By G. Delazar. Missouri Southern State College. 2018.

Self tissues are recognized by distinctive protein phocytes are activated and antibodies are produced rapidly cheap colospa 135mg mastercard, molecules on the surface membranes of body cells purchase colospa 135mg. This characteristic 632 SECTION 7 DRUGS AFFECTING HEMATOPOIESIS AND THE IMMUNE SYSTEM allows booster doses of antigen to increase antibody levels Immune Responses to Antigens and maintain active immunity against some diseases order 135 mg colospa. The immune response involves antigens that induce the for- Passive immunity occurs when antibodies are formed by mation of antibodies or activated T lymphocytes cheap colospa 135 mg otc. The initial the immune system of another person or animal and trans- response occurs when an antigen is first introduced into the ferred to the host buy discount colospa 135mg line. B lymphocytes recognize the antigen as foreign and de- tected for several months by maternal antibodies received velop antibodies against it. Antibodies are proteins called im- through the placenta during gestation. Also, antibodies pre- munoglobulins that interact with specific antigens. These antibodies act against antigen–antibody complexes, agglutination or clumping of antigens immediately. Passive immunity is short-term, last- cells, neutralization of bacterial toxins, destruction of pathogens ing only a few weeks or months. Activated complement stimulates chemotaxis T lymphocytes in body tissues) and humoral immunity (of monocytes, neutrophils, basophils, and eosinophils) and the (mainly involving B lymphocytes and antibodies in the blood). With a later ex- nected, that virtually all antigens elicit both cellular and hu- posure to the antigen, antibody is rapidly produced. The number moral responses, and that most humoral (B cell) responses of exposures required to produce enough antibodies to bind a require cellular (T cell) stimulation. Thus, an allergic re- Although most humoral immune responses occur when action may occur with the second exposure or after several ex- antibodies or B cells encounter antigens in blood, some occur posures, when sufficient antibodies have been produced. The and function of other T lymphocytes and help to regulate anti- antibodies in body fluids other than blood are produced by a body production by B lymphocytes. T cells are involved in de- part of humoral immunity sometimes called the secretory or layed hypersensitivity reactions, rejection of tissue or organ mucosal immune system. The B cells of the mucosal system transplantats, and responses to neoplasms and some infections. The antibodies (mostly immunoglobulin A [IgA], some IgM and IgG) secreted at these sites act locally rather than systemically. IMMUNE CELLS This local protection combats foreign substances, especially pathogenic microorganisms, that are inhaled, swallowed, or Immune cells (Fig. When exposure to an antigen occurs and an im- mune response is aroused, WBCs move toward the antigen in Antigens a process called chemotaxis. Specific WBCs are granulocytes Antigens are the foreign (nonself) substances (eg, micro- (neutrophils, eosinophils, basophils), and nongranulocytes organisms, other proteins, or polysaccharides) that initiate (monocytes and lymphocytes). Antigens have specific sites that inter- role, neutrophils, monocytes, and lymphocytes are especially act with immune cells to induce the immune response. Granulo- number of antigenic sites on a molecule depends largely on cytes often contain inflammatory mediators or digestive en- its molecular weight. Sub- molecules (eg, animal danders, plant pollens, and most stances (eg, complement) released from infected or inflamed drugs) are incomplete antigens (called haptens) and cannot tissue cause neutrophils to migrate to the affected tissue. However, they have anti- WBCs arrive first, usually within 90 minutes of injury. They genic sites and can combine with carrier substances to be- localize the area of injury and phagocytize organisms or parti- come antigenic. In cles by releasing digestive enzymes and oxidative metabolites discussions of allergic conditions, antigens are often called that kill engulfed pathogens or destroy other types of foreign allergens. The number of neutrophils increases greatly during CHAPTER 42 PHYSIOLOGY OF THE HEMATOPOIETIC AND IMMUNE SYSTEMS 633 Pluripotential stem cells Pluripotential stem cells Committed stem cells CFU* blast cells CFU megakaryocytes CFU Lymphoid stem cells granulocytes/monocytes Erythrocytes Platelets Granulocytes Monocytes Neutrophils Macrophages Eosinophils Basophils T lymphocytes B lymphocytes (Thymus) T cell + antigen Memory cells Activated T cells (Bone marrow) Helper T cells Cytotoxic T cells Suppressor T cells B cell + antigen Plasma cells Memory cells Antibodies (immunoglobulins G, M, A, E, D) * CFU = colony-forming unit Figure 42–1 Hematopoiesis and formation of immune cells. These cells circulate in the blood- Each T or B lymphocyte reacts only with a specific type of stream for approximately 10 hours, then move into tissues antigen and is capable of forming only one type of antibody where they live for 1 to 3 days. When a specific antigen attaches to cell Eosinophils increase during allergic reactions and para- membrane receptors to form an antigen–antibody complex, sitic infections.

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Foods that the prototype best 135 mg colospa, are similar drugs that produce a high incidence interact contain tyramine generic colospa 135mg visa, a monoamine precursor of nor- of adverse effects such as sedation buy generic colospa 135 mg, orthostatic hypotension cheap colospa 135mg with visa, epinephrine generic 135mg colospa mastercard. Normally, tyramine is deactivated in the gas- cardiac dysrhythmias, anticholinergic effects (eg, blurred trointestinal tract and liver so that large amounts do not CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 167 Drugs at a Glance: Antidepressant Agents Generic/Trade Name Indications for Use Routes and Dosage Ranges Tricyclic Antidepressants Amitriptyline (Elavil) Depression PO 50–100 mg once daily at bedtime, gradually increased to 150 mg daily if necessary. IM 80–120 mg daily in 4 divided doses Adolescents and older adults: PO 10 mg 3 times daily and 20 mg at bedtime. Amoxapine (Asendin) Depression PO 50 mg 2 or 3 times daily, increased to 100 mg 2 or 3 times daily by end of 1 week. Older adults: PO 25 mg 2 or 3 times daily, increased to 50 mg 2 or 3 times daily by end of 1 week. Clomipramine (Anafranil) Obsessive-compulsive PO 25 mg daily, increased to 100 mg daily by end of 2 weeks, in divided doses, disorder with meals. Maximum dose, 250 mg daily Children and adolescents: PO 25 mg daily, increased to 3 mg/kg or 100 mg, whichever is smaller, over 2 weeks. Desipramine (Norpramin) Depression PO 100–200 mg daily in divided doses or as a single daily dose. Maximum dose, 300 mg/d Adolescents and older adults: PO 25–100 mg daily in divided doses or as a single daily dose. Maximum dose, 150 mg/d Doxepin (Sinequan) Depression PO 75–150 mg daily, in divided doses or a single dose at bedtime. Imipramine (Tofranil) Depression PO 75 mg daily in 3 divided doses, gradually increased to 200 mg daily if necessary. Childhood enuresis Maintenance dose, 75–150 mg daily Adolescents and older adults: PO 30–40 mg daily in divided doses, increased to 100 mg daily if necessary Children >6 y: Enuresis, PO 25–50 mg 1 hour before bedtime Nortriptyline Depression PO 25 mg 3 or 4 times daily or in a single dose (75–100 mg) at bedtime. Maximum (Aventyl, Pamelor) dose, 150 mg/d Adolescents and older adults: 30–50 mg/d, in divided doses or a single dose once daily Protriptyline (Vivactil) Depression PO 15–40 mg daily in 3 or 4 divided doses. Adolescents and older adults: PO 5 mg 3 times daily, increase gradually if necessary Trimipramine maleate Depression PO 75 mg daily, in divided doses or a single dose at bedtime, increased to 150 mg/d (Surmontil) if necessary. Adolescents and older adults: PO 50 mg daily, increased to 100 mg/d if necessary Selective Serotonin Reuptake Inhibitors (SSRIs) Citalopram (Celexa) Depression PO 20 mg once daily, morning or evening, increased to 40 mg daily in 1 week, if necessary Elderly/hepatic impairment: PO 20 mg daily Fluoxetine (Prozac, Depression PO 20 mg once daily in the morning, increased after several weeks if necessary. Give Sarafem) Obsessive-compulsive doses larger than 20 mg once in the morning or in 2 divided doses, morning and disorder noon; maximum daily dose 80 mg Bulimia nervosa Prozac weekly (delayed-release capsules), PO 90 mg once each week, starting 7 days Premenstrual after the last 20-mg dose dysphoric disorder (Sarafem) Fluvoxamine (Luvox) Obsessive-compulsive PO 50 mg once daily at bedtime, increased in 50-mg increments every 4–7 days if nec- disorder essary. Maximum dose, 300 mg/d Children 8–17 y: PO 25 mg once daily at bedtime, increased in 25-mg increments every 4–7 days if necessary. Maximum dose 200 mg/d Paroxetine (Paxil, Depression PO 20 mg once daily in the morning, increased at 1 week or longer intervals, if neces- Paxil CR) Generalized anxiety sary; usual range, 20–50 mg/d; maximum dose, 60 mg/d disorder Controlled-release tablets, PO 25 mg once daily in the morning, increased up to Obsessive-compulsive 62. Maximum Panic disorder dose, 40 mg Social anxiety disorder Severe renal or hepatic impairment: Same as for older adults (continued) 168 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Antidepressant Agents (continued) Generic/Trade Name Indications for Use Routes and Dosage Ranges Sertraline (Zoloft) Depression Depression, OCD, PO 50 mg once daily morning or evening, increased at 1-week or Obsessive-compulsive longer intervals to a maximum daily dose of 200 mg disorder (OCD) Panic, PTSD, PO 25 mg once daily, increased after 1 week to 50 mg once daily Panic disorder Children: OCD, 6–12 y, 25 mg once daily; 13–17 y 50 mg once daily Post-traumatic stress disorder (PTSD) Monoamine Oxidase Inhibitors Isocarboxazid (Marplan) Depression PO 10 mg twice daily, increased to 60 mg/d if necessary, in 2 to 4 divided doses Phenelzine (Nardil) Depression PO 15 mg 3 times daily, increased to 90 mg/d if necessary Tranylcypromine Depression PO 30 mg daily in divided doses, increased to 60 mg/d if necessary (Parnate) Miscellaneous Antidepressants Bupropion (Wellbutrin, Depression (Wellbutrin) Immediate release tablets, PO 100 mg twice daily, increased to 100 mg 3 times daily Wellbutrin SR, Zyban) Smoking cessation (at least 6 h apart) if necessary. Maximum single dose, 150 mg Maprotiline Depression PO 75 mg daily in single or divided doses, increased to a maximum of 300 mg daily if necessary Mirtazapine (Remeron) Depression PO 15 mg/d, in a single dose, at bedtime. Increase by 15 mg/d (at least 1–2 weeks between increments) up to 45 mg/d if necessary Nefazodone (Serzone) Depression PO 200 mg daily in 2 divided doses; increase at 1-week intervals in increments of 100–200 mg/d; usual range, 300–600 mg/d. Elderly or debilitated adults: PO initially 100 mg/d in 2 divided doses Trazodone (Desyrel) Depression PO 100–300 mg daily, increased to a maximum dose of 600 mg daily if necessary Venlafaxine Depression Immediate release tablets, PO initially 75 mg/d in 2 or 3 divided doses, with food. Increase by 75 mg/d (4 days or longer between increments) up to 225 mg/d if necessary. Hepatic or renal impairment: Reduce dose by 50% and increase very slowly Mood-Stabilizing Agent Lithium carbonate Bipolar disorder (mania) PO 600 mg 3 times daily or 900 mg twice daily (slow release forms) (Eskalith, Lithobid) Maintenance dose, PO 300 mg 3 or 4 times daily to maintain a serum lithium level of 0. However, when deactivation After an oral dose, peak plasma levels are reached in is blocked by MAOIs, tyramine is absorbed systemically and about 2 hours. Several metabolites are pharmacologically ac- that should be avoided include aged cheeses and meats, con- tive. Dosage should be reduced with impaired hepatic or centrated yeast extracts, sauerkraut, and fava beans. Acute episodes of depression usually require that should be avoided include CNS stimulants (eg, am- several months of drug therapy. Bupropion is also used as a phetamines, cocaine), adrenergics (eg, pseudoephedrine), smoking cessation aid. In addition to seizures, however, the drug has CNS stimulant effects (agitation, anxiety, excitement, increased Miscellaneous Antidepressants motor activity, insomnia, restlessness) that may require a sedative during the first few days of administration. These Bupropion (Wellbutrin, Zyban) inhibits the reuptake of effects may increase the risk of abuse. It was marketed verse effects include dry mouth, headache, nausea and vom- with warnings related to seizure activity.

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For example buy generic colospa 135mg online, carbon filaments spinal cord transplants are among the sub- helped direct axon growth across a spinal con- stances that may permit central axon regener- tusion when combined with fetal grafts purchase 135 mg colospa overnight delivery. Bridges in Polymers seeded with Schwann cells order 135 mg colospa mastercard, everyday life are passive structures 135mg colospa mastercard, meant to OECs buy generic colospa 135mg line,147 or neural stem cells259a add to the get a person across a barrier and on the road effects of biologic signals for regeneration. For regeneration, axons and cells must Collagen gels and porous, 3-dimensional hy- go past the bridge to find their targets. Per- drogels that are biocompatible may integrate missive substrates255 must lace the lanes at the with the host and can be biodegradable. Such end of the bridge, as well as along the road gels, which are still a work in progress, offer ahead if regenerating axons are going to grow considerable flexibility for repair strate- past the nurturing haven of the bridge. With micron-sized pores, the produce effort, Cheng and colleagues smoothly bridges may encourage directional regenera- Biologic Adaptations and Neural Repair 123 tion, receive nutrients from the host and graft, tained axons. The animals that received BDNF and allow diffusion of embedded neu- or NT-3 neurotrophins filled the site with the rotrophins and other molecules. Indeed, the largest number of axons, myelin proteins, and biocompatible microenvironment may be de- new oligodendrocytes. The two neurotrophins, signed to incorporate neurons, glia, and blood then, induced significant proliferation and mi- vessels and release molecules on demand over gration of host oligodendrocytes or their pre- time. Thus, growth cones coaxed into the poly- cursors and myelinated ingrowing axons over mer graft may also be coaxed out of it so they lengths of 1. Surgeons may tained cholinergic, serotonergic, and other phe- implant, in the near future, smart biopolymers notypes. In another model, oligodendrocytes with feedback sensors or an architecture that derived from embryonic stem cells were able releases embedded substances and cell types to myelinate mutant mice spinal cords that on demand. A more sophisticated polymer as- lacked myelin and myelinate the dorsal columns sembly could contain simple neural networks of rats after chemical demyelination. For example, Grafts of cultured Schwann cells have also a biohybrid microprobe was described that may successfully aided axonal regeneration and re- stimulate encapsulated neurons implanted into myelination, and improved the conduction of the spinal cord. Up to 3% of the cells taken Demyelination with intact axons has been ob- from excised temporal lobe tissue during sur- served in pathological specimens in animal gery for epilepsy have, in tissue culture, dif- models264 and in humans265 after compressive ferentiated into oligodendrocytes and type II SCI, along with regions of remyelination. For example, regulate the expression of ion channels on ax- neurospheres were induced from stem cells of ons and partially myelinated fibers by injecting the subventricular zone of human brain tissue growth factors. The cells dif- impulse conduction by blocking potassium ferentiated into neuronal and oligodendro- channels with drugs such as 4-aminopyri- cyte/Schwann cell precursors. The re- The normal spinal cord may have ongoing en- myelinated axons recovered normal conduc- dogenous proliferation and migration of oligo- tion velocities. Remyelination associ- ated with the regeneration of oligodendrocyte precursors also appears to have a signaling Other Transplantation Strategies mechanism in man that could be switched on. The chal- implanted into the contusion site 2 days after lenges for successful transplantation into the the injury. Ten weeks later, all transplants con- spinal cord are no less formidable than those 124 Neuroscientific Foundations for Rehabilitation for intracerebral grafts of CNS tissue. Many studies have pointed to pression, and pharmacologic modulation of the the beneficial effect of serotonergic input to lo- expression of the graft will interact with task- comotor neurons, including the use of a direct oriented practice to affect graft survival and its 5-hydroxytryptophan agonist combined with an physiologic and behavioral function. The sected in another rat model, spinal embryonic following studies suggest that by combining transplants supported the regeneration of brain several interventions, a modest amount of de- stem–spinal and segmental dorsal root projec- scending input to the L-1 motor pools below tions, associated with recovery of hindlimb the SCI, enough to provide some trunk control placement and aspects of locomotion; this and some supraspinal and propriospinal drive growth was enhanced by providing neutraliz- to the lumbar locomotor pools, will restore ing antibodies to neurite inhibitors. This scending serotonergic, noradrenergic, and cor- finding needs to be demonstrated in a nonhu- ticospinal fibers traversed the transplant only man primate. In adults, the implant seemed to serve as a relay, rather than as a bridge. Pro- priospinal neurons sent axons into the embry- EMBRYONIC TISSUE onic tissue, providing segmental and interseg- Intraspinal transplants of supraspinal neurons mental input that could account for the and embryonic spinal cord have mostly aimed locomotor gains in the adults. These studies, which began to show a havioral gains and the regeneration of axons variety of regenerative processes in the late have improved as investigator experience has 1970s, can be divided into two general cate- increased, especially with the addition of be- gories. A more tissue to provide a favorable milieu for regen- recent study in adult rats by Bregman and col- eration. The optimal milieu includes cells for a leagues showed that the transplantation of fe- synaptic relay, a favorable substrate for axonal tal rat spinal cord tissue, plus the administra- elongation, and new cells that may migrate.

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