Prazosin

By I. Bandaro. Kentucky Christian College.

Obviously generic prazosin 1mg without a prescription order cholesterol test online, radioiodine abla- rotroph sensitivity to thyrotropin-releasing hormone tion or surgical removal of the thyroid gland also causes (TRH) 1mg prazosin sale lower cholesterol foods best. Consequently, when the circulating concentration thyroid hormone deficiency. Hypothyroidism is the dis- of free thyroid hormones is high, thyrotrophs are relatively ease state that results from thyroid hormone deficiency. The resulting fall of TSH levels in the blood re- of most tissues in the body. As described earlier, a defi- duces the rate of thyroid hormone release from the follicu- ciency of thyroid hormones at birth that is not treated lar cells in the thyroid. When the free thyroid hormone during the first few months of postnatal life causes irre- level falls in the blood, however, the negative-feedback ef- versible mental retardation. Thyroid hormone deficiency fect of T3 on thyrotrophs is reduced, and the rate of TSH later in life also influences the function of the nervous sys- secretion increases. For example, all cognitive functions, including the thyroid gland to secrete thyroid hormones at a greater speech and memory, are slowed and body movements rate. These changes can usually be reversed to changes in gene expression in these cells. The physiological actions of the thyroid hormones de- Metabolism is also reduced in thyroid hormone-defi- scribed above are summarized in Table 33. Basal metabolic rate is reduced, resulting in impaired body heat production. Vasoconstriction occurs in the skin as a compensatory mechanism to conserve body THYROID HORMONE DEFICIENCY AND heat. Food in- take is reduced, and the synthetic and degradative EXCESS IN ADULTS processes of intermediary metabolism are slowed. In severe A deficiency or an excess of thyroid hormones produces hypothyroidism, a substance consisting of hyaluronic acid characteristic changes in the body. These changes result and chondroitin sulfate complexed with protein is de- from dysregulation of nervous system function and altered posited in the extracellular spaces of the skin, causing wa- metabolism. This effect gives a puffy ap- pearance to the face, hands, and feet called myxedema. All of the above disorders can be normalized with thyroid hor- Thyroid Hormone Deficiency Causes Nervous mone therapy. For example, iodide deficiency may result in a re- Nervous and Other Disorders duction in thyroid hormone production. Autoimmune dis- eases, such as Hashimoto’s disease, impair thyroid hor- The most common cause of excessive thyroid hormone mone synthesis (see Clinical Focus Box 33. Other causes production in humans is Graves’ disease, an autoimmune CHAPTER 33 The Thyroid Gland 605 CLINICAL FOCUS BOX 33. The disease is occur when an individual’s immune system fails to recog- also observed in patients known to have Graves’ disease. This usually triggers both increased immune system function following the suppres- humoral and cellular immune responses. Of these women, about 50% have opposite effects on thyroid function are Hashimoto’s dis- transient thyrotoxicosis alone, 25% have transient hy- ease and Graves’ disease. In Hashimoto’s disease, the thy- pothyroidism alone, and the remaining 25% have both roid gland is infiltrated by lymphocytes, and elevated lev- phases of the disease. The prevalence of the disease has els of antibodies against several components of thyroid prompted a clinical recommendation suggesting that thy- tissue (e. The thyroid gland is de- postpartum at 2, 4, 6, and 12 months in all women with thy- stroyed, resulting in hypothyroidism. In Graves’ disease, roid peroxidase antibodies or symptoms suggestive of thy- stimulatory antibodies to the TSH receptor activate thyroid roid dysfunction. Patients who have experienced one hormone synthesis, resulting in hyperthyroidism (see text episode of postpartum thyroiditis should also be consid- for details). A third, fairly common autoimmune disease is postpar- Treatment for thyrotoxicosis commonly involves in- tum thyroiditis, which usually occurs within 3 to 12 months hibiting thyroid hormone synthesis and secretion. The disease is characterized by a transient amides are a class of drugs that inhibit the oxidation and thyrotoxicosis (hyperthyroidism) often followed by a pe- organic binding of thyroid iodide to reduce thyroid hor- riod of hypothyroidism lasting several months. Some drugs in this class also inhibit the tients eventually return to the euthyroid state. Thyroid the hypothyroid phase of the disease may be observed, oc- hormone replacement is required to treat hypothyroidism.

Abbreviations AbdNu Abducens nucleus SpTNu Spinal trigeminal nucleus ALS Anterolateral system SpTTr Spinal trigeminal tract BP Basilar pons SSNu Superior salivatory nucleus DVagNu Dorsal motor nucleus of vagus TecSp Tectospinal tract FacNr Facial nerve TriMoNu Trigeminal motor nucleus FacNu Facial nucleus TriNr Trigeminal nerve GINr Glossopharyngeal nerve VagNr Vagus nerve HyNu Hypoglossal nucleus ISNu Inferior salivatory nucleus Ganglia MesNu Mesencephalic nucleus 1 Pterygopalatine ML Medial lemniscus 2 Submandibular MLF Medial longitudinal fasciculus 3 Otic NuAm Nucleus ambiguus 4 Terminal and/or intramural PSNu Principal (chief ) sensory nucleus Review of Blood Supply to TriMoNu buy generic prazosin 2mg online cholesterol medication causing joint pain, FacNu 1mg prazosin visa chart of cholesterol lowering foods, DMNu and NuAm, and the Internal Course of Their Fibers STRUCTURES ARTERIES TriMoNu and Trigeminal Root long circumferential branches of basilar (see Figure 5–21) FacNu and Internal Genu long circumferential branches of basilar (see Figure 5–21) DMNu and NuAm branches of vertebral and posterior inferior cerebellar (see Figure 5–14) Motor Pathways 203 Cranial Nerve Efferents (V, VII, IX, and X) Position of Nucleus and Internal Route of Fibers TriMotNu MesNu MLF PSNu TecSp Motor root Structures Innervated ALS of TriNr Masticatory muscles and ML tensor tympani, TriMotNu tensor veli palatini, Motor root mylohyoid, BP of TriNr digastric (ant. Also illustrated is the somatotopy of those fibers originating ataxia one might expect to see in patients with a spinal cord hemisection from the spinal cord. These fibers enter the cerebellum via the resti- (as in the Brown-Sequard syndrome) is masked by the hemiplegia resulting form body, the larger portion of the inferior cerebellar peduncle, or from the concomitant damage to lateral corticospinal (and other) fibers. After these fibers Friedreich ataxia (hereditary spinal ataxia) is an autosomal recessive dis- enter the cerebellum, collaterals are given off to the cerebellar nuclei order the symptoms of which usually appear between 8 and 15 years while the parent axons of spinocerebellar and cuneocerebellar fibers of age. There is degeneration of anterior and posterior spinocerebellar pass on to the cortex, where they end as mossy fibers in the graunular tracts plus the posterior columns and corticospinal tracts. Although not shown here, there are important ascending spinal tive changes are also seen in Purkinje cells in the cerebellum, in poste- projections to the medial and dorsal accessory nuclei of the inferior rior root ganglion cells, in neurons of the Clarke column, and in some olivary complex (spino-olivary fibers). The axial and appendicular ataxia seen (as well as the principal olivary nucleus) project to the cerebellar cor- in these patients correlates partially with the spinocerebellar degener- tex and send collaterals into the nuclei (see Figure 7-18 on page 206). Abbreviations ACNu Accessory (external or lateral) cuneate PSCT Posterior (dorsal) spinocerebellar tract nucleus PSNu Principal (chief ) sensory nucleus of ALS Anterolateral system trigeminal nerve AMV Anterior medullary velum Py Pyramid ASCT Anterior (ventral) spinocerebellar tract RB Restiform body Cbl Cerebellum RSCF Rostral spinocerebellar fibers CblNu Cerebellar nuclei RuSp Rubrospinal tract CCblF Cuneocerebellar fibers S Sacral representation DNuC Dorsal nucleus of Clarke SBC Spinal border cells FNL Flocculonodular lobe SCP Superior cerebellar peduncle IZ Intermediate zone SpTNu Spinal trigeminal nucleus L Lumbar representation SpTTr Spinal trigeminal tract MesNu Mesencephalic nucleus T Thoracic representation ML Medial lemniscus TriMoNu Trigeminal motor nucleus PRG Posterior (dorsal) root ganglion VesNu Vestibular nuclei Review of Blood Supply to Spinal Cord Grey Matter, Spinocerebellar Tracts, RB, and SCP STRUCTURES ARTERIES Spinal Cord Grey branches of central artery (see Figure 5–6) PSCT and ASCT in Cord penetrating branches of arterial vasocorona (see Figure 5–6) RB posterior inferior cerebellar (See Figure 5–14) SCP long circumferential branches of basilar and superior cerebellar (see Figure 5–21) Cerebellum posterior and anterior inferior cerebellar and superior cerebellar Cerebellum and Basal Nuclei (Ganglia) 205 Spinocerebellar Tracts Position of SCP AMV ASCT SCP MesNu TriMoNu ML PSNu ASCT on SCP Lobules II-IV Lobules II-IV Ant. Lobe Lobule V Lobule V Recrossing ASCT fibers in Cbl CblNu CblNu RB RB FNL Post. Lobe CCblF Lobule VIII Lobule VIII ACNu RSCF PRG Somatotopy Position Lamina VII VesNu at C4-C8 PSCT RB ASCT SpTTr & Nu DNuC ASCT ALS + RuSp Intermediate zone (IZ) and "spinal border" Py cells (SBC) PRG DNuC PSCT PSCT T L S IZ ASCT L T ASCT SBC 206 Synopsis of Functional Components, Tracts, Pathways, and Systems Pontocerebellar, Reticulocerebellar, Olivocerebellar, Ceruleocerebellar, Hypothalamocerebellar, and Raphecerebellar Fibers 7–18 Afferent fibers to the cerebellum from selected brainstem ar- ticotropin ( )-releasing factor are present in many olivocerebellar eas and the organization of corticopontine fibers in the internal capsule fibers. Ceruleocerebellar fibers contain noradrenalin, histamine is and crus cerebri as shown here. The cerebellar peduncles are also indi- found in hypothalamocerebellar fibers, and some reticulocerebellar cated. Pontocerebellar axons are mainly crossed, reticulocerebellar fibers contain enkephalin. Serotonergic fibers to the cerebellum arise fibers may be bilateral (from RetTegNu) or mainly uncrossed (from from neurons found in medial areas of the reticular formation (open LRNu and PRNu), and olivocerebellar fibers (OCblF) are exclusively cell in Figure 7–18) and, most likely, from some cells in the adjacent crossed. Raphecerebellar, hypothalamocerebellar, and ceruleocerebel- raphe nuclei. Although all af- Clinical Correlations: Common symptoms seen in patients with ferent fibers to the cerebellum give rise to collaterals to the cerebellar lesions involving nuclei and tracts that project to the cerebellum are nuclei, those from pontocerebellar axons are relatively small, having ataxia (of trunk or limbs), an ataxic gait, dysarthria, dysphagia, and dis- comparatively small diameters. Olivocerebellar axons end as climbing orders of eye movement such as nystagmus. These deficits are seen in fibers, reticulocerebellar and pontocerebellar fibers as mossy fibers, and some hereditary diseases (such as olivopontocerebellar degeneration, ataxia hypothalamocerebellar and ceruleocerebellar axons end in all cortical telangiectasia, or hereditary cerebellar ataxia), in tumors (brainstem layers. These latter fibers have been called multilayered fibers in the lit- gliomas), in vascular diseases (lateral pontine syndrome), or in other con- erature because they branch in all layers of the cerebellar cortex. Abbreviations AntLb Anterior limb of internal capsule PonNu Pontine nuclei CblNu Cerebellar nuclei PO Principal olivary nucleus CerCblF Ceruleocerebellar fibers PPon Parietopontine fibers CPonF Cerebropontine fibers PRNu Paramedian reticular nuclei CSp Corticospinal fibers Py Pyramid DAO Dorsal accessory olivary nucleus RB Restiform body FPon Frontopontine fibers RCblF Reticulocerebellar fibers Hyth Hypothalamus RetLenLb Retrolenticular limb of internal capsule HythCblF Hypothalamocerebellar fibers RNu Red nucleus IC Internal capsule RetTegNu Reticulotegmental nucleus LoCer Nucleus (locus) ceruleus SCP Superior cerebellar peduncle LRNu Lateral reticular nucleus SubLenLb Sublenticular limb of internal capsule MAO Medial accessory olivary nucleus SN Substantia nigra MCP Middle cerebellar peduncle TPon Temporopontine fibers ML Medial lemniscus NuRa Raphe nuclei Number Key OCblF Olivocerebellar fibers 1 Nucleus raphe, pontis OPon Occipitopontine fibers 2 Nucleus raphe, magnus PCbIF Pontocerebellar fibers 3 Raphecerebellar fibers PostLb Posterior limb of internal capsule Review of Blood Supply to Precerebellar Relay Nuclei in Pons and Medulla, MCP, and RB STRUCTURES ARTERIES Pontine Tegmemtum long circumferential branches of basilar plus some from superior cerebellar (see Figure 5–21) Basilar Pons paramedian and short circumferential branches of basilar (See Figure 5–21) Medulla RetF and IO branches of vertebral and posterior inferior cerebellar (see Figure 5–14) MCP long circumferential branches of basilar and branches of anterior inferior and superior cerebellar (see Figure 5–21) RB posterior inferior cerebellar (see Figure 5–14) Cerebellum and Basal Nuclei (Ganglia) 207 Pontocerebellar, Reticulocerebellar, Olivocerebellar, Ceruleocerebellar, Hypothalamocerebellar, and Raphecerebellar Fibers Position of Associated Tracts and Nuclei AntLb (FPon) PostLb (PPon) IC SubLenLb Hyth (TPon) RetLenLb (OPon) CPonF HythCblF LoCer ML RetTegNu CerCblF RNu SCP SN PPon MCP OPon 1 TPon FPon PonNu NuRa PCblF 3 2 CblNu RetTegNu OCblF MCP ML DAO RB CPonF PCblF RCblF CSp PO LRNu PonNu PRNu MAO PRNu RB OCblF LRNu PO Py OCblF PCblF CerCblF 208 Synopsis of Functional Components, Tracts, Pathways, and Systems Cerebellar Cortioconuclear, Nucleocortical, and Corticovestibular Fibers 7–19 Cerebellar corticonuclear fibers arise from all regions of the Lesions involving midline structures (vermal cortex, fastigial nu- cortex and terminate in an orderly (mediolateral and rostrocaudal) se- clei) and/or the flocculonodular lobe result in truncal ataxia (titubation quence in the ipsilateral cerebellar nuclei. These patients may also have a fibers from the vermal cortex terminate in the fastigial nucleus, those wide-based (cerebellar) gait, are unable to walk in tandem (heel to toe), from the intermediate cortex terminate in the emboliform and globo- and may be unable to walk on their heels or on their toes. Generally, sus nuclei, and those from the lateral cortex terminate in the dentate nu- midline lesions result in bilateral motor deficits affecting axial and cleus. Also, cerebellar corticonuclear fibers from the anterior lobe typ- proximal limb musculature. Cerebellar corticovestibu- emboliform, and dentate nuclei results in various combinations of the lar fibers originate primarily from the vermis and flocculonodular lobe, following deficits: dysarthria, dysmetria (hypometria, hypermetria), dysdi- exit the cerebellum via the juxtarestiform body, and end in the ipsilat- adochokinesia, tremor (static, kinetic, intention), rebound phenomenon, un- eral vestibular nuclei. One of the more Nucleocortical processes originate from cerebellar nuclear neurons commonly observed deficits in patients with cerebellar lesions is an in- and pass to the overlying cortex in a pattern that basically reciprocates tention tremor, which is best seen in the finger-nose test. The finger-to-fin- that of the corticonuclear projection; they end as mossy fibers. Some ger test is also used to demonstrate an intention tremor and to assess nucleocortical fibers are collaterals of cerebellar efferent axons. The heel-to-shin test will show dysmetria in the lower cerebellar cortex may influence the activity of lower motor neurons extremity. If the heel-to-shin test is normal in a patient with his/her through, for example, the cerebellovestibular-vestibulospinal route. If this test is repeated in the same Neurotransmitters: Gamma-aminobutyric acid (GABA) ( ) is patient with eyes closed and is abnormal, this would suggest a lesion in found in Purkinje cells and is the principal transmitter substance pres- the posterior column-medial lemniscus system. Cerebellar damage in intermittent and lateral areas (nuclei or cor- However, taurine ( ) and motilin ( ) are also found in some Purk- tex plus nuclei) causes movement disorders on the side of the lesion inje cells. GABA-ergic terminals are numerous in the cerebellar nuclei with ataxia and gait problems on that side; the patient may tend to fall and vestibular complex.

Those linked to a fast ionotrophic effect are classified as P2x discount 2 mg prazosin fast delivery high cholesterol foods avoid list, with currently six subtypes and those with slow metabotropic effects as P2y with seven subtypes buy prazosin 2mg cholesterol medication and muscle breakdown. It is the P2x receptors that mediate the primary transmitter effects of ATP. They have been most studied and while all may be found in the CNS, P2x2,P2x4 and P2x6 predominate. A schematic representation of a possible ATP (purinergic) synapse is shown in Fig. The role of ATP in the neural control of smooth muscle function is now, as indicated above, well established but its central actions are less clear and have only been studied closely in two areas. In slices of rat medial habenula the synaptic currents, recorded with the whole-cell patch-clamp technique that were evoked by electrical stimulation in the presence of both glutamate and GABA antagonists, were inhibited by the P2x (P2x2 preferred) antagonist suramin and by ab-me-ATP an agonist that desensitises some P2x receptors but not normally the P2x2 form. Thus while it is difficult to characterise the precise receptor subunit involved this provides strong evidence for a neurotransmitter OTHER TRANSMITTERS AND MEDIATORS 267 268 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION role for ATP, although it is not known to what extent blocking P2x2 receptors modifies synaptic transmission when the amino acid receptors are functional. Thus in contrast to NMDA currents, those for ATP are less likely to be involved in the temporal integration of synaptic activity (Gibb and Halliday 1996). This above effect of ATP has also been demonstrated on neurons in lamina II of the dorsal horn in transverse slices of rat cord. Here blockade of glutamate GABA and glycine effects left a current, produced by local tissue or dorsal root stimulation which was again sensitive to the P2x2 antagonist suramin (Bardoni et al. Although only 5% of neurons showed this response, the expression of P2x receptors there and the long established release of ATP from the peripheral terminals of dorsal root ganglia neurons and presumably therefore the central ones, have obviously raised interest in ATP being yet another NT involved in the mediation of afferent painful nociceptive stimuli (Chapter 21). Thus the neurotransmitter role of ATP is well established in the periphary and also in sensory systems but its importance in the CNS remains to be elucidated (see Burnstock 1996). That requires the development of more specific antagonists and methods of mapping its location. The strong linkage of its P2x receptors to calcium currents may also provide a role for ATP in more long-term effects such as plasticity and neuronal development and death. ADENOSINE This is not considered to be a neurotransmitter but it may be an important modulator of neuronal activity through its various receptors, A1,A2 and A3. The normal evoked EPSC of about 160 pA obtained by focal stimulation of nearby tissue was dramatically reduced by addition of a cocktail (CABS) of CNQX 10 mM, D-APV 50 mM, bicuculline 10 mM and strychnine 5 mM to block glutamate, GABAA and glycine receptors. The small residual EPSC shown was blocked by the ATP P2 receptor antagonist suramin and is therefore probably mediated by released ATP. The A receptor appears to be 2 1 negatively linked to adenylate cyclase through Gi and may mediate the presynaptic inhibition of NT release, with the A2 acting positively through Gs. Its basal extracellular level is 2 mM but this can increase rapidly when neuronal firing increases and can rise some twentyfold during seizures. The two enzymes responsible for its breakdown are adenosine kinase (Km ˆ 2 mM) and adenosine deaminase (Km ˆ 50 mM). It will be clear that as more adenosine is released during seizures, it will quickly saturate the kinase and its concentration can therefore only be controlled by deaminase. In fact deaminase but not kinase inhibitors are anticonvulsant as is adenosine and its analogues, while its antagonist theophylline is proconvulsant and a central stimulant. While that may not be realistic, the antiepileptic benzodiazepine drugs, in addition to their effects on GABA receptors, have been shown to increase the efflux of [73H] adenosine from the rat cortex probably by blocking its uptake and adenosine is often considered to be an endogenous limiter of neuronal activity. Despite this it has also been shown to reduce fast inhibitory postsynaptic potentials (IPSPs) in the rat lateral amygdala probably by presynaptic A1 inhibitory effect on GABA release (Henbockel and Pap 1999). Adenosine has also been considered to play a role in sleep induction (Chapter 22). Recently much interest has been shown in the possible neuroproctive effects of adenosine but the responses are complex. Thus A3 agonists can offer some protection given chronically before ischaemic challenge but given acutely post-challenge they can be neurotoxic (see Jacobsen 1998). HISTAMINE The belief that histamine (HT) has a central effect stems from the knowledge that all the classical antihistamines (H1 receptor antagonists) used to treat allergic reaction, such as hay fever, caused marked sedation if, like mepyramine and promethazine, they can cross the blood±brain barrier, but fail to do so if, like terfenedine and cetirizine, they do not. The major problem in establishing histamine as a transmitter in the CNS has been the difficulty in demonstrating its actual presence in neurons rather than just in the invading mast cells, in which it is concentrated and from which it is released in the periphery during allergic reactions. The development of immunohistochemical methods for the visualisation of histamine, and its synthesising enzyme histidine decarboxylase, now show there to be definite histaminergic nerves (see Tohyama et al. These are concentrated in the tuberomammillary nucleus in the posterior hypothalamus, not only in the rat but also in humans, and like the other monoaminergic systems (NA and 5- HT) they give off long highly branched axons which ascend in the medial forebrain bundle projecting to the cerebral cortex and hippocampus. Most histamine neurons also contain other transmitters such as GABA, substance P or enkaphalin.