Tricyclic antidepressants absorption

The absorption of some drugs may also be reduced if they are given with adsorbents such as charcoal or kaolin, or anionic exchange resins such as colestyramine or colestipol. The absorption of propranolol, digoxin, warfarin, tricyclic antidepressants, ciclosporin and levothyroxine is reduced by colestyramine. 

Gastric acidity will also affect the absorption of medication. An acidic environment increases the absorption of weak acids, whereas the absorption of weak bases is facilitated by a less acidic environment. Many psychotropic agents such as tricyclic antidepressants (TCAs] and benzodiazepines are weak bases. Older studies of gastric acid secretion found that women have approximately 33%-40% lower basal gastric acid secretion than do men [Yonkers and Hamilton 1995]. Gastric acid secretion may be further decreased in the luteal phase of the menstrual cycle (Booth et al. 1957]. 

Antacids reduce the absorption and enzyme-inducing drugs may decrease serum levels. Cimetidine and propranolol both increase serum levels. There can be competition for metabolic pathways by some tricyclic antidepressants (TCAs) and SSRIs (especially fluoxetine) which may increase serum levels. 

Various factors may account for the variability in response to neuroleptics. These include differences in the diagnostic criteria, concurrent administration of drugs which may affect the absorption and metabolism of the neuroleptics (e.g. tricyclic antidepressants), different times of blood sampling, and variations due to the different type of assay method used. In some cases, the failure to obtain consistent relationships between the plasma neuroleptic concentration and the clinical response may be explained by the contribution of active metabolites to the therapeutic effects. Thus chlorpromazine, thioridazine, levomepromazine (methotrime-prazine) and loxapine have active metabolites which reach peak plasma concentrations within the same range as those of the parent compounds. As these metabolites often have pharmacodynamic and pharmacokinetic activities which differ from those of the parent compound, it is essential to determine the plasma concentrations of both the parent compound and its metabolites in order to establish whether or not a relationship exists between the plasma concentration and the therapeutic outcome. 

The anticholinergic effects of imipramine and other tricyclic antidepressants can delay gastrointestinal motility enough to interfere with the absorption of various other drugs. Such was the case in an experimental study of the absorption of levodopa in four healthy subjects (177). It is likely that this effect may interfere with absorption of other drugs, especially those, such as chlorpromazine, that are extensively metabolized in the gut. 

Doxepin is a tricyclic antidepressant that has also been used topically in the treatment of atopic dermatitis and other forms of eczematous dermatitis. It causes the adverse effects that one would expect, and systemic effects can result from absorption after topical administration. 

If, following absorption, medications were undisturbed by the body, we would need to take only one dose for an eternal effect. Of course, this is not the case. As soon as drugs enter the bloodstream, the process of metabolism ensues. The body recognizes the drug as a foreign substance and eliminates it outright (say, via the kidneys, as in the case of lithium) or transforms it chemically, using a complex enzyme mechanism located in the liver. This chemical transformation enables the medication to be eliminated from the body. In some cases, the chemical transformation produces a new compound that may also have therapeutic effects (or, in some rare instances, a toxic effect). For example, fluoxetine (trade name Prozac) is transformed into norfluoxetine, which is also an antidepressant. A similar situation occurs with the old tricyclic antidepressants (amitriptyline—trade name Elavil—to nortriptyline the latter, in fact, is... 

Both drugs and compounds naturally present in foods may compete with vitamins for absorption. Chlorpromazine, tricyclic antidepressants, and some antimalarial dmgs inhibit the intestinal transport and metabolism of riboflavin (Section 7.4.4) carotenoids lacking vitamin A activity compete with /S-carotene for intestinal absorption and metabolism (Section 2.2.2.2) and alcohol inhibits the active transport of thiamin across the intestinal mucosa (Section 6.2). 

Carbamazepine is structurally related to phenytoin and to the tricyclic antidepressant, imipramine. The oral bioavailability of carbamazepine, which may depend on a particular pharmaceutical preparation, is 75 to 85%. After absorption, it is bound to plasma proteins to the extent of 60 to 70%. Carbamazepine is metabolized to its 10,11-epoxide and 10,11-dihydroxide derivatives, some of which are... 

Since most drugs are largely absorbed in the upper part of the small intestine, drugs that alter the rate at which the stomach empties can affect absorption. Propantheline, for example, delays gastric emptying and reduces paracetamol (acetaminophen) absorption, (p.l92), whereas metoclopra-mide , (p.l91), has the opposite effect. However, the total amount of drug absorbed remains unaltered. Propantheline also increases the absorption of hydrochlorothiazide , (p.959). Drugs with antimuscarinic effects decrease the motility of the gut, thus the tricyclic antidepressants can increase the absorption of dicoumarol , (p.457), probably because they... 

The tricyclic antidepressants can delay the absorption of phenylbutazone and oxyphenbutazone from the gut, but their antirheumatic effects are probably not affected. 

The absorption of a single 400-mg dose of phenylbutazone in 4 depressed women was considerably delayed (time to maximum level, 4 to 10 hours compared with 2 hours), but the total amount absorbed (measured by the urinary excretion of oxyphenbutazone) remained unchanged when they were pretreated with desipramine 75 mg daily for 7 days. In another 5 depressed women the half-life of oxyphenbutazone was found to be unaltered by 75 mg of desipramine or nortriptyline dailyAnimal studies have confirmed that the absorption of phenylbutazone and oxyphenbutazone are delayed by the tricyclic antidepressants, probably because their antimuscarinic effects reduce the motility of the gut, - but there seems to be no direct clinical evidence that the antirheumatic effects of either drug are reduced by this interaction. No particular precautions appear to be needed. 

Not understood. One suggestion is that the tricyclic antidepressants inhibit the metabolism of the anticoagulant (seen in animals with nortriptyline or amitriptyline and warfarin, but not with desipramine and acenocoumarol ), but tricyclics are not established known inhibitors of the metabolism of any drug so this seems unlikely. Another idea is that the tricyclics slow gastrointestinal motility thereby increasing the time available for the dissolution and absorption of dicoumarol. ... 

Drugs with antimuscarinic effects, such as the tricyclic antidepressants and disopyramide, depress salivation and many patients complain of having a dry mouth. In theory sublingual glyceryl trinitrate tablets will dissolve less readily under the tongue in these patients, thereby reducing their absorption and... 

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