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The herbal form is sometime made into a cigarette without using tobacco or it can also be smoked in a pipe order extra super levitra 100mg amex, brewed into a tea or cooked into cakes purchase extra super levitra 100mg with visa. Of course, the fibre of the cannabis plant is non-psychoactive and hemp has a long history, being used to make rope, mats, clothing, cooking oil, fuel and varnishes. Cannabis is the most widely used illegal drug in the UK and easily the illegal drug most likely to have been tried by young people. Probably over 5 million people have used it at least once and many people are regular users. It is not surprising that cannabis is the most-seized drug and that the large majority of court cases involve this drug. Others are very much against the idea on both health and moral grounds but the former view has been taken by many police forces who now no longer prosecute those found with small amounts of the drug. There are many issues to debate, few of which have been discussed in detail in the UK. Currently, there is discussion of the medical aspects of the pharmacology of cannabis. There are suggestions, based on anecdotes, animal studies or pressure group opinions, that the drug can be useful to treat glaucoma, in the control of the muscle spasms that are one of the symptoms of multiple sclerosis and for appetite stimulation in cases of chemo- and radiotherapy. The status of cannabis is such that doctors cannot prescribe smokable cannabis to their patients, although synthetic THC preparations (nabilone) are available for nausea. There is growing pressure on the British government to change the law so that the required controlled clinical studies on the potential effects of cannabis can be carried out. A particular restriction on cannabis (and opium) is the offence of allowing your house (or any other premises you have responsibility for) to be used for growing cannabis or smoking it. These maximum penalties are only rarely imposed except where there is very large-scale supplying or trafficking. Most prison sentences for cannabis possession and small-scale supply are less than one year. Effects/risks Smoking cannabis causes a number of physical effects including increased heart rate, decreased blood pressure, bloodshot eyes, increased appetite and mild dizziness. The effects are rapid in onset and start within a few minutes and may last several hours depending on how much is taken. When eaten the effects are slower in onset but then DRUG DEPENDENCE AND ABUSE 509 longer in duration. Eating cannabis may mean a large dose is taken at once, making it difficult to avoid any unpleasant reactions. Cannabis has a mild sedative effect, not unexpected with the receptors for this drug being inhibitory. Many people find that when they first use cannabis nothing much happens. Generally cannabis makes people relax and they may become giggly and very talkative or alternatively quieter and subdued. The former effects may be due to disinhibitory actions of the cannabinoids. Users often report that they become more aware of music and colours and that time seems to stand still. While under the influence of cannabis, short-term memory may be impaired but this goes as the effects of the drug wear off. Accidents are more likely especially if people drive or operate machinery while on the drug since judgement and motor coordination are reduced and a mild ataxia ensues. Some people find that cannabis makes them anxious and paranoid, both inexperienced users or people who are anxious or those who consume strong varieties or high doses of cannabis. Very heavy use by people who already have a predisposition to mental health problems may lead to very distressing experiences. There is no conclusive evidence that moderate, long-term use of cannabis causes lasting damage to physical or mental health. However, it is probable that frequent inhalation of cannabis smoke over a period of years will contribute towards bronchitis and other respiratory disorders and possible cancers of the lung and parts of the digestive system. Regular users who stop smoking do not suffer withdrawal symptoms in the same way as with drugs like alcohol or the opioids. Even so, regular users can become psychologically dependent and come to rely on using cannabis, either as an aid to relaxation or as a social prop. Someone who uses cannabis excessively may appear apathetic, lack energy and motivation and perform poorly at their work or education. However, such a condition seems rare, is similar to what would be expected from someone who drinks too much or regularly uses other depressant drugs and it is likely that the effects of cannabis suit someone who is amotivational rather than the drug leading to a particular syndrome.

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The endometrium 100 mg extra super levitra for sale, the inner mucosal lining of the uterus extra super levitra 100 mg free shipping, is composed of two distinct layers. The vagina The extent to which the uterus enlarges during pregnancy is is about 9 cm (3. It is situated between the urinary pelvis, it grows to occupy the bulkof the abdominal cavity, becoming bladder and the rectum, and is continuous with the cervical about 16 times heavier than it was before conception. After parturition (childbirth), the uterus rapidly shrinks, but it may remain somewhat canal of the uterus. The cervix attaches to the vagina at a nearly enlarged until menopause, at which time there is marked atrophy. The deep recess surrounding the protrusion of the cervix into the vagina is called the fornix (see fig. Uterine Blood Supply and Innervation The fornix is of clinical importance because it permits palpa- The uterus is supplied with blood through the uterine arteries, tion of the cervix during a gynecological examination. Occa- sionally, the deep posterior portion of the fornix provides surgical which arise from the internal iliac arteries, and by the uterine access to the pelvic cavity through the vagina. Each of these paired is important in the placement of two birth control devices—the cervi- vessels anastomose on the upper lateral margin of the uterus. The vaginal wall is composed of three layers: an inner mu- cosal layer, a middle muscularis layer, and an outer fibrous layer. Female Reproductive © The McGraw−Hill Anatomy, Sixth Edition Development System Companies, 2001 Chapter 21 Female Reproductive System 737 FIGURE 21. They also provide friction ridges for stimulation of the penis dur- ing coitus. The additives within semen, however, temporarily neutralize the acidity of the vagina to assist the survival of the spermatozoa deposited within the vagina. The mons pubis is the subcutaneous pad of adipose con- The muscularis layer consists of longitudinal and circular nective tissue covering the symphysis pubis. At puberty, the bands of smooth muscle interlaced with distensible connective mons pubis becomes covered with coarse pubic hair in a some- tissue. The distension of this layer is especially important during what triangular pattern, usually with a horizontal upper border. Skeletal muscle strands near the vaginal orifice, in- The elevated and padded mons pubis cushions the symphysis cluding the levator ani muscle, partially constrict this opening. This layer consists of dense regular con- are two thickened longitudinal folds of skin that contain loose nective tissue interlaced with strands of elastic fibers. The labia majora contain numerous sebaceous and sweat course of the arteries. They are homologous to the scrotum of the male and The vagina has sympathetic innervation from the hypogas- function to enclose and protect the other organs of the vulva. An episiotomy may be done during parturition to facilitate delivery and accommodate the head of an emerging fetus when lac- eration seems imminent. Vulva Medial to the labia majora are two smaller longitudinal The external genitalia of the female are referred to collectively as folds called the labia minora (singular, labium minus). The structures of the vulva sur- minora are hairless but do contain sebaceous glands. This increased blood flow causes the ture and origin to the penis in the male; it is, however, much erectile tissues to swell. The unexposed portion of the clitoris is vestibular glands to secrete mucus near the vaginal orifice. The composed of two columns of erectile tissue called the corpora vestibular secretion moistens and lubricates the tissues of the cavernosa that diverge posteriorly to form the crura and attach vaginal vestibule, thus facilitating the penetration of the erect to the sides of the pubic arch. Mucus continues to be secreted during The vaginal vestibule is the longitudinal cleft enclosed by coitus so that the male and female genitalia do not become irri- the labia minora. The openings for the urethra and vagina are lo- tated, as they would if the vagina became dry. If stimulation of the clitoris is of suffi- ately in front of the vaginal orifice. The vaginal orifice is lubri- cient intensity and duration, a woman will usually experience a cated during sexual excitement by secretions from paired major culmination of pleasurable psychological and physiological re- and minor vestibular glands (Bartholin’s glands) located within lease called orgasm. The Associated with orgasm is a rhythmic contraction of the ducts from these glands open into the vaginal vestibule near the muscles of the perineum and the muscular walls of the uterus and lateral margins of the vaginal orifice. These reflexive muscular actions are thought to sue, called vestibular bulbs, are located immediately below the aid the movement of spermatozoa through the female reproduc- skin forming the lateral walls of the vaginal vestibule. The vestibu- tive tract toward the upper end of a uterine tube, where an ovum lar bulbs are separated from each other by the vagina and urethra, might be located.

Neither tyramine nor octopamine have distinct behavioural effects discount extra super levitra 100 mg fast delivery, unlike phenylethylamine trusted 100 mg extra super levitra, 280 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION and little is known of their central effects, although depressed patients have been shown to excrete less conjugated tyramine than normal subjects after challenge with tyrosine. PROSTAGLANDINS The main problem with any study of prostaglandins (PGs) is that although brain concentrations can exceed 0. Also specific effective antagonists remain to be developed and PGs are widely and evenly distributed, unlike many NTs. Thus any analysis of their central effects rests heavily on either studying PG release, or their effects when applied directly (icv injection). Certainly the brain has the enzymatic ability to synthesise both prostaglandins (cycloxygenase) and leukotrienes (lypoxygenase) from arachidonic acid (AA) (see Fig. When injected into the brain (often in rather large concentrations) PGE2 but not PGF2 is a depressant and causes sedation and catatonia. PGEs can be found in superfusates of cat cortex and their concentration is increased by direct electrical stimulation as well as by afferent nerve activation. In fact, when given intraventricularly PGE1 and PGE2 antagonise convulsions induced by leptazol and electroshock but whether PGs have any Figure 13. The action of cyclooxygenase produces the cyclic endoperoxides PGG2 and PGH2 and the prostaglandins PGE2,PGF2a and PGD2: lypoxygenase activity gives rise to leukotrienes. The classification D,E,F,G,H depends on the number and position of the hydroxy groups. OTHER TRANSMITTERS AND MEDIATORS 281 role in initiating or controlling convulsive activity is uncertain. The levels of a number of PGs, especially PGD2 and PGE2, are reported to be significantly lowered in spontaneously convulsing gerbils and in these animals the levels of brain lypoxygenase derivatives have also been found to increase after the onset of seizures (Simmet, Seregia and Hertting 1987), although such changes could result from, rather than cause, the convulsions. PGD2 and PGE2 receptors are concentrated in the preoptic region of the basal forebrain which is known to be imporant in sleep production and when injected into that area PGD2 does induce sleep. In fact PGD2 synthesis increases in rat cortex in the light period of a dark/light cycle when rats normally sleep and when infused into the third ventricle it induces a seemingly natural sleep at very low (7mM) concentrations. One area of particular interest, in view of the anti-pyretic effects of cyclo-oxygenase inhibitors like aspirin, is the possible role of PGs in the control of body temperature. Thus icv injections of PGE1 and PGE2 elevate body temperature and PGE levels increase in CSF following pyrogen-induced fever. Unfortunately this release does not occur near the anterior hypothalamus, which is considered to control body temperature, and iontophoretically applied PGE2 does not affect the firing of hypothalamic neurons. Also lesions of the anterior hypothalamus abolish PGE-but not pyrogen-induced fever. Interest in the PGs has recently reverted to their precursor arachidonic acid (AA), which seems to be able to act intracellulary as a second messenger, and also extra- cellularly. It is known that AA produces a long-lasting enhancement of synaptic transmission in the hippocampus that resembles LTP and in fact activation of NMDA receptors leads to the release of AA by phospholipase A2 (see Dumuis et al. AA has also been shown to block the uptake of glutamate (see Williams and Bliss 1989) which would potentiate its effects on NMDA receptors. NITRIC OXIDE INTRODUCTION The results of a number of studies demonstrate that the gas nitric oxide (NO) plays a functional role in the central nervous system. This all originated with the discovery that the so-called endothelium-derived relaxing factor (EDRF), found in blood vessels, and thought to be a peptide, was in fact NO. The potential roles of this freely diffusible gas have subsequently been extended to many other tissues and organs but we will concen- trate on the possible neuronal roles of what is obviously a novel mediator. There are also suggestions that the closely related carbon monoxide may also have a function in the central nervous system. Many brain and spinal cord neurons have the capacity to produce NO and experi- mental evidence indicates a role for this gas in neuronal transmission in animals. A major issue is that the effects of a gas are not limited to the release site and interpretation of the apparent neuronal actions of NO is complicated by the fact that some of the observed effects may be via changes in local blood flow. Being a gas, NO can diffuse freely once produced, and so is not constrained by the usual mechanisms of release and uptake that confine most transmitters to the synapse. Likewise, the fact that it is not stored means that the criteria of presence and storage are 282 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION not met by this highly labile and freely diffusible molecule. Finally, its ability to cross lipid barriers means that it is a transcellular mediator rather than a molecule that acts on a surface receptor close to its release site. Thus while it cannot be considered as a neurotransmitter, NO can still have important actions in the central nervous system. SYNTHESIS NO is the product of the oxidation of one of the guanidino nitrogens of the amino acid, L-arginine by the enzyme nitric oxide synthase (NOS). L-arginine is then hydroxylated and a second oxygen atom is incorporated to produce NO and citrulline (see Fig. There are three isoforms of the enzyme, endothelial (eNOS), inducible (iNOS) and neuronal (nNOS).

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For the most part discount extra super levitra 100 mg with mastercard, insulin no longer therapy is to optimize blood levels of glu- requires refrigeration for storage order 100 mg extra super levitra, but ex- cose. Individuals with diabetes mellitus posure to extremes in temperature and to must consider, in addition to proper intense light should be avoided. Other nutrition, the total number of calories individuals may choose an insulin pump, ingested as well as the distribution of calo- which provides a slow, continuous subcu- ries consumed throughout the day. Insulin is delivered to subcuta- especially careful to consume a specified neous (fatty) tissue in the abdominal wall number of calories at consistent times through a needle and an open loop delivery throughout the day to maintain a balance device consisting of a small insulin pump, of insulin and glucose in the blood. For about the size of a pager, that is worn 24 the most part, calories should be distrib- Conditions of the Endocrine System 267 uted evenly throughout the day so that balance between the amount of insulin there is not a large concentration of calo- previously taken and the amount of glu- ries at any one time. Considerable time and effort may there is correct timing between the inges- be spent in learning how exercise of a giv- tion of food and the time course of action en intensity and duration affects blood of the insulin they have injected. In addi- glucose levels, and what adjustments tion to being cautious of the caloric val- must be made in eating patterns and ue of food, individuals must also monitor insulin dosages to compensate. Counseling by a dietitian or levels helps to determine the efficiency of nutritionist (individuals who study and the insulin dosage prescribed. Individuals counsel individuals on the therapeutic use who take insulin should monitor blood of food) is imperative in the treatment of glucose levels at least several times a day. Diabetic diets are individualized Many individuals monitor glucose levels based on many personal factors, such as before breakfast, lunch, and dinner, as well weight, age, and type of daily activity (e. If the blood sugar Individuals who engage in sedentary level is too high, they may need to inject activities throughout the day do not additional insulin. Individuals may monitor their own scribed diet is usually better if lifestyle, blood glucose levels by lancing their fin- religious, and cultural habits are consid- ger and using a small portable machine ered as much as possible when dietary rec- called a glucometer to assess the glucose ommendations are made. Blood glucose may Exercise is important for the general also be monitored through a device for health and well-being of all individuals. The monitor records the amount of activity to be performed as up to 288 readings per day for up to 3 well as with the amount of insulin taken. At the end of 3 days the sensor is Unplanned exercise that is not coordinat- removed and the stored data are down- ed with caloric intake can create an im- loaded to a computer. The data enable 268 CHAPTER 9 ENDOCRINE CONDITIONS physicians to make appropriate changes in ly elevated. Individuals may become con- insulin doses based on the glucose read- fused, drowsy, and then eventually slip ings (Bode, Sabbah, & Davidson, 2001). They may have dif- During the time the continuous monitor- ficulty breathing or experience nausea, ing device is being used, individuals vomiting, and flushing of the skin, which continue to use standard methods of meas- remains dry. Water depletion and dehy- uring blood glucose, since the monitor does dration are common. Indi- the breath of individuals in diabetic coma viduals may learn to alter their own in- has a fruity odor. Diabetic coma is a med- sulin levels in accordance with their home ical emergency that can result in death if blood glucose reading; however, such appropriate treatment is not initiated. Insulin shock is the opposite of diabet- Although many of the same aspects of ic coma, occurring when there is too treatment for Type I diabetes also apply to much insulin in the blood for the amount individuals with NIDDM, some individu- of glucose present. Insulin shock may als with NIDDM may control blood sugar result from injecting too much insulin, levels with diet alone. In other instances, from engaging in an unusual amount of weight loss may help to control the con- exercise that burns up the glucose normal- dition. When blood sugar levels are not ly available, or from failing to take in suf- controlled by following a carefully planned ficient amounts of food for the amount of diet, individuals may need to take hypo- insulin injected. Individuals going into glycemic agents/oral agents (oral medica- insulin shock may feel hungry, weak, and tions that are effective in lowering blood nervous. There are several different types of although their skin is cold to the touch. When oral Confusion and personality changes may medications do not adequately control also occur. If insulin shock is untreated, blood sugar, individuals with NIDDM may individuals may lapse into unconscious- need to also take supplemental insulin. If it continues to go untreated, brain damage and eventual death can result. Diabetic Coma and Insulin Shock Treatment of insulin shock is directed to- ward raising blood sugar levels. If individ- Careful control of blood sugar is impor- uals are conscious, simple sugars such as tant to prevent complications, as dis- candy, orange juice, or honey may be cussed later in the chapter; however, ingested orally; if individuals are uncon- another major concern is the potentially scious, glucose must be infused intra- fatal acute conditions of diabetic coma or venously. Diabetic coma occurs when there is too much circulating glucose in Complications of Diabetes Mellitus the blood.

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The two main forms are: (1) Grand mal (GM) or tonic±clonic seizures (TCS) discount extra super levitra 100mg line. It starts with a tonic spasm of all musculature and rigid extension of the body cheap extra super levitra 100 mg visa, a temporary cessation of respiration, generally salivation and often defecation and micturition. After about one minute this gives way to violent synchronous clonic jerking movements (convulsions) which may continue for a few minutes. The patient may remain unconscious for a longer period before recovering. In some cases the tonic and occasionally the clonic phrase can exist alone. They entail a brief and abrupt loss of awareness (consciousness) in which the patient suddenly ceases ongoing activity or speech and stares vacantly for a few seconds before recovering equally quickly. Motor disturbances are rare apart from blinking of the eyes and the patient has no recollection of the event. In addition to the above main categories seizures can be just myoclonic, isolated clonic jerks, or atonic, loss of postural control with just head drooping or the patient actually falling. Convulsions associated with metabolic disturbances are not considered to be epileptic. Perhaps the most striking is the 3 per second spike wave activity seen in most leads (cortical areas) in absence seizures, which can be invoked by hyperventilation. Otherwise distinctive EEG patterns are usually only found during an actual seizure, with burst spiking seen alongside clonus in TCS and abnormal discharges with the behavioural patterns of partial epilepsy and in particular that originating in the temporal lobe. ANIMAL MODELS OF EPILEPSY These are normally based on the use of either electrical stimulation or chemical convulsants. If they are applied locally to specific brain areas, the same approaches induce activity indicative of partial seizures. Also some animals can be bred in which seizures either occur spontaneously or can be induced easily by appropriate sensory stimulation. MODELS OF GENERALISED SEIZURES (1) Electric shock In the maximal electric shock (MES) test a supramaximal stimulus is applied bilaterally through corneal or auricular electrodes to induce tonic hind limb extension in rats or THE EPILEPSIES 327 (b) Generalised seizure (grand mal) (a) Normal Ð tonic±clonic type 1s (c) Generalised seizure (petit mal) (d) Partial seizure Ð absence seizure type Figure 16. Electroencephalograms are shown for, a normal subject (a), those suffering from general tonic±clonic seizures (grand mal, (b)), generalised absence seizures (petit mal, (c)), and partial seizures (d). Spikes are seen in both right- and left- sided leads from all three cortical areas, frontal (F), temporal (T) and occipital (C) in the generalised seizures (b, c) but only in the occipital leads in the example of partial seizures (d). In the EEG recorded during the generalised tonic±clonic seizure the normal tracing (1) is followed by the onset of the tonic phase (2), the clonic (convulsive) phase 3 and post-convulsive coma 4. The typical 3 s71 spike and wave discharge of petit mal (c) may be seen during routine recording or induced by procedures such as hyperventilation but the spiking of grand mal and partial epilepsy is only seen during seizures. Anticonvulsant activity is determined by measuring the dose of drug required to protect 50% of the stimulated animals (ED or PD50) and is predictive of efficacy in TCS. Strychnine convulsions have no predictive value since they arise through antagonism of spinal (glycine-mediated) rather than cortical inhibition. The most commonly used agent is pentylenetetrazol (PTZ), also called leptazol. Anti- convulsant activity is again assessed as the dose required to protect 50% of animals, usually mice, against the clonic seizures induced by a dose of PTZ that would otherwise produce them in almost every mouse injected, the so-called CD97 (convulsive dose in 328 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION 97% of animals). The anticonvulsant activity of a drug may also be evaluated by measuring its ability to raise the convulsive threshold, i. Comparison of the efficacy of drugs in the threshold and maximal seizure tests may distinguish between their abilities to raise seizure threshold or reduce seizure spread and development. MODELS OF PARTIAL SEIZURES (3) Focal Partial seizure activity can be induced by the localised application of chemicals such as cobalt or alumina to the cortex or the injection of chemicals such as PTZ or kainic acid directly into particular brain areas like the hippocampus. A similar effect can be obtained by the repeated localised injection of subconvulsive doses of some convulsants. The ability of a drug to reduce the kindled seizure itself may be indicative of value in partial seizure but if it slows the actual development of kindling that may indicate some ability to retard epileptogenesis. SPONTANEOUSLY EPILEPTIC (GENETIC) ANIMALS Various animals show spontaneous epilepsy or seizures that can be readily induced by sensory stimulation (see Jobe et al. Tottering mice display seizures that resemble absence attacks behaviourally, in their EEG pattern and response to drugs. DBA/2 mice show reflex seizures to audiogenic stimuli while photically-induced seizures can be obtained in the Senegalese baboon, Papiopapio, which are similar to generalised tonic± clonic epilepsy. PREDICTIVE VALUE It has become clear that drugs which are effective in protecting mice against PTZ are effective in absence seizures while those able to control the tonic response to maximal electroshock are effective in tonic±clonic seizure. Some drugs are effective in only one test and clinical condition whilst a few are active in both (Table 16. It could be argued that an antiepileptic drug should really stop the development of epilepsy, i. If the development of kindling reflects the process of epilepto- genesis then drugs effective against its progression should stop the development of THE EPILEPSIES 329 Table 16. Clinical comparisons are not related to recommended doses but simply indicate whether a drug is effective (‡) or not (7). Generally, drugs that are to be used clinically to control tonic± clonic seizures control electroshock but not pentylenetetrazol-induced convulsions in rats and mice, whilst the converse applies to drugs effective in absence seizures.