Prednisone
By Q. Cruz. Trinity Christian College.
This changes in rates of thyroid gland secretion or hormone arrangement allows for control of thyroid hormone ac- metabolic clearance on plasma concentrations of free tion at the cellular level generic 10 mg prednisone free shipping allergy testing histamine. The source and quantity of T3 thyroid hormones are minimized, and (3) a hormone- releasing function that allows the very small free hor- mone pool to be continuously replenished and made TABLE 65. Sodium iodide symporter H2O2 generation activity Thyroglobulin synthesis I conductance of the apical Cellular Uptake and Intracellular membrane Binding of T3 to Nuclear Thyroid Thyroperoxidase synthesis Hormone Receptors Hormone synthesis Endocytosis and hydrolysis Free T4 and T3 can enter cells by carrier-mediated facil- of colloid itated diffusion or active transport. After gaining access Hormone secretion Type 1 deiodinase activity to the cell interior, T4 may undergo 5 -monodeiodina- Hypertrophy tion to yield T3. The T3 thus mixes with T3 entering the 746 VII DRUGS AFFECTING THE ENDOCRINE SYSTEM bound to nuclear TRs may vary among tissues depend- toskeleton, sarcoplasmic reticulum, mitochondria, and ing on the distributions and relative activities of D1, D2, contractile elements of vascular smooth muscle. PHYSIOLOGICAL EFFECTS MECHANISMS OF ACTION OF THYROID HORMONES OF THYROID HORMONES There is no discrete target tissue for thyroid hormones; Thyroid hormone mechanisms of action can be classi- virtually every cell in the body is affected by thyroid fied into two types: (1) genomic or nuclear and hormones in some way. These hormones are intimately (2) nongenomic, including effects at the plasma mem- involved in the maintenance of normal function in vir- brane and mitochondria. Genomic effects involve modi- tually every cell type, including cellular responsiveness fication of gene transcription, are mediated only by T3, to other hormones, to the availability of metabolic sub- and require at least several hours to detect. Thyroid dysfunc- actions are generally rapid in onset and occur in response tion can produce dramatic changes in the metabolism to T4 and some T4 metabolites (e. Some of the clinical Thyroid hormone receptors are members of a super- manifestations of thyroid dysfunction are presented family of nuclear receptors that includes receptors for next in the discussions of hypothyroid and hyperthy- estrogen, glucocorticoid, mineralocorticoid, retinoic roid states. Similar to the mechanism of action of lipophilic steroid hormones, the lipophilic T3 binds to a protein HYPOTHYROID STATES receptor to form a complex and the hormone–receptor complex binds to an appropriate hormone response el- Hypothyroidism refers to the exposure of body tissues ement on DNA to alter the transcription of specific to a subnormal amount of thyroid hormone. As a conse- hormone action differs from that for steroid hor- quence of the lack of thyroid hormone, a wide variety of mones, however, in three major ways: (1) There are ap- physiological and clinical disturbances involving virtu- parently no cytosolic receptors for thyroid hormones. Other causes of primary hypothyroidism include spontaneous degeneration of glandular tissue (idio- pathic hypothyroidism), thyroid ablation with radioac- Nongenomic Actions of Thyroid Hormone 131 tive iodine uptake ( I), and total or subtotal surgical The nongenomic actions of thyroid hormone are in- thyroidectomy. An enlargement of the thyroid, or stimulation and respond to a range of thyroid hormone goiter, usually develops with increasing duration of the metabolites (T4,T,r3 T,T). Examples include in the latter category is lithium, widely used to treat psy- effects on cellular respiration, cell morphology, vascular chiatric disorders and associated with the development tone, and ion homeostasis. It is concentrated by the of thyroid hormone include the plasma membrane, cy- thyroid, where it inhibits thyroidal I uptake, incorpora- 65 Thyroid and Antithyroid Drugs 747 tion of I into Tg, coupling of iodotyrosine, and, eventu- succeeding months, especially in severe cases, protuber- ally, thyroid hormone secretion. Patients include somnolence, slow mentation, dryness and loss of with secondary hypothyroidism exhibit undetectable or hair, increased fluid in body cavities (e. In sec- sac), low metabolic rate, tendency to gain weight, hy- ondary hypothyroidism, a normal thyroid gland lacks perlipidemia, subnormal temperature, cold intolerance, the normal level of TSH stimulation necessary to syn- bradycardia, reduced systolic and increased diastolic thesize and secrete thyroid hormones. Such patients pulse pressure, hoarseness, muscle weakness, slow re- usually also have impaired secretion of TSH in response turn of muscle to the neutral position after a tendon to exogenous thyrotropin-releasing hormone (TRH) jerk, constipation, menstrual abnormalities, infertility, administration. Tumors, trauma, radiation ther- serum TSH concentrations) are usually treated with apy, or infiltrative disease of the hypothalamus can thyroxine with the aim of relieving symptoms and re- cause such damage. This relatively rare form of hy- ducing the serum TSH concentration into the normal pothyroidism is also characterized by inappropriately reference range. Iodine Clinical Manifestations supplementation alone may lead to the development of of Hypothyroidism acute hyperthyroidism. During the perinatal period, there is an absolute re- Patients with secondary or tertiary hypothyroidism quirement for thyroid hormone for the development are also usually treated with thyroxine, but the serum and maturation of the nervous and musculoskeletal sys- TSH concentration is not a reliable guide to therapy. In the perinatal nervous system, thyroid hormone The efficacy of thyroid hormone replacement in these plays a critical role in normal growth of the cerebral and patients must be assessed clinically and by measure- cerebellar cortices, the proliferation of axons, the ment of the serum T4 concentration. Hypothyroidism-induced impairment of ing hypothyroidism with the classic symptoms of hy- linear growth can lead to dwarfism in which the limbs pothyroidism. Decompensation into myxedema coma are disproportionately short in relation to the trunk may occur when the homeostatic mechanisms of the se- with the apparent bone age retarded in relation to verely hypothyroid patient are subject to a stressful pre- chronological age. The principal manifestation of tardation of mental development and growth) become myxedema coma is a deterioration of mental status (ap- manifest only in later infancy and are largely irre- athy, confusion, psychosis, but rarely coma). Consequently, early recognition and initiation mon clinical features include hypothermia, diastolic hy- of replacement therapy are crucial. In the absence of pertension (early), hypotension (late), hypoventilation, thyroid hormone therapy, the symptoms of infantile hy- hypoglycemia, and hyponatremia. If myxedema coma is pothyroidism include feeding problems, failure to suspected, the patient is usually admitted to an inten- thrive, constipation, a hoarse cry, and somnolence. In sive care unit for pulmonary and cardiovascular support 748 VII DRUGS AFFECTING THE ENDOCRINE SYSTEM and treated with intravenous T4 (or sometimes T3).
In these patients cheap prednisone 40 mg with mastercard allergy shots water retention, repetitive stimulation (B) Replacing pyridostigmine with neostigmine promotes facilitation of transmitter release, and this (C) Giving dantrolene to decrease sarcoplasmic re- is seen clinically as an improvement in muscle lease of calcium strength with increased physical activity. This is the (D) Adding succinylcholine to her regimen opposite of myasthenia gravis, the autoimmune at- (E) Allowing pyridostigmine to be eliminated tack against postjunctional ACh receptors, in which muscle strength decreases with increased physical ac- ANSWERS tivity. Rapacuronium is a skeletal muscle relaxant that in patients with spinal cord damage in which central works by competing with ACh for receptors at the inhibition of reflexes is impaired. Nicotine and succinyl- cholinesterase does not affect neuromuscular trans- choline also act at the end plate receptors but cause mission except with regard to breakdown of succinyl- depolarization. Malignant hyperthermia is due to a defect in blocker that has essentially no activity at the end the contractile apparatus of skeletal muscle and not plate receptors, and scopolamine blocks cholinergic in neuromuscular transmission. The patient has a rare genetic defect that results Atracurium and rocuronium are nondepolarizing in susceptibility to malignant hyperthermia. Acute neuromuscular blockers that act specifically at the attacks are manifested by heat generation, muscle postjunctional receptors of the skeletal neuromus- rigidity, and high oxygen consumption, all of which cular junction. It has a fatality rate in ex- acting muscle relaxants that stimulate presynaptic cess of 70% if left untreated. Attacks can be precip- GABAB receptors and benzodiazepine sites on itated by stress or infection but are generally a re- postsynaptic GABAA receptors, respectively. These appear to trigger excessive re- overtreated with anticholinesterases, that is,, when lease of Ca from the sarcoplasmic reticulum due acetylcholinesterase at the neuromuscular junction is to a defect in the calcium release channels. The depolarizing neuromuscular to depolarization and desensitization of the end plate blocking agent succinylcholine may also appear to receptors so that they cannot respond to further stim- be a viable possibility. Unlike the irreversible organophos- since it is rapidly broken down to natural products phates, pyridostigmine has a short to intermediate du- by plasma cholinesterase and would not have been ration of action, and treatment should be to allow detected by the toxicological tests. Continuous in- can be used to reverse the effect of nondepolarizing trathecal baclofen infusion in severe spasticity after blockers. Case Study Generalized Muscle Weakness 30-year-old white woman is referred to a neu- ANSWER: The patient shows classic signs of myasthenia Arologist after complaining of a general loss of gravis, an autoimmune disease that results from anti- strength at the end of the day and drooping eyelids body attack against the end plate receptors of skele- that make reading difficult. The disease the adductor pollicis using train-of-four 50-Hz stim- may be triggered by disorders of the thymus, which ulation reveals a progressive decrease in the com- contains a protein antigenically related to skeletal pound muscle action potential. Subsequent administration of edro- action potentials) and a postjunctional cause (such as phonium results in an improvement in muscle myasthenia gravis). The neurologist larizing neuromuscular blocker (mivacurium) fol- prescribes oral pyridostigmine and prednisone, lowed by a short-acting acetylcholinesterase inhibitor which lead to clinical improvement over the next (edrophonium) is an almost conclusive test for myas- few weeks. In many instances, edrophonium alone patient has a thymoma and increased titers of anti- may be used (the Tensilon test). Following removal of the thy- long-acting cholinesterase inhibitor that can provide moma, the patient no longer shows signs of muscle palliative relief, whereas prednisone is used to sup- weakness and appears to be in remission. Taylor DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Amphetamine 350 Pemoline 350 Caffeine 351 Pentylenetetrazol 349 Doxapram 349 Sibutramine 351 Fenfluramine 351 Phentermine 351 Methamphetamine 350 Theobromine 351 Methylphenidate 350 Theophylline 351 Modafenil 351 Central nervous system (CNS) stimulation is the pri- pounds within this category do possess some clinical mary action of a diverse group of pharmacological utility. Historically, general CNS stimulants were used agents and an adverse effect associated with the admin- primarily as respiratory stimulants in the treatment of istration of an even larger group of drugs. Several factors have contributed to the almost vation in alertness, increased nervousness and anxiety, complete lack of use of CNS stimulants in this clinical and convulsions. First, since the stimulants were not specific an- In general, any hyperexcitability associated with tagonists of the depressant agents, they frequently were drug administration (as either a desired or an undesired not effective in reversing severe pharmacologically in- effect) results from an alteration in the fine balance nor- duced CNS depression. Second, the duration of action mally maintained in the CNS between excitatory and of the CNS stimulant was generally shorter than that of inhibitory influences. Third, the dose of most CNS stimulants tion by this class of drugs reside in adjusting the inte- required to reverse severe CNS depression was quite gration of excitatory and inhibitory influences at the close to the dose that produced convulsions and cardiac level of the individual neuron. In such cases, the CNS stimulant often ex- CNS stimulation appears to act by one or more of the acerbated the clinical picture by producing severe life- following mechanisms: (1) potentiation or enhance- threatening complications. Another factor contributing ment of excitatory neurotransmission, (2) depression or to the decline in CNS stimulant use for drug-induced antagonism of inhibitory neurotransmission, and (3) al- CNS depression has been the development of generally tered presynaptic control of neurotransmitter release. With GABA in particular, the interaction appears to occur through specific membrane-associated Analeptic Psychomotor GABAA-receptors that form an integral part of the chlo- Stimulants Stimulants Methylxanthines ride channel (see Chapter 24). The chloride channel ap- pears to contain other regulatory sites with high affinity Doxapram Amphetamine Caffeine Nikethamide Methamphetamine Theophylline for such agents as the benzodiazepines, picrotoxin, alco- Pentylenetetrazol Methylphenidate Theobromine hol, neuroactive steroids, and the barbiturates. Strychnine Pemoline Chloride movement across neuronal membranes can Picrotoxin Ephedrine be regulated at this ion channel by at least three distinct Bicuculline Phentermine molecular entities: (1) a GABA-binding site, (2) a benzo- Fenfluramine Phenylpropanolamine diazepine-binding site, and (3) a picrotoxin-binding site.
It Constipation is defined as the infrequent passage of is employed primarily in patients who must avoid stool generic prednisone 20mg with visa allergy medicine red eyes. It may be secondary to sluggish colonic motility, in straining at stool, including persons with hemorrhoids which soft stool is seen throughout the colon, or to dif- and other painful anal lesions. Leakage of mineral oil ficulties with evacuation in which firm stool is seen pri- past the anal sphincter may lead to soiling of clothing. Docusate dioctyl sodium sulfosuccinate (Colace), The dangers of excessive purging are salt and fluid dioctyl calcium sulfosuccinate (Surfak), and dioctyl loss and gradually increasing desensitization of the potassium sulfosuccinate (Diocto-K) are surface-active bowel to normal stimuli; the latter effect forces the agents that produce fecal softening in 1 or 2 days. Orally ingested do- laxatives and pure osmolar laxatives do not predispose cusate may also act as a stool softener by stimulating patients to formation of a cathartic-type colon and the secretion of water and electrolytes into the intes- should be the initial agents used for chronic constipa- tinal lumen. Docusate has been used both alone and in tion after a structural obstructing lesion has been ex- combination with other laxatives. Laxatives are also used before radiological, en- appears to be relatively nontoxic, it may, when taken in doscopic, and abdominal surgical procedures; such combination with other laxatives, increase their absorp- preparations quickly empty the colon of fecal material. Caution is necessary when Nonabsorbable hyperosmolar solutions or saline laxa- docusate is prescribed together with mineral oil, since tives are used for this purpose. Bulk Forming Laxatives Stool Softeners The bulk-forming laxative group includes the hy- Fecal softeners are substances that are not absorbed drophilic substances described previously: calcium from the alimentary canal and act by increasing the polycarbophil (FiberCon, Equalactin), methylcellulose bulk of the feces and softening the stool so that it is eas- (Citrucel), and various psyllium seed derivatives ier to pass. All act by increasing the bulk of the feces, either as the oil or as a white emulsion; it is a mixture of part of this action being due to their capacity to attract liquid hydrocarbons. It dissolves the fat-soluble vitamins and ces stretches the walls of the GI tract and stimulates prevents their absorption. Their action may not be evident for 2 to 3 and appears in the mesenteric lymph nodes, and if it is days after starting treatment. These salts should always be given with substantial The use of high-fiber diets has recently received a amounts of water; otherwise the patient may be purged great deal of publicity, and many claims have been at the expense of body water, resulting in dehydration. Fiber in the diet is de- Sodium-containing laxatives should not be used in pa- rived entirely from plant material, either from fruit and tients with congestive heart failure, since the patient vegetables or from cereals, the latter being known as may absorb excessive sodium. The fiber content in each case is a complex carbo- failure, magnesium or phosphate-containing products hydrate in the form of cellulose, pectin, and lignin. A high-fiber diet is effective in the prevention of Enemas may contain water, salts, soap, mineral de- constipation and diverticulitis. Claims also have been tergent (docusate potassium), or hypertonic (sorbitol, made that such diets prevent cancer of the colon. Many of Since clear advantages accrue from a high-bran diet these solutions irritate the mucosa and may produce ex- (a reduction in both constipation and diverticulitis) and cessive mucus in the stool. Excessive use of these enema since there is no associated toxicity, a bulk-forming lax- products may result in water intoxication and hypona- ative is the laxative of choice for constipated patients. A new formulation of a saline laxative, Visicol, that Osmotic Laxatives is useful to prepare patients for procedures, was ap- proved for use in 2001. Visicol tablets, taken in two creases, and fluid movement occurs secondary to os- doses of 30 g approximately 12 hours apart, induce di- motic pressure. Lactulose is a synthetic disaccharide arrhea that rapidly and effectively cleanses the entire that is poorly absorbed from the GI tract, since no colon. Each administration has a purgative effect for mammalian enzyme is capable of hydrolyzing it to its approximately 1 to 3 hours. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic Stimulant Cathartics acids. Since lactulose does contain galactose, it is con- The stimulant cathartics contain a variety of drugs traindicated in patients who require a galactose-free whose exact mode of action is not known, although it is diet. Metabolism of lactulose by intestinal bacteria may thought that they act on the mucosa of the intestine to result in increased formation of intraluminal gas and stimulate peristalsis either by irritation or by exciting abdominal distention. Polyethylene glycol (Miralax) is another osmotic They produce irritation of the mucosa if given in large laxative that is colorless and tasteless once it is mixed. It has been suggested that these drugs may Saline laxatives are soluble inorganic salts that contain act by stimulating afferent nerves to initiate a reflex in- multivalent cations or anions (milk of magnesia, mag- crease in gut motility.
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