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PubMed1997

Atropine role in the pharmacological erection test: study of 228 patients.

PURPOSE: We determined the efficacy of atropine sulfate combined with papaverine hydrochloride, prostaglandin E1 and phentolamine mesylate in the pharmacological erection test. MATERIALS AND METHODS: A total of 230 consecutive patients with erectile dysfunction was randomized for pharmacological erection test and received an intracorporeal combination of 50 mg. papaverine hydrochloride, 10 micrograms. prostaglandin E1, 0.2 mg. phentolamine mesylate and 0.075 mg. of atropine sulfate (group 1), or the same combination without atropine sulfate (group 2). Erectile response was evaluated subjectively and by intracorporeal pressure measurement. RESULTS: In group 1, 40 patients (35.1%) showed only tumescence, and 22 (19.3%) had poor erection. In group 2, 45 patients (39.5%) had tumescence and 17 (14.9%) poor erection. In both groups 52 patients (45.6%) had rigid erection. There was no statistically significant difference regarding erectile response and intracorporeal pressure. CONCLUSIONS: The addition of atropine sulfate did not improve results of the pharmacological erection test when combined with 50 mg. papverine hydrochloride, 10 micrograms, prostaglandin E1, and 0.2 mg. phentolamine mesylate.

Adult↗
PubMed1996

Pharmacologic treatment options for non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health concern for clinicians who are responsible for the care of an aging population. The relationship between hyperglycemia and the chronic complications of retinopathy, nephropathy, and neuropathy has been established in patients with insulin-dependent diabetes mellitus, and it is extremely likely that such a relationship exists in patients with NIDDM as well. Diet and exercise are the cornerstone for the management of NIDDM. The assessment of glycemic control should determine which patients with NIDDM need more aggressive intervention to control hyperglycemia. Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin. Extensive education about diabetes and self-monitoring of blood glucose levels are important components in maximizing glycemic control. Additional pharmacologic treatment options are necessary when adequate individualized treatment goals are not attained. The goal of therapy is to prevent the onset or progression of long-term microvascular and macrovascular complications. In this review, we present the therapeutic options and outline our approach to the pharmacologic treatment of NIDDM. Relevant medical literature on each treatment modality is reviewed, and the cost of therapy with use of each medication is provided.

Acarbose↗
PubMed2001

Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors.

The present study determined the detailed pharmacological profile of heterologously expressed human (h) homomeric 5-HT3A receptors in direct comparison to heteromeric h5-HT3A/3B receptors. The very minor differences in their respective pharmacological profiles indicates that the 5-HT3B receptor subunit alters, predominantly, the biophysical rather than the pharmacological properties of the 5-HT3 receptor.

Free Radical Scavengers↗
PubMed2002

Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor.

The pharmacology of histamine H(3) receptors suggests the presence of distinct receptor isoforms or subtypes. We herein describe multiple, functionally distinct, alternatively spliced isoforms of the human H(3) receptor. Combinatorial splicing at three different sites creates at least six distinct receptor isoforms, of which isoforms 1, 2, and 4, encode functional proteins. Detailed pharmacology on isoforms 1 (unspliced receptor), and 2 (which has an 80 amino acid deletion within the third intracellular loop of the protein) revealed that both isoforms displayed robust responses to a series of known H(3) agonists, while all agonists tested displayed increased potency at isoform 2 relative to isoform 1. Histamine, N(alpha)-methylhistamine, and R(-) and S(+)-alpha-methylhistamine are 16-23-fold more potent, while immepip and imetit are three to fivefold more potent. Antagonist experiments revealed a rank order of potency at both isoforms of clobenpropit>iodophenpropit>thioperamide, and these drugs are fivefold less potent at isoform 2 than isoform 1. To further explore the pharmacology of H(3) receptor function, we screened 150 clinically relevant neuropsychiatric drugs for H(3) receptor activity, and identified a small number of antipsychotics that possess significant antagonist activity.

Amino Acid Sequence↗
PubMed2002

Pharmacological separation of cannabinoid sensitive receptors on hippocampal excitatory and inhibitory fibers.

Our earlier studies demonstrated that in the hippocampus, cannabinoids suppress inhibitory synaptic transmission via CB(1) cannabinoid receptors, whereas a novel cannabinoid-sensitive receptor modulates excitatory synapses (Katona, I. et al., Journal of Neuroscience 19 (1999) 4544; Hájos, N. et al., European Journal of Neuroscience 12 (2000) 3239; Hájos, N. et al., Neuroscience 106 (2001) 1). The novel receptor does not correspond to CB(2), since this receptor type is not expressed in the brain (Munro, S. et al., Nature 365 (1993) 61). Recent binding experiments revealed that the synthetic cannabinoid WIN 55,212-2 binds with lower affinity to brain membranes of CB(1) receptor-knockout mice indicating that pharmacological differences exist between these two types of cannabinoid receptors in the hippocampus (Breivogel et al., Molecular Pharmacology 60 (2001) 155). To analyze this difference in detail, we first determined the EC(50) values of WIN 55,212-2 for excitatory and inhibitory transmission in rat hippocampal slices using whole-cell patch-clamp recordings. The estimated EC(50) value for inhibitory postsynaptic currents (IPSC) evoked by electrical stimulation in CA1 pyramidal cells was 0.24 microM, whereas for excitatory postsynaptic currents (EPSC) it was 2.01 microM, respectively. The cannabinoid antagonist, AM251, blocked the WIN 55,212-2-induced inhibition of evoked IPSCs, but not of EPSCs, providing evidence for its selectivity for CB(1). We then tested the hypothesis of whether the cannabinoid effect on hippocampal excitatory neurotransmission is mediated via receptors with an affinity for vanilloid ligands. Co-application of the vanilloid receptor antagonist capsazepine (10 microM) with cannabinoids (WIN55,212-2 or CP55,940) prevented the reduction of EPSCs, but not of IPSCs. The amplitude of evoked EPSCs was also suppressed by superfusion of the vanilloid receptor agonist capsaicin (10 microM), an effect which could also be antagonized by capsazepine. In contrast, capsaicin did not change the amplitude of evoked IPSCs. These results demonstrate that WIN 55,212-2 is an order of magnitude more potent in reducing GABAergic currents via CB(1) than in inhibiting glutamatergic transmission via the new CB receptor. The sensitivity of the new CB receptor (and EPSCs) to vanilloid ligands, but not to the cannabinoid antagonist AM251, represents another pharmacological tool to distinguish the two receptors, since CB(1) (and its effect on IPSCs) is not modulated by vanilloids, but is antagonized by AM251.

Animals↗
PubMed2003

Pharmacology and expression analysis of glycine transporter GlyT1 with [3H]-(N-[3-(4'-fluorophenyl)-3-(4'phenylphenoxy)propyl])sarcosine.

In the central nervous system, re-uptake of the neurotransmitter glycine is mediated by two different glycine transporters, GlyT1 and GlyT2. GlyT2 is found in brainstem and spinal cord, whereas GlyT1 is expressed in rat forebrain regions where it is responsible for most glycine transport activity. Initially, GlyT1 and GlyT2 were pharmacologically differentiated by sarcosine, a weak selective inhibitor of GlyT1. The recently described selective and potent GlyT1 antagonist, NFPS/ALX-5407 provided an important additional tool to further characterize GlyT1 pharmacology. In the present study, we have radiolabeled the racemic form of NFPS (N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (also known as ALX-5407) to investigate its interaction with GlyT1, as well as define GlyT1 expression in the rat central nervous system. Kinetic studies indicated that [3H]NFPS binds rapidly to rat forebrain membranes and dissociates with a t(1/2) of 28 +/- 5 min. [3H]NFPS labeled a saturable population of sites in rat forebrain with a Kd of 7.1+/-1.3 nM and a B(max) of 3.14 +/- 0.26 pmol/mg protein. Bound [3H]NFPS was fully and potently displaced by unlabeled NFPS, whereas glycine and sarcosine were weak, Na+-dependent inhibitors with IC50 of 1,008 and 190 microM, respectively. Additional saturation experiments indicated that glycine and sarcosine were non-competitive antagonists of [3H]NFPS binding. Functional studies revealed that NFPS was a non-competitive inhibitor of [3H]glycine uptake and does not interact with Na+ and Cl- binding sites of GlyT1. Overall, this work shows that [3H]NFPS is a valuable tool in studying GlyT1 expression and pharmacology and that NFPS interacts with GlyT1 at a site different from the transporter translocation and ion binding sites.

Amino Acid Transport Systems, Neutral↗
PubMed1996

Pharmacological properties of recombinant "diazepam-insensitive" GABAA receptors.

Both native and recombinant "diazepam-insensitive" GABAA receptors (DI) are characterized by the very low affinities of prototypic 1,4-benzodiazepines such as diazepam and the high affinity of an imidazobenzodiazepine, Ro 15-4513. The presence of either an alpha 4 or alpha 6 subunit imparts this unusual pharmacological profile to DI. Based on the affinities of these compounds at recombinant DI, the pharmacological properties of alpha 4- and alpha 6-bearing receptor isoforms appear to be very similar if not identical. Using a larger sample of structurally diverse compounds, we now demonstrate distinct but related ligand binding profiles of recombinant alpha 4 beta 2 gamma 2 and alpha 6 beta 2 gamma 2 DI. Comparison of 18 ligands drawn from three principal structural groups (beta-carbolines, imidazobenzodiazepines and pyrazoloquinolinones) revealed that the affinity of at least one representative from each group differed by > 5-fold between alpha 4- and alpha 6 beta 2 gamma 2 receptors. While the high correlation (r2 = 0.926; p < 0.001) obtained between the affinities of these ligands at alpha 4- and alpha 6-containing receptors underscores the similarity between these receptor isoforms, a significant deviation of the slope of this correlation (0.792; 95% C.I. 0.673-0.911) from unity is substantive evidence that these DI possess distinct pharmacological profiles. These findings indicate that it is feasible to develop selective ligands for these DI isoforms.

Animals↗
PubMed1996

Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology.

GABAA and glycine receptors are close relatives in the "gene superfamily" of ligand-gated ion channels, but have distinctly different pharmacology. For example, barbiturates have two effects on GABAA receptors (GABAA-R): at low micromolar concentrations (2-5 microM), the anesthetic barbiturate methohexital potentiates submaximal chloride current responses to GABA; at higher concentrations (20-50 microM), the barbiturate causes direct gating of the channel in the absence of agonist. Neither of these barbiturate effects is seen on the glycine receptor (Gly-R). In order to study the structural parts of the GABAA-R involved in this barbiturate pharmacology, two unique restriction sites were introduced into the cDNAs encoding the alpha 2 and beta 1 subunits of the human GABAA-R and the alpha 1 subunit of the human gly-R. The first site ('X') corresponded to the C-terminal end of the third transmembrane domain (M3) in each subunit and enabled exchange of C-terminal fragment of approximately 100 amino acids (which includes the large 'cytoplasmic loop' and M4 segment) between GABAA-R and Gly-R subunits. The second site ('S') was approximately 30 amino acids 3'- from the N-terminal end of each subunit and enabled exchange of a small N-terminal fragment between GABAA-R and Gly-R subunits. Several chimeric receptor subunit cDNAs were constructed and the resulting receptors tested for their ability to respond to GABA and glycine and for sensitivity to the barbiturate methohextial (MTX). The results show that neither the large C-terminal fragment nor the smaller N-terminal fragment is associated with the enhancement or direct activation of the GABAA-R by MTX. These results demonstrate the viability of chimeric GABAA/Gly-R and suggest that the method will be suitable for further investigation of the molecular basis of the barbiturate pharmacology of the GABA-R.

Anesthetics, General↗
PubMedDate not supplied

Pharmacological differentiation between neuronal and recombinant glutamate receptor channels expressed in Xenopus oocytes.

To determine the molecular components of neuronal glutamate receptors, it is important to identify pharmacological tools that allow differentiation between different glutamate receptor types. Here, we utilized the naphthalene derivative Evans Blue (EB) and a collection of other subtype-specific compounds (polyamine toxins, concanavalin A, cyclothiazide) to compare the pharmacological profile of neuronal and recombinant glutamate receptors GluR1-GluR6 expressed in Xenopus oocytes. Submicromolar concentrations of EB selectively reduced the activity of homomeric glutamate receptors GluR1, GluR2(Q) and GluR4. Applied at concentrations above 100 microM, EB potentiated kainate responses of receptors GluR1, GluR3 and GluR4, while receptors GluR2(Q) and GluR6(Q) were completely blocked. Similar experiments were performed on identified neurones in brain slices and after injection of rat brain RNA in Xenopus oocytes. Neuronal kainate responses were (i) potentiated by 100 microM cyclothiazide, (ii) slightly blocked after preincubation in 10 microM concanavalin A, and (iii) not significantly affected by either low (< 1 microM) or high (> 100 microM) concentrations of EB. Their pharmacological properties were markedly different from those of recombinant glutamate receptor channels GluR1-GluR6 investigated in heterologous expression systems.

Animals↗
PubMed1999

Human CRF2 alpha and beta splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay.

Corticotropin releasing factor (CRF) receptors belong to the super-family of G protein-coupled receptors. These receptors are classified into two subtypes (CRF1 and CRF2). Both receptors are positively coupled to adenylyl cyclase but they have a distinct pharmacology and distribution in brain. Two isoforms belonging to the CRF2 subtype receptors, CRF2alpha and CRF2beta, have been identified in rat and man. The neuropeptides CRF and urocortin mediate their actions through this CRF G protein-coupled receptor family. In this report, we describe the pharmacological characterization of the recently identified hCRF2, receptor. We have used radioligand binding with [125I]-tyr0-sauvagine and a gene expression assay in which the firefly luciferase gene expression is under the control of cAMP responsive elements. Association kinetics of [125I]-tyr0-sauvagine binding to the hCRF2beta receptor were monophasic while dissociation kinetics were biphasic, in agreement with the kinetics results obtained with the hCRF2alpha receptor. Saturation binding analysis revealed two affinity states in HEK 293 cells with binding parameters in accord with those determined kinetically and with parameters obtained with the hCRF2alpha receptor. A non-hydrolysable GTP analog, Gpp(NH)p, reduced the high affinity binding of [125I]-tyr0-sauvagine to both hCRF2 receptor isoforms in a similar manner. The rank order of potency of CRF agonist peptides in competition experiments was identical for both hCRF2 isoforms (urocortin > sauvagine > urotensin 1 > r/hCRF > alpha-helical CRF(9-41) > oCRF). Similarly, agonist potency was similar for the two isoforms when studied using the luciferase gene reporter system. The peptide antagonist alpha-helical CRF(9-41) exhibited a non-competitive antagonism of urocortin-stimulated luciferase expression with both hCRF2 receptor isoforms. Taken together, these results indicate that the pharmacological profiles of the CRF2 splice variants are identical. This indicates that the region of the N-terminus that varies between the receptors is probably not important in the binding of peptide CRF receptor ligands or functional activation of the receptor.

Alternative Splicing↗
PubMed2001

The pharmacology of bimatoprost (Lumigan).

Bimatoprost (Lumigan) is a pharmacologically unique and highly efficacious ocular hypotensive agent. It appears to mimic the activity of a newly discovered family of fatty acid amides, termed prostamides. One biosynthetic route to the prostamides involves anandamide as the precursor. Bimatoprost pharmacology has been extensively characterized by binding and functional studies at more than 100 drug targets, which comprise a diverse variety of receptors, ion channels, and transporters. Bimatoprost exhibited no meaningful activity at receptors known to include antiglaucoma drug targets as follows: adenosine (A(1-3)), adrenergic (alpha(1), alpha(2), beta(1), beta(2)), cannabinoid (CB(1), CB(2)), dopamine (D(1-5)), muscarinic (M(1-5)), prostanoid (DP, EP(1-4), FP, IP, TP), and serotonin (5HT(1-7)). Bimatoprost does, however, exhibit potent inherent pharmacological activity in the feline iris sphincter preparation, which is prostamide-sensitive. Bimatoprost also resembles the prostamides in that it is a potent and highly efficacious ocular hypotensive agent. A single dose of bimatoprost markedly reduces intraocular pressure in dogs and laser-induced ocular hypertensive monkeys. Decreases in intraocular pressure are well maintained for at least 24 hr post-dose. Human studies have demonstrated that systemic exposure to bimatoprost is low and that accumulation does not occur. The sclera is the preferred route of accession to the eye. The high scleral permeability coefficient Papp is a likely contributing factor to the rapid onset and long-acting ocular hypotensive profile of bimatoprost.

Amides↗
PubMed1997

Chemical modification of histidine and lysine residues of myotoxic phospholipases A2 isolated from Bothrops asper and Bothrops godmani snake venoms: effects on enzymatic and pharmacological properties.

Lysine and histidine residues of two myotoxic phospholipases A2, Bothrops asper myotoxin III and Bothrops godmani myotoxin I, were chemically modified in order to study the effects of these treatments on enzymatic and pharmacological properties. After lysine acetylation the overall basicity of these toxins was lost and their enzymatic activity was significantly reduced, although a residual effect remained, which corresponded to 25% of the activity of native toxins. This treatment abolished both myotoxic and anticoagulant effects, and partially reduced liposome-disrupting activity. Histidine alkylation with p-bromophenacyl bromide affected phospholipase A2, myotoxic and anticoagulant effects in a parallel way. After 24 hr of incubation with the alkylating reagent, these three activities were totally inhibited, in contrast to the liposome-disrupting effect which was only partially affected by this treatment. It is suggested that; (1) catalytic activity plays a role in the pharmacological effects of these myotoxins; (2) lysine residues are relevant for the toxic effects induced by these phospholipases A2; and (3) despite the apparent relevance of enzymatic activity to the pharmacological properties of these toxins, the dissociation observed in lysine acetylation experiments suggests that these myotoxins have a molecular region, different from the catalytic site, which might be also involved in the toxic effects observed.

Acetophenones↗
PubMed1998

Pharmacological aspects of mouse hind-paw oedema induced by Lachesis muta rhombeata venom.

Pharmacological aspects of mouse hind-paw oedema induced by subplantar injections of Lachesis muta rhombeata (LMR) venom were investigated. The oedema induced by subplantar injections of 10 to 50 ng/g of LMR venom is dose dependent, with onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar injection of 30 ng/g of Bothrops jararaca (BJ) venom induced oedema that has the same intensity as 30 ng/g of LMR venom but lasts for more than 4 h suggesting different time course. Systemic effects or haemorrhage were not observed with doses less than 50 ng/g. Oedema is not due to the presence of oedematogenic amines since dialysis did not change the oedema induced by 30 ng/g of LMR venom. Part of the oedema induced by LMR venom is due to a thermolabile fraction since pre-heating the venom at 100 degrees C for 15 min induced a significant reduction (56.19 +/- 6.8%) of the oedematogenic activity. The oedema induced by LMR venom is possibly induced by release of a pharmacological active substance at the site of injection. Histamine, arachidonate metabolites, nitric oxide and serotonin may play important roles in the oedematogenic effect of LMR venom since pre-treatment of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and methysergide induced a significant reduction (49.86 +/- 10%; 51.06 +/- 5.9%; 77.66 +/- 3.6%; 73.30 +/- 6.1% and 93.77 +/- 2.8%, respectively) of the oedema formation. The present results demonstrate that the oedema induced by LMR and BJ venoms may be triggered and maintained by different pharmacological mechanisms. Since methysergide and L-NAME were the most active inhibitors of the oedema we can suggest that a link between serotonin release by the venom and a NO synthase activation may be an important step in the oedema formation induced by LMR venom.

Animals↗
PubMed2002

Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction.

The scientific rationale of pharmacologically inhibiting phosphodiesterase type 5 (PDE5) in the treatment of erectile dysfunction (ED) is reviewed. Published literature on the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway for penile erection and on PDE5 inhibition using sildenafil as the model for pharmacologic PDE5 inhibition are assessed. The key second messenger in the mediation of penile erection is cGMP. PDE5 is the predominant PDE in the corpus cavernosum, and cGMP is its primary substrate. Therefore, in men with ED, elevation of cGMP in corpus cavernosal tissue via selective inhibition of cGMP-specific PDE5 is a means of improving erectile function at minimal risk of adverse events. This approach is validated by the clinical efficacy and safety of sildenafil, the pioneering drug for selective PDE5 inhibitor therapy for ED. Sildenafil exhibits inhibitory potency against PDE5 and a 10-fold lower dose-related inhibitory potency against rod outer segment PDE6, the predominant PDE in the phototransduction cascade in rods. Thus, its pharmacologic profile is predictable, with close correlation between pharmacodynamic and pharmacokinetic properties. Clinically, sildenafil improves erectile function in a large percentage of men with ED. The most common adverse events are due to PDE5 inhibition in vascular and visceral smooth muscle; similar adverse events are expected during therapeutic use of all PDE5 inhibitors. As free sildenafil plasma concentrations approach concentrations sufficient to inhibit retinal PDE6, usually at higher therapeutic doses, transient, reversible visual adverse events can occur, albeit infrequently. Selective inhibition of PDE5 is a rational therapeutic approach in ED, as proved by the clinical success of sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Pharmacologic options for the overactive bladder.

OBJECTIVES: To review the current pharmacologic options for treatment of the overactive bladder and to describe potential therapies on the horizon. METHODS: The literature on the clinical efficacy and safety of the currently available agents is described. RESULTS: According to the guidelines issued by the Agency for Health Care Policy and Research (AHCPR), anticholinergic agents should be the first-line pharmacologic therapy for patients with detrusor instability. Oxybutynin is the anticholinergic of choice for this indication, whereas propantheline is the second-line therapy. Although calcium antagonists have been investigated, the one such drug introduced for the treatment of overactive bladder (terodiline) was withdrawn from the market because of a risk of cardiac arrhythmia. Studies of potassium channel openers have found either a lack of clinical efficacy or an unacceptable level of side effects. Alpha-adrenergic antagonists may be useful for decreasing bladder overactivity in patients who have autonomous bladders as the result of conditions such as spinal cord injury. Tricyclic antidepressants (particularly imipramine) may be effective in decreasing bladder contractility, although the AHCPR guidelines caution that these drugs should be reserved for use in carefully evaluated patients. Future developments in the treatment of detrusor overactivity are likely to occur in 3 categories: drugs that affect peripheral excitatory mechanisms, drugs that inhibit afferent mechanisms, and drugs that affect more central actions at either the ganglionic, spinal cord, or supraspinal level. CONCLUSIONS: Although pharmacologic management of the overactive bladder has progressed little in the past 10 years, the future may hold the promise of more effective therapies.

Antidepressive Agents, Tricyclic↗
PubMed1995

Doxazosin in physiologically and pharmacologically normotensive men with benign prostatic hyperplasia.

OBJECTIVES: To compare the effects of doxazosin on blood pressure when used for the treatment of benign prostatic hyperplasia (BPH) in men who are either physiologically or pharmacologically normotensive. METHODS: Sixty-three men with BPH were enrolled in two open-label, parallel, randomized studies. Thirty-one were physiologically normotensive and 32 had hypertension controlled by antihypertensive therapy (pharmacologically normotensive). Of these, 17 were taking calcium channel blockers; 6, angiotensin-converting enzyme inhibitors; and 9, beta blockers. After a 3-week titration period, patients from one study received doxazosin (4 mg/day) for 3 months, given as a single dose in either the morning or evening, and in the second study patients were randomized to receive either 4 mg or 8 mg daily, either in the morning or evening. Effects on blood pressure, maximum uroflow, and the Boyarsky symptom score were measured. RESULTS: Doxazosin produced statistically significant but clinically unimportant reductions in blood pressure in both physiologically and pharmacologically normotensive groups. Statistically and clinically significant improvements in BPH symptoms and maximal perfusion occurred in both groups within 1 month, and further improvements were improved after 3 months. These effects were evident whether doxazosin was administered in the morning or evening. Doxazosin was well tolerated, the only adverse events being dizziness in 5 patients and fatigue in 4. By protocol, all patients reporting adverse events were required to be discontinued from the study. Adverse events did not differ between the groups. There was some indication that patients experiencing adverse events also experienced greater reductions in blood pressure. CONCLUSIONS: Doxazosin may be introduced for the treatment of BPH in hypertensive men whose blood pressure is already controlled by another antihypertensive agent, without a further clinical reduction in blood pressure. It is effective and well tolerated as a once-daily dose given in the morning or evening.

Adrenergic alpha-Antagonists↗
PubMed1999

Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints.

BACKGROUND: Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). METHODS: Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. FINDINGS: We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0.55 [95% CI 0.34-0.90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0.37 [0.25-0.55], and 0.44 [0.22-0.90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2.4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. INTERPRETATION: Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

Aminocaproates↗
PubMedDate not supplied

A clinical pharmacological approach to treating Tourette syndrome in children and adolescents.

Tourette Syndrome (TS) is a neuropsychiatric movement disorder characterized by the presence of multiple motor and phonic tics. Monoamine neurotransmitter dysfunction has been implicated in the expression of the condition. Standard as well as novel pharmacologic treatments for TS as a sole entity or as a condition co-morbid with attention deficit-hyperactivity disorder (ADHD) and/or obsessive-compulsive disorder (OCD) target these presumed neurotransmitter abnormalities. Choice of a specific medication is also predicated upon an individual patient's symptom profile, a cost-benefit analysis of desired effects versus side effects, and the impact on co-morbid conditions. Maximum involvement of the patient and parent or significant other is encouraged. It is emphasized that pharmacologic treatment is primarily symptomatic, usually not affecting the longer term outcome of specific syndromes per se. The integration of pharmacologic with psychoeducational interventions is encouraged.

Adolescent↗