressants have been shown to improve the coat condition of mice while reducing depression-like symptoms (29-31). For example, the reduction of corticotropin-releasing factor (CRF) has been associated with improved coat state (and is implicated in depression) (32). Of importance here, antidepressants (e.g., imipramine) and anxiolytics (e.g., chlordiazepoxide) have been shown to interact with corticotropin-releasing factor (33) (see Note 7). 

Unlike some of the other P450s, CYP1A2 does not have a clear preference for acidic or basic molecules. It is able to metabolize basic compounds such as imipramine, but is inhibited by acidic compounds such as enoxacin. It is perhaps not surprising, then, that octanol/buffer partition coefficients or overall lipophilicity is not reflective per se of the interaction between CYP1A2 and its substrates or inhibitors. 

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