By G. Curtis. Claremont Graduate University.
Even in rats buy discount abana 60pills on line, significant interspecies and in- Laboratory rodents are kept in separate trastrain variablity may foil the results of stud- cages in most instances cheap abana 60 pills with mastercard, so they do not injure ies carried out in different laboratories. Although the rodents animals depend largely upon rules that evolved came from the same strain, different vendors from interactions with natural environments. Indeed, although highly in- than others to develop a glial scar after the bred transgenic mice are wonderful tools for same SCI that produces a large barrier to ax- the study of the effects of specific genes, envi- onal regeneration in another species. Differ- ronmental conditions have led to a reversal of ences in injury-induced T-cell responses and in those gene effects. The biologic effects of an in- Biologic Adaptations and Neural Repair 131 tervention and its behavioral outcomes have, produce a uniform lesion with particular fea- for example, been repeatedly confounded by tures that represent a partial equivalent to hu- differences in caloric intake, whether sponta- man damage, the model may not serve a study neous or secondary to the experimental of repair. Some injury models originally aimed to search for repair mechanisms may yield results evaluate NMDA receptor-mediated neuronal in rats that are not clearly relevant to people. Most hu- For example, I discussed trials in which run- man lesions from stroke or TBI do not even ning in an enriched environment increased involve the hippocampus, unless global hypo- production of a variety of neurotrophins, as perfusion or hypoxia develop. The AMPA recep- ural environments evolved to find food and tors of oligodendrocytes mediate cytotoxic in- shelter by scurrying about as they vigilently at- jury, not NMDA receptors. Aimless tions across tissues help account for the failure exercise, such as jogging on a treadmill or wan- of human clinical trials of interventions for dering in a shopping mall, may be much less NMDA receptor-mediated injury. Differences of an inducement for the stimulation of BDNF in receptor types within regions of the brain and other growth factors, genes that promote and spinal cord and further changes brought plasticity, memory molecules, or neurons in pa- on by injury will also have to be reckoned with tients with neurologic diseases. If such stimu- in the translation of models to human neural lation is part and parcel to human learning, as repair. Among other queries, the reader of an it seems, learning paradigms will need to be experiment carried out with animals or cell cul- designed for rehabilitation that stimulate genes tures must always wonder how similar the re- and cells. Is the model of injury and repair in ro- had been used and how applicable the partic- dents similar enough to what happens to peo- ular model of injury and repair will be to the ple?
A major non-monoamine is corticotropin re- these receptors are stimulated quality abana 60 pills, they inhibit the release of nor- leasing factor discount abana 60 pills with visa, or hormone (CRF or CRH), whose secretion epinephrine. There is evidence that alpha2 receptors are also is increased in depression. CRF-secreting neurons are wide- down-regulated by antidepressant drugs, thus allowing in- spread in the CNS, and CRF apparently functions as a neuro- CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 165 transmitter and mediator of the endocrine, autonomic, immune, stimulate the CNS can cause manic and hypomanic behaviors and behavioral responses to stress as well as a releasing that are easily confused with schizophreniform psychoses. Hypothalamic CRF is part of the hypothalamic-pituitary-adrenal (HPA) axis, which becomes hyperactive in depression. As a result, there is increased se- ANTIDEPRESSANT DRUGS cretion of CRF by the hypothalamus, adrenocortiocotropic hormone (ACTH) by the anterior pituitary, and cortisol by Drugs used in the pharmacologic management of depressive the adrenal cortex. The increased cortisol (part of the nor- disorders are derived from several chemical groups. Older mal physiologic response to stress) is thought to decrease antidepressants include the tricyclic antidepressants (TCAs) the numbers or sensitivity of cortisol receptors (down- and the monoamine oxidase inhibitors (MAOIs). This view is supported drugs include the selective serotonin reuptake inhibitors by animal studies indicating that antidepressant drugs re- (SSRIs) and several individual drugs that differ from TCAs, store the ability of cortisol receptors to bind with cortisol. General characteristics of antidepres- This alteration of cortisol receptors takes about two weeks, sants include the following: the approximate time interval required for the drugs to im- • All are effective in relieving depression, but they differ prove symptoms of depression. Secretion of both hypothala- • All must be taken for 2 to 4 weeks before depressive mic and extrahypothalamic CRF apparently returns to nor- symptoms improve. Many antidepressants and other drugs are me- Additional Factors tabolized by the 2D6 or 3A4 subgroup of the enzymes. Additional factors thought to play a role in the etiology of Thus, antidepressants may interact with each other and depression include the immune system, genetic factors, and with a wide variety of drugs that are normally metabo- environmental factors. Immune cells (eg, T lymphocytes and B lymphocytes) produce cytokines (eg, interleukins, interferons, and tumor necrosis factor), which affect neurotransmission. Possible Mechanisms of Action mechanisms of cytokine-induced depression include in- creased CRF and activation of the HPA axis, alteration of Although their actions are still being studied in relation to monoamine neurotransmitters in several areas of the brain, newer information about brain function and the etiology of or cytokines functioning as neurotransmitters and exerting mood disorders, antidepressant drugs apparently normalize direct effects on brain function. Changes endings, the molecules that are not bound to receptors are nor- have been identiﬁed in CRF, the HPA axis, and the noradren- mally inactivated by reuptake into the presynaptic nerve ﬁbers ergic neurotransmission system, all of which are activated as that released them or metabolized by monoamine oxidase part of the stress response. Most antidepressants prevent the reuptake of multiple a hypersensitive or exaggerated response to later stressful neurotransmitters; SSRIs selectively inhibit the reuptake of events, including mild stress or daily life events. MAOIs prevent the metabolism of neurotransmitter have involved early life trauma such as physical or sexual molecules.
By contrast 60pills abana otc, the hippocampal region is not required for the ac- quisition of a variety of skills and biases that can be expressed unconsciously through alterations in performance on a broad variety of tasks buy abana 60 pills with visa. These kinds of memory are instead mediated by pathways through the neostriatum, cerebellum, amygdala, and other brain areas. Through the use of animal models, we are beginning to characterize the neural circuitry and information-processing mechanisms that mediate the capacity for con- scious recollection. Recent studies have shown that the general pattern of memory deﬁcits and spared capacities following damage to the hippocampal region in mon- keys and rats parallels the phenomenology of amnesia in humans (for a full review, see Squire, 1992; Eichenbaum, 2000). Sensory, motor, motivational, and cognitive processes are intact following hippocampal damage, conﬁrming that this region serves a selective role in memory in animals as it does in humans. A Protocol for Reading the Mind 93 In addition, as in humans, the scope of memory that depends on the hippocampal region in animals is broad but selective to a particular type of memory processing. It is impossible to assess in animals some aspects of declarative memory, such as con- scious recollection. Nevertheless, several studies have been successful in demonstrat- ing a selective role for the hippocampal region in mediating other central features of declarative memory, including the linking of memories within a network of semantic knowledge and ﬂexible, inferential expression of memories, as outlined later. By con- trast, there is abundant evidence that other brain systems in animals mediate other types of learning (for reviews, see McDonald and White, 1993; Eichenbaum and Cohen, 2001). These ﬁndings validate the use of animal models to study memory and set the stage for a detailed neurobiological analysis aimed at identifying the rele- vant pathways and functional mechanisms of the declarative memory system that mediates conscious memory. A Brain System for Conscious Recollection The full system of brain structures that mediate conscious recollection is composed of three major components: cerebral cortical areas, the parahippocampal region, and the hippocampus itself (ﬁgure 5. DG, dentate gyrus; EC, entorhinal cortex; FF, ﬁmbria-fornix; Hipp, hippocampus proper; OF, orbitofrontal cortex; Pir, piriform cortex; PR, perirhinal cortex; Sub, subiculum. They project in di¤erent ways to the parahippocampal region, a set of intercon- nected cortical areas immediately surrounding the hippocampus that in turn project into the hippocampus itself. The main outputs of the hippocampus return to the para- hippocampal region, which sends back projections broadly to the same cortical asso- ciation areas that provided the inputs to the parahippocampal region. This pattern of anatomical organization complements the ﬁndings from studies of amnesia, leading to the working hypothesis that the parahippocampal region and hippocampus make their contributions to memory by altering the nature, persistence, and organization of memory representations within the cerebral cortex.
Nonpharmacologic treatment includes bed rest purchase abana 60pills without prescription, all the time and 800 mcg or more during pregnancy buy cheap abana 60 pills. Drug therapy is most effective when plemental vitamin K is usually needed during the last the cervix is dilated less than 4 cm and membranes are intact. An Ritodrine, terbutaline, magnesium sulfate, and nifedipine injection of vitamin K is also given to the infant immedi- are used as tocolytics (see Drugs at a Glance: Abortifacients, ately after birth. Ritodrine and There has been controversy as to whether teratogenic terbutaline are beta-adrenergic agents that relax uterine smooth effects stemmed from epilepsy or AEDs. Moreover, the rate of taline is not FDA approved for use in premature labor, but is birth defects in infants exposed to one AED was signiﬁcantly used widely for that purpose. Hypermagnesemia may occur took AEDs for bipolar disorder rather than epilepsy also had because tocolytic serum levels (4 to 7 mEq/L) are higher than higher rates of birth defects. Close monitoring of serum 974 SECTION 11 DRUGS USED IN SPECIAL CONDITIONS Drugs at a Glance: Abortifacients, Prostaglandins, Tocolytics, and Oxytocics Generic/Trade Name Routes and Dosage Ranges Progesterone Antagonist Mifepristone (Mifeprex) PO 600 mg as a single dose or smaller amounts for 4–7 d Prostaglandins Carboprost tromethamine (Hemabate) IM 250 mcg q1. Termination usually complete within 48 h Tocolytics Ritodrine (Yutopar) IV infusion 0. The infusion should be continued for 12 h after uterine contractions cease. PO 10 mg 30 min before discontinuing the IV infusion, then 10 mg q2h for 24 h, then 10–20 mg q4–6h as long as necessary to maintain the pregnancy. Maximal oral dose, 120 mg daily Terbutaline (Brethine) Magnesium sulfate IV infusion 10 mcg/min, titrated up to a maximum dose of 80 mcg/min until contractions cease PO 2. Maintenance dose 1–2 g/h, according to serum magnesium levels and deep tendon reﬂexes. Nifedipine (Procardia) PO 10 mg every 20 min for 2–3 doses; maximum dose 40 mg in 1 h Oxytocics Oxytocin (Pitocin) During labor and delivery, IV 2 milliunits/min, gradually increased to 20 milliunits/min, if necessary, to produce three or four contractions within 10-min periods. Methylergonovine maleate (Methergine) To prevent excessive postpartum bleeding, PO 0. Oxytocin stimulates uterine contractions to initiate labor and promotes letdown of breast milk to the nipples in lactation. Pitocin is a synthetic DRUGS USED DURING LABOR form used to induce labor at or near full-term gestation and AND DELIVERY AT TERM to augment labor when uterine contractions are weak and in- effective.