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PubMed1999

Little evidence that "denicotinized" menthol cigarettes have pharmacological effects: an EEG/heart-rate/sujective-response study.

RATIONALE: A substantial portion of cigarette smokers prefer menthol-flavored cigarettes. To date, however, no studies have examined whether menthol in cigarettes has central pharmacological effects. OBJECTIVE: We investigated psychophysiological and subjective effects of smoking menthol versus non-menthol cigarettes in both menthol and non-menthol smokers. To assess these effects independently of the immediate effects of nicotine, all cigarettes employed were "denicotinized" (FTC nicotine yield = 0.06 mg). METHODS: The psychophysiological measures were EEG and heart rate (HR). The subjective measures assessed mental alertness, muscular relaxation, anxiety/nervousness, and how much a participant wanted to smoke one of his usual brand of cigarettes. Menthol and non-menthol smokers participated in a single session in which each participant smoked both a menthol and a non-menthol denicotinized cigarette (order balanced across participants). The psychophysiological and subjective measures were recorded before and after smoking each cigarette. RESULTS: Out of 48 F-ratios spanning 22 analyses of variance involving the critical interaction between pre-/post-smoking and menthol/non-menthol cigarette, only one unambiguously fit a "pharmacological" pattern, a result indistinguishable from a type-I statistical error. We report evidence that menthol smokers may be chronically less aroused and more sensitive to the effects of nicotine than non-menthol smokers. CONCLUSIONS: We found little evidence that menthol in cigarettes has central pharmacological effects.

Adolescent↗
PubMed2001

Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

RATIONALE: Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). OBJECTIVE: This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. METHODS: All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. RESULTS: The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. CONCLUSIONS: Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.

Humans↗
PubMed2001

The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor.

RATIONALE: s-Fluorocarazolol [(S)-FCZ] is the major positron emission tomography (PET) ligand currently used to visualize central beta-adrenergic receptors in vivo, although its pharmacology is incompletely known. OBJECTIVE: Our objective was to comprehensively characterize the in vitro pharmacology of (S)- and (R)-FCZ to determine its suitability for study of central and peripheral beta-adrenergic receptors. METHODS: We characterized the in vitro pharmacology of (S)-FCZ at 42 biogenic amine receptors and transporters in vitro using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. RESULTS: As expected (R)- and (S)-FCZ had high affinities for beta-adrenergic receptors (Ki values=0.08-0.45 nM) and negligible affinities (Ki values>100 nM) for nearly all other tested receptors and transporters with the exception of the h5-HT1A receptor for which (S)-FCZ had high affinity (Ki=34 nM). Interestingly, (R)-FCZ had low affinity for the h5-HT1A receptor (Ki=342 nM). CONCLUSION: The high affinity of (S)-FCZ for the h5-HT1A receptor is not likely to interfere with studies of peripheral beta-adrenergic receptors, since 5-HT1A receptors are expressed at very low levels outside the central nervous system. Indeed, computer simulations predict that even at low ligand concentrations, 5-HT1A binding in brain regions like hippocampus are likely to be substantial. Thus, (S)-FCZ may not be a suitable PET ligand for studies of central nervous system beta-adrenergic receptors unless the contribution by 5-HT1A sites can be shown to be negligible.

Adrenergic beta-Antagonists↗
PubMed1997

Voltage-dependent anion channel of Arabidopsis hypocotyls: nucleotide regulation and pharmacological properties.

Plasma membrane anion channels are thought to play important roles in osmoregulation and signal transduction in higher plant cells. Knowledge of their pharmacology and regulation is of importance to unravel their physiological functions. In this study, we explore the pharmacological properties and the nucleotide regulation of the voltage-dependent anion channel of Arabidopsis hypocotyls. The pharmacological profile of this channel is characterized by a low sensitivity to most anion channel blockers. It is inhibited by niflumic acid with an IC50 of 80 microM, but poorly sensitive to IAA-94 and NPPB and insensitive to 9-AC and DIDS. Nucleotides alter the amplitude, the kinetics and the voltage-dependence of the channel. The main effect of nucleotides is a shift of the voltage-dependent gate of the channel toward depolarized potentials leading to a strong reduction of the current amplitude. This regulation does not require ATP hydrolysis as nonhydrolyzable ATP analogues-AMPPNP and ATP gamma S-also regulate the anion current. This suggests that a nucleotide binding site is involved in the regulation. The study of the properties of this putative nucleotide binding site reveals that (i) ATP regulates the channel with an EC50 of 0.7 mM, (ii) adenyl nucleotides modulate the channel with the following order of effectiveness: ATP > ADP > > AMP, and (iii) thiophosphate nucleotide analogues are the most potent agonists with EC50 in the range of 80 microM. The hypothesis that this regulation may couple the electrical properties of the membrane with the metabolic status of the cell is discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2002

Ictal brain SPET during seizures pharmacologically provoked with pentylenetetrazol: a new diagnostic procedure in drug-resistant epileptic patients.

Functional brain imaging plays an important role in seizure focus localisation. However, truly ictal single-photon emission tomography (SPET) studies are not routinely performed owing to technical problems associated with the use of tracers and methodological and logistical difficulties. In this study we tried to resolve both of these issues by means of a new procedure: technetium-99m ethyl cysteinate dimer (ECD) brain SPET performed during seizures pharmacologically provoked with pentylenetetrazol, a well-known central and respiratory stimulant. We studied 33 drug-resistant epileptic patients. All patients underwent anamnestic evaluation, neuropsychological and psychodynamic assessment, magnetic resonance imaging, interictal and ictal video-EEG monitoring, and interictal and ictal SPET with (99m)Tc-ECD. In order to obtain truly ictal SPET, 65 mg of pentylenetetrazol was injected every 2 minutes and, immediately the seizure began, 740 MBq of (99m)Tc-ECD was injected. The scintigraphic findings were considered abnormal if a single area of hyperperfusion was present and corresponded to the site of a single area of hypoperfusion at interictal SPET: the "hypo-hyperperfusion" SPET pattern. In 27 of the 33 patients (82%), interictal-ictal SPET showed the hypo-hyperperfusion SPET pattern. Video-EEG showed a single epileptogenic zone in 21/33 patients (64%), and MRI showed anatomical lesions in 19/33 patients (57%). Twenty-two of the 27 patients with hypo-hyperperfusion SPET pattern underwent ablative or palliative surgery and were seizure-free at 3 years of follow-up. No adverse effects were noted during pharmacologically provoked seizure. It is concluded that ictal brain SPET performed during pharmacologically provoked seizure provides truly ictal images because (99m)Tc-ECD is injected immediately upon seizure onset. Using this feasible procedure it is possible to localise the focus, to avoid the limitations due to the unpredictability of seizures, to avoid pitfalls due to late injection, to avoid intracranial EEG recording and to minimise costs. The clinical value of our method is confirmed by the good outcome after 3 years of follow-up in those patients submitted to ablative or palliative surgery.

Adolescent↗
PubMed2005

Modulation of the cellular pharmacology of JM118, the major metabolite of satraplatin, by copper influx and efflux transporters.

Satraplatin is an orally bioavailable platinum analog that has activity in prostate cancer. JM118 is the most abundant species found in the plasma following the oral ingestion of satraplatin and has anti-tumor activity in vitro against cell lines that are resistant to cisplatin (DDP). The goal of the current study was to determine whether the activity of JM118 in some DDP-resistant cells can be explained by differences in the cellular pharmacology of the two drugs. The effect of each of the Cu transporters CTR1, ATP7A and ATP7B on sensitivity to the growth inhibitory effect of JM118 and its cellular pharmacology was examined to identify the characteristics of JM118 that distinguish it from DDP. These studies were performed using wild type and CTR1-/- homozygous knockout mouse embryo cells, and human Me32a Menkes disease fibroblasts that do not express either ATP7A or ATP7B plus sublines molecularly engineered to express either ATP7A (MeMNK cells) or ATP7B (MeWND cells). Knockout of the Cu influx transporter CTR1 in murine embryo cells increased their resistance to DDP and reduced its cellular accumulation but had no effect on sensitivity to JM118 or its uptake. In the case of DDP, forced expression of either of the two Cu efflux transporters, ATP7A or ATP7B, in Me32a cells rendered them resistant to DDP, increased whole cell accumulation of Pt but reduced the amount of Pt in DNA. In the case of JM118, forced expression of either ATP7A or ATP7B rendered Me32a cells resistant, increased not only whole cell Pt accumulation but also increased rather than decreased the amount of Pt in DNA. These results demonstrate that both ATP7A and ATP7B mediate resistance to JM118 as well as DDP and suggest that they sequester both DDP and JM118 into vesicular compartments within the cell resulting in enhanced whole cell accumulation and reduced cytotoxicity. We conclude that there are two important differences between DDP and JM118 with respect to the effect of Cu transporters on their cellular pharmacology. First, whereas CTR1 is involved in DDP accumulation it does not play a role in the uptake of JM118. Second, ATP7A and ATP7B, while they both mediate resistance, have opposite effects on the accumulation of Pt in DNA following exposure to the two drugs. ATP7A and ATP7B appear to be able to modulate the toxicity of the Pt that accumulates in DNA following exposure to JM118. These results suggest that JM118 will retain activity in cells in which DDP resistance is due to the loss of CTR1, but not in cells in which resistance is due to enhanced expression of ATP7A or ATP7B.

Animals↗
PubMed2001

Pharmacological study of paclitaxel duration of infusion combined with GFR-based carboplatin in the treatment of ovarian cancer.

PURPOSE: To determine the effect on systemic pharmacology and clinical toxicity of dose and mode of administration of paclitaxel combined with carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS: A total of 18 patients were treated with a dose of carboplatin determined by GFR, to attain a target AUC of 6 or 7 mg/ml x min. The paclitaxel dose was 175 or 200 mg/m2 administered over approximately 1 or 3 h. The duration of infusion was randomized, crossing over to the alternative treatment for the second course. Blood samples were analysed for carboplatin, paclitaxel and for the excipients of the paclitaxel formulation, ethanol and Cremophor. RESULTS: Overall the three-weekly schedule of administration of the combination of carboplatin and paclitaxel was well tolerated. There were no clinical differences in the toxicities observed between courses where a 1-h infusion was used compared with those with a 3-h infusion. The target AUC of carboplatin was achieved (mean +/- SD 114 +/- 20% of target). Analysis of paclitaxel pharmacokinetics did not show a difference in the AUC or time above a pharmacological threshold for the two infusion durations. The peak concentration of paclitaxel obtained at the end of the infusion (9.1 vs 4.5 microg/ml), and the plasma ethanol concentration (40.0 vs 20.5 mg/dl) were higher following the shorter duration infusion. Peak concentrations of Cremophor were not different. CONCLUSION: The combination of paclitaxel at a dose of 175 mg/m2 and carboplatin at a target AUC of 6-7 mg/ml min can safely be administered every 3 weeks. Also, a 1-h infusion of paclitaxel has no acute clinical disadvantage over a 3-h infusion and these durations of administration are pharmacologically equivalent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Nutritional-pharmacological combinations--a novel approach to reducing colon cancer incidence.

BACKGROUND: Recent studies have suggested that n-9 fatty acids in olive oil prevent colon carcinogenesis while n-6 PUFA seems to activate this process. AIMS: To evaluate the effects of nutritional-pharmacological combinations made up of olive or soy oil-based diets and the drug sulindac, on colon cancer incidence in a chemically induced (1,2-dimethylhydrazine, DMH) rat cancer model. METHODS: Male rats were assigned to two different dietary regimes based on a standard murine defined diet (AIN-76A) containing either a low (4%) or high (15 %) concentration of olive or soy oil. Some groups also received sulindac in their food (80 mg/kg food) starting from the ninth week following the first DMH or vehicle administration. RESULTS: Oleic and linoleic acid reached higher levels in plasma and liver lipids when rats were fed high concentrations of olive or soy oil, respectively. Rats fed a low or high soy oil-based diet showed no significant difference in the number of aberrant crypt foci (ACF) in proximal or distal colon specimens. In contrast, rats fed a higher olive oil-based diet developed a significantly lower number of ACF than rats fed a low concentration of olive oil. Addition of sulindac reduced the number of ACF in rats fed the 4%, but not the 15%, soy oil diet. In contrast, the effect of sulindac was significant when combined with both the low and high concentrations of olive oil. High soy oil-based diet or DMH treatment upregulated colon expression of Bcl-2, but not that of cyclooxygenase-2 (COX-2). In contrast, olive oil dose-dependently downregulated the expression of both Bcl-2 and COX-2 in colonic mucosa and also abrogated the upregulation of Bcl-2 by DMH. Olive oil/sulindac combinations were effective in downregulating colonic mucosa Bcl-2 expression (with the 4% oil diet) and COX-2 expression (with the 15% oil diet). These effects were not observed in rats fed the soy oil/sulindac combinations. Caspase-3 activity in colonic mucosa was unaffected by soy oil or soy oil/sulindac combinations. The addition of olive oil, on the other hand, significantly enhanced colonic caspase-3 activity. CONCLUSIONS: Diets containing high levels of olive oil exert a significant protective effect from tumor development that is additive with the inhibitory effect of sulindac. These inhibitory effects are mediated by regulating the expression and activity of key proteins involved in prostaglandin-biosynthesis and apoptosis-induction pathways. It may be concluded that appropriate dietary-pharmacological combination can improve anti-tumor efficacy over either dietary or pharmacological intervention alone.

Animals↗
PubMed2003

Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation.

Voltage-gated K+ currents expressed in two rat prostate cancer ("Dunning") cell lines of markedly different metastatic ability were characterised using electrophysiological, pharmacological and molecular approaches. Whole-cell patch-clamp recordings showed that both strongly metastatic MAT-LyLu and weakly metastatic AT-2 cell lines possessed outward (delayed-rectifier type) K+ currents, which activated at around -40 mV. From the parameters measured, several characteristics of the two cell lines were similar. However, a number of statistically significant differences were noted for MAT-LyLu versus the AT-2 cells as follows: (1) current densities were smaller; (2) the slope factor for channel activation was smaller; (3) the voltage at which current was half-inactivated, and the slope factor for channel inactivation were greater; (4) the time constants for current decay at -20 and 0 mV were smaller; and (5) the residual peak current was larger following 60 s of repetitive voltage pulses for stimulation frequencies in the range 0.05-0.2 Hz. On the other hand, the K+ currents in both cell lines showed similar pharmacological profiles. Thus, the currents were blocked by 4-aminopyridine, tetraethylammonium, verapamil, margatoxin, and charybdotoxin, with highly similar IC(50)s for given blockers. The electrophysiological and pharmacological data taken together suggested expression of voltage-gated K+ channels of the Kv1 family, expression of the Kv1.3 subunit being predominant. Western blot and RT-PCR tests both confirmed that the cells indeed expressed Kv1.3 and to a lesser extent Kv1.4 and Kv1.6 channel alpha-subunits. In view of the similarity of channel expression in the two cell lines, voltage-gated K+ channel activity may not be a primary determinant of metastatic potential in the rat model of prostate cancer, but the possible contribution of K+ channel activity to the metastatic process is discussed.

4-Aminopyridine↗
PubMed2006

Pharmacology of P2X channels.

Significant progress in understanding the pharmacological characteristics and physiological importance of homomeric and heteromeric P2X channels has been achieved in recent years. P2X channels, gated by ATP and most likely trimerically assembled from seven known P2X subunits, are present in a broad distribution of tissues and are thought to play an important role in a variety of physiological functions, including peripheral and central neuronal transmission, smooth muscle contraction, and inflammation. The known homomeric and heteromeric P2X channels can be distinguished from each other on the basis of pharmacological differences when expressed recombinantly in cell lines, but whether this pharmacological classification holds true in native cells and in vivo is less well-established. Nevertheless, several potent and selective P2X antagonists have been discovered in recent years and shown to be efficacious in various animal models including those for visceral organ function, chronic inflammatory and neuropathic pain, and inflammation. The recent advancement of drug candidates targeting P2X channels into human trials, confirms the medicinal exploitability of this novel target family and provides hope that safe and effective medicines for the treatment of disorders involving P2X channels may be identified in the near future.

Adenosine Triphosphate↗
PubMed2006

[Ethical aspects of pharmacological cognition enhancement and the use of psychostimulants by children and young persons].

DEFINITION OF THE PROBLEM: Pharmacological cognition enhancement aims at an improvement of cognitive activity and performance in healthy people by means of appropriate drugs. Ethical implications of this kind of cognition enhancement stand in need of reflection. ARGUMENTS: For a number of reasons, the distinction between treatment and enhancement is fuzzy with regard to Attention Deficit Hyperactivity Disorder (ADHD). In consideration of the growing number methylphenidate prescriptions, one question addressed in this article is whether or not psychostimulants are used not only for therapy but also for cognitive enhancement by children and young people. The possibility of a "grey zone" between treatment and enhancement seems to open the field for medicalization of social and pedagogical problems as well as for "hidden enhancement." In clinical practice, the use of stimulants is associated with certain ethical problems concerning diagnosis, treatment and prevention of ADHD. Some of these problems are associated with the possibility of cognition enhancement. In order to evaluate ethical problems of pharmacological cognition enhancement, short-term and long-term consequences of stimulant use need to be taken into account. This refers to the level of transmitter balance in the learning process, to the level of individual learning strategies as well as to the level of interaction. This raises the question (1) of how well adapted the means of enhancement are with regard to the end of a comprehensive education and socialization, and (2) whether there are justifiable limits to the standardization of behavior and knowledge. (3) Moreover, stipulating an autonomous decision as a minimum prerequisite for legitimate cognition enhancement seems inadequate in the case of children and young persons. CONCLUSION: Considering the evidence and the many open questions associated with pharmacological cognition enhancement for children and young persons, it is concluded that it is indeed a morally problematic technique.

Adolescent↗
PubMed2000

Eating disorders in children and adolescents: pharmacological therapies.

Anorexia nervosa and bulimia nervosa do exist in childhood, frequently have their onset in adolescence, and can result in serious medical and psychiatric sequelae that impede physical, emotional, and behavioral development. Although we use the same Diagnostic and Statistical Manual of Mental Disorders-Version 4 [DSM-IV] definitions to diagnose eating disorders in children, adolescents, and adults, these disorders may be expressed somewhat differently in younger populations, requiring assessment and treatment procedures that are tailored to their developmental needs. Significant advances have been made in recent years in our understanding of treatments for eating disorders in adults, and specifically pharmacological treatments for these disorders. Multiple double-blind, placebo-controlled studies have documented the short-term efficacy of antidepressant medications in bulimia nervosa. While the usefulness of pharmacological treatments for the acute treatment of anorexia nervosa is less clear, recent evidence suggests a role for medication in the relapse-prevention stage of the illness. The majority of the medication trials for the eating disorders have been conducted with adults, and the literature on the pharmacological treatment of children and adolescents with these disorders is very limited. This review article summarizes the current literature on the role of medication in the treatment of anorexia nervosa and bulimia nervosa, with particular emphasis on studies conducted in child and adolescent populations.

Adolescent↗
PubMed2006

Pharmacologic and pharmacokinetic assessment of anti-TGFbeta2 aptamers in rabbit plasma and aqueous humor.

PURPOSE: The aim of the study is to determine the bioactivity and effects of PEGylation on the pharmacokinetics in rabbit aqueous humor and plasma of an aptamer directed against TGFbeta2. METHODS: Pharmacological activity of anti-TGFbeta2 aptamer in rabbit ocular fluid was demonstrated using a mink lung epithelial cell proliferation assay. For pharmacokinetic analyses, concentrations of aptamers in plasma and aqueous humor were determined over time following bilateral subconjunctival administration to Dutch-belted rabbits using a hybridization-based pseudo-enzyme-linked immunosorbent assay (ELISA) assay. RESULTS: Anti-TGFbeta2 aptamer (ARC81) binds to human TGFbeta2 with a K(D) of approximately 5 nM and inhibits the activity of human TGFbeta2 in vitro in a cell-based assay with an IC(50) of approximately 100 nM. ARC81 blocks endogenously derived TGFbeta2 in rabbit aqueous humor in vitro with an IC(50) of approximately 200 nM and an IC(90) of approximately 1 microM. In vivo in rabbit, ARC81 [no polyethylene glycol (PEG)] entered systemic circulation rapidly (t(max) = 1 h in plasma) relative to aptamer conjugates ARC117 (20 kDa PEG) and ARC119 (40 kDa PEG), which showed prolonged residence in the subconjunctival space and aqueous compartment (t(max) = 6 and 12 h, respectively, in plasma). Both 20- and 40-kDa aptamer conjugates reached maximal concentrations (C(max)) in aqueous humor of 23-30 nM and remained at or above 1 nM for as long as 12 h. CONCLUSIONS: Pharmacologically active levels of anti-TGFbeta2 aptamers can be sustained in the ocular fluid and local tissue environment over a 12-h period after single administration. Daily subconjunctival administration of PEGylated anti-TGFbeta2 aptamers should allow further pharmacological evaluation of these agents in a rabbit conjunctival scarring model. Perioperative administration, via subconjunctival injection, may prove to be an effective means to deliver therapeutic quantities of TGFbeta2 aptamer conjugates in trabeculectomy procedures.

Animals↗
PubMed2006

Pharmacologic therapy for gastrointestinal bleeding due to portal hypertension and esophageal varices.

Cirrhosis results in portal hypertension in many patients. The major complications of portal hypertension include development of ascites and esophageal or gastric varices. Varices lead to hemorrhage and death in a significant proportion of patients. This review focuses on the pharmacologic approach to management of portal hypertension in patients at risk of variceal hemorrhage, or those who have already had variceal bleeding. Pharmacologic therapy is used for 1) primary prevention of bleeding, 2) management of acute bleeding, and 3) prevention of recurrent bleeding (secondary prophylaxis). For acute esophageal variceal hemorrhage, a variety of pharmacologic agents are used, including somatostatin, octreotide, vapreotide, lanreotide, terlipressin, and vasopressin (with nitrates). For primary and secondary prevention of esophageal variceal hemorrhage, beta-blockers remain the mainstay therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Pharmacologic and genetic therapy for childhood muscular dystrophies.

The outstanding advances in the molecular characterization of muscle diseases, including muscular dystrophies, inflammatory myopathies, and ion channel disorders, have resulted in the identification of potential targets for pharmacologic and genetic therapy in the best characterized of these diseases. The most common myopathy in children, Duchenne muscular dystrophy (DMD), is the focus of active pharmacologic clinical trials. Genetic transfer therapy research for this and other dystrophies is rapidly moving forward. However, as new approaches for treatment are being actively investigated, the current modality of treatment for all myopathies is still in the realm of physical medicine and rehabilitation. The focus of this review is on the advances in pharmacologic and genetic therapy research in DMD and limb girdle muscular dystrophies.

Animals↗
PubMed2005

Pharmacologic treatment of fibromyalgia.

Fibromyalgia is a syndrome of widespread pain, nonrestorative sleep, disturbed mood, and fatigue. Optimal treatment involves a multidisciplinary approach with a team of health care providers using pharmacologic and nonpharmacologic treatment. Because of the heterogeneity of the illness, management should be individualized for the patient. Pharmacologic treatment should address issues of pain control, sleep disturbance, fatigue, and any underlying coexisting mood disorder. Nonpharmacologic treatment should include patient education, a regular exercise and stretching program, and cognitive behavioral therapy. All of these are essential to improving functional capacity and quality of life. This review provides general guidelines in initiating a successful pharmacologic treatment program for patients with fibromyalgia.

Analgesics↗
PubMed2004

Neurochemical predictors of response to pharmacologic treatments for bipolar disorder.

Bipolar disorder is a common psychiatric disorder that is characterized by recurrent episodes of mania and often depression. Mood stabilizers and antipsychotics are first-line pharmacologic options for patients with bipolar disorder. However, the exact mechanisms by which these medications exert the mood stabilizing effects are unknown. Additionally, individuals with bipolar disorder often try several medications unsuccessfully before achieving mood stabilization. Magnetic resonance spectroscopy (MRS) is a noninvasive neuroimaging technique that can be used to identify the neurochemical effects and predictors of response to medications commonly used to treat bipolar disorder. MRS may facilitate targeted treatment interventions and decrease the morbidity and mortality associated with this illness. Examining the mechanisms of action of pharmacologic agents used to treat bipolar disorder may clarify the neurophysiologic basis of bipolar disorder. We will review recent MRS investigations that have evaluated the neurochemical effects of pharmacologic treatments and predictors of treatment response in patients with bipolar disorder.

Antimanic Agents↗
PubMed1981

Effects of digitalis on the human sick sinus node after pharmacologic autonomic blockade.

To study the effects of digitalis on the sinus node and the mechanisms involved, 16 patients with the sick sinus syndrome had electrophysiologic assessment of sinus nodal function during (1) control study, (2) after pharmacologic autonomic blockade with propranolol (0.2 mg/kg body weight and atropine sulfate 0.04 mg/kg intravenously), and (3) 10 minutes after 0.01 mg/kg of intravenous ouabain. The study was completed within 30 minutes of pharmacologic autonomic blockade. During the control study 50 percent of patients had an abnormal corrected sinus nodal recovery time or abnormal sinoatrial conduction time, or both. The effects of ouabain on sinus nodal function were compared with those after pharmacologic autonomic blockade. Ouabain significantly increased both intrinsic sinus cycle length (ouabain 975 +/- 194 ms [mean +/- standard deviation]; autonomic blockade 1,025 +/- 218 ms, probability [p] less than 0.001) and corrected sinus nodal recovery time (ouabain 615 +/- 503 ms; autonomic blockade 575 +/- 536 ms, p less than 0.05). In contrast there was no significant change in sinoatrial conduction time after ouabain (ouabain 141 +/- 56 ms; autonomic blockade 132 +/- 45 ms; difference not significant). The effects of ouabain were similar in patients with both normal and abnormal sinus nodal function. These findings suggest that (1) digitalis in therapeutic doses has a depressant effect on intrinsic sinus nodal automaticity in patients with normal as well as abnormal sinus nodal function; (2) digitalis has no significant effects on sinoatrial conduction; and (3) the effects of digitalis on sinus nodal automaticity are primary and independent of its vagal and antiadrenergic effects.

Aged↗