| Current
Drug Therapy
ISSN: 1574-8855
Current Drug Therapy
Volume 1, Number 2, May 2006
Contents
Beta-Blocker Therapy for Septic Cardiac Shock: Fiction
Or Realism? Pp. 131-133
Karim Bendjelid
[Abstract]
Recombinant Tissue-Type Plasminogen Activator (Alteplase)
in the Management of Acute Ischemic Stroke: A Review of its
Pharmacological Properties, Efficacy, Safety and Pharmacoeconomic
Aspects Pp. 135-146
Naveed Akhtar, Dirk Deleu and Sadaat Kamran
[Abstract]
Consequences of Secondary Hyperparathyroidism
on Vascular Calcification and Cardiovascular Mortality: Potential
Benefit of Calcimimetics Pp. 147-155
Emanuel Zitt and Alexander R. Rosenkranz
[Abstract]
Statins: Are They All the Same? Pp. 157-172
Walter F. Riesen
[Abstract]
Treatment of Infections Caused by Extended-Spectrum
β
Lactamase Producing Enterobacteriaceae Pp. 173-179
Kevin B. Laupland and Johann D.D. Pitout
[Abstract]
Is There a Place for Nebulized Magnesium Sulfate in
the Treatment of Acute Asthma? A Systematic Review Pp.
181-185
Gustavo J. Rodrigo and Luís J. Nannini
[Abstract]
Cholinergic Treatment of Traumatic Brain Injury
Pp. 187-209
Olli Sakari Tenovuo
[Abstract]
The Use of Progesterone in Clinical Practice: Evaluation
of its Efficacy in Diverse Indications Using Different Routes
of Administration Pp. 211-219
Vittorio Unfer, Gian C. di Renzo, Sandro Gerli
and Maria L. Casini
[Abstract]
Novel Therapeutic Agents for Hyperuricemia in Patients
with Gout Pp. 221-229
Geoffrey C. Wall, Carrie F. Koenigsfeld and Kristin S.
Meyer
[Abstract]
Current Outcomes and Future Perspectives of Cochlear
Implants Pp. 231-239
Zanetti Diego and Guida Maurizio
[Abstract]
Abstracts
[Back to top]
Beta-Blocker Therapy for Septic Cardiac Shock: Fiction
Or Realism?
Karim Bendjelid
Beta-blockers, previously considered contraindicated
in heart failure are today amongst the most important drugs
in heart failure. They improve survival and retard the need
for cardiac transplantation. Since most clinical trials demonstrating
the benefits of beta-blockers have been done in patients with
mild to moderate heart failure, the use of these agents in
patients with advanced heart failure remains contraindicated.
In this brief review, the author theorizes that due to their
immunomodulatory effects, beta-blockers may also play a helpful
role in patients presenting cardiogenic shock related to septic
shock. However, intensivists should keep in mind that no clinical
data are available so far on the role of beta-blockers in
septic cardiac shock. Thereby, because the use of beta-blockers
in this setting is not established, nor recommended, it should
only be applied under controlled trial conditions.
[Back to top]
Recombinant Tissue-Type Plasminogen Activator (Alteplase)
in the Management of Acute Ischemic Stroke: A Review of its
Pharmacological Properties, Efficacy, Safety and Pharmacoeconomic
Aspects
Naveed Akhtar, Dirk Deleu and Sadaat Kamran
Ischemic stroke ranks as one of the major leading cause
of death and the most common cause of acquired neurological
disability in adults. The treatment of acute ischemic stroke
remains one of the most challenging areas in medicine today.
Timely recognition and treatment is imperative to reduce its
morbidity and mortality. So far, intravenous recombinant tissue-type
plasminogen activator (rt-PA or alteplase) is the only approved
thrombolytic by the European Agency for the Evaluation of
Medicinal Products (EMEA) and Food and Drug Administration
(FDA) for treating acute ischemic stroke within three hours
of onset of symptoms. Though encouraging, the data for a larger
therapeutic window between 3 and 6 hours remains controversial.
Other treatment strategies (using intra-arterial alteplase
combined intravenous/intra-arterial alteplase, other thrombolytic
agents, mechanical disruption of clot and ultrasonic augmentation
of thrombolysis) although still under investigation, have
shown beneficial in selected conditions. Still thrombolytic
therapy has not been widely adopted and practiced. This limited
implementation may be because of many factors including clinical
and time criteria, and most of all lack of public and professional
education for understanding stroke as acute emergency. The
objective of this paper is to provide an updated overview
of the use of alteplase in acute ischemic stroke in all its
aspects: mechanism of action, pharmacokinetics, drug interactions,
efficacy and tolerability via different routes of administration
in the anterior and posterior circulation, and last but not
least the pharmacoeconomic issues. The rationale for thrombolytic
therapy and its limits will be addressed. Educating the general
public, training emergency caregivers and allied health professionals,
and addressing long-term cost savings to health institutions
will make stroke management optimized and widely available.
[Back to top]
Consequences of Secondary Hyperparathyroidism on Vascular
Calcification and Cardiovascular Mortality: Potential Benefit
of Calcimimetics
Emanuel Zitt and Alexander R. Rosenkranz
Chronic kidney disease and especially end-stage renal
disease (ESRD) are regularly associated with profound disturbances
in the mineral metabolism characterized by secondary hyperparathyroidism
(SHPT), hyperphosphatemia, hypercalcemia, elevated calcium-phosphorus
product and renal osteodystrophy. These metabolic changes
are either the result of the disease itself or due to toxicity
from current therapeutic options. There is growing evidence
that besides the classical cardiovascular risk factors, non-traditional
uremia-specific risk factors, including abnormal mineral metabolism
and SHPT, play a key role in the excessively increased cardiovascular
mortality and morbidity in these patients. Calcimimetics represent
an innovative new therapeutic compound in the treatment of
SHPT, acting as allosteric activators of the calcium-sensing
receptor. In this review we will discuss the consequences
of SHPT in ESRD patients on vascular calcification, its impact
on cardiovascular morbidity and mortality and the potential
role of calcimimetics in preventing the cardiovascular consequences
of SHPT.
[Back to top]
Statins: Are They All the Same?
Walter F. Riesen
Statins are a diverse group of drugs, which share the
ability to inhibit HMG CoA reductase and thereby the conversion
of acetoacetyl CoA to mevalonate, the rate-limiting step in
cholesterol biosynthesis. By inhibiting mevalonate production
statins inhibit the pathway leading to the generation of farnesylpyrophosphate
and geranylgeranyl pyrophosphate, two pyrophosphates that
are critical for the induction of a variety of signal transduction
pathways, which promote a cascade of events leading to endothelial
dysfunction, inflammation, proliferation, apoptosis and other
effects important for atherogenesis.
Even though statins share a common mode of action they differ
by several features like chemical structure, affinity towards
HMG CoA reductase and their relative lipophilicity. These
features translate into marked differences in LDL cholesterol
lowering efficacy, pharmacokinetic properties and differences
in lipophilicity associated with different tissue affinity
and penetration. Rosuvastatin and atorvastatin produce the
greatest percentage change in LDL cholesterol. Fluvastatin
and pravastatin are less prone to drug interactions, because
they are not metabolized through the CYP450 3A4 system. The
hydrophilic pravastatin does not inhibit proliferation and
migration of vascular smooth muscle cells. Data from clinical
trials with statins suggest that the efficacy in LDL cholesterol
lowering plays the overriding role in cardiovascular event
reduction.
[Back to top]
Treatment of Infections Caused by Extended-Spectrum
β
Lactamase Producing Enterobacteriaceae
Kevin B. Laupland and Johann D.D. Pitout
The Enterobacteriaceae, most notably Escherichia coli
and Klebsiella pneumoniae, are among the most important
causes of serious nosocomial and community-acquired bacterial
infections of humans. These organisms may produce extended-spectrum
β-lactamases
(ESBLs) that result in broad spectrum resistance to the β-lactam
antibiotics, a major class of anti-bacterial agents. The majority
of ESBL enzymes in Enterobacteriaceae are encoded on large
plasmids typically with other antibiotic resistance genes
that are transmissible among different strains and species.
Although there is considerable geographic variation, the rate
of infections due to ESBL-producing Enterobacteriaceae is
rising and these infections have been increasingly recognized
to occur in community-based patients. As a result of their
broad spectrum resistance profile, empiric treatment failure
is common with ESBL-producing Enterobacteriaceae infections.
Largely because of their resistance to both hydrolysis and
the innoculum effect, the carbapenem class of antibacterials
have become widely accepted as the agents of choice for the
treatment of serious infections due to ESBL-producing Enterobacteriaceae.
However, the superiority of carbapenems over other classes
of active agents in the treatment of these infections is inconsistently
supported by observational studies and there is a lack of
clinical trial data. Future prospective studies are needed
to determine the optimal management of these important infections.
[Back to top]
Is There a Place for Nebulized Magnesium Sulfate in
the Treatment of Acute Asthma? A Systematic Review
Gustavo J. Rodrigo and Luís J.
Nannini
Objective: To evaluate the use of aerosolized magnesium
sulfate (MgSO4) in combination with inhaled beta-agonists
compared to inhaled beta-agonists alone in the treatment of
acute asthma.
Methods: Published (1966-2005) randomized controlled trials
were retrieved using different databases, bibliographic reviews
of primary research, review articles, and citations from texts.
The primary outcome measure was pulmonary function.
Results: Five out of 16 potentially eligible studies met criteria
for inclusion in the meta-analysis. They included 187 adults
and 62 children who were treated in an emergency department.
Patients that received MgSO4 showed non-significant
improvement in pulmonary function (SMD = -0.21, 95%CI:-0.52
to 0.10, p = 0.18). The advantage of the use of MgSO4
was demonstrated only in patients with life-threatening acute
asthma (baseline FEV1 or PEF < 30% predicted)
(SMD = -1.10; 95%CI: -1.80 to -0.39, p = 0.002; I2
= 0%). Nebulized MgSO4 with beta-agonists showed
a marginal significant reduction in admission rate compared
to beta-agonists alone (RR = 0.63, 95% CI: 0.39 to 1.01, p
= 0.06, I2 = 0%).
Conclusions: Data suggests that MgSO4 presents
a beneficial effect in terms of pulmonary function only in
the subgroup of life-threatening acute asthma patients. However,
the small number of studies selected, the standard treatment
used in all trials, and the beta-agonist delivery method restricts
this conclusion.
[Back to top]
Cholinergic Treatment of Traumatic Brain Injury
Olli Sakari Tenovuo
In spite of affecting the life of millions of people,
chronic traumatic brain injury (TBI) has not been hitherto
treatable with effective pharmacological tools. This review
gives a comprehensive summary of the theoretical data supporting
the pharmacological manipulation of the cholinergic system
in TBI, pointing out the most urgent targets for further studies.
The published clinical evidence of cholinergic treatment in
TBI is critically reviewed, with emphasis on modern available
cholinergic agents. The lessons from these studies are converted
to detailed suggestions for further clinical testing. In addition,
the treating clinicians are provided with practical advice,
based on personal experience of the cholinergic treatment
in over 350 TBI patients. It is concluded that cholinergic
agents offer several very promising potentials for the treatment
of TBI. However, the final breakthrough requires further well-conducted
studies and the potential caveats of the treatment have to
be acknowledged.
[Back to top]
The Use of Progesterone in Clinical Practice: Evaluation
of its Efficacy in Diverse Indications Using Different Routes
of Administration
Vittorio Unfer, Gian C. di Renzo, Sandro Gerli
and Maria L. Casini
Introduction: Progesterone is a hormone of paramount
importance in the reproductive physiology. Its multiple physiological
roles and pharmacology have been extensively studied throughout
the years. However, the use of progesterone in the pathophysiology
of pregnancy as well as in its other indications remains arguable
for diverse reasons. One of these reasons concerns the fact
that there have been few large randomised controlled trials,
which are not easily comparable because of the different dosages,
populations and routes of administration used. Regarding this
last issue, the route of progesterone administration may have
a strong influence on the efficacy of the treatment since
the distribution and concentration of the hormone at the tissutal
level varies considerably.
Objective: To review the literature concerning the
efficacy of progesterone in its diverse indications in correlation
to the different routes of administration used.
Methods: The search strategy included a literature
search of PubMed, MEDLINE and the Cochrane Database from 1949
to April 2005, as well as a review of reference lists of identified
studies and a hand search of relevant textbooks and reference
works. Search terms used included: progesterone, pregnancy,
preterm birth, preterm labor, threatened miscarriage, recurrent
miscarriage, menopause, contraception, pharmacology, route
of administration. Study designs included experimental studies,
observational studies, case control studies, reviews, letters,
and editorials.
Results: The search on MEDLINE identified approximately
3800 articles. We found only limited literature relating to
some of the administration route of progesterone (transnasal,
transdermic, sublingual, rectal).
Conclusion: Many routes of progesterone administration
have been studied, but the only routes of administration used
in the clinical practice are the i.m., oral and vaginal one.
Among these options, the intramuscular administration is the
only one that ensures adequate and verifiable plasmatic levels
of progesterone.
[Back to top]
Novel Therapeutic Agents for Hyperuricemia in Patients
with Gout
Geoffrey C. Wall, Carrie F. Koenigsfeld and Kristin
S. Meyer
Objective: To review the current literature concerning
the treatment of hyperuricemia in patients with gout with
novel agents not primarily used for this condition.
Data Sources: Computerized MEDWATCH and International
Pharmaceutical Abstracts search engines were utilized with
the following terms: gout, uric acid, losartan, fenofibrate,
sevelamer, febuxostat, and treatment. Bibliographies from
key articles were also searched, and all pertinent articles
were procured and reviewed.
Data Extraction: All available primary literature
accounts in English of hyperuricemia treatment with the agents
listed above were considered for this review. Pertinent review
articles were also utilized.
Data Synthesis: Although several drugs effectively
treat hyperuricemia in gout, existing agents may not always
be effective or well tolerated. Losartan, fenofibrate, and
sevelamer have been shown to exert a hypouricemic effect and
may be effective adjunct agents for gout, especially in patients
with concomitant co-morbid conditions. Additionally, febuxostat,
a novel non-purine hypouricemic agent, will soon become available
for the treatment of this disorder.
Conclusion: As the incidence of gout increases in
Western countries the availability of several effective medications
for lowering uric acid levels will be necessary. The agents
described in this review can be considered in patients with
gout, especially if current drugs are ineffective or not tolerated.
[Back to top]
Current Outcomes and Future Perspectives of Cochlear
Implants
Zanetti Diego and Guida Maurizio
Cochlear implants (CI) are semi-implantable devices for
the rehabilitation of profound deafness due to loss of sensory
hair cells in the cochlea. They have enabled more than 60,000
deaf people with no benefit from traditional acoustic amplification
to restore a functional hearing. Although individual performance
is variable, most adults with post-verbal onset of deafness
can talk on the phone in a quiet environment. Children born
deaf who receive a CI before the age of two years can develop
normal language perception and production, and the majority
can attend the mainstream schools. Technological advances
and positive outcomes have expanded the CI candidacy. Current
areas of clinical research are: 1) the sparing of residual
hearing in the low frequencies in order to allow the combined
use of an hearing aid; 2) the use of perimodiolar electrodes
which minimize the spread of neural excitation and the battery
consumption; 3) new hardware, such as the behind-the-ear speech
processors, and more flexible speech processing strategies;
4) binaural implantation, for stereophonic sound processing.
The present paper reviews expected performances in different
categories of subjects undergoing cochlear implantation. Future
developments such as the totally implantable device and the
delivery of pharmacologic agents to the inner ear via
an adjunctive channel are discussed.
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