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Introduction : Autonomic dysfunction is an integral part of Parkinson disease (PD) complex and can be seen both in early and advanced stages. There is a paucity of medicines available to manage autonomic dysfunction in PD and this adds to the considerable morbidity associated with the illness. Areas covered : The pathophysiology and the available therapeutic options of autonomic dysfunction seen in PD are discussed in detail. The potential targets for novel regimens are reviewed and the available literature on the drugs emerging in management of autonomic dysfunction in PD is highlighted. Expert opinion : In the current scenario, there are several drugs that can be tried for constipation viz stool laxatives, prucalopride, prokinetic agents and a high fiber diet. Bladder dysfunction has been treated with β-agonists and with mirabegron, a selective β-3 agonist, the anticholinergic side effects are minimized, and the drug has been found to be effective. Orthostatic hypotension is managed with midodrine while droxidopa is a new drug with promising efficacy. Botulinum toxin works best for management of sialorrhea, but repeated injections are needed.

Postural tachycardia syndrome (POTS) is a disorder characterized by the presence of orthostatic symptoms (including lightheadedness, palpitations, nausea, dyspnea, and tremulousness) as well as excessive upright tachycardia. POTS predominantly affects women of childbearing age. Treating POTS involves a multi-faceted approach using non-pharmacological and pharmacological interventions. There are no pharmacological treatments that are currently United States Food and Drug Administration (FDA) approved for POTS due to lack of randomized controlled trials. Yet, several medications can improve POTS symptoms and are supported by small prospective studies or retrospective case series. Drugs that are most commonly used for POTS target the following mechanisms 1) blood volume expansion, 2) reduction of heart rate, 3) peripheral vasoconstriction and 4) sympatholysis. Pharmacological approaches can also be used to target specific symptoms including "brain fog," fatigue, sleep, and depression. This review outlines pharmacological approaches for treating POTS and summarizes evidence supporting each treatment approach., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Kuan-Sin-Yin (KSY) is a traditional Chinese medicine (TCM) decoction, which has been shown to have cytostatic effects on cancer cells and involved in the TCM theory of promoting yin-yang balance.Sonce many cancer patients suffer from autonomic dysfunction (AD), which correspond to yin-yang imbalance in TCM. The aim of this study is to evaluate the possible effect of KSY in metastatic colon cancer (mCRC) patients with AD., Methods: We conducted a single-group experiment. Total 52 qualified patients were enrolled. Participants took the KSY daily for 2 weeks. The primary outcome was KSY efficacy as reflected in the heart rate variability (HRV) and electrical conductivity (µA) over 12 meridian points. Autonomic function was examined before and after the KSY intervention. The vagal and sympathetic tone were recorded by HRV; 12 meridian energies were measured using a meridian energy analysis device. Secondary outcomes were cancer-related symptoms and patient quality of life (QoL)., Results: The results showed that the KSY intervention improved AD via increasing the vagal tone (HF: P = .041), but not the sympathetic tone (LF: P = .154); total autonomic activity was significantly enhanced (HRV activity: P = .013). Intriguingly, energy increased more over the yin meridian (P = .010) than over the yang meridian (P = .015). Cancer-related symptoms and QoL were significantly improved (P < .05)., Conclusion: The safety and effectiveness of KSY in improving AD in mCRC patients are through regulating the vagal-sympathetic dynamic balance, which correspond to the TCM yin-yang concept of energy., (© The Author(s) 2015.)

Patients with autonomic failure are characterized by orthostatic hypotension, supine hypertension, high blood pressure variability, blunted heart rate variability, and often have a "non-dipping" or "reverse dipping" pattern on 24-h ambulatory blood pressure monitoring. These alterations may lead to cardiovascular and cerebrovascular changes, similar to the target organ damage found in hypertension. Often patients with autonomic failure are on treatment with anti-hypotensive drugs, which may worsen supine hypertension. The aim of this review is to summarize the evidence for cardiac, vascular, renal, and cerebrovascular damage in patients with autonomic failure.

Objective: To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH)., Methods: Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities., Results: From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events., Conclusions: In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated., Classification of Evidence: This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days., (© 2014 American Academy of Neurology.)

One characteristic of the most common types of glaucoma is increased intraocular pressure (IOP), which has a damaging effect on optic nerve axons, leading to progressive loss of retinal ganglion cells. Therefore, ocular hypotensive drugs are the mainstay of pharmacological therapy for glaucoma. This review article, which is the first part of a two-part series, is dedicated to autonomic drugs which lower IOP by increasing the outflow of aqueous humour. These agents are subdivided into two groups: (a) drugs that lower IOP by increasing the trabecular outflow and the uveoscleral outflow (i.e. nonselective adrenergic agonists), and (b) medications that lower IOP by opening of the drainage angle and by increasing the conventional outflow via the trabecular outflow (i.e. parasympathomimetics). This paper summarizes the current state of knowledge on the mechanism of action of these drugs and their effect on IOP in dogs and cats. Moreover, it discusses possible undesirable side effects of these medications and presents the current ideas about their role and position in the medical management of glaucoma in small animals.

One characteristic of the most common types of glaucoma is increased intraocular pressure (IOP), which has a damaging effect on optic nerve axons, leading to progressive loss of retinal ganglion cells. Therefore, ocular hypotensive drugs are the mainstay of pharmacological therapy for glaucoma. This review article, which is the second part of a two-part series, is dedicated to autonomic drugs which lower IOP by decreasing the aqueous humour production. These agents are subdivided into two groups: β-adrenergic antagonists and selective α2-adrenergic agonists. This paper summarizes the current state of knowledge on the mechanism of action of these drugs and their effect on IOP in dogs and cats. Moreover, it discusses their possible undesirable side effects of these medications and presents the current ideas about their role and position in the medical management of glaucoma in small animals.

Introduction: Autonomic dysfunction, including orthostatic hypotension (OH), sialorrhea, sexual dysfunction, urinary dysfunction and constipation is a common feature of Parkinson's disease (PD). Even though its treatment has been recognized as a major unmet need in PD, there is a paucity of clinical trials to assess their treatment., Areas Covered: Evidence about the efficacy and safety of available treatments for autonomic dysfunction is summarized. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of each disorder in PD. Proof-of-concept trials and circumstantial evidence about treatments for autonomic dysfunction as well as upcoming clinical trials are discussed. Finally, critical aspects of clinical trials design are considered., Expert Opinion: Botulinum toxin (BTX) or glycopyrrolate might be used for sialorrhea whereas macrogol could be useful in constipation. There is preliminary evidence suggesting that fludrocortisone, domperidone, droxidopa or fipamezole may be effective for the treatment of OH. Tropicamide, clonidine or radiotherapy are under development for sialorrhea. Sildenafil may be effective for the treatment of erectile dysfunction; BTX or behavioral therapy for urinary incontinence and lubiprostone and probiotics for constipation. Sound clinical trials are needed in order to allow firm evidence-based recommendations about these treatments.

This study reviewed Kentucky Medicaid claims data for children with autism spectrum disorders to determine psychotropic drug (PTD) use in this population. Children with autism spectrum disorders (ICD-9 code 299.XX) in 3 different age-groups from 2005 to 2008 were identified; PTD use was defined as at least 1 prescription per year. PTD use in all age ranges was higher than in previously reported studies. High PTD use in children between 1 and 5 years is particularly of concern and may reflect perceived inadequacies of comprehensive educational/behavioral services for these children.

Effects of ranolazine alone and in the presence of phenylephrine (PE) or isoproterenol (ISO) on hemodynamics, coronary blood flow and heart rate (HR) in the absence and presence of hexamethonium (a ganglionic blocker) were studied in conscious dogs. Ranolazine (0.4, 1.2, 3.6, and 6 mg/kg, intravenous) alone caused transient (<1 minute) and reversible hemodynamic changes. PE (0.3-10 μg/kg) caused a dose-dependent increase in blood pressure and decrease in HR. ISO (0.01-0.3 μg/kg) caused a dose-dependent decrease in blood pressure and an increase in HR. Ranolazine at high (11-13 mM), but not at moderate (4-5 mM) concentrations partially attenuated changes in mean arterial blood pressure and HR caused by either PE or ISO in normal conscious dogs. However, in dogs treated with hexamethonium (20 mg/kg) to cause autonomic blockade, ranolazine (both 4-5 and 11-13 μM) significantly attenuated both the PE- and ISO-induced changes in mean arterial blood pressure. The results suggest that a potential antiadrenergic effect of ranolazine was masked by autonomic control mechanisms in conscious dogs but could be observed when these mechanisms were inhibited (eg, in the hexamethonium-treated dog). Ranolazine, at plasma concentrations <10 μM and in conscious dogs with intact autonomic regulation, had minimal antiadrenergic (α and β) effects.

Purpose: Istaroxime is a new luso-inotropic compound. It exerts inotropic action by reducing Na+/K+-ATPase activity, and simultaneously it stimulates sarcoplasmic reticulum Ca(2+)-ATPase function, thus also inducing lusitropic action. The aim of present study is to assess the effect of chronic istaroxime treatment on cardiac function and heart rate variability in Bio TO.2 Syrian hamster model of progressive heart failure., Methods: Bio TO.2 hamsters were daily treated, from 12 to 28 weeks of age, with 30 mg/kg/day oral istaroxime. Age-matched Bio TO.2 and Bio F1B hamsters were treated with vehicle and used as diseased and healthy controls. At the end of treatment, hearts function and autonomic cardiac control were evaluated., Results: Hearts from vehicle-treated Bio TO.2 when compared with hearts from Bio F1B showed higher heart/body weight ratio, and lower left ventricular systolic pressure (LVSP), positive and negative derivative of LV pressure (dP/dT), coronary flow rate (CFR). Hearts from istaroxime-treated when compared with those of vehicle-treated hamsters, showed the reduction of heart/body weight ratio, and the increase of LVSP, of both positive and negative dP/dT, and of CFR. Autonomic cardiac control, evaluated by HRV analysis, indicated in vehicle-treated Bio TO.2 hamsters, when compared to healthy, a shift towards increased sympathetic and decreased parasympathetic activities. Istaroxime-treatment preserved parasympathetic activity., Conclusions: Chronic istaroxime improves cardiac function and heart rate variability in Bio TO.2 Syrian hamster model of progressive heart failure.

Background: Hot flushes are the most common complaints reported by men undergoing androgen suppression treatment for prostate cancer. We designed a randomised double-blind trial to compare the efficacy of three drugs, each of which has proven effective for preventing hot flushes in previous studies., Methods: Men with prostate cancer with an indication for androgen suppression were enrolled in the study at 106 urology centres in France between April 14, 2004, and April 20, 2007. All patients were treated for 6 months with leuprorelin (11.25 mg). At month 6, patients who spontaneously asked for treatment, or those who presented with 14 hot flushes or more during the week before the visit, were randomly assigned to either venlafaxine 75 mg daily, medroxyprogesterone acetate 20 mg daily, or cyproterone acetate 100 mg daily. All patients received two indistinguishable pills in the morning and one in the evening from week 1 to week 8, and one indistinguishable pill in the morning from week 9 to week 10, to comply with the double-blind design. Random assignment with a block size of three was done centrally, by fax, and each patient was given a randomisation number. The allocation sequence was stratified by centre. Assessment was done at inclusion, at randomisation, and then at 4 weeks, 8 weeks, and 12 weeks after randomisation. Participants completed a daily hot-flush diary for 1 week, and a quality of life questionnaire before each visit throughout the study. The primary outcome was the change in median daily hot-flush score between randomisation and 1 month. All patients who received at least one study treatment dose were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01011751., Findings: Of the 919 men initially enrolled, 311 were randomly assigned to one of the study treatments at 6 months: 102 to venlafaxine, 101 to cyproterone, and 108 to medroxyprogesterone. 309 patients were included in the efficacy analysis, since two were excluded for protocol deviations (one in the cyproterone and one in the medroxyprogesterone group; both were excluded because they were already undergoing treatment with serotonin reuptake inhibitor antidepressants at randomisation). The change in median daily hot-flush score between randomisation and 1 month was -47.2% (IQR -74.3 to -2.5) in the venlafaxine group, -94.5% (-100.0 to -74.5) in the cyproterone group, and -83.7% (-98.9 to -64.3) in the medroxyprogesterone group. The decrease from baseline was significant for all three groups (p<0.0001). Pairwise comparison of treatment groups adjusted by the Bonferroni method confirmed that the decreases in hot-flush score were significantly larger in the cyproterone and medroxyprogesterone groups than in the venlafaxine group, regardless of the interval considered (p<0.0001 in all cases). There was no significant difference between the cyproterone and medroxyprogesterone groups (p>0.2 in all cases). Serious side-effects occurred in four, seven, and five patients in the venlafaxine, cyproterone, and medroxyprogesterone groups, respectively, of which none, one (dyspnoea), and one (urticaria) were considered related to the drug, respectively., Interpretation: After 6 months of treatment with leuprorelin, venlafaxine, cyproterone, and medroxyprogesterone proved to be effective in reducing hot flushes. However, the hormonal treatments cyproterone and medroxyprogesterone were significantly more effective than venlafaxine. As cyproterone is a recognised treatment in prostate cancer, and its use could interfere with hormonal therapy, medroxyprogesterone could be considered to be the standard treatment for hot flushes in men undergoing androgen suppression for prostate cancer., Funding: Takeda Laboratories, Puteaux, France., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Autonomic nervous system dysfunction may manifest with a variety of symptoms, with orthostatic intolerance (including orthostatic hypotension or tachycardia) and sweating abnormalities (increased or decreased sweating) being common problems requiring medical evaluation and treatment. Determination of the underlying diagnosis for these symptoms is critical in terms of classification of the disorder and its prognosis. Recent advances in evaluation of patients with these conditions and treatment modalities have enabled physicians to improve overall management of patients with these disorders. These advances include testing for ganglionic acetylcholine receptor antibody in patients with suspected autoimmune autonomic neuropathy and use of pyridostigmine for treatment of patients with orthostatic hypotension or tachycardia.

Over the past 2 decades our understanding of the pathologic mechanisms that lead to heart failure (HF) has evolved from simplistic hemodynamic models to more complex models that have implicated neurohormonal activation and adverse cardiac remodeling as important mechanisms of disease progression. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become a standard part of the armamentarium in the prevention and treatment of coronary artery disease. Apart from their lipid-lowering capabilities, statins seem to have non-lipid-lowering effects that impact neurohormonal activation and cardiac remodeling. This review will examine the potential benefits of statins in HF patients with ischemic and nonischemic cardiomyopathy as well as potential concerns regarding the use of statins in these patients.

The tachykinins and their receptors are strategically distributed within the gut wall, spinal cord, and central nervous system to be potential targets of therapeutic agents for gastrointestinal motility disorders. However, the development of effective tachykinin receptor agonists or antagonists to treat these disorders has had very limited success so far. This is, in part, due to the complex and multilevel of regulation of gastrointestinal motility function and the challenges faced in targeting the specific type of gut contraction to normalize function in disease state., (Copyright 2006 S. Karger AG, Basel.)

Chondroitin sulfate proteoglycans are synthesized and deposited in the spinal cord following injury. These proteoglycans may restrict regeneration and plasticity and contribute to the limited recovery seen after an injury. Chondroitinase, a bacterial enzyme that catalyzes the hydrolysis of the chondroitin chains on proteoglycans, has been shown to improve motor and sensory function following partial transection lesions of the spinal cord. To assess the effects of chondroitinase in a clinically relevant model of spinal cord injury, 128 female Long-Evans rats received either a severe, moderate, or mild contusion injury at the vertebral level T9/T10 with a forceps model and were treated for 2 weeks with chondroitinase ABCI at 0.06 Units per dose, penicillinase, or vehicle control via an intrathecal catheter placed near the injury. Motor behavior was measured by open-field testing of locomotion and bladder function monitored by measuring daily residual urine volumes. Animals treated with chondroitinase showed significant improvements in open-field locomotor activity as measured by the Basso, Beattie and Bresnahan scoring system after both severe and moderate SCI (p<0.05 and 0.01, respectively). No significant locomotor differences were observed in the mild injury group. In the moderate injury group, residual urine volumes were reduced with chondroitinase treatment by 2 weeks after injury (p<0.05) and in the severe injury group, by 6 weeks after injury (NS). These results demonstrate that chondroitinase is effective at promoting both somatic and autonomic motor recovery following a clinically relevant contusion spinal cord injury and is a candidate as a therapeutic for human spinal cord injury.

Stimulants have been the mainstay of the psychopharmacological treatment of attention deficit hyperactivity disorder (ADHD) for over 60 years. In the last 5 years, there have been a number of important developments in terms of potential new treatments for ADHD. Since stimulants have such a short half-life, considerable research has focused on the development of new delivery systems that will allow once-a-day dosing. New formulations of both amphetamine (AMP) and methylphenidate (MPH) have appeared which differ in terms of their optical isomers from the commonly used compounds. A wide variety of compounds are currently in development as therapeutic agents for ADHD. Some, like the stimulants, primarily impact the noradrenergic and dopaminergic neurotransmitter systems, while others have novel effects on the cholinergic, histaminergic and peptidergic systems. Advances in the pharmacogenetics of ADHD may lead to the development of yet more compounds in the near future.

The autonomic nervous system links the brain and the heart. Efferent links in the neural control of the heart consist of sympathetic and parasympathetic (vagal) fibers innervating the sinus node. Because sympathetic and vagal firing alter spontaneous sinus node depolarization, cardiac rate and rhythm convey information about autonomic influences on the heart. The easy availability of ECG rendered possible the assessment of sinus rhythm as an index of autonomic outflow. The frequency-domain approach uses non-invasive recordings and appears to provide a quantitative evaluation of the autonomic modulation of cardiovascular function. Spectral profiles resulting from vagal or sympathetic blockades at the cardiac (or vascular) level might be used as references to unravel the mechanism of action of the drug under examination. A more comprehensive assessment will be obtained if spectral analysis is used as a complement to existing techniques applied for describing the neurohumoral status of patients (microneurographic recordings, norepinephrine spillover). This review also reports some pitfalls encountered in variability studies.

The disorders of autonomic control associated with orthostatic intolerance are a diverse group that can result in syncope and near-syncope. A basic understanding of these disorders is essential to diagnosis and proper treatment. Ongoing studies should help to define better the spectrum of these disorders and to elaborate better diagnostic and treatment modalities.

The disorders of autonomic control associated with orthostatic intolerance are a diverse group of infirmities that can result in syncope and near syncope (as well as a host of other complaints). A basic understanding of these disorders is essential to both diagnosis and proper treatment. These infirmities are not new, what has changed is our ability to recognize them. It has been said that "the world undergoes change in the human consciousness. As this consciousness changes, so does the world." On going studies will continue to help better define the broad spectrum of these disorders, and to elaborate better diagnostic and treatment modalities.

Many advances in medical therapy for chronic glaucoma have taken place in the past few years that have altered previous concepts of stepwise medical therapy for glaucoma. beta-adrenergic blockers are still the most common medicine prescribed as monotherapy. However, latanoprost and brimonidine are often given as monotherapy as well as early adjunctive therapy. In addition, newer treatments that are used as early adjunctive therapy are dorzolamide, brinzolamide, apraclonidine, and the combination products, consisting of dorzolamide/timolol maleate and pilocarpine/timolol maleate. Older adjunctive treatments are now often prescribed as late adjunctive therapy including pilocarpine, epinephrine compounds, and acetazolamide. The extent of maximum tolerated medical therapy and the decision to perform either laser or conventional filtration surgery depend on the physician's judgment and on the patient's needs and preferences. In the future, newer medical therapies that may protect the health of the optic nerve directly could be developed including blood flow-based, neuroprotective, and genetically based agents.

Background: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response., Patients and Methods: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg)., Results: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels., Conclusions: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.

The results of examining the mechanisms of development of neurogenic visceral abnormalities induced by the body's extreme exposures, search for modes of its pharmacological correction are presented. Experiments have provided evidence for that the neutropic agents recovering the functional activity of the sympathetic nervous system, normalizing energy and plastic exchange have a positive effect in the treatment of the cardiovascular and gastroduodenal diseases which are caused by a neurogenic agent. A basically new approach to treating peptic ulcer, coronary heart diseases, and myocardial infarction is proposed depending on the stage of a disease.

Ocular pulse amplitude (OPA) and intraocular pressure (IOP) were measured in groups of human subjects with primary open-angle glaucoma (POAG), ocular hypertension (OHT), low-tension glaucoma (LTG), retinal degenerations (RD), in OHT volunteers treated with single doses of 2% epinephrine, 4% pilocarpine, 0.5% timolol or 1% p-amino-clonidine, and in normal subjects before and after exercise. Compared to normal controls, OHT subjects showed significantly higher IOP and OPA, while OPA was significantly lower in ocular normotensive LTG and RD subjects groups. All drug treatments lowered IOP in OHT subjects, but did not change OPA significantly. Exercise in normal volunteers increased calculated ocular perfusion pressure by 22.5%, lowered IOP by 32%, but showed no significant change in OPA. When IOP was elevated > or = 5 mmHg in lasered monkey eyes peak pulse volume (PPV) was increased significantly in the unlasered eyes. Epinephrine 2% or 1% p-aminoclonidine lowered IOP moderately with no change in PPV, while treatment with 4% pilocarpine or 0.5% timolol reduced IOP and increased PPV significantly. The findings suggest that LTG may be associated with an ocular vascular abnormality. OPA in OHT or normal human subjects did not change when IOP was decreased by antiglaucoma drug treatments or exercise, respectively. These results indicate that OPA may be physiologically autoregulated in human subjects with IOPs in the 11-21 mmHg range. However, laser-induced glaucomatous monkey eyes with higher IOP (30-35 mmHg) did not autoregulate, but showed a low peak pulse volume, which increased when IOP was reduced 5 mmHg or more by means of antiglaucoma drug treatment.

Antihypertensive drug therapy is used in children primarily to treat secondary forms of hypertension, because the prevalence of essential hypertension in the first decade of life is considerably less than 1% of the childhood population. This prevalence increases during the second decade of life, but the percentage of teenagers with essential hypertension continues to be low. Pharmaceutical companies have been able to target drug development to specific physiologic and biochemical systems. The converting enzyme inhibitors and calcium-channel blockers have greatly improved the success of therapy concomitant with a reduction in the incidence of adverse effects. The result has been a major change during the past decade in the recommendations for antihypertensive drug therapy.

Aim of this study was to analyze the relationships between esophageal motility and pharmacology. The use of a drug during manometry may have three goals: physiopathologic, diagnostic and therapeutic. In the first case, the manometric examination after administration of drugs, hormones and neurotransmitters allows to study esophageal receptors and innervation and to understand the alterations that are at the basis of esophageal motility disorders. Pharmacological stimulations with Bethanechol and Edrophonium is useful in the diagnosis of non cardiac chest pain, when alterations of esophageal motility are sporadic and difficult to diagnose with a standard manometric examination. Finally esophageal manometry is indispensable in clinical practice to establish therapeutic activity and mechanism of action of drugs.

This paper presents a personal approach to the diagnosis and management of asthma, which is in the author's opinion the most underdiagnosed, underestimated and undertreated condition in medicine.

Stress ulcers were induced by subjecting rats to forced immobilisation and cold (4 degrees to 7 degrees C) for 4 hrs. The nature of drugs which afford varying degrees of protection against such ulceration, bring out the complexity of the factors involved in the study of pathogenesis of acute gastric ulceration due to stress.