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Current
Drug Therapy
ISSN: 1574-8855
Current Drug Therapy
Volume 3, Number 1, January 2008
Contents
New Insights for Multifactorial Disease Therapy:
The Challenge of the Symbiotic Drugs Pp. 1-13
Eliezer J. Barreiro and Carlos Alberto Manssour Fraga
[Abstract]
Current Prevention and Treatment of Postoperative
Nausea and Vomiting after Gynecological Laparoscopic Surgery
Pp. 14-25
Yoshitaka Fujii
[Abstract]
Preventative and Therapeutic Potential of Lipopolysaccharide
Derived from Edible Gram-Negative Bacteria to Various Diseases
Pp. 26-32
Hiroyuki Inagawa, Takashi Nishizawa, Noriko Yoshioka,
Yoshie Taniguchi, Chie Kohchi and Gen-Ichiro Soma
[Abstract]
Review of Rational Approaches to the Treatment of
Pain Management-Role for Opioids Therapies Pp. 33-43
Pankaj Modi
[Abstract]
New Cancer Chemotherapy Agents: Inhibitors of DNA Polymerase
Pp. 44-53
Kengo Sakaguchi and Fumio Sugawara
[Abstract]
New and Investigational Antimicrobials for the Treatment
of Severe Skin Infections Pp. 54-69
Angelina De Sarro and Maria Teresa Fera
[Abstract]
Xanthan and Locust Bean Gum (from Ceratonia siliqua)
Matrix Tablets for Oral Controlled Delivery of Metoprolol
Tartrate Pp. 70-77
M.P. Venkataraju, D.V. Gowda, K.S. Rajesh and H.G. Shivakumar
[Abstract]
Abstracts
[Back to top]
New Insights for Multifactorial Disease Therapy:
The Challenge of the Symbiotic Drugs
Eliezer J. Barreiro and Carlos Alberto Manssour Fraga
Some physiopathological processes involved in the genesis
of diseases could suggest the necessity of designing bioligands
or prototypes that aggregate, in only one molecule, dual pharmacodynamical
properties, becoming able to be recognized by two elected
bioreceptors. This approach can have distinct aspects and,
when a novel ligand or a prototype acts in two elected targets
belonging to the same biochemical pathway, e.g. arachidonic
acid cascade, it receives the denomination of dual or mix
agent. On the other hand, if these two targets belong to distinct
biochemical routes and both are related to the same disease,
we can characterize the agents able to modulate it as symbiotic
ligands or prototypes. In the present work, we provide some
examples and applications of the molecular hybridization concept
for the structural design of new symbiotic ligands and prototypes,
especially those applied in the treatment of chronic-degenerative
disorders.
[Back to top]
Current Prevention and Treatment of Postoperative Nausea and
Vomiting after Gynecological Laparoscopic Surgery
Yoshitaka Fujii
Postoperative nausea and vomiting (PONV) are two of the
commonest and most distressing complications of general anesthesia
and surgery, with a remarkably high incidence after gynecological
laparoscopic surgery.
Numerous antiemetics have been studied for the prevention
of PONV after gynecological laparoscopic surgery. Traditional
antiemetics, including butyrophenones (e.g., droperidol) and
benzamide (e.g., metoclopramide), are used for preventing
PONV. The available non-traditional antiemetics for the prophylaxis
against PONV are propofol, dexamethasone, and ephedrine. Serotonin
receptor antagonists (ondansetron, granisetron, and dolasetron),
compared with traditional antiemetics, are highly effective
for PONV prophylaxis. None of the available antiemetics is
entirely effective, perhaps because most of them act through
the blockade on one type of receptor. There is a possibility
that combined antiemetics with different sites of activity
would be more effective than one drug alone for preventing
PONV Combination antiemetic therapy with ondansetron and droperidol
or dexamethasone is highly effective in the prevention of
PONV. P6 acupoint injection is non-pharmacological technique
and is as effective as droperidol for preventing PONV.
Management of PONV after gynecological laparoscopic surgery
depends on the prophylaxis. If the prophylactic therapy fails,
treatment would be required. Ondansetron is effective in the
treatment of established PONV.
Knowledge regarding antiemetics is necessary to completely
prevent and treat PONV in women undergoing gynecological laparoscopic
surgery.
[Back to top]
Preventative and Therapeutic Potential of Lipopolysaccharide
Derived from Edible Gram-Negative Bacteria to Various Diseases
Hiroyuki Inagawa, Takashi Nishizawa, Noriko Yoshioka,
Yoshie Taniguchi, Chie Kohchi and Gen-Ichiro Soma
Gram-negative bacteria contain lipopolysaccharides (LPS),
which are generally considered to be an endotoxin that has
negative impacts on humans. There have been very few therapeutic
drugs developed that contain LPS. Recently, it has been reported
that hygienic improvements have decreased exposure to LPS,
and this is correlated with an increase in allergenic diseases.
Lack of exposure to LPS may adversely affect the immune balance
in the body.
LPS is the substance that has the greatest known effect in
activating macrophages which play a central role in the innate
immune system. We have hypothesized the existence of a network
formed by tissue macrophages and have termed this putative
communications network a macrophage network. We studied certain
edible Gram-negative bacteria that have a long history of
use in traditional food production, in order to discover ways
to improve and/or maintain health.
In 1991 we discovered that the LPS of Pantoea agglomerans
(named IP-PA1 by us) was a macrophage-activating substance
that could be obtained from water extracts of wheat flour.
LPS is also part of the make-up of cells of other well known
Gram-negative bacteria used in food processing such as
Acetobacter (vinegar, yogurt) and Xanthomonas
(xanthan gum). This demonstrates that humans have a long history
of consuming Gram-negative bacteria and LPS.
In this manuscript, we discuss the potential for utilizing
IP-PA1 and other LPS from edible Gram-negative bacteria. Forms
of LPS can be used in various fields, such as in health food,
to prevent and improve metabolic syndromes and allergies.
They can also be used in feedstuffs for stockbreeding and
in aquatic culture as defenses against infection where they
can replace antibiotics or chemical substances.
[Back to top]
Review of Rational Approaches to the Treatment of Pain Management-Role
for Opioids Therapies
Pankaj Modi
Opioids remain an important cornerstone and the most effective
mainstay analgesics for acute and terminal cancer pain treatments.
Effective analgesia is obtained in the majority of cancer
pain patients with the application of fairly straightforward
rational treatment algorithms using opioids as the main therapy.
A major barrier to be overcome, however, is that chronic pain
is often not viewed as a physical illness worthy of treatment.
Many studies demonstrating that specific changes occur in
the peripheral and central nervous systems of patients with
chronic pain provide the rationale for changing the approaches
to chronic pain management and instituting more aggressive
and comprehensive treatment.
This review describes the role of opioids in the treatment
of cancer pain, including a brief overview of cancer pain
syn-dromes, essential aspects of opioid therapy, opioid pharmacology,
opioid rotation, properties of the individual opioids, and
management of common side effects of opioids. As understanding
of the pharmacology of this class of drugs becomes more sophisticated,
clinicians may anticipate dosage-limiting adverse effects
and variations in individual response.
[Back to top]
New Cancer Chemotherapy Agents: Inhibitors of DNA Polymerase
Kengo Sakaguchi and Fumio Sugawara
The purpose of this review is 1) to introduce our studies
of newly-discovered mammalian DNA polymerase inhibitors; 2)
to elucidate their precise molecular action based on three-dimensional
structural models and comparisons with the spatial positioning
on the smallest DNA polymerase, β,
of specific amino acids binding to them; and 3) to document
their promising clinical anti-tumor activity. Multiple DNA
polymerases have been identified in eukaryotes, and recent
investigations have revealed at least sixteen types. An effective
approach to study the in vivo roles of each of these
is to use selective DNA polymerase inhibitors to distinguish
between them. Using a broad natural product screening approach,
we have identified many different types of novel DNA polymerase
inhibitor which we have exploited to analyze the structure
and function of the DNA polymerases. The aim was not only
to understand the function of each inhibitor in vitro,
but also to develop a drug design strategy for cancer chemotherapy
agents. We have found a class of such DNA polymerase inhibitors,
the sulfoquinovosylacylglycerols (SQAG), which could represent
clinically-promising anti-tumor agents. We discussed about
the mechanism of the anti-tumor action, and suggested new
concept about cancer chemotherapy.
[Back to top]
New and Investigational Antimicrobials for the Treatment of
Severe Skin Infections
Angelina De Sarro and Maria Teresa Fera
With increasing antibiotic resistance reported worldwide,
there is a great interest in the development of new antibacterial
agents for the treatment of severe skin and skin structure
infections (SSSIs). SSSIs mainly involve Gram-positive pathogens.
Although many of older antibiotics remain effective, new drug
development remains crucial owing to the increase in drug
resistance among the major Gram-positive pathogens. Since
1999 new antibacterial agents have entered the market or are
being evaluated in clinical trials for the treatment of SSSIs.
These agents have novel mechanism of action and sufficient
improvements in potency to overcome resistance. Linezolid,
quinupristin-dalfopristin, daptomycin and tigecycline have
been approved by the FDA for the treatment of SSSIs. Other
antimicrobials (dalbavancin, oritavancin, telavancin) are
currently in clinical development for this indication. This
review focuses on the chemistry, microbiology, pharmacology,
clinical efficacy and safety of several novel antibacterial
agents for the treatment of SSSIs.
[Back to top]
Xanthan and Locust Bean Gum (from Ceratonia siliqua)
Matrix Tablets for Oral Controlled Delivery of Metoprolol
Tartrate
M.P. Venkataraju, D.V. Gowda, K.S. Rajesh and H.G. Shivakumar
Purpose: Development of a controlled delivery of metoprolol
tartrate using the synergistic activity of locust bean gum
(LBG) and Xanthan gum (X). Method: Metoprolol tartrate
granules were prepared using different ratios of drug: gum
(X, LBG and mixture of XLBG). To increase the flowability
and compressibility of the granules, and to prevent its adhesion
to punch and die, magnesium stearate and talc were added to
the granules in 1:2 ratio respectively before punching. The
tablets were analysed for their hardness, friability, % assay
and in vitro release study was carried out. Results:
The release of drug from a gelatinous swollen mass, which
controls the diffusion of drug molecules through the polymeric
material into aqueous medium. The XLBG matrices show precise
controlled release than the X and LBG matrices because of
burst effect and fast release in case of X and LBG alone respectively.
FTIR and DSC thermogram studies confirmed that there was no
chemical interaction between drug and polymers in XLBG formulation.
First pass effect of metoprolol tartrate can be avoided by
this formulation. However, according to the similarity factor
(f2) XLBG3 was most
similar to Meto-ER as the reference standard. Conclusion:
The XLBG matrices leads to more precise result than X and
LBG matrices due the utilization of synergistic interaction
between two biopolymers and lower average size of this allowing
a uniformity with the tablet hydration in dissolution media.
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