Tricyclic antidepressants administration

Administration of atropine with meperidine (Demerol), flurazepam (Dalmane), diphenhydramine (Benadryl), phenothiazines, and the tricyclic antidepressants may increase the effects of atropine. There is a decreased effectiveness of haloperidol when administered with the anticholinergic dragp. 

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

The tricyclic antidepressant clomipramine also has been studied for PMDD. In placebo-controlled trials, both continuous daily dosing and luteal phase administration proved effective.17 Compared with the SSRIs, however, clomipramine has a less desirable side-effect profile with low tolerability. 

Virtually all types of drug that have been shown to be effective in major depression exert profound effects on the functioning of the serotoninergic or noradrenergic systems, or both. Although some treatments have been shown to decrease the sensitivity of certain postsynaptic 5-HT and NE receptors, it is generally believed that it is an enhancement of neurotransmission in these systems that is responsible for the improvement of the core symptoms of depression. For instance, long-term administration of tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) decreases the density of (3-adrenoceptors and cortical 5-HT2 receptors (Blier and Abbott 2003). 

Sodium bicarbonate administration for cardiac arrest is controversial because there are few clinical data supporting its use, and it may have some detrimental effects. Sodium bicarbonate can be used in special circumstances (i.e., underlying metabolic acidosis, hyperkalemia, salicylate overdose, or tricyclic antidepressant overdose). The dosage should be guided by laboratory analysis if possible. 

Lucki, I., and Frazer, A. (1982) Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants. Psychopharmacology, 77 205-211. 

Monoamine Hallucinogens and Concurrent Psychotherapeutic Medications Administration of certain therapeutic psychotropic medications has been shown to alter responsiveness to hallucinogenic drugs. This is not surprising, because they both have actions on monoamine systems, sometimes even the same receptor subtytpes. Tricyclic antidepressants and... 

Bonson KR, Buckholtz JW, Murphy DL. (1996). Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology. 14(6) 425-36, Bonson KR, Murphy DL. (1996). Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors, or lithium. Behav Brain Res. 73(1-2) 229-33. 

Another tricyclic antidepressant, amineptine (104), acting essentially by inhibition of dopamine uptake, differs from the other drugs by its aminohepta-noic side-chain. After oral administration to rat, dog or human, the main metabolites were acids with shortened C5 and C3 side-chains (105, 106), together with the corresponding 10-hydroxylated derivatives, the relative and absolute... 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

Apart from symptomatic, general measures (gastric lavage, cooling with ice water), therapy of severe atropine intoxication includes the administration of the indirect parasympathomimetic physostigmine (p. 102). The most common instances of atropine" intoxication are observed after ingestion of the berry-like fruits of belladonna (children) or intentional overdosage with tricyclic antidepressants in attempted suicide. 

Mechanism of Action A tricyclic antidepressant that blocks the reuptake of neu-rotransmitters, such as norepinephrine and serotonin, at presynaptic membranes, in-creasing their concentration at postsynaptic receptor sites. Therapeutic Effect Results in antidepressant effect. Anticholinergic effect controls nocturnal enuresis, Pharmacohinetics Rapidly, completely absorbed after PO administration, and not affected by food. Protein binding 95%, Metabolized in liver (significant first-pass effect), Primarily excreted in urine. Not removed by hemodialysis. Half-life 16-40 hr. 

The prototypical serotonin reuptake inhibitor (SRI) medication is the non-selective agent clomipramine, a tricyclic antidepressant (TCA). The Selective SRIs (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalo-pram (Celexa). The Food and Drug Administration (FDA) approved clinical indications for these medications are described in Table 22.1. 

CBC, complete blood cell count EKG, electrocardiogram HS, hora sotnnis, bedtime administration NE, norepinephrine TCA, tricyclic antidepressant. 

Chuang DM, Gao X-M, Paul SM N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells. Mol Pharmacol 42 210-216, 1992 Chugh Y, Saha N, Sankaranarayanan A, et al Enhancement of memory retrieval and attenuation of scopolamine-induced amnesia following administration of S-HTj antagonist ICS 205-930. Pharmacol Toxicol 69 105-106, 1991 Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146, 1981 Ciraulo DA, Barnhill JG, Jaffe JH Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. Pharmacol Ther 43 539-548, 1988... 

Tricyclic antidepressants are the most commonly used drugs. They produce antidepressant effect by blocking the neuronal uptake of noradrenaline and exert anti-cholinergic activity. They also inhibit neuronal uptake of 5HT and dopamine. The exact mechanism of action is not known. The antidepressant effect is noticed after three to four weeks of drug administration. 

ECT is superior in efficacy when compared with placebo, sham ECT, and active drug therapy. Upon the introduction of effective pharmacotherapy for severe depression, the relative efficacy of drug versus ECT was frequently studied. Our review of the relevant literature led to an extrapolation of the data from selected studies (primarily class I or II designs) for a quantitative analysis of the efficacy of ECT versus other treatments for an acute depressive episode ( 53). The comparisons with ECT included simulated (or sham) ECT, placebo, the standard tricyclic antidepressants, and the monoamine oxidase inhibitors [ Table 8-1 (54, 55, 56, 57, 58 and 59), Table 8 2 (0g 6i 62 and 63), Table 8-3 (56, 61, 62, 63, 64, 65 and 66), and Table 8-4 (55, 60, 61, 62 and 63)]. We also compared the relative efficacy of the bilateral versus the UNID forms of administration [Table 8-5 (42, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77 and 78)]. A meta-analysis was... 

Hyponatmemia is common with the thiazides and to a lesser extent with the loop diuretics. It occurs when the osmolality of the urine persistently exceeds that of the fluid intake and is associated with the inability of the kidney to produce a dilute urine. It is not usually severe. The origin is multifactorial and involves unrestricted fluid intake and increased ADH activity due to volume depletion. Co-administration of dipsogenic drugs, such as the tricyclic antidepressants, or those with ADH-like effects, such as chlorpropamide, can exacerbate the problem. There are rare occasions when hyponatraemia (Nan- concentration less than 100 mmol-L-l) can be of sufficient severity to be life threatening. 

Adverse effects of flumazenil include agitation, confusion, dizziness, and nausea. Flumazenil may cause a severe precipitated abstinence syndrome in patients who have developed physiologic benzodiazepine dependence. In patients who have ingested benzodiazepines with tricyclic antidepressants, seizures and cardiac arrhythmias may follow flumazenil administration. 

Levodopa or dopamine agonists produce diverse dyskinesias as a dose-related phenomenon in patients with Parkinson s disease dose reduction reverses them. Chorea may also develop in patients receiving phenytoin, carbamazepine, amphetamines, lithium, and oral contraceptives, and it resolves with discontinuance of the offending medication. Dystonia has resulted from administration of dopaminergic agents, lithium, serotonin reuptake inhibitors, carbamazepine, and metoclopramide and postural tremor from theophylline, caffeine, lithium, valproic acid, thyroid hormone, tricyclic antidepressants, and isoproterenol. 

Sawynok, J. and Reid, A. Antinociception by tricyclic antidepressants in the rat formalin test differential effects on different behaviours following systemic and spinal administration, Pain 2001, 93, 51-59. 

Synergistic effects as described for the supraspinal interaction of opioids with either KCOs or serotonin are interesting in terms of providing a rationale for reducing opioid doses by using co-administration regimes, e.g. with tricyclic antidepressants which are known to increase serotonin levels in the synaptic cleft. 

One of the most important drug interactions that SSRIs can cause through inhibition of 2D6 is to raise plasma levels of tricyclic antidepressants (TCAs) if these TCAs are given concomitantly with SSRIs or if there is switching between TCAs and SSRIs. Since TCAs are substrates for 2D6 (Fig. 6—14) and SSRIs are inhibitors of 2D6 (Fig. 6—15), concomitant administration will raise TCA levels, perhaps to toxic levels (Fig. 6—16). Concomitant administration of an SSRI and a TCA thus... 

These result from the drug s sympathoplegic actions. The major adverse effect is postural hypotension. This effect can be almost totally prevented by concomitant administration of a tricyclic antidepressant agent such as protriptyline. Nausea and vomiting may occur after the intravenous administration of a bolus of bretylium. 

Acetylcholine-blocking drugs should be avoided in patients with prostatic hyperplasia, obstructive gastrointestinal disease (eg, pyloric stenosis or paralytic ileus), or angle-closure glaucoma. In parkinsonism patients receiving antimuscarinic medication, concomitant administration of other drugs with antimuscarinic properties (eg, tricyclic antidepressants or antihistamines) may precipitate some of the complications mentioned above. 

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