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A case report notes severe multiple malformations in an infant whose mother used diazepam during pregnancy but does not establish cause and effect cheap 50 mg viagra super active free shipping. Researchers tracked medical histories of several thousand women whose babies had major malformations and found an association between diazepam and cleft lip, the association becoming even stronger if women had smoked while taking diazepam during pregnancy. Additional research has associated diazepam with birth defects involving the heart, stomach obstruc- tion, and hernia. In- deed, other research has found no association between diazepam and cleft lip or any other congenital malformation. One study found that newborns with fetal exposure to diazepam tend to weigh less than normal, but they soon gain weight and reach a normal level. Infants have exhibited withdrawal symptoms Diazepam 121 if their mothers used diazepam during pregnancy; those symptoms may not appear immediately after birth. Nursing mothers are advised to avoid the drug, which can continue to pass into breast milk long after drug use is halted. The drug can build up in babies, enough that they can be sedated by milk from mothers using diazepam, and the infants may lose weight while nursing. Methaqualone and diazepam each have the nick- name “Ludes,” but the drugs are different substances. Humans find the drug’s effects similar to those of dextroamphetamine but at a weaker level. One experiment found dextroamphetamine 6 to 11 times stronger than diethylpropion when given orally, 10 to 20 times stronger when given by subcutaneous injection. Although diethylpropion was created in the 1920s, this amphetamine derivative was not marketed for weight loss until around 1960. The compound breaks up sleep and interferes with dreaming but has fewer stimulant effects than some other anorectics. Users feel less fatigue than with fenfluramine, and undesirable effects of diethylpropion disappear faster than those of fenfluramine when the drug is stopped. Studies of weight loss patients using diethylpropion found only trivial impact on heart rate or blood pressure, and the compound is considered a good choice for patients with high blood pressure. Diethylpropion has been used experimentally to reduce craving for cocaine, with some success. Some researchers question that finding, however, pointing out that craving for cocaine diminishes in a hospital setting regardless of Diethylpropion 123 whether patients receive diethylpropion or a placebo. In a two-week study, former crack cocaine users receiving diethylpropion showed no change in tests of thinking abilities. That result is interpreted as meaning that short-term use of diethylpropion may cause no measurable harm to brain function. Patients experienced increase of comfort but no increase in ability to use af- fected joints. In a study of 132 patients taking the drug, about 3% had experiences such as euphoria, muscle tremors, or trouble with sleeping. As- sorted scientific reports indicate the drug rarely has untoward physical effects; the medical literature mentions an addict who ingested 30 to 100 times the recommended amount each day without major impact. Diethylpropion is suspected of being involved in a case where someone suffered minor strokes (transient ischemic attacks), is suspected of contributing to a case of heart trouble, and is known to cause heart trouble if an overdose is taken. A rare affliction ascribed to the drug is overdevelopment of the vestigial male mammary glands. One user felt under assault from persons using mental telepathy; another heard voices; another thought a television set was observing her; an- other began worrying about someone using the “evil eye” to kill a child. In some cases those problems ceased after the diet drug stopped; in others the affliction reappeared. A therapist reporting on the latter type of cases sus- pected that the persons would have developed psychosis regardless of whether they used diethylpropion. The typical sufferer is a female 25 to 40 years old, leading a troubled life with a history of mental instability and drug abuse. Drugs abused by these women often include amphetamines, an im- portant factor because a former amphetamine abuser who later takes another stimulant can quickly shift back into the old abuse mode. Often such persons begin taking diethylpropion to help them lose weight but afterward continue taking it for pleasurable psychic effect. That special group’s experience, how- ever, is not commonplace among users in general. The drug’s amphetamine-type effects are strong enough to have produced an illicit market for diethylpropion in the 1960s, but large surveys determining levels of abuse for various drugs yielded no mention of diethylpropion during the drug’s peak of popularity in the mid-1970s. In that era analysis of 5,204 street drug samples found 1 containing diethylpropion. Because the compound is described as producing effects resembling those of amphetamine, diethylpropion is not recommended for persons who have suf- fered from psychological illness or drug abuse.

Ca2+ ions carry the key message that controls contraction in smooth muscle buy viagra super active 50mg on-line, as in striated muscles. However, there are some fundamental differences in the mechanism of activation by Ca2+ ions. You will recall that Ca2+ activates skeletal or cardiac muscle by binding to the Ca2+ -binding molecule troponin in a highly cooperative fashion. The Ca2+ -bound troponin in turn triggers conformational changes in tropomyosin, which normally blocks the active sites on the underlying actin filament. Activation of contraction follows delivery of Ca2+ to the myoplasm by mechanisms described in Fig. The possibility remains that Ca2+ plays a dual regulatory role through interactions with regulatory systems residing on the thin filament and acting through tropomyosin. The candidates for the Ca2+ -sensitive protein on the thin filament include proteins called leiotonin or caldesmon. In single smooth muscle cells, simultaneous measurements of contractile force and free cytoplasmic Ca2+ concentration ([Ca2+ ]i) give some idea of the sensitivity and dynamics of the process of Ca2+ -activation (Fig. This is incredibly slow compared to the onset of contraction in skeletal muscle (less than 5 milliseconds) or even cardiac muscle (roughly 20 milliseconds). Even if it is slow, the contraction of smooth muscle is extremely Ca2+ -sensitive. If measurements of steady contractile force and steady Ca2+ are plotted against each other (Fig. The steepness of the [Ca2+ ]i -force relationship can probably be accounted for by the steeply cooperative binding of four Ca2+ ions to a single calmodulin molecule. During sustained stimulation, [Ca2+ ]i rises to a peak and then decays to a much lower plateau level. Despite the falling off of [Ca2+ ]i, contractile force can remain elevated Smooth Muscle - Richard Tsien, Ph. Somehow, the muscle is able to give sustained forces, despite the reversal of the normal steps of activation. The mechanism is not known, but the current hypothesis is that myosin crossbridges can form a "latch" state. The "latch" state can be maintained with a slight elevation of [Ca2+ ]i above basal levels, but is abolished quickly once [Ca2+ ]i finally returns to its original value. In many respects then, the physiological behavior of smooth muscle seems well adapted to the task of maintaining vessel diameter and blood pressure constant over long periods of time. The somewhat slow but highly responsive activation system purrs along by comparison to skeletal or cardiac muscle. Whatever the molecular mechanism, the "latch" state provides sustained force in a very energy efficient manner. Experiments which illustrate the ability of smooth muscle to produce sustained force are shown in Figures 10 and 11. Sympathetic control of blood vessel diameter Controlling blood vessel tone largely involves the regulation of [Ca2+ ]i within smooth muscle cells by transmitters released from prejunctional sympathetic nerve varicosities or circulating hormones or local factors. Let us consider the sequence of events leading from sympathetic nerve excitation to vascular smooth muscle contraction. Some veins have Na channels but these are unusual in their insensitivity to tetrodotoxin). The repolarization is driven by outward current through K channels activated by depolarization and/or Ca2+ 4. Ca2+ -induced Ca2+ release from intracellular stores (also triggered by caffeine, blocked by ryanodine). Disorders of smooth muscle function and vasoactive drugs: Inappropriate contractions of vascular smooth muscle occur in vasospasm or hypertension. These disorders are not completely understood but may involve defects in sympathetic inputs and/or vascular smooth muscle. Primarily caused by coronary artery stenosis (fixed) and/or sudden occlusion decreasing coronary blood flow. Increased heart rate increases demand and lessens the perfusion (by shortening the relative time of diastole when coronary perfusion occurs). Angina pectoris: When ischemia is less severe and does not cause death of cardiac muscle. Prinzmetal angina pectoris: Angina at rest due to coronary artery spasm; responds to vasodilators. More than 75% stenosis can lead to symptomatic ischemia induced by exercise (typical angina) B. With such “critical stenosis,” compensatory coronary vasodilation is no longer sufficient to meet even moderate increases in myocardial demand. You can get an Acute Myocardial Infarct with fixed stenosis, but usually in a restricted subendocardial pattern, when there are other factors that create an imbalance of myocardial oxygen supply and demand.

Specific Symptomatology—Myrrh is specifically indicated in a general sense where there is adynamia or extreme asthenia cheap viagra super active 50mg free shipping, with weak, inefficient capillary circulation, cold skin, weak pulse and deficient circulation. It increases the power and frequency of the heart and respiratory action, and conduces to a general sense of warmth and increased vigor. Therapy—This agent has always been highly esteemed as a stimulant, although its influence is more of a local than a general character. It exercises the characteristic influence of most of the stimulants upon the excretions and secretions, acting as a diaphoretic, expectorant, sialagogue, and to a certain extent emmenagogue. As a most active general stimulant in ulcerative, engorged, flabby and atonic conditions of the mucous membranes of the mouth and throat this agent acts promptly. It stimulates the capillary circulation, restores tone and normal secretion and causes the healing of ulcerations. It is useful in sore mouths of all kinds, and especially in syphilitic sore mouth and sore Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 146 throat. It will quickly cure the beginning of syphilitic ulcerations in the throat and mouth. In the spongy gums and aphthous sore mouth of children, in stomatitis materni if combined with an alterative and tonic astringent it will assist in the cure of the very worst cases without taking the child from the breast. An infusion made of white oak bark, yellow dock root and myrrh, to which may be added a mild antiseptic, as baptisia, echinacea, or boric acid, will cure the most intractable cases of this latter named disease. Myrrh is excellent in the sore mouth and extreme ulceration of mercurial ptyalism. It quickly increases the power of the digestive function, stimulating the peptic glands to extreme action. It increases the appetite and promotes the absorption and assimilation of nutrition. It is given in atonic dyspepsia in the absence of inflammatory action, especially if there is excessive mucous discharge from the bowels. It is exceedingly useful in the apepsia and extreme inactivity of the stomach in alcoholics, either alone or combined with capsicum. While it is expectorant, and stimulates the secretion from the mucous membranes when inactive, it influences to a satisfactory extent the restoration of the functions of those membranes when the secretion is excessive, as in catarrhal conditions. In atonic catarrhal diarrheas of a subacute or chronic character its influence is specific and satisfactory. In some cases of catarrh of the bladder it is used internally, and in the irrigation fluid also. It is an old popular remedy in amenorrhea given in combination with aloes and iron, especially in chlorotic and anemic patients. There is great variation in the quality of the different preparations of conium, and care must be exercised in selecting a good one. Physiological Action—When given in a sufficient dose, conium causes complete relaxation of the whole muscular system; the eyes close, the movements of the eyeballs are sluggish, mastication and swallowing are difficult, speech is slow and maintained by an effort, the voice is hoarse, while the heart and intelligence are not disturbed. In a fatal dose, the lower limbs become paralyzed, the effect gradually ascending to the upper part of the body, intelligence being retained to the last. Administration—If the characteristic odor of this substance is absent, the probabilities are that it is devoid of value, as it is the volatile principle which possesses the odor, and it is that upon which its value as a therapeutic agent depends to a great extent. It is of much importance in ulceration of the stomach either acute or chronic, and in incipient gastric cancer. It will soothe the pain more efficiently than other apparently more powerful agents. It must be given in large doses; as much as fifteen minims of the fluid extract are sometimes needed. It relieves distress in the glandular Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 148 organs and in glandular enlargements, when there is a scrofulous or cancerous cachexia, dull aching pains not usually acute, not sharp cutting pains. In the pain of cancer of the pelvic organs or of the mammae it gives relief, and, indeed, it gives relief to pain in the pelvic organs whatever the cause or character. Therapy—The anodyne and antispasmodic soothing properties of the agent suggest its use in spasmodic affections and irregular muscular movenients—movements attended by extreme activity of the motor nerves. In paralysis agitans, in chorea and in hysteria, in delirium tremens and acute mania it is thus advised. Its use in trismus, laryngeal spasm, in irregular muscular twitchings and spasmodic wry neck, will be attended with excellent results. In profound spasm, as in convulsions, epilepsy and tetanus, while of some benefit, it is of no marked value and more potent agents are prescribed. In its adminis-tration, hypodermic injections of Hydrobromate of Conine are sometimes much more prompt and satisfactory in their action. It is valuable in laryngitis and in dry irritable bronchial coughs and in phthisis. In all such coughs the vapors inhaled from the fluid extract or juice dropped on the surface of hot water, in a rather close-mouthed vessel, is sometimes of marked benefit.

The human sleep-wake rhythm is a marker of the interplay between process C and process S and some of the detrimental effects of sleep deprivation are due to disruption in the synergy between the two processes (Borbely et al viagra super active 25mg without prescription. The needed amount of sleep is individual, but there is evidence that women need more sleep and actually sleep longer than men and also that sleep duration decrease with increasing age (Ferrara and De Gennaro, 2001; Jackson et al. The population average sleep duration is 7 to 8 hours and people sleeping far more or less than this average are called long and short sleepers, respectively (Ferrara and De Gennaro, 2001). From a population perspective short sleep is more common than long sleep (Luyster et al. Sleep quality and sleep duration are separate even if partly overlapping and correlated characteristics of sleep (Buysse et al. Sleep quality issues are often referred to as insomnia symptoms or insomnia-like symptoms that include difficulties initiating or maintaining sleep, non-restorative sleep or global dissatisfaction with sleep (Ohayon, 2002). Depending on the way to operationalize sleep quality the average population prevalence of poor or disturbed sleep vary between 6% and 30% (Ohayon, 2002). In Finland, epidemiological data from 1972 to 2013 indicate a continuing considerable increase in occasional insomnia-like symptoms in the working-aged population (Kronholm et al. Sleep related problems more often occur in women than in men, and are also more common along with increasing age (Barclay and Gregory, 2013; Kronholm et al. There are also some questionnaires that are being used in population studies to assess both the duration and quality of sleep, as for example the Pittsburgh Sleep Quality 26 Index (Buysse et al. It is also possible to assess times for going to bed and getting up from bed (Kronholm et al. Self-reported measures of sleep in population-based research can be held sufficiently valid when compared to polysomnography (Zinkhan et al. The golden standard method to measure sleep is the polysomnography that simultaneously measures the electrical activity of the brain, heart, and muscles, movements of the eye and respiratory actions while the person is at sleep (Knutson, 2010; Krystal and Edinger, 2008). In large scale studies polysomnography is an inconvenient method due to its practical and economical requirements. Developments in accelerometer technology have enabled the increasing use of accelerometry as a means to assess sleep in large scale settings (Ferrie et al. The agreement between wrist worn accelerometers with polysomnography has shown to be superior to that of hip placement with polysomnography (Zinkhan et al. The validity of wrist worn accelerometers in sleep assessment seem to be accepted in the literature relative to polysomnography, at least in terms of total sleep time and sleep efficiency (Girschik et al. In middle- aged the day-to-day variation in actigraphy is high, whereas the year-to-year variation is not significant, indicating that one multiple day collection will likely be reflecting a true habitual average for that person (Knutson et al. According to differences in the timing of sleep and wake, and differences in preferences for performing physical and mental tasks, different chronotypes can be identified (Adan et al. Those with early bed times and morning awakenings and high morning alertness are called morning types and those with peak alertness later in the afternoon with a preference for later bed times are called evening types (Adan et al. Approximately 60% of people do not belong to either of these two extreme chronotypes, but rather have an intermediate type (Adan et al. The chronotype is affected by individual and environmental factors such as age, gender, daylight and activity (Adan et al. There is some evidence from cross-sectional data that chronotype shifts with age, with young children being morning type and a pronounced tendency to evening type during adolescence where after morning preference again becomes more prevalent with increasing age (Adan et al. Women experience the maximum in eveningness at an earlier age than men, and women also have a shorter intrinsic circadian period than men (Adan et al. However, a different distribution of morning type and evening type by gender is not altogether supported by the literature (Paine et al. In Finland the population prevalence of evening types among men seem to have increased from the 1980’s to the 2000’s (Broms et al. In a large sample of mainly central European participants a significant change in the average chronotype to more evening types from 2002 to 2010 was observed (Roenneberg et al. The risk for social jetlag is often higher in evening types because they are more often forced to follow an earlier social rhythm compared to their intrinsic circadian phase (Roenneberg et al. Different self-report tools have been created to provide non- invasive, more practical ways to assess chronotypes, particularly in large- scale studies (Di Milia et al. Since then several other questionnaires and ways to assess this trait have been developed (Adan et al. One discussed limitation with self-report questionnaires of chronotype is the cutoff values that are being used to distinguish between different chronotypes (Di Milia et al. More evidence is needed regarding the modifying effect of factors such as light exposure, body composition and diet (Chennaoui et al. Also in Finland, adults with mid-range sleep are more often physically active than short or long sleepers (Kronholm et al.

However cheap viagra super active 25 mg on line, patients with sustained ventricular tachycardia or fibrillation which does not occur Arrhythmias - Paul J. This type of device is implanted subcutaneously and connected via a special lead which is inserted via the cephalic or subclavian vein and advanced to the right ventricle. The device automatically monitors the heart rate using this lead and when a programmed is achieved, the device will deliver a synchronized electrical shock to the lead in the right ventricle (and possibly right atrium or superior vena cava) which will reuslt in conversion of the ventricular tachycardia or ventricular fibrillation. For some reentrant ventricular tachycardias, the implantable defibrillator may pace in the heart at rates faster than the ventricular tachycardia, resulting in termination of the arrhythmia without the need for an electrical shock. For the acute treatment of ventricular arrhythmias, intravenous lidocaine and amiodarone and less commonly procainamide may be administered. Catheter ablation techniques for ventricular tachycardia may be used but are more complex than for supraventricular tachycardias. Such a device may be used to quantitate frequency symptomatic or asymptomatic arrhythmias. Patients with less frequent but prolonged (> 1 minute) episodes of arrhythmias without syncope may use an event monitor which is carried with the patient and connected only in the event of an arrhythmia. Patients with episodes of syncope or very brief episodes of arrhythmias may use a “loop” monitor which is connected to the patient for several weeks to several months. The recorder saves the preceding several minutes and may be transmitted via a telephone hookup Autonomic Drugs (Sympathomimetics 1) - James Whitlock, M. Understand the differences between direct-acting and indirect acting sympathomimetic drugs. Become familiar with the major structure-activity relationships among sympathomimetic drugs. Continue to learn the tissue distribution of adrenergic receptor subtypes and their responses following agonist administration. The primary role of each atrium is to act as a reservoir and "booster pump" for venous blood entering the ventricles. Recently, with the discovery of atrial naturetic hormone, other homeostatic roles of the atrium have been proposed. The primary physiologic function of each ventricle is to maintain circulation of blood to the organs of the body. The left heart receives oxygenated blood from the pulmonary circulation, and contraction of the muscles of the left ventricle provide energy to propel that blood through the systemic arterial network. The right ventricle receives blood from the systemic venous system and propels it through the lungs and onward to the left ventricle. The reason that blood flows through the system is because of the pressure gradients set up by the ventricles between the various parts of the circulatory system. In order to understand how the heart performs its task, one must have an appreciation of the force-generating properties of cardiac muscle, the factors which regulate the transformation of muscle force into intraventricular pressure, the functioning of the cardiac valves, and something about the load against which the ventricles contract, i. You have learned about the properties of cardiac muscle and vascular systems in previous lectures. This session will focus on a description of the pump function of the ventricles with particular attention to a description of those properties as represented on the pressure-volume diagram. The ventricles are chambers whose walls are composed predominantly of cardiac muscle. Therefore, when considering the properties of the ventricle as a mechanical pump, one should keep in mind the underlying force-generating properties of cardiac muscle and the structural features of the ventricle which determine how muscle force translates into pressure inside the ventricle. The force generated by a muscle is directly influenced by the initial (or "diastolic") length of the muscle -- increased diastolic length results in greater force production. When the volume of the heart is changed, so too is the length of the muscles in the wall of the heart. There are at least four factors that contribute to determining the relationship between muscle properties (length and force) and ventricular properties (volume and pressure): 1. Muscle Mass It is intuitively obvious that the more muscle that comprises the chamber wall the stronger the ventricle will be. As one example of this, compare the functioning of the right and left ventricles of the same heart. The left ventricle generates about 4 to 5 times the pressure of the right ventricle when the wall stress (stress = force/unit area of muscle) is the same. There are several factors which contribute to this difference, but the predominant one is that left ventricular weight (the amount of muscle) is roughly 3 to 4 times that of the right. Ventricular Geometry Compare a chamber with a circular cross-section to one with an elliptical cross-section. The mathematical equations relating wall stress and chamber pressure will be different. Thus for the same muscle mass and wall stress, the pressure inside these two chambers would be different. Architecture of the wall This refers to the how the fibers are put together to form the ventricular wall. Histologic studies have shown that the fiber bundles wrap around the ventricular chamber in a standard way. If one cuts out a small piece of the ventricular wall and examines the fibers, one finds that the angle at which the fibers run relative to the axis of the chamber varies with the depth of the layer within the wall.