Clinical practice minorities

VI. Taking Account of Pharmacogenomic Differences Among Minorities in Clinical Practice... 

Another important line of research was the synthesis of 3,4,5-trialkoxybenzamides, as some of these derivatives showed outstanding psychopharmacological activities. Among these compounds, 4-(3,4,5-trimethoxybenzoyl)morpholine (named Trioxazin) was introduced as a minor tranquilizer, N-cyclopropyl-4-(decyloxy)-3,5-dimethoxybenz-amide (Denegit) as an antiepileptic agent, and 2-(l-pyrrolidinyl)ethyl 4-butoxy-3,5-dimethoxybenzoate (Vasopenton) as a spasmolytic, for use in clinical practice. 

There are a range of more minor adverse effects, however, which are often not mentioned in formal reviews of methadone treatment but which are discussed more in practical handbooks. In clinical practice these can be very problematic, variously leading to distress for individuals, limitations in compliance and requests for alternative treatments, and the most troublesome such effects are listed in Table 1.4. 

What are the potential pitfalls of combining hypothermia with other treatment modalities Perhaps the most important is the possibility that there will be some adverse interaction between the combined treatments. This is not a minor concern, as it is well known that many pharmaceutical agents exhibit adverse effects when used in combination with other agents. Many of these adverse effects can be serious if not life threatening. In fact, this problem with drug interactions is a major reason why many pharmaceutical treatments are not used in clinical practice. 

Noncovalent interaction of dyes and related compormds with various biomacromolecules attracts considerable attention due to the possibility of proceeding of a variety of photochemical processes in vivo [1]. It makes possible to use dyes both in biomedical studies as DNA labels and in clinical practice [2], Complex formation of cyanine dyes with doublehelical DNA is of great interest due to rmique photophysical and photochemical properties of these dyes, which change dramatically in the presence of DNA [1, 3, 4], There are two main types of dye-DNA bonding complexes of dyes intercalated between DNA base pairs and complexes in which dye molecules are located in the minor groove of the double helix of the biopolymer (superficial bonding) [5],... 

Initial target dose of 400-800 mg/day should be reached in most cases to optimize the chances of success in treating acute psychosis and acute mania, but only a minority of patients are adequately dosed in clinical practice... 

Best efficacy in schizophrenia and bipolar disorder Is af doses >120 mg/day, but only a minority of pafienfs are adequately dosed In clinical practice... 

Topical ocular anesthetics have many uses in clinical practice. Most commonly, they are used to improve patient tolerance of various diagnostic procedures. In addition, these drugs often provide sufficient anesthesia for minor operations on the cornea, conjimctiva, and nasolacrimal system. 

As mentioned in chapter 2, individuals particular personality style and unique psychodynamics will often dramatically influence how they respond to pharmacotherapy. Robert Michaels (1992) has commented that in general clinical practice two-thirds of patients with Axis I disorders appear to respond quite well either to medication treatment or to brief, targeted psychological interventions, such as cognitive-behavioral or interpersonal therapy. However, a significant minority of patients with clear-cut Axis I disorders don t respond well to such treatments, primarily due to serious co-morbid character pathology. In treating these people, at the very least the clinician must be alert to how personality factors influence treatment outcome often medication treatment must be accompanied by more intensive psychotherapy that addresses the personality disorder. 

An immediate improvement in the drug properties could be obtained by the replacement of the sulfamido group with a more lipophilic group such as halogen. Compound (70) inhibited apomorphine-induced stereotypy in rats at a 30-fold lower dose than sulpiride (330). Whereas the racemic 2,6-di-methoxy derivative (71) was equipotent with sulpiride against apomorphine mediated behaviors, the S-enantiomer of the 3-bromo-2,6-dimethoxy derivative (remoxipride) (72) closely resembled haloperidol in its ability to block apomorphine-induced hyperactivity. The sevenfold ratio of stereotypy to hyperactivity for remoxipride suggested a low propensity to produce EPS in the clinic. Remoxipride was briefly used in clinical practice, but the development of aplastic anemia in a minority of patients led to its eventual withdrawal (331). 

The principal asthma therapies have all been in clinical practice since the early 1970s and before, yet their mechanisms and potential hazards in many cases remain obscure. The trend towards inhaled corticosteroids continues to raise concerns about their long-term side-effects. This has fuelled efforts to develop safer anti-inflammatory therapies, despite the advent of fluticasone, which is 100 per cent first-pass metabolized in the liver and has fewer systemic effects (Harding, 1990). Suggestions that the long-actingy 2-agonists (salmeterol, formoterol) may be anti-inflammatory appear to be unfounded, but the possibility of an antiinflammatory effect of theophylline (Ward et al., 1993) has accelerated development of selective phosphodiesterase (PDE IV) inhibitors, which may have reduced side-effects and a better therapeutic index than theophylline itself. The immunosuppressants, such as cyclosporin A which prevents expression of IL-2 and IL-2R in T cells, are limited by toxicity to a small minority of very severe corticosteroid-dependent asthmatics. 

The importance of this possible displacement interaction in clinical practice is uncertain. The suggestion made by the authors is that, although lidoeaine has only a minor cardiac depressant effect, a transient 20% increase in levels of free and active lidoeaine plus the negative inotropic effects of the disopyramide might possibly be hazardous in patients with reduced cardiac function. 

Inherent in these observations lies the major drawback of EMLA cream. In busy clinical practice, anticipatory application of the cream is challenging. Most often, when decisions to perform minor needle-based procedures are made, they are in an acute clinical setting. Therefore, time will often preclude application. In addition, the cream is available in 5 g (2-4 applications) and 30 g tubes with a significant cost associated with use. As noted below, there are some additional constraints associated with use. 

Simpler molecules with two positively charged centres joined by a chain of varying length, like decamethonium (57) and esters of the suxamethonium (or disuccinylcholine) (58) type and their analogues, were likewise shown to be muscle relaxants, but with a rather short period of activity—leptocurares (510, 511). Both these substances were introduced into clinical practice, but only suxamethonium has kept its position because its brief duration of action, about 5 minutes only, has made it of use in minor surgical procedures such as intubation (501). 

Previously published clinical observations of daily atropine and scopolamine effects usually did not include precise recording time of onset and recovery from each dose. At least one journal report, however, did note that a certain degree of tolerance to atropine developed in the course of daily use for several months or years. This may or may not be based on a mechanism similar to the second-dose effect that we observed with BZ. Conceivably, this might have military implications if the target population had previously been exposed to an attack with BZ on one or more occasions. The practical significance of the slightly earlier onset and recovery, however (Fig. 12), seems to be relatively minor. 

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