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Depending on the nature of the operation buy cheap fml forte 5 ml line, the patient may also receive a muscle relaxant buy 5 ml fml forte overnight delivery. The patient experiences four stages of anesthesia buy discount fml forte 5 ml, some of which are not observable because they occur rapidly. These stages are: Stage one: analgesia The patient experiences analgesia (a loss of pain sensation) but remains con- scious and can carry on a conversation. This stage is typically bypassed by administering a barbiturate such as sodium pentothal before the anesthesia. Stage four: medullary paralysis Breathing and other vital functions cease to function because the respiratory cen- ter (medulla oblongata) is paralyzed. These properties make it especially useful in developing countries and during warfare medical treatment. Ketamine is frequently used in pediatric patients because anesthesia and analgesia can be achieved with an intramus- cular injection. It is also used in high-risk geriatric patients and in shock cases, because it also provides cardiac stimulation. Opioids Fentanyl, sufentanil, and alfentanil are frequently used prior to anesthesia and surgery as a sedative and analgesic, as well as a continuous infusion for primary anesthesia. Because opioids rarely affect the cardiovascular system, they are particularly useful for cardiac surgery and other high-risk cases. Opioids act directly on spinal cord receptors, and are frequently used in epidurals for spinal anesthesia. Side effects may include nausea and vomiting, itching, and respiratory depression. Propofol Nonbarbiturate hypnotic agent and the most recently developed (Diprivan) intravenous anesthetic. Its rapid induction and short duration of action are identical to thiopental, but recovery occurs more quickly and with much less nausea and vomiting. Also, propofol is rapidly metabolized in the liver and excreted in the urine, so it can be used for long durations of anesthesia, unlike thiopental. Because of their small molecular size, they are able to penetrate the cell wall reasonably well and can be used to deliver medications. Other topical anesthetics can be delivered using iontophoresis—a therapy that uses a local electric current to introduce the ions of a medicine into the tissues—and anesthetic patch. Tetracaine (Pontocaine) Long-acting—ester—used for spinal anesthesia and topical Bupivicaine Long-acting—amide—can be cardiotoxic at high concentrations, used for infiltration, epidural and nerve blocks. It is commonly used for dental procedures, suturing of skin lacerations, short-term surgery at a local- ized area, spinal anesthesia by blocking nerve impulses (nerve block) below the insertion of the anesthetic, and diagnostic procedures such as lumbar punctures. Local anesthetics are divided into two groups according to their basic chem- ical structure. An ester is a chemical compound formed from the reaction between an acid and an alcohol. Amides are an organic chemical compound formed by reaction of an acid chloride, acid anhydride, or ester with an amine. If it is given too high, the respiratory muscles could be affected and respiratory distress or failure could result. There are 4 types of spinal anesthesia: subarachnoid block, epidural block, the saddle block, and a caudal block. A subarachnoid block is the injection into the subarachnoid space in the third or fourth lumbar space to produce anesthesia. The saddle block is given at the lower end of the spinal column to block the perineal area for procedures such as childbirth. The patient may experience headaches and hypotension as a result of these procedures because of a change in cerebrospinal fluid pressure when the needle is inserted into the spine. The patient should remain in the supine position fol- lowing the procedure and increase fluid intake. Sensory neurons send impulses to the central nervous system, which are transmitted to the brain where they are interpreted. The brain then sends a response to the motor neuron’s brain through the spinal cord that directs specific organ cells to respond to the sensory neuron’s impulse. Previously in this chapter you learned that the autonomic nervous system has two branches. The sympathetic branch stimulates a response and the parasympathetic branch depresses a response by the organ cell. The sympathetic branch stimulates a response using norepinephrine, a neuro- transmitter. Medications that mimic the effect of norepinephrine are called adrenergic drugs or sympathomimetics (mimic sympathetic nervous system actions) (see chart). These drugs are also known as adrenergic agonists because they start a response at the adrenergic receptor sites. Adrenergic blockers prevent the norepinephrine response at the adrenergic receptor sites. The parasympathetic branch is sometimes referred to as the cholinergic sys- tem because an acetylcholine neurotransmitter is used to innervate muscle cells at the end of the neuron. Alpha2 Inhibits the release of norepinephrine, dilates blood vessels, and produces hypoten- sion; decreases gastrointestinal motility and tone. However, the enzyme acetylcholinesterase can inactivate the acetyl- choline before it reaches the receptor cell. Drugs that mimic acetylcholine are cholinergic agonists because they initiate a response. Drugs that block the effect of acetylcholine are called anticholinergic, or parasympatholytics. They are also known as cholinergic antagonists because they inhibit the effect of acetylcholine on the organ. In a fight response, eyes dilate so you can see better and lungs inspire more oxygen while increasing your heart rate. Salivary glands reduce the secretion of saliva giving the person the dry mouth feeling in an emergency. Instead, the flight response is really the opposite of fight and allows the individual to relax and function normally. Beta2-adrenergic receptors are in the smooth muscle of the lungs, arterioles of skeletal muscles, and the uterine muscles. Adrenergics also stimulate the dopaminergic receptor located in the renal, mesenteric, coronary, and cerebral arteries to dilate and increase blood flow. They promote reuptake of the transmitter back into the neuron (nerve cell terminal). Transmitters are transformed or degraded by enzymes making them unable to attach to a receptor. Sympathomimetic drugs stimulate andrenergic receptors and are classified into three categories according to its effect on organ cells. Indirect-acting sympathomimetics—stimulate the release of norepineph- rine from terminal nerve endings.

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To remember buy generic fml forte 5 ml line, use the word “occipital” to bring to mind the word “optic discount 5 ml fml forte overnight delivery,” which of course is related to visual activity generic 5 ml fml forte free shipping. Controls motor coordination and refinement of muscular movement Chapter 15: Feeling Jumpy: The Nervous System 263 U Medulla oblongata: b. Contains the centers that control cardiac, respiratory, and vasomotor functions V Cerebrum: e. Contains the corpora quadrigemina and nuclei for the oculomotor and trochlear nerves X The largest quantity of cerebrospinal fluid originates from the c. Y The part of the brain that contains the thalamus, pituitary gland, and the optic chiasm is the a. Count them: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral — plus 1 tailbone (coccygeal). It has two divisions that are antagonistic to each other, meaning that one counteracts the effects of the other one. Lens : The area of the eyeball that contains cells that are sensitive to light is the b. They reshape the lens by contracting and relaxing as needed to bring things into focus. The structure in the eye that responds to the ciliary muscles during focusing is the b. Otherwise known as the eardrum, this membrane sometimes bursts or tears as a result of infection or trauma. Hairs in this structure are what ultimately send the signal down the auditory nerve. These little endolymph- filled sacs have hairs and chunks of calcium carbonate that detect changes in gravitational forces. Pinna Chapter 16 Raging Hormones: The Endocrine System In This Chapter Absorbing what endocrine glands do Checking out the ringmasters: Pituitary and hypothalamus glands Surveying the supporting glands Understanding how the body balances under stress he human body has two separate command and control systems that work in harmony Tmost of the time but also work in very different ways. Designed for instant response, the nervous system cracks its cellular whip using electrical signals that make entire systems hop to their tasks with no delay (refer to Chapter 15). By contrast, the endocrine system’s glands use chemical signals called hormones that behave like the steering mechanism on a large, fully loaded ocean tanker; small changes can have big impacts, but it takes quite a bit of time for any evidence of the change to make itself known. At times, parts of the nervous system stimulate or inhibit the secretion of hormones, and some hormones are capable of stimulating or inhibiting the flow of nerve impulses. The word “hormone” originates from the Greek word hormao, which literally translates as “I excite. Each chemical signal stimulates some specific part of the body, known as target tissues or target cells. The body needs a constant supply of hormonal signals to grow, maintain homeostasis, reproduce, and conduct myriad processes. In this chapter, we go over which glands do what and where, as well as review the types of chemical signals that play various roles in the body. You also get to practice discerning what the endocrine system does, how it does it, and why the body responds like it does. No Bland Glands Technically, there are ten or so primary endocrine glands with various other hormone- secreting tissues scattered throughout the body. Unlike exocrine glands (such as mammary glands and sweat glands), endocrine glands have no ducts to convey their secretions. Instead, hormones move directly into extracellular spaces surrounding the gland and from there move into capillaries and the greater bloodstream. Although they spread throughout the body in the bloodstream, hormones are uniquely tagged by their chemical composition. Thus they have separate identities and stimulate specific receptors on target cells so that usually only the intended cells or tissues respond to their signals. All of the many hormones can be classified either as steroid (derived from cholesterol) or nonsteroid (derived from amino acids and other proteins). The steroid hormones — which include testosterone, estrogen, progesterone, and cortisol — are the ones most closely Part V: Mission Control: All Systems Go 266 associated with emotional outbursts and mood swings. Steroidal hormones, which are nonpolar (see Chapter 2 for details on cell diffusion), penetrate cell membranes easily and initiate protein production at the nucleus. Nonsteroid hormones are divided among four classifications: Some are derived from modified amino acids, including such things as epineph- rine and norepinephrine, as well as melatonin. Protein-based nonsteroid hormones include such crucial substances as insulin and growth hormone as well as prolactin and parathyroid hormone. Hormone functions include controlling the body’s internal environment by regulating its chemical composition and volume, activating responses to changes in environmen- tal conditions to help the body cope, influencing growth and development, enabling several key steps in reproduction, regulating components of the immune system, and regulating organic metabolism. Glands that secrete their product into the interstitial fluid, which flows into the blood, are a. Rickets cells Chapter 16: Raging Hormones: The Endocrine System 267 Mastering the Ringmasters The key glands of the endocrine system include the pituitary (also called the hypophy- sis), adrenal (also referred to as suprarenal), thyroid, parathyroid, thymus, pineal, islets of Langerhans (within the pancreas), and gonads (testes in the male and ovaries in the female). But of all these, it’s the pituitary working in concert with the hypothalamus in the brain that really keeps things rolling (see Figure 16-1). The hypothalamus is the unsung hero linking the body’s two primary control systems — the endocrine system and the nervous system. Part of the brain and part of the endocrine system, the hypothalamus is connected to the pituitary via a narrow stalk called the infundibulum that carries regular system status reports to the pituitary. In its supervisory role, the hypothalamus provides neurohormones to control the pituitary gland and influences food and fluid intake as well as weight control, body heat, and the sleep cycle. The hypothalamus sits just above the pituitary gland, which is nestled in the middle of the human head in a depression of the skull’s sphenoid bone called the sella turcica. The pituitary’s anterior lobe, also called the adenohypophysis or pars distalis, is some- times called the “master gland” because of its role in regulating and maintaining the other endocrine glands. Hormones that act on other endocrine glands are called tropic hormones; all the hormones produced in the anterior lobe are polypeptides. Two capil- lary beds connected by venules make up the hypophyseal portal system, which connect the anterior lobe with the hypothalamus. Hypothalamus Anterior pituitary gland Adrenocortico- tropic hormone Thyroid- stimulating hormone Figure 16-1: The working Level of thyroxin relationship has control over anterior Thyroid pituitary gland and of the hypo- gland hypothalamus thalamus and the pituitary gland. This is the only hormone secreted by the anterior lobe that has a general effect on nearly every cell in the body (also regarded as nonendocrine targets). For a review of the male and female reproductive systems, flip to Chapters 13 and 14. The posterior lobe, or neurohypophysis, of the pituitary gland stores and releases secre- tions produced by the hypothalamus. This lobe is connected to the hypothalamus by the hypophyseal tract, nerve axons with cell bodies lying in the hypothalamus.

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There are exceptions for the processing of sensitive personal data (as defined in section 2 of the Act) for medical purposes by a health professional (as defined in section 69) buy fml forte 5 ml visa. Medical purposes include the provision of pre- ventative medicine generic 5 ml fml forte with mastercard, medical diagnosis order 5 ml fml forte fast delivery, medical research, the provision of care and treatment, and the management of health care services. Readers are referred to texts on the provisions of the Act for a more detailed exposition of its provisions and ramifications. If access is denied on this ground the individual has a right of challenge in the county court (England and Wales) or Sheriff’s court (Scotland). Individuals who exercise their right of access but dispute the content of the report may request amendments. If these are not agreed to by the doctor, the individual may either refuse to allow the report to be dispatched or may request that it be accompanied by a statement prepared by the individual. The statute applies only to reports prepared by a doctor who is or has been responsible for the care of the patient and not to an independent occupa- tional physician who has not provided care. Management of Head-Injured Detainees 405 Appendix 3 Management of Head Injured Detainees Table 1 Glasgow Coma Scale Score Eye opening • Spontaneous 4 • To speech 3 • To painful stimulus 2 • None 1 Best motor response • Obeys commands 6 • Localises painful stimulus 5 • Withdraws (normal flexion) 4 • Flexes abnormally (spastic flexion) 3 • Extension 2 • No response 1 Best verbal response • Orientated 5 • Confused 4 • Says inappropriate words 3 • Makes incomprehensible sounds 2 • No verbal response 1 Maximum 15 From Jennett, B. Table 2 Detained Person: Observation List If any detainee fails to meet any of the following criteria, an appropriate health care professional or ambulance must be called. Response to commands—can they respond appropriately to commands such as: • Open your eyes! Remember—take into account the possibility or presence of other illnesses, injury, or mental condition. A person who is drowsy and smells of alcohol may also have the following: • Diabetes • Epilepsy • Head injury • Drug intoxication or overdose • Stroke From Home Office. The Mini-Mental State Examination 407 Appendix 4 The Mini-Mental State Examination Score Orientation What is the (year) (season) (date) (day) (month)? Alternatively, if patient makes errors on serial subtraction: spell ‘world’ backwards: D L R O W. Have you ever neglected your obligations, your family or your work for more than 2 days in a row because you were drinking? Have you ever had a drink first thing in the morning to steady your nerves, or to get rid of a hang over (Eye-opener)? Some content that appears in print may not be available in electronic books Library of Congress Cataloging-in-Publication Data Thomas, Gareth, Dr. Ltd, Pondicherry, India Printed and bound in Great Britain by Antony Rowe Ltd This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production. C ontents Preface xi Acknowledgements xii Abbreviations/Acronyms xiii 1 Biological Molecules 1 1. It is also intended for students whose degree courses contain a limited reference to medicinal chemistry. The text assumes that the reader has a knowledge of chemistry at level one of a university life sciences degree. The text discusses the fundamental chemical principles used for drug discovery and design. Chapter 1 gives a brief review of the structures and nomenclature of the more common classes of naturally occurring compounds found in biological organ- isms. It is included for undergraduates who have little or no background knowledge of natural product chemistry. For students who have studied natural product chemistry it may be used as either a revision or a reference chapter. The basic approaches used to discover and design drugs are outlined in Chapters 3–6 inclusive. Chapter 7 is intended to give the reader a taste of main line medicinal chemistry. It illustrates some of the strategies used, often within the approaches outlined in previous chapters, to design new drugs. For a more encyclopedic coverage of the discovery and design of drugs for specific conditions, the reader is referred to appropriate texts such as some of those given under Medicinal Chemistry in the Selected Further Reading section at the end of this book. Chapters 8 and 9 describe the pharmacokinetics and metabolism respectively of drugs and their effect on drug design. Chapter 10 attempts to give an introductory overview of an area that is one of the principal objectives of the medicinal chemist. For a more in depth discussion, the reader is referred to the many specialized texts that are available on organic synthesis. Drug develop- ment from the research stage to marketing the final product is briefly outlined in Chapter 11. Answers, sometimes in the form of references to sections of the book, are listed separately. A list of recommended further reading, classified according to subject, is also included. Gareth Thomas A cknow ledgem ents I wish to thank all my colleagues, past and present without, whose help this book would have not been written. P Cox for the molecular model diagrams and his patience in explaining to me the intricacies of molecular modelling and Mr. I wish also to thank the following friends and colleagues for proof-reading chapters and supplying information: Dr. Finally, I would like to thank my wife for her support whilst I was writing the text. Some of these naturally occuring compounds and ions (endogenous species) are present only in very small amounts in specific regions of the body, whilst others, such as peptides, proteins, carbohydrates, lipids and nucleic acids, are found in all parts of the body. A basic knowledge of the nomenclature and structures of these more common endogenous classes of biological molecules is essential to under- standing medicinal chemistry. This chapter introduces these topics in an attempt to provide for those readers who do not have this background knowledge. The structures of biologically active molecules usually contain more than one type of functional group. This means that the properties of these molecules are a mixture of those of each of the functional groups present plus properties characteristic of the compound. The latter are frequently due to the interaction of adjacent functional groups and/or the influence of a functional group on the carbon–hydrogen skeleton of the compound. This often involves the electronic activation of C–H bonds by adjacent functional groups. Their structures contain both an amino group, usually a primary amine, and a carboxylic acid. The structures of amino acids can also contain other functional groups besides the amine and carboxylic acid groups (Table 1. Methionine, for example, contains a sulphide group, whilst serine has a primary alcohol group.

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This injury affects the central gray matter and the most central portions of the pyramidal and spinothalamic tracts buy fml forte 5 ml low price. Patients often have greater neurologic deficits in the upper extremities cheap fml forte 5 ml otc, compared to the lower extremities fml forte 5 ml amex, since nerve fibers that innervate distal structures are located in the periphery of the spinal cord. In addition, patients with central cord syndrome usually have decreased rectal sphincter tone and patchy, unpredictable sensory deficits. Its hallmark is preservation of vibratory sensation and proprioception because of an intact dorsal column. Blood products should be administered if vital signs transiently improve or remain unstable despite resuscitation with 2 to 3 L of crystalloid fluid. However, if there is obvious major blood loss and the patient is unstable, blood transfusion should be started concomitantly with crystalloid adminis- tration. The main purpose in transfusing blood is to restore the oxygen- carrying capacity of the intravascular volume. Fully cross-matched blood is preferable (eg, type B, Rh-negative, antibody negative); however, this process may take more than 1 hour, which is inappropriate for the unstable trauma Trauma Answers 163 patient. Type-specific blood (eg, type A, Rh negative, unknown antibody) can be provided by most blood banks within 30 minutes. If type-specific blood is unavailable, type O packed cells are indicated for patients who are unstable. To reduce sensitization and future complications, type O, Rh-negative blood is reserved for women of childbearing age. Whole blood is not used because the extra plasma can contribute to transfusion associated circulatory overload, a potentially dan- gerous complication. However, if type O, Rh-negative blood is unavailable, then type O, Rh-positive blood should be administered to women. The retroperitoneum can accommodate up to 4 L of blood after severe pelvic trauma. However, the initial and simplest modality to use in a patient in shock from a pelvis fracture is placement of a pelvic binding garment. This device can be applied easily and rapidly and is typically effective in tamponading bleeding and stabiliz- ing the pelvis. However, venography is not useful in managing these patients: even when venous bleeding is localized, embolization is ineffective because of the exten- sive anastomoses and valveless collateral flow. Angiography is indicated when 164 Emergency Medicine hypovolemia persists in a patient with a major pelvic fracture, despite con- trol of hemorrhage from other sources. Since angiography typically takes place in the angiography suite, patients should have a pelvic binding device applied, prior to being transferred to angiography. It may also occur from vascular pathology, such as laceration or thrombosis of the anterior spinal artery. The syndrome is characterized by different degrees of paralysis and loss of pain and temper- ature sensation below the level of injury. Its hallmark is the preservation of the posterior columns, maintaining position, touch, and vibratory sensation. Central cord syndrome (b) is often seen in patients with degenerative arthritis of the cervical vertebrae, whose necks are subjected to forced hyperextension. This is seen typically in a forward Syndrome Neurologic Deficits Anterior cord B/L paralysis below lesion, loss of pain and tempera- ture, preservation of proprioception and vibratory function Central cord Lower extremity paralysis > upper extremity paralysis, some loss of pain and temperature with upper > lower Brown-Séquard Ipsilateral: paresis, loss of proprioception, and vibratory sensation Contralateral: loss of pain and temperature Cauda equina Variable motor and sensory loss in lower extremities, bowel/bladder dysfunction, saddle anesthesia Trauma Answers 165 fall onto the face in an elderly person. Patients often have greater sensorimo- tor neurologic deficits in the upper extremities compared to the lower extremities. Cauda equina injury (d) causes peripheral nerve injury rather than direct spinal cord damage. Its presentation may include variable motor and sensory loss in the lower extremities, sciatica, bowel and bladder dys- function, and saddle anesthesia. Brown-Séquard syndrome (e) results in ipsi- lateral loss of motor strength, vibratory sensation, and proprioception, and contralateral loss of pain and temperature sensation. The simplest and quickest way to establish this is by inserting a 14-gauge catheter into the thoracic cavity in the second intercostal space in the midclavicular line. Needle thoracos- tomy is necessary when a patient’s vital signs are unstable; otherwise, direct insertion of a chest tube is adequate for suspicion of a hemo- or pneumoth- orax. This increased pressure causes the ipsilateral lung to collapse, shifting the mediastinum away from the injured lung, compromising vena caval blood return to the heart. The severely altered preload results in reduced stroke volume, increased cardiac output, and hypotension. As the brain mass decreases in size with age, there is greater stretching and tension of the bridging veins that pass from the brain to the dural sinuses. Geriatric patients are thus more susceptible to the development of hypoxia and respiratory infections following trauma. Fractured pelvic bones bleed briskly and can lacerate surrounding soft tissues and disrupt their extensive arterial and venous networks. Once an abdominal source of bleeding is ruled out as a source of hypoten- sion, the patient should undergo pelvic angiography with embolization of bleeding vessels. Motor vehicle Trauma Answers 167 collisions with another vehicle or with pedestrians are the major causes of blunt abdominal trauma. The spleen is the organ most often injured, and in approximately 66% of these cases, it is the only damaged intraperitoneal organ. The liver (a) is the second-most commonly injured intra-abdominal organ, third is the kidney (c), fourth is the small bowel (d), and fifth is the bladder (e). Anterior ure- thral injuries are most often attributed to falls with straddle injuries or a blunt force to the perineum. Approximately 95% of posterior urethral injuries are secondary to pelvic fractures. Signs and symptoms of urethral injury include perineal pain, inability to void, gross hematuria, blood at the urethral mea- tus, perineal or scrotal swelling or ecchymosis, and an absent, high-riding, or boggy prostate. A retrograde urethrogram is the study of choice when there is suspicion of a urethral injury. This procedure is performed by inserting an 8F urinary catheter 2 cm into the meatus and inflating the catheter balloon with 2 cc saline to create a seal. Then, 30 cc of radiopaque contrast is admin- istered and a radiograph is obtained looking for extravasation of contrast from the urethra. The blunt force causes an increase in intraorbital pressure causing a fracture along the weakest part of the orbit, usually the inferior or some- times medial wall. They may have impaired ocular motility or diplopia if the inferior rectus muscle becomes entrapped. They may also present with infraorbital hypoesthesia because of compression of the infraorbital nerve.