It evidently possesses medicinal properties order discount methocarbamol online spasms vitamin deficiency, and I have seen good effects from its local use buy methocarbamol toronto muscle relaxant 4211 v. It is claimed to be poisonous when taken internally methocarbamol 500 mg cheap spasms to right side of abdomen, yet I have known it taken with safety in doses of ten to thirty drops. The limited use I have known made of it internally was to relieve muscular pains, lame back, and stiffness of joints. As the agent is very common, and easily cultivated, it would be well to prepare a tincture from the fresh fruit, ℥viij. Of such a preparation the dose would be quite small, say commencing with one drop. Solve the extract (imported from Brazil) in dilute alcohol, or in water, adding alcohol sufficient to preserve it. The Monesia is a mild stimulant and tonic, and may be given in atonic dyspepsia, in convalescence from the malarial fevers, in chronic diarrhœa, chronic bronchitis, and incipient tuberculosis. Anstie (The Practitioner, December, 1868), which treats principally of the employment of this remedy for the relief of (1) various kinds of pain, and (2) of certain cases of suspended secretion dependent on nervous exhaustion. Before very briefly describing some of the applications mentioned, we think it right to state that we are by no means prepared to coincide in Dr. Under the first class the disease termed myalgia is said to be specially amenable to treatment by Muriate of Ammonia. Doses from ten to twenty grains are recommended, and by their use this disease may be cured as certainly as ague by quinia. This class also includes various neuralgias proper, such as migraine (usually referred to disorders of digestion) and clavus hystericus; both of which Dr. Of all the internal remedies that can be employed in these headaches, none is apparently so beneficial as the Muriate of Ammonia, its virtue depending on its mildly stimulant properties. As the Bayberry deteriorates unless carefully kept, it would be better to test a tincture of the fresh bark of the root. It has been extensively employed as a general stimulant, and as a special stimulant to mucous membranes, and with excellent results. Thomson recommended it in all cases where there was increased secretion from mucous membranes, whether it was catarrh or sore throat, bronchitis, disease of stomach or intestinal canal, or leucorrhœa. The same combination will prove very valuable in typhoid fever, in typhoid dysentery, and in diarrhœa with increased mucous secretion. The tincture prepared as above will furnish a much better form of dispensing, as well as a more reliable remedy than much of the powder sold, and when once used, will become a prominent agent in the office and the pocket case. Dusted over a larded cloth, it sometimes makes a good application to the bowels in cholera infantum, and over the stomach to check vomiting. As a local application myrrh may be used for spongy and ulcerated gums, chronic pharyngitis, where the mucous membrane is pallid and tumid, elongation of uvula, and spongy and enlarged tonsils. Internally it is given in chronic gastritis and dyspepsia, the tongue and mucous membranes being pallid and full, and to rectify wrongs of the reproductive apparatus, there being a sense of weight and dragging, with leucorrhœa. It was claimed to be specific to the poison of the rattlesnake, and to have been used with much success. It influences the nervous system directly, and experiment may develop a valuable use for it. It is not in the market, and we will therefore have to depend upon those who can procure it green, to determine its properties. It has been employed in epilepsy, in diseases showing epileptiform movements of the muscles, in chorea, and in rheumatism with unpleasant muscular contraction. It may also be given (in small dose) in diseases of the brain, the eyes being dull and the pupils dilated. Employed in the form named, it will give satisfaction and well repay its preparation. A teaspoonful added to four tablespoonfuls of hot water and sweetened, may be given freely, and is better than a tea of the dried herb. Unzicker, of this city, recommends the preparation of a tincture from the green plant, and its use as a sedative and in the treatment of diseases of the respiratory apparatus of children. We value the local use of tobacco as a fomentation in cases of strangulated hernia, in some acute local inflammations, and in pseudo- membranous croup when the danger is imminent. It will also prove the best application to wounds and injuries where there are symptoms of tetanus. In tetanus the alkaloid, Nicotine, has been employed with marked success, and it is probably our most certain remedy. It is given in doses of half to one drop, or if not tolerated by the stomach, it may be used by hypodermic injection. If the alkaloid can not be procured, an infusion may be used by mouth, by injection, or if not retained in sufficient quantity in these ways, it may be given by hypodermic injection. The preparation advised is the “Aqua Nicotianæ Tabacum Spirituosæ Rademacheri,” for which a formula is given. This preparation is recommended highly in affections of the brain accompanying fever, in rheumatismus acutus fixus et vagus, in other affections of the brain and spinal marrow, in cholera morbus, and in cholera Asiatica. To prepare it: Take of choice fresh green leaves of Nicotianæ Tabacum eight pounds, and cut them finely. The leaves are to be cut and the distillation effected immediately after they are pulled, with great care that there shall be no over-heating of the liquid, as, if the liquor be over heated it will have a very disagreeable odor of tobacco, which it does not have when the water is properly prepared. The great majority of cases treated with this mixture recovered immediately from the attack. In those cases where the attack was followed with a typhoid condition, he gave: ℞ Tinct. There are certain conditions of disease in which Nitric Acid is a very valuable remedy, and if it is possible to tell when it is indicated it will prove one of the most valuable of our specifies. There is a certain condition of stomach, in which there is irritability with enfeebled function, in which Nitric Acid is the remedy. And there is a lesion of digestion and blood-making other than the derangement of the stomach named, in which Nitric Acid is a direct remedy. There is also added to this, or separate from it in some cases, an impaired nutrition as well as a slow and imperfect retrograde metamorphosis of tissue and failure of excretion, in which Nitric Acid will prove a direct remedy. Freeman informs me that he has employed it for some time in a class of stubborn cases, presenting some of these features, with most marked success. His cases have embraced those of enfeebled digestion and blood making, and enfeebled and depraved nutrition; taking some cases of scrofula, bad blood, and even phthisis. The first employs them haphazard, in groups, singly or combined, simply because they have been used in diseases covered by a name. The second is a better form of empiricism, and employs them one after another, in their supposed order of goodness, until some one hits the case in hand. The third generalizes the symptoms, and determines the quality of the lesion, and for this prescribes with some directness. The fourth tries to determine the principal lesion - basic lesion we have called it - by some positive signs or symptoms, and prescribes for this.
Pharmacology 415 Abbreviations This section introduces endocrine-related abbreviations and their meanings 500 mg methocarbamol visa spasms esophagus problems. Complete each activity and review your answers to evaluate your understanding of the chapter discount methocarbamol on line spasms jaw muscles. Learning Activity 13-1 Identifying Endocrine Structures Label the following illustration using the terms listed below order methocarbamol on line quad spasms. Enhance your study and reinforcement of word elements with the power of Davis Plus. We recommend you complete the flash-card activity before completing activity 13–2 below. Learning Activities 417 Learning Activity 13-2 Building Medical Words Use glyc/o (sugar) to build words that mean: 1. Addison disease glycosuria myxedema cretinism hirsutism pheochromocytoma Cushing syndrome hyperkalemia type 1 diabetes diuresis hyponatremia type 2 diabetes exophthalmic goiter insulin virile 1. Complete the ter- minology and analysis sections for each activity to help you recognize and understand terms related to the endocrine system. Medical Record Activity 13-1 Consultation Note: Hyperparathyroidism Terminology Terms listed below come from Consultation Note: Hyperparathyroidism that follows. Use a medical dictionary such as Taber’s Cyclopedic Medical Dictionary, the appendices of this book, or other resources to define each term. Then review the pronunciations for each term and practice by reading the medical record aloud. Surgery evidently has been recommended, but there is confusion as to how urgent this is. She has a 13-year history of type 1 diabetes mellitus, a history of shoulder pain, osteoarthritis of the spine, and peripheral vascular disease with claudication. Her first knowledge of parathyroid disease was about 3 years ago when laboratory findings revealed an elevated calcium level. She was further evaluated by an endocrinologist in the Lake Tahoe area, who determined that she also had hypercalciuria, although there is nothing to sug- gest a history of kidney stones. If the patient smoked 548 packs of cigarettes per year, how many packs did she smoke in an average day? Use a medical dictionary such as Taber’s Cyclopedic Medical Dictionary, the appendices of this book, or other resources to define each term. Then review the pronunciations for each term and practice by reading the medical record aloud. S: This 200-pound patient was admitted to the hospital because of a 10-day histo- ry of polyuria, polydipsia, and polyphagia. She has been very nervous, irritable, and very sensitive emotionally and cries easily. During this period, she has had headaches and has become very sleepy and tired after eating. Family history is significant in that both parents and two sisters have type 1 diabetes. Cellular Structure of the Nervous System • Describe the functional relationship between the Neurons nervous system and other body systems. Neuroglia • Recognize, pronounce, spell, and build words related Nervous System Divisions to the nervous system. Central Nervous System Peripheral Nervous System • Describe pathological conditions, diagnostic and Connecting Body Systems–Nervous System therapeutic procedures, and other terms related to Medical Word Elements the nervous system. Pathology • Explain pharmacology related to the treatment of Radiculopathy nervous disorders. Cerebrovascular Disease • Demonstrate your knowledge of this chapter by Seizure Disorders completing the learning and medical record Parkinson Disease activities. It senses physical and chemical changes in Despite its complexity, the nervous system is com- the internal and external environments, processes posed of only two principal types of cells: neurons them, and then responds to maintain homeostasis. Neurons are cells that transmit Voluntary activities, such as walking and talking, impulses. They are commonly identified by the and involuntary activities, such as digestion and direction the impulse travels as afferent when the circulation, are coordinated, regulated, and inte- direction is toward the brain or spinal cord or effer- grated by the nervous system. The entire neural ent when the direction is away from the brain or network of the body relies on the transmission spinal cord. Nervous impulses are elec- rons and bind them to other neurons or other tis- trochemical stimuli that travel from cell to cell as sues of the body. Although they do not transmit they send information from one area of the body impulses, they provide a variety activities essential to another. Along with almost instantaneous, thus providing an immedi- neurons, neuroglia contitute the nervous tissue of ate response to change. Anatomy and Physiology Key Terms This section introduces important nervous system terms and their definitions. Axons are long, The three major structures of the neuron are the single projections ranging from a few millimeters cell body, axon, and dendrites. Axons transmit The (1) cell body is the enlarged structure of the impulses to dendrites of other neurons as well as neuron that contains the (2) nucleus of the cell and muscles and glands. Its branching cytoplasmic pro- Axons in the peripheral nervous system and the jections are (3) dendrites that carry impulses to the central nervous system possess a white, lipoid cov- cell body and (4) axons that carry impulses from ering called (5) myelin sheath. Dendrites resemble tiny branches on as an electrical insulator that reduces the possibility (3) Dendrites (1) Cell body (6) Schwann cell A. Schwann cell nucleus (2) Nucleus (7) Neurilemma (4) Axon (4) Axon (5) Myelin sheath (8) Node of Ranvier (10) Axon terminal (10) Axon terminal Mitochondrion Synaptic bulb (11) Neurotransmitter (9) Synapse Dendrite of receiving neuron B. The neurilemma When sufficient receptor sites are occupied, it sig- does not disintegrate after an axon has been crushed nals an acceptance “message” and the impulse pass- or severed, as does the axon and myelin sheath, but es to the receiving neuron. This intact sheath provides a pathway immediately inactivates the neurotransmitter, and for possible neuron regeneration after injury. The myelin sheath covering the axons in the cen- tral nervous system is formed by oligodendrocytes Neuroglia rather than Schwann cells. Oligodendrocytes do not The term neuroglia literally means nerve glue produce neurilemma, thus injury or damage to neu- because these cells were originally believed to serve rons located in the central nervous system is irrepara- only one function: to bind neurons to each other ble. They are now known to segments of myelin sheath are called (8) nodes of supply nutrients and oxygen to neurons and assist Ranvier. They also play an impulses down the axon because an impulse jumps important role when the nervous system suffers across the nodes at a faster rate than it is able to trav- injury or infection. They provide three-dimensional Impulses must travel from the (10) axon terminal mechanical support for neurons and form tight of one neuron to the dendrite of the next neuron or sheaths around the capillaries of the brain. Anatomy and Physiology 429 sheaths provide an obstruction, called the blood- of the brain and spinal cord. The brain is protect- brain barrier, that keeps large molecular substances ed by the bony skull and the spinal cord is protect- from entering the delicate tissue of the brain. Researchers must take the the body, the brain is highly complex in structure blood-brain barrier into consideration when and function. Microglia, the smallest of • cerebellum the neuroglia, possess phagocytic properties and • diencephalon may become very active during times of infection. Ependyma are ciliated cells that line fluid-filled cavities of the central nervous system, especially Cerebrum the ventricles of the brain.
And most people have shed a tear or two watching a sad movie or a news story about a poignant tragedy methocarbamol 500mg sale spasms pelvic floor. But when sadness ﬁlls most of your days or worries saturate your mind buy methocarbamol 500 mg spasms calf, that’s not so normal buy methocarbamol in united states online muscle relaxant medications back pain. Anxiety and depression can affect how you think, behave, feel, and relate to others. The discussion and quizzes in this chapter help you ﬁgure out how depression and anxiety affect your life. Don’t freak out if the quizzes in this chapter reveal that you have a few symptoms of anxiety or depression. If your symptoms are numerous and severe or your life seems out of control, you should consult your primary care physician or a mental health professional. These quizzes aren’t meant to replace trained mental health professionals — they’re the only people who can really diagnose your problem. Dwelling on Dismal and Worried Thoughts If you were able to listen in on the thoughts that reverberate through a depressed person’s head, you might hear “I’m a failure,” “My future looks bleak,” “Things just keep on getting worse,” or “I regret so many things in my life. The very darkest thoughts usually lead to depression, whereas anxiety usually stems from thoughts about being judged or hurt. Take the quiz in Worksheet 1-1 to determine if your thoughts reﬂect a problem with anxiety or depression. Although these thoughts can occur to someone who’s either depressed or anxious (or both), the odd-numbered items are most indicative of depression, and the even-numbered items reﬂect anxious thinking. However, the more items you endorse, the more you have cause for concern; speciﬁcally, if you check more than eight or ten items, you should think seriously about addressing your condition. At the same time, if you very strongly believe in any of these items, you just may have too much anxiety or depression. If you have any thoughts of suicide or utter hopelessness, you should consult your primary care physician or a mental health professional immediately. Chapter 1: Sorting Out Signs of Anxiety and Depression 11 Walking in Quicksand: Apprehensive and Blue Behavior If you were to follow a depressed or anxious person around, you might see some behavioral signs of their emotional turmoil. That’s because depression and anxiety on the inside affect what people do on the outside. For example, a depressed person may look tired, move slowly, or withdraw from friends and family; an anxious person may avoid socializing or have a trembling voice. Take the quiz in Worksheet 1-2 to see if your behavior indicates a problem with anxiety and/or depression. I feel compelled to repeat actions (such as hand washing, checking locks, arrang- ing things in a certain way, and so on). Even-numbered items are most consistent with anxiety, and odd-numbered items largely indicate depression. And, of course, like many people, you may have symptoms of both types of problems. In fact, some people primar- ily suffer from changes in appetite, sleep, energy, or pain while reporting few problematic thoughts or behaviors. These symptoms directly affect your body, but they’re not as easily observed by other people as the behavioral signs covered in the preceding section. Part I: Analyzing Angst and Preparing a Plan 12 Take The Sad, Stressed Sensations Quiz in Worksheet 1-3 to see if your body is trying to tell you something about your emotional state. The symptoms in this quiz can also result from various physical illnesses, drugs in your medicine cabinet, or even your three-cup coffee ﬁx in the morning. Be sure to consult your primary care physician if you’re experiencing any of the symptoms in The Sad, Stressed Sensations Quiz. It’s always a good idea to have a checkup once a year and more frequently if you experience noticeable changes in your body. Although physical sensations overlap in anxiety and depression, even-numbered items in the quiz above are most consistent with anxiety, and the odd-numbered items usually plague those with depression. Reflecting upon Relationships When you’re feeling down or distressed for any length of time, odds are that your relation- ships with those around you will take a hit. Although you may think that your depression or anxiety affects only you, it impacts your friends, family, lovers, co-workers, and acquaintances. Take the quiz in Worksheet 1-4 to see if your emotions are causing trouble with your rela- tionships. Chapter 1: Sorting Out Signs of Anxiety and Depression 13 Worksheet 1-4 The Conﬂicted Connections Quiz ❏ 1. You guessed it; there’s no cutoff score here to tell you deﬁnitively whether or not you’re anxious or depressed. But the more items you check off, the more your relationships are suffering from your anxiety, depression, or both. Odd-numbered items usually indicate prob- lems with depression, and even-numbered items particularly accompany anxious feelings. You may feel somewhat anxious meeting new people and may be uncomfortable in the spotlight — these feelings aren’t necessarily any- thing to be concerned about. However, such issues become problematic when you ﬁnd yourself avoiding social activities or meeting new people because of your shyness. Plotting Your Personal Problems Profile The Personal Problems Proﬁle provides you with an overview of your problematic symp- toms. One good thing about this proﬁle is that you can track how these symptoms change as you progress through the rest of this book. Tyler, a middle-aged engineer, doesn’t consider himself depressed or plagued with any emotional problems. But when he sees his primary care doctor, Tyler complains of fatigue, recent weight gain, and a noticeable loss in his sex drive. Filling out his Personal Problems Proﬁle helps Tyler see that he has a depression that he wasn’t even consciously aware of. It’s also making me withdraw from my girlfriend, which I can see from my loss of sex drive and lack of desire to be with her. Of course, you can skip a few exercises, but the more you do, the sooner you’ll start feeling better. Writing helps you remember, clariﬁes your thinking, and increases focus and reﬂection. Look back at the quizzes earlier in this chapter and underline the most problematic thoughts, feelings, behaviors, and relationship issues for you. Then choose up to ten of the most signiﬁcant items that you’ve underlined and write them in the My Personal Problems Proﬁle space that’s provided. Chapter 1: Sorting Out Signs of Anxiety and Depression 15 In addition, put an A by the symptoms that are most indicative of anxiety (even-numbered items in the preceding quizzes) and a D by symptoms that are most consistent with depres- sion (odd-numbered items). And do they seem to mostly affect your thoughts, feelings, behaviors, or relationships?
Since patients’ presentations can be confusing buy generic methocarbamol canada muscle relaxant with least side effects, it is necessary for the physician to develop a systematic evaluation of a patient discount 500 mg methocarbamol fast delivery muscle relaxer jokes. This sys- tematic organized approach cheap methocarbamol 500mg line spasms movie 1983, in fact, forms the essence of the surgical approach. As a surgical resident frequently called to the emergency room or clinic to evaluate a patient with a “surgical” problem, always approach the patient with the following questions in mind: (1) Does the patient need to be operated on? If the answer is no, then the problem is not sur- gical and appropriate medical therapy or consultation can be set up. This leads to the next question: (2) Does the patient need to be admitted to the hospital? If the answer is yes, then the appropriate therapy needs to be started (intravenous ﬂuid, antibiotics, standard preoperative testing) (See Algorithm 1. History and Physical Examination The foundation of both medicine and surgery begins with a thorough history and physical examination. We have become dependent on myriad diagnostic studies that, while at times helpful, are sometimes unnecessary, expensive, overutilized, time-consuming, and, occasionally, dangerous. Perioperative Care of the Surgery Patient 5 History and Physical Exam Nonsurgical Problem Surgical Problem Needs hospital admit Does not need hospital admit Appropriate medical referral Needs emergent Needs nonemergent Outpatient— surgery surgery referred to surgeon for workup Minimal diagnostic Tests and workup O. While speciﬁcs of the history and physical exam differ depending on the speciﬁc complaint of the patient and are discussed in greater detail in the ensuing chapters, there are a few constants to keep in mind. As simple and as seemingly easy as this is to do, it is something that all physi- cians, on occasion, fail to do. It can be time-consuming, since patients do not always clearly and concisely articulate their problem. Based on the chief complaint or complaints, the physician then can ask more directed questions to illuminate the problem further. Very often, the physician needs to act like a good newspaper reporter, concisely obtaining the What, Where, When, and How of a problem: What is the problem? Another critically important component of the patients’ history includes a listing of their past medical history, usually starting with whether or not they have ever experienced earlier episodes of their current problem. If they have, then a description of the type and success of the therapy may be helpful. One should inquire, in a systematic manner, about any history of major medical illnesses. The patient’s past medical history in the case presented at the beginning of this chapter is critically important. This certainly will give the examiner a clearer understanding of what the patient does and what sort of familial or social support the patient may have. Always inquire, in as nonjudgmental manner as pos- sible, about social habits such as smoking, alcohol intake, illegal drug 6 R. As delicate and uncomfortable as these ques- tions may be to both the patient and examiner, the answers are clini- cally and at times critically important. A thorough listing, including dosages, of medications is necessary and frequently provides insight into the patient’s underlying medical conditions. Inclusion of any adverse reactions or allergies to medications is of obvious import. This so-called “eyeball” test, while difﬁcult to scientiﬁcally validate, can be helpful, particularly when the patient’s presenting problem requires urgent or emergent surgical intervention. This makes intuitive sense, and, if one performs the examination in the same order each time, the likelihood of missing an important physical ﬁnding decreases. Avoid the tendency to examine ﬁrst, and sometimes only, the body area for which the patient has a complaint. The speciﬁcs of the physical exam will be dealt with more thoroughly in later chapters. Risk Assessment Cardiac It is estimated that more than 3 million patients with coronary artery disease undergo surgery every year in the United States. The challenge is proper assessment of an individual for coronary artery disease and whether preoperative intervention actu- ally improves the patient’s ﬁnal outcome or merely shifts morbidity and mortality to another procedure or healthcare professional. This is one area where evidence-based medicine has made an attempt to provide healthcare professionals/surgeons with guidelines (Tables 1. One cannot emphasize enough the need to optimize the patient’s underlying cardiac conditions prior to surgery. Congestive heart failure should be controlled, blood pressure optimized, cardiac rhythm stabilized, and medications ﬁne-tuned. Frequently, the surgeon must handle these issues, but a cardiologist or primary care physician can be extremely helpful in achieving these goals. The amount of testing that goes on in the name of cardiac risk assess- ment is staggering. The American College of Cardiology/American Heart Association Guideline Algorithm for Perioperative Cardiovas- cular Evaluation of Noncardiac Surgery provides useful and reason- able recommendations, which, if followed, may avoid unnecessary and expensive studies. Pulmonary In patients with a history of pulmonary disease or for those who will require lung resection surgery, preoperative assessment of pul- monary function is of value. Postoperative respiratory complications are leading causes of postoperative morbidity and mortality, ranking second only to cardiac complications as immediate causes of death. History and physical exam can be helpful in assessing a patient’s risk of pulmonary problems, and, frequently, these are all that are necessary. Perioperative Care of the Surgery Patient 9 normal physical exam and at low risk based on history. Preoperative laboratory testing is generally not predictive of peri- operative pulmonary problems. Studies often conﬁrm what a careful physician already has deciphered from a history and physical exam. If emergent, detailed risk assessment must be deferred to the postoperative period. If so, further testing is generally unnecessary if the patient is stable/asymptomatic. If so, further testing is generally unnecessary if the patient is stable/asymptomatic. Unstable chest pain, decompensated congestive heart failure, symptomatic arrhythmias, and severe valvular heart disease require evaluation and treatment before elective surgery. Does the patient have intermediate clinical predictors of risk, such as prior myocardial infarction, angina pectoris, prior or compensated heart failure, or diabetes? Consideration of the patient’s capacity to function and the level of risk inherent in the proposed surgery can help identify patients who will beneﬁt most from perioperative noninvasive testing. Patients with intermediate risk and good-to-excellent functional capacity can undergo intermediate-risk surgery with very little risk. Consider additional testing for patients with multiple predictors about to undergo higher-risk surgery. Further testing can be performed on patients with poor functional capacity in the absence of clinical predictors of risk, especially if vascular surgery is being planned.
The limited surface area available for absorption often means that a2 penetration enhancer is necessary to ensure: • an effective dose can be delivered from a patch of reasonable size; • the range of transmucosal drug delivery candidates can be extended generic methocarbamol 500mg otc muscle relaxant injection for back pain, for example purchase methocarbamol 500mg mastercard muscle spasms zyprexa, to include poorly absorbed moieties such as therapeutic peptides and proteins discount 500 mg methocarbamol fast delivery spasms under left breastbone. Penetration enhancers are discussed extensively for the transdermal nasal route in Sections 8. Comparatively few penetration enhancers have been tested for buccal absorption enhancement; those which have been investigated include bile salts. In addition, the buccal delivery of insulin in rabbits has been shown to be increased from approximately 3–5% by co-administration of edetate (least effective), sodium dextransulfate, sodium methoxysalicylate, sodium deoxycholate, sodium lauryl sulfate, sodium taurocholate and Brij 35 (most effective); with Brij 35 increasing the bioavailability of insulin to 12% by this route. A smooth surface and good flexibility are prerequisites to prevent mechanical irritation or local discomfort. Adequate evaluation of patient acceptability and compliance of buccal patches should include a clinical examination to observe local tolerance, and the incidence and degree of irritation. Trials should also involve the use of questionnaires, in order to determine a subject assessment of such factors as: • overall comfort; • sensation (taste, movement, swelling); • pain (during wear, on removal); • whether the patch interferes with normal activities (talking, eating, drinking, sleeping). The pill-sized patch uses a new bioadhesive which sticks to the gum, the cheek or the lip without causing irritation and is designed to deliver drugs for short and extended periods (up to 24 h). Cydot technology accommodates both uni-directional and multidirectional release, and both reservoir- and matrix-type systems are possible. However, when administered orally, melatonin shows low and variable bioavailability, presumably due to the extensive first-pass metabolism and/or variable absorption. Its low molecular weight (Mw=232 Da) and the fact that it is largely non-ionized at salivary pH make this drug a suitable candidate for transmucosal delivery. Gingival delivery of melatonin has been investigated using Cydot technology, using a uni-directional, matrix-type patch (Figure 7. Various pharmacokinetic evaluations in humans, including those illustrated in Figure 7. In contrast, transdermal delivery of melatonin results in a significant delay in systemic melatonin levels and a gradual decline in drug delivery after patch removal, possibly due to deposition of melatonin in the skin (Figure 7. Moreover, plasma levels tend to be lower after transdermal delivery and inter-subject variability to be higher. Pharmacokinetic evaluations comparing transmucosal, oral-controlled release and transdermal delivery of melatonin clearly demonstrated that the transmucosal route is the best dosage form to mimic endogenous secretion of this drug (Figure 7. Acceptability and compliance studies have shown that the patch is accepted favorably by patients. They are recommended for use in the post-operative prevention of thromboembolic disorders and are conventionally administered via the subcutaneous route. To maximize transmucosal absorption, the active was incorporated in a Cydot uni-directional reservoir system. Use of a reservoir system allows a high degree of drug loading and also permits absorption enhancers to be included with the drug in the central reservoir compartment. Studies have demonstrated that the patches: • possess prolonged adhesion properties; • are of low irritancy; • have bioavailabilites ranging from 50% to 75%. The TheraTech buccal delivery system comprises a bilayer tablet, with an adhesive layer on one side, and an active layer on the other side, which lies in contact with the cheek mucosa. However, the route is associated with many advantages for drug delivery and there is clearly considerable ongoing research in this area. In the past decade, new and highly sophisticated formulations have been developed; drug delivery using the new types of retentive systems for buccal absorption is a particularly promising area. Some success has also been attained in the transbuccal delivery of peptides and proteins. Thus it can be expected that a more exponential growth phase will develop in the coming years. Name 3 differences between the buccal mucosa and the mucosa of the gastrointestinal tract. What advantages does the buccal route offer for the systemic delivery of peptides? What is the main structural difference between the gingival and the cheek epithelium? Rank the permeability of the gastrointestinal mucosa, the skin and the buccal mucosa in the order lowest to highest. Evolution has provided the mammalian organism with an external covering, the principal function of which is to act as a barrier, specifically to the loss of tissue water. Think about it: the concentration of water inside the human body is 190 on the order of 50 M, while that in the atmosphere is clearly very much less. Thus, there is a strong driving force for water to be lost from the body and, to prevent desiccation, an efficient barrier at the interface is therefore required. The skin, and more specifically skin’s outermost layer, the stratum corneum, provides this shield. Of course, in so doing, the skin also presents a formidable resistance to the absorption, either deliberate or accidental, of chemicals which contact the external surface. Nevertheless, the challenge of transdermal drug delivery has been accepted by pharmaceutical scientists and, over the past 25 years, considerable progress and achievement have been recorded. So, what led to the investigation of the skin as a potential route for systemic drug input in light of the formidable challenges posed by the stratum corneum? First, the skin offers a large (1–2 m ) and very accessible surface for drug2 delivery. Second, transdermal applications, relative to other routes, are quite noninvasive, requiring the simple adhesion of a “patch” much like the application of a Band-Aid. As a result, thirdly, patient compliance is generally very good—that is, in general, people are quite comfortable with the use of a simple-looking patch (no matter how complex the interior machinery). And, fourth, with again a positive aspect for the patient, a transdermal system is easily removed either at the end of an application period, or in the case that continued delivery is contra-indicated—with the exception of intravenous infusions, no other delivery modality offers this advantage. Although transdermal administration is limited at present to relatively few drugs, it has proven to be a considerable commercial success when compared to other “controlled release” technologies. The current worldwide market for transdermal systems is about $2 billion annually. Macroscopically, skin comprises two main layers: the epidermis and the dermis (~0. The dermal-epidermal junction is highly convoluted ensuring a maximal contact area. Other anatomical features of the skin of interest are the appendageal structures: the hair follicles, nails and sweat glands. The keratinocytes comprise the major cellular component (>90%) and are responsible for the evolution of barrier function. The epidermis per se can be divided into five distinct strata which correspond to the consecutive steps of keratinocyte differentiation. The ultimate result of this differentiation process is formation of the functional barrier layer, the stratum corneum (~0.
The left leg is somewhat larger on exam than the right leg buy cheap methocarbamol 500 mg online spasms under ribs, but cost of methocarbamol muscle relaxant gel india, other than a sensation of “fullness cheap methocarbamol online master card muscle relaxant gel uk,” the patient denies any discomfort. History and Physical Examination As in all things that pertain to patient care, the history and the phys- ical exam are the cornerstones to getting at the etiology of the swollen leg. Giving the patient adequate time to explain the problem is critical and frequently can save valuable time and useless diagnostic studies. Of critical importance, however, is obtaining a sense of the immediacy of the problem. Once the timing of the swelling is ascertained, then a relatively simple thought process can be followed. The physical exam is critically important in the evaluation of the swollen leg, and, while not 100% accurate, it helps narrow the differ- ential diagnosis of the problem. The chronic nature of the situa- tion may alter somewhat the aggressiveness of the workup. Things to focus on include any obvious trauma, evidence of infection, or bony abnormality. Ultimately, one must decide if the swelling is systemic in nature, due to a vascular (venous) abnormality, or secondary to lymphedema. The unilateral nature of the swelling described by the patient in the case presented leads one to think that the etiology of the swelling is not systemic in nature. Systemic conditions like obesity or congestive heart failure generally lead to bilateral lower extremity swelling. Head and neck evaluation, with particular attention to the presence or absence of jugular venous distention, is important. Documentation of any masses may be telling when considering the etiology of venous or thromboembolic disease. The chest exam is important with regard to the presence or absence of rales or rhonchi. The presence of abdominal masses, which may be a source of venous or lymphatic obstruction, must be noted. Abdominal masses also may be indicative of an intraabdominal tumor and therefore a nidus for a hypercoaguable state. Checking the patient’s stool for occult blood also is important as an indicator of a possible neoplasm but also in planning therapy, particularly if anticoagulation is indicated. Obesity, a frequent cause of a “swollen” extremity, frequently is overlooked or disregarded as an etiology. Unilateral swelling, as in the case patient, certainly could be due to an intrabdominal mass or deep venous thrombosis. This implies that the swelling is bilateral in nature or that the “swelling” may be due to some other process. The nature of the swelling, the presence or absence of edema, the nature of the edema, the evidence of trauma, cellulitis, the nature and texture of the skin, the presence of ulcerations, and the locations and nature of the ulcerations all are important to document. The presence of pain, the location of pain, and the presence or absence of varicosi- 514 R. Incidence rate of clinically recognized deep vein thrombosis and/or pulmonary embolism per 100,000 population. The increase in rates for both male and female patients is well approximated by an exponential func- tion of age. A population-based perspective of the hospital incidence and case- fatality rates of deep venous thrombosis and pulmonary embolus. While arterial insufﬁciency rarely presents as swelling, the presence of peripheral pulses is important to document. Acute versus Chronic When the history obtained from the patient indicates that the swelling has occurred acutely, the differential veers toward disease processes that need to be diagnosed quickly and treated aggressively. Rudolf Virchow, a 19th century pathologist, surmised that three conditions tended toward thrombosis: intimal injury, stasis of blood ﬂow, and a hypercoaguable state. These observations have stood the test of time and are as true today as they were in Virchow’s time. A population-based perspective of the hospital incidence and case-fatality rates of deep venous thrombosis and pulmonary embolus. If the patient had a normal extremity and suddenly developed a painful swollen extremity, the diagnosis is straightforward. Unfor- tunately, patients frequently present in a less than straightforward manner. In those cases, it is best to err on the side of caution and treat the patient as if he/she has an acute problem. Number (%) of Injury pattern Number pulmonary emboli Odds ratio Head + spinal cord injury 195 3 (1. Risk factors associated with pulmonary embolism despite routine prophylaxis: implications for improved pro- tection. Venography or phlebography involves the cannulation of a peripheral hand or foot vein, application of a tourniquet to occlude the superﬁcial venous system and to direct blood ﬂow into the deep system, and injection of radiopaque contrast medium. The procedure is painful for the patient, technically difﬁcult to perform, and not always easy to interpret. The study allows determination of vein compressibility as well as ﬂow characteristics. Veins that are incompressible with ﬁrm pressure applied by the ultrasound probe are considered thrombosed. Flow can be increased by distal compression and decreased by increasing intraabdominal pressure. There are no strict criteria to achieve the differentiation; however, there are some “soft” signs that can be helpful. If the thrombus is acute, it generally is not echogenic on duplex and is relatively soft on compression. A randomized comparison of the clinical utility of real time compression ultra-sonography versus impedance plethysmography in the diagnosis of deep-vein thrombosis in symptomatic outpatiens. A new rapid assay currently is available to detect D-dimer, which is a speciﬁc derivative of cross-linked ﬁbrin that is released when ﬁbrin is lysed by plasmin. Its utility is questionable, however, if duplex ultrasonography is available readily. It is performed by placing a catheter into the pulmonary artery, usually via a femoral vein puncture, and injecting contrast into both lungs. Pulmonary embolism as a cause of death; the changing mortality in hospitalized patients. The study is invasive and has a signiﬁcant list of complications, includ- ing cardiac arrthymias, contrast reaction, and bleeding. Perfusion scans involve the injection of radiolabeled colloid into a peripheral vein, followed by scanning of the lung in several positions.
Which of the following is/are an example(s) of non-biodegradable matrix-type implant? What is the principle that has been utilized in the development of the Alzet and the Duros implant pumps in which a drug solution or suspension is confined in a semi-permeable membrane that allows only water molecules to move through it? The release rate (dM/dt) of a drug from an osmotic pump can be described as C (dV/dt)d where Cd is the drug solubility in its reservoir compartment purchase methocarbamol with american express muscle relaxant orange pill. The effective surface area methocarbamol 500 mg amex quinine spasms, permeability coefficient purchase methocarbamol with paypal spasms in upper abdomen, thickness, and osmotic reflection coefficient of the semi-permeable membrane used for the pump are 3. If we change the reservoir medium and osmotic agent to increase C ofd the drug from 100 to 300 mg/ml and to increase ∆π from 100 to 300 atm, by how much will the release rate of the drug increase? The most important routes of injection of these sterile products are intramuscular (im), intravenous (iv) and subcutaneous (sc). The detailed description of 106 these areas of pharmaceutics lie outside the remit of this text and the reader is refered to information provided in the further reading section of Chapter 1. This chapter focuses on advanced drug delivery and targeting systems administered via the parenteral route and serves to provide the reader with a basic understanding of the principal approaches to drug targeting. An intravenously administered drug is subject to a number of pharmacokinetic processes in vivo which can decrease the drugs therapeutic index, including: • Distribution: intravenously administered drugs distribute throughout the body and reach non-target organs and tissues, resulting in drug wastage and (possibly) toxic side-effects. As a result of these processes, only a small fraction of the drug will reach the target tissue. Moreover, it may be cleared rapidly from this site and, therefore, not be available long enough to induce the desired effect. Reaching the target cell is often not the ultimate goal; in many cases the drug has to enter the target cell to reach an intracellular target site. Again, as discussed in Chapter 1, many drugs do not possess the required physicochemical properties to enter target cells; they may be too hydrophilic, too large or not transportable by the available active-transport systems. For example, the drug may work outside the cell, thus cell penetration may not be necessary. In this chapter there are also examples mentioned of passive targeting approaches (see below), where the drug does not have to be specifically targeted to the cell or tissue. The parenteral route of administration is associated with several major disadvantages (see Section 3. Parenteral administration is invasive and may require the intervention of trained medical professionals. Strict regulations for parenteral formulations govern their use and generally dictate that they are as simple as possible and the inclusion of excipients in the formulation is kept to an absolute minimum. Such drugs include those used in treatment of cancer, as well as life-threatening microbial, viral and fungal diseases. If prolonged release of a drug via the parenteral route is required, subcutaneous or intramuscular injection of a controlled-release system is the first option to consider. For example, galactose receptors are present on liver parenchymal cells, thus the inclusion of galactose residues on a drug carrier can target the carrier to these cells. A number of different target-specific recognition moieties are available and discussed further below. However, an important point to note here is that target-specific recognition moieties are not the idealized “magic bullets”, capable of selectively directing the drug to the appropriate target and ignoring all other non-target sites. Although the homing device can increase the specificity of the drug for its target site, the process must rely on the (random) encounter of the homing device with its appropriate receptor, during its circulation lifetime. The carrier systems that are presently on the market or under development can be classified in two groups on the basis of size: • soluble macromolecular carriers; • particulate carrier systems. This classification is sometimes rather arbitrary, as some soluble carriers are large enough to enter the colloidal size range. Another useful distinction is that with macromolecular carrier systems the drug is covalently attached to the carrier and has to be released through a chemical reaction. In contrast, with colloidal carriers, the drug is generally physically associated and does not need a chemical reaction to be Table 5. Soluble carriers include antibodies and soluble synthetic polymers such as poly(hydroxypropyl methacrylate), poly(lysine), poly(aspartic acid), poly(vinylpyrrolidone), poly(N-vinyl-2-pyrrolidone-co- vinylamide) and poly (styrene co-maleic acid/anhydride). Many particulate carriers have been designed for drug delivery and targeting purposes for intravenous administration (Table 5. They usually share three characteristics: • Their size range: minimum size is approximately 0. A full appreciation of the respective advantages and disadvantages of soluble and particulate carriers cannot be gained without first considering the anatomical, physiological and pathological considerations described below. The endothelium is continuous with tight junctions between adjacent endothelial cells. The endothelium exhibits a series of fenestrae which are sealed by a membranous diaphragm. The subendothelial basement is either absent (liver) or present as a fragmented interrupted structure (spleen, bone marrow) 5. The degree of body-compartmentalization, or in other words, the ability of a macromolecule or particulate to move around, depends on its physicochemical properties, in particular its: • molecular weight/size; • charge; • surface hydrophobicity; • the presence of homing devices for interaction with surface receptors. The smaller the size, the easier a molecule can passively move from one compartment to another. An important question is whether and where the carriers can pass through the endothelial lining of the blood circulation. The endothelial lining is continuous in most parts of the body and the endothelial cells are positioned on a basal membrane. The exact characteristics of this barrier are still under investigation, but it is clear that particulate systems greater than 10 nm cannot pass this barrier through pores. Only in the sinusoidal capillaries of the liver, spleen and bone marrow can “pores” (so-called fenestrae) be found. In the lining of these capillaries the basal membrane is fragmented or even completely missing. This anatomical information has important implications for the rational design of targeted carrier systems. If a therapeutic target is located outside the blood circulation and if normal anatomical conditions exist around the target site, a small-sized macromolecular carrier must be selected, in order to achieve 110 sufficient “escaping tendency” from the blood circulation. Particulate carriers will generally fail to extravasate, simply because there is no possibility for endothelium penetration. In addition to the issue of endothelial permeability, the effect of macrophages in direct contact with the blood circulation (e. Kupffer cells in the liver) on the disposition of carrier systems must be considered. Unless precautions are taken, particulate carrier systems are readily phagocytosed by these macrophages and tend to accumulate in these cells. Particle charge For liposomes, it has been shown that negatively charged vesicles tend to be removed relatively rapidly from the circulation whereas neutral vesicles tend to remain in the circulation for longer periods. Surface hydrophobicity Hydrophobic particles are immediately recognized as “foreign” and are generally rapidly covered by plasma proteins known to function as opsonins, which facilitate phagocytosis. The extent and pattern of opsonin adsorption depends highly on surface characteristics such as charge and hydrophilicity.