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By I. Jose. Central Missouri State University.

She seems anxious and confused buy discount hoodia on line, and she calls her daughter several times a day purchase hoodia 400 mg line, worried that the neighbors buy discount hoodia line, previously good friends, are spying on her. She denies bowel or urinary incontinence, and she has had no trouble with headaches or gait instability. Overall the patient has been very healthy, and she only receives treatment with hydrochlorothiazide for hyperten- sion. On examination, her blood pressure is 116/56 mm Hg,heart rate is 78 bpm,temperature is 98. She is noted to be well developed, but her affect throughout the examination is rather flat. Th e e xt re m it ie s a re wit h o u t e d e m a, cya n o sis, o r clu b b in g. Ne u ro lo g ic examination reveals that the cranial nerves are intact, and the motor and sensory examinations are within normal limits. Next diagnostic step: Assess for d epr ession an d r ever sible cau ses of d ement ia. As in ot her cases of major organ system failure (heart and kidney failures), demen- tia (brain failure) necessitates investigation into treatable or reversible causes before assigning a diagnosis such as Alzheimer disease, which is progressive and incurable, and for which no highly effect ive therapy exist s ( Table 37– 1). The impairment represents a decline from previous level of abilit y, int erferes wit h daily funct ioning and independent living, and is not occur- ring exclusively during the course of delirium. Risk factors are advanced age, posit ive family history, and presence of apolipoprotein E4 allele. To answer the first quest ion, the most import ant invest igat ion is the h ist ory of sympt oms. If t he pat ient has an acut e or subacut e onset of confusion or has a fluc- tuating level of consciousness, the most likely diagnosis is a delirium r esu lt in g from infect ion, int oxicat ion, or adverse medicat ion effect s, or met abolic derangement s such as hyponat remia, hypercalcemia, or hypoglycemia. If cognitive decline occurs with prominent mood disturbance, then one consid- erat ion is depression or pseudodementia. Distinguishing which occurred first is often difficult because many elderly patients with cognitive decline and a declining level of independent funct ion ing suffer from a react ive depression. H ist ory pro- vid ed b y in volved fam ily m em b er s r egar d in g the on set of sym p t om s or h ist or y of prior depression or other psychiatric illness may help establish the diagnosis, and an empiric t rial of ant idepressant s may be considered. If the patient has a history of irregular stepwise decline in functioning, especially if the pat ient h as h ad apparent st roke sympt oms or t ransient isch emic event s or h as a known cardiovascular disease or at rial fibrillat ion, t hen vascular, or multi-infarct, dementia is the most likely diagnosis. T his t ype of vascular dement ia is the second most common cause of dementia in the United States, composin g 10% t o 20% of dementias. This con d it ion is oft en r efer r ed t o as Binswanger disease or subcor t ica l arteriosclerotic leukoencephalopathy. Other common causes of dementia include cognitive decline as a result of long- st anding alcoholism or dementia associated with parkinsonism. Bot h of t h ese underlying conditions may be discovered by the appropriate history or physical findings (eg, rest ing tremor with bradykinesia and masked faces of parkinsonism). Other dementia syndromes include behavioral changes with intact navigation in frontotemportal dementia, or r apid pr ogression of dement ia wit h muscu lar r igidit y and myoclonus in Creutzfeld-Jakob disease. A variety of primary central ner- vo u s syst em ( C N S ) d iseases can lead t o d em en t ia o r o t h er co gn it ive d ysfu n ct io n, including H unt ington disease, mult iple sclerosis, neoplast ic diseases such as primary or metastatic brain tumors (although they are much more likely to produce seizures or focal deficits rather than dementia), or leptomeningeal spread of various cancers. Normal pressure hydrocephalus is a potentially reversible form of dementia in wh ich the cerebral vent ricles slowly enlarge as a result of disturbances t o cerebral spinal fluid resorpt ion. The classic triad is dementia, gait disturbance, and urinary or bowel incontinence. Relief of h ydr oceph alu s t h rough placement of a vent r icu- loperit oneal shunt may reverse the cognit ive decline. D escript ions of the primary neurologic diseases associated with cognitive dysfunction are listed in Table 37– 2. Once likely diagnoses have been established by history and physical examina- tion, investigation should be undertaken to look for treatable or reversible causes. The choice of laboratory or imaging tests is not straightforward because of the numerous, yet uncommon, causes of reversible dementia, so testing is generally low yield. Test s that may be considered for the evaluat ion of dement ia are list ed in Table 37– 1. The clinical course is characterized by progressive decline of cognitive functions (memory, orientation, attention, and concentration) and the development of psy- ch ological an d beh avioral sympt oms (wan der ing, aggression, an xiet y, depr ession, and psychosis; Table 37– 3). Donepezil, rivastigmine, and galantamine are ch oli n est er a se i n h i bi - tors that are effective in improving co gnitive function and global clinical state. Risperidone reduces psychot ic symptoms and aggression in patient s with dementia. Other issues include wakefulness, nightwalking and wandering, aggression, incont inence, and depression. T h e Alzh eim er Associat ion is a nat ional organizat ion developed to give support t o family members and can be cont act ed t h r ou gh it s web sit e at www. W hich of the following agents is most likely to help with the cognitive function? H is wife noted that 6 months ago his function deteriorated noticeably, and 2 months ago another level of deterioration was noted. Which of the following is most likely to reveal the etiology of his functional decline? H e has difficulty making it to the bathroom in time and com- plains of feeling as though “he is walking like he was drunk. C or t ical at r o p h y wit h at r o p h y of m ed ial t em p or al st r u ct u r es C. Cholinesterase inhibitors help with the cognitive function in Alzheimer disease and may slow the progression. The stepwise decline in function is typical for multi-infarct dementia, diagnosed by viewing multiple areas of the brain infarct. The classic triad for normal pressure hydrocephalus is dementia, inconti- nence, and gait disturbance; one treatment is shunting the cerebrospinal fluid. Alzheimer disease has no pathognomonic structural imaging criteria, but may include cortical atrophy and mesial temporal atrophy, whereas normal pressure hydrocephalus has enlarged brain ventricles without sig- nificant brain atrophy. She has had a fairly severe headache for the last 3 weeks (she rates it as an 8 on a scale of 1-10). She describes the pain as constant, occasionally throb b ing b ut mostly a dull ache, and localized to the right side of her head. She thinks the pain is worse at night, especially when she lies with that side of her head on the pillow. She has had headaches before, but they were mostly occipital and frontal, which she attributed to “stress,”and they were relieved with acetaminophen. Her medical history is significant for hypertension, which is controlled with hydrochlorothiazide, and “arthritis” of her neck, shoulders, and hips for which she takes ibuprofen when she feels stiff and achy. Her visual acuity is normal, visual fie ld s a re in t a ct, a n d h e r fu n d u sco p ic e xa m in a t io n is sig n ifica n t fo r a rt e rio la r n a r- rowin g b ut n o p ap ille d e m a or h e m orrh ag e. Sh e h as m od e rate te n d e rn e ss ove r the right side of her head but no obvious scalp lesions. Her chest is clear, and her heart rhythm is regular, with normal S and S but an S gallop.

Increased Therapeutic Effects The interaction between sulbactam and ampicillin represents a beneficial potentiative interaction purchase hoodia 400mg with amex. When administered alone buy hoodia canada, ampicillin undergoes rapid inactivation by bacterial enzymes cheap 400mg hoodia overnight delivery. Increased Adverse Effects The interaction between aspirin and warfarin represents a potentially detrimental potentiative interaction. Both aspirin and warfarin suppress formation of blood clots; aspirin does this through antiplatelet activity, and warfarin does this through anticoagulant activity. As a result, if aspirin and warfarin are taken concurrently, the risk for bleeding is significantly increased. Reduction of Effects Interactions that result in reduced drug effects are often termed inhibitory. As with potentiative interactions, inhibitory interactions can be beneficial or detrimental. Conversely, inhibitory interactions that reduce therapeutic effects are detrimental. Reduced Therapeutic Effects The interaction between propranolol and albuterol represents a detrimental inhibitory interaction. Propranolol, a drug for cardiovascular disorders, can act in the lung to block the effects of albuterol. Reduced Adverse Effects The use of naloxone to treat morphine overdose is an excellent example of a beneficial inhibitory interaction. When administered in excessive dosage, morphine can produce coma, profound respiratory depression, and eventual death. Creation of a Unique Response Rarely, the combination of two drugs produces a new response not seen with either agent alone. When alcohol and disulfiram are combined, a host of unpleasant and dangerous responses can result; however, these effects do not occur when disulfiram or alcohol is used alone. Basic Mechanisms of Drug-Drug Interactions Drugs can interact through four basic mechanisms: (1) direct chemical or physical interaction, (2) pharmacokinetic interaction, (3) pharmacodynamic interaction, and (4) combined toxicity. Direct Chemical or Physical Interactions Some drugs, because of their physical or chemical properties, can undergo direct interaction with other drugs. Frequently, the interaction produces a precipitate; however, direct drug interactions may not always leave visible evidence. Because drugs can interact in solution, it is essential to consider and verify drug incompatibilities when ordering medications. Pharmacokinetic Interactions Drug interactions can affect all four of the basic pharmacokinetic processes. That is, when two drugs are taken together, one may alter the absorption, distribution, metabolism, or excretion of the other. Altered Absorption Drug absorption may be enhanced or reduced by drug interactions. There are several mechanisms by which one drug can alter the absorption of another. For example, when epinephrine is injected together with a local anesthetic, the epinephrine causes local vasoconstriction, thereby reducing regional blood flow and delaying absorption of the anesthetic. Altered Distribution There are two principal mechanisms by which one drug can alter the distribution of another: (1) competition for protein binding and (2) alteration of extracellular pH. When two drugs bind to the same site on plasma albumin, coadministration of those drugs produces competition for binding. As a result, binding of one or both agents is reduced, causing plasma levels of free drug to rise. However, because the newly freed drug usually undergoes rapid elimination, the increase in plasma levels of free drug is rarely sustained or significant unless the patient has liver problems that interfere with drug metabolism or has renal problems that interfere with drug excretion. A drug with the ability to change extracellular pH can alter the distribution of other drugs. For example, if a drug were to increase extracellular pH, that drug would increase the ionization of acidic drugs in extracellular fluids (i. As a result, acidic drugs would be drawn from within cells (where the pH was below that of the extracellular fluid) into the extracellular space. The ability of drugs to alter pH and thereby alter the distribution of other drugs can be put to practical use in the management of poisoning. For example, symptoms of aspirin toxicity can be reduced with sodium bicarbonate, a drug that elevates extracellular pH. By increasing the pH outside cells, bicarbonate causes aspirin to move from intracellular sites into the interstitial fluid and plasma, thereby minimizing injury to cells. Altered Metabolism Altered metabolism is one of the most important—and most complex— mechanisms by which drugs interact. Some drugs increase the metabolism of other drugs, and some drugs decrease the metabolism of other drugs. Drugs that increase the metabolism of other drugs do so by inducing synthesis of hepatic drug-metabolizing enzymes. Drugs that decrease the metabolism of other drugs do so by inhibiting those enzymes. When it is essential that an inducing agent is taken with another medicine, dosage of the other medicine may need adjustment. For example, if a woman taking oral contraceptives were to begin taking phenobarbital, induction of drug metabolism by phenobarbital would accelerate metabolism of the contraceptive, thereby lowering its level. If drug metabolism were increased enough, protection against pregnancy would be lost. To maintain contraceptive efficacy, dosage of the contraceptive should be increased. Conversely, when a patient discontinues an inducing agent, dosages of other drugs may need to be lowered. If dosage is not reduced, drug levels may climb dangerously high as rates of hepatic metabolism decline to their baseline (noninduced) values. The interactions of ketoconazole (an antifungal drug) and cyclosporine (an expensive immunosuppressant) provide an interesting case in point. If ketoconazole is combined with cyclosporine, the serum drug level of cyclosporine will rise. Although inhibition of drug metabolism can be beneficial, as a rule inhibition has undesirable results. That is, in most cases, when an inhibitor increases the level of another drug, the outcome is toxicity. Accordingly, when a patient is taking an inhibitor along with his or her other medicines, you should be alert for possible adverse effects. Unfortunately, because the number of possible interactions of this type is large, keeping track is a challenge.

The β2-adreno- produces vasoconstriction and increases vascular resistance ceptor agonists cause smooth muscle relaxation in several and blood pressure purchase cheap hoodia online. These drugs produce bronchodilation and are benef- leads to contraction of the iris dilator muscle and dilation of cial in the treatment of asthma and chronic obstructive the pupil (mydriasis) cheap hoodia line. Phenylephrine is used as a nasal deconges- been introduced to treat asthma generic hoodia 400mg free shipping, including pirbuterol, tant in patients with viral rhinitis, an infection that can be fenoterol, formoterol, arformoterol, levalbuterol, and caused by more than a hundred serotypes of rhinovirus, as salmeterol, known collectively as long-acting β-agonists well as other viruses, and is referred to as the “common cold. The properties and use of these drugs are described Phenylephrine is also used by patients with allergic rhinitis, in Chapter 27. The drug relaxes reduces vascular congestion and mucus secretion so as to the uterus and maintains pregnancy for 24 to 48 hours in open the nasal passages and facilitate breathing. In contrast to the muscarinic receptor women for prevention or prolonged treatment (beyond 48 antagonists used for this purpose (e. The adverse effects of albuterol and other selective β2- Phenylephrine can be administered intravenously to treat adrenoceptor agonists include tachycardia, muscle tremor, forms of hypotension and shock caused by decreased and nervousness caused by activation of β2-adrenoceptors peripheral vascular resistance. These include hypotension in the heart, skeletal muscle, and central nervous system. Some imidazolines are administered by topical ocular or nasal administration, whereas others are administered by Midodrine systemic routes. After systemic administration, the imidazo- Midodrine forms an active metabolite that selectively acti- lines have a duration of action of several hours and are partly vates α1-adrenoceptors in the arteriolar and venous circula- metabolized and excreted in the urine. The drug is clinical use, the imidazolines can be divided into three rapidly absorbed after oral administration and is used to groups. The frst group consists of oxymetazoline and treat postural (orthostatic) hypotension in persons who are similar drugs that activate α1-adrenoceptors and cause vaso- considerably impaired by this condition (e. Oxymetazoline is available as a nasal treat hypotension caused by infections in infants or induced spray and ophthalmic solution without prescription. Because by psychotropic agents, and hypotension in persons under- it may increase blood pressure, it should not be used by going renal dialysis. The primary adverse effect of midodrine persons with hypertension or heart disease without consult- is hypertension when persons are supine. Topical nasal decongestants should never be used for more than 3 to 5 days, to avoid Albuterol, Pirbuterol, Terbutaline, rebound congestion that results from excessive vasocon- and Related Drugs striction and tissue ischemia. Albuterol (known as decongestants can also cause central nervous system and salbutamol in many countries), pirbuterol, and terbutaline are cardiovascular depression if they are absorbed into the sys- examples of selective β2-adrenoceptor agonists that can be temic circulation and distributed to the brain. After topical ocular system effects of cocaine are discussed further in Chapter administration, these agents activate ocular α2-adrenoceptors 21. Cocaine also blocks the reuptake of dopamine, leading in the ciliary body and thereby reduce aqueous humor secre- to its rewarding effects and drug abuse, as discussed in tion (see Box 6-1). Activation of these Ephedrine and Pseudoephedrine receptors leads to a reduction in sympathetic outfow from Pharmacokinetics the vasomotor center in the medulla, and clonidine is used Ephedrine is a naturally occurring compound obtained from to treat hypertension (see Chapter 10). Dexmedetomidine is indicated for ephedrine, an isomer of ephedrine, has been used as a nasal sedation of intubated and mechanically ventilated patients decongestant in the treatment of colds and allergies. It has also been availability of pseudoephedrine is now restricted in many used as an adjunct to anesthesia during surgical procedures states because the drug has been used to illegally make because of its ability to facilitate sedation and analgesia and methamphetamine for illicit sale and use. Via the activation of Amphetamine and Tyramine α1-adrenoceptors, these drugs produce vasoconstriction, Amphetamine and related compounds have high lipid solu- making them useful as nasal decongestants in the treatment bility and increase synaptic concentrations of norepineph- of viral and allergic rhinitis. By activating β-adrenoceptors, rine in the central and peripheral nervous systems by these drugs produce bronchodilation, but selective β2- mechanisms previously described, causing vasoconstriction, adrenoceptor agonists are more safe and effective for this cardiac stimulation, increased blood pressure, and central purpose. The central nervous system The adverse effects of ephedrine and pseudoephedrine effects are discussed in greater detail in Chapters 22 and 25. Urinary Tyramine is a naturally occurring amine found in a retention may result from α1-adrenoceptor activation and number of foods, including bananas. Tyramine is not available for Because of the risks of toxicity and limited evidence of clinical use. These products typically contain combinations of Cocaine, a naturally occurring alkaloid, acts as a local anes- antihistamines, cough suppressants, and decongestants, such thetic and also stimulates the sympathetic nervous system as phenylephrine and pseudoephedrine. The vasoconstrictive effect can cause ischemia and necrosis of the nasal mucosa • Activation of α1-adrenoceptors mediates smooth muscle in people who abuse cocaine. The sympathomimetic effects contraction, leading to vasoconstriction, dilation of the Chapter 8 y Adrenoceptor Agonists 77 pupils, and contraction of the bladder sphincter 4. She receives oxygen and administration of an norepinephrine from sympathetic neurons, decreases adrenoceptor agonist. Which action would lead to the secretion of aqueous humor, and decreases the bronchodilation? These drugs are rapidly metabolized, must be administered parenterally, and are used primarily to treat cardiac disorders and various types of shock. Answers And explAnAtions • In addition to activating adrenoceptors, dopamine activates D1 receptors and thereby increases renal 1. Phenylephrine increases systemic vascular resistance or counteracts pos- activates α-adrenoceptors and causes vasoconstric- tural hypotension. Adrenoceptor agonists such as apraclonidine are used for short-term control of intraocular pressure after cataract surgery. Which drug would be most benefcial to this muscle and prevent bronchospasm in persons with patient? These drugs also activate β-adrenoceptors in the (A) dobutamine heart and increase heart rate, but do not typically cause (B) albuterol low blood pressure, blurred vision, sedation, or muscle (C) midodrine weakness. The preferred (E) isoproterenol treatment for severe hypersensitivity reactions (anaphy- 2. Which mechanism would most by activation of β2-adrenoceptors in bronchial smooth likely lead to the desired effect? A child with asthma is being treated with an adrenocep- (E) causes muscle relaxation, but this action is not invoked tor agonist to prevent bronchospasm. Phenoxybenzamine is a noncompetitive • Alfuzosin (Uroxatral) antagonist, and phentolamine is a competitive antagonist. Phenoxy- Nonselective β-Blockers benzamine is administered orally and undergoes nonenzy- • Propranolol (Inderal) matic chemical transformation to an active metabolite that • Timolol (Timoptic) forms a long-lasting covalent bond with α-adrenoceptors, b resulting in noncompetitive receptor blockade (Fig. Phenoxybenzamine decreases α- and β-Adrenoceptor Antagonists vascular resistance and lowers both supine and standing • Carvedilol (Coreg) blood pressure. As shown in Table 9-1, phenoxybenzamine • Labetalol (Trandate) is used to treat hypertensive episodes in patients with pheochromocytoma, which is a tumor of the adrenal aAlso prazosin (Minipress), terazosin (Hytrin). In this setting, phenoxybenzamine is used to control hypertension until surgery can be performed to remove the tumor (Box 9-1). Phentolamine is an a number of diseases, including common cardiovascular dis- imidazoline compound that is structurally related to oxym- orders such as hypertension, angina pectoris, and cardiac etazoline and other agents in the imidazoline class of arrhythmias. After intravenous sympatholytic drugs, are used in the management of car- administration, the onset of action is almost immediate, and diovascular diseases and other diseases such as glaucoma, the duration of action is 10 to 15 minutes. The adrenocep- cular or subcutaneous administration, the onset of action tor antagonists are the most important group of sympatho- is 15 to 20 minutes, and the duration is 3 to 4 hours. The sympathetic neuronal blocking drug is metabolized chiefy in the liver before excretion in agents discussed in Chapter 5 also have a sympatholytic the urine. Phentolamine The adrenoceptor antagonists include drugs that block is a competitive adrenoceptor antagonist (see Fig. Their therapeu- that produces vasodilation, decreases peripheral vascular tic effects are almost entirely caused by blockade of α1- and resistance, and decreases blood pressure.

As you can see order hoodia visa, these features are nearly identical to those of the parasympathetic nervous system cheap hoodia 400mg visa. Like the parasympathetic nervous system buy 400 mg hoodia fast delivery, the sympathetic nervous system employs two neurons in the pathways leading from the spinal cord to organs under its control. As with the parasympathetic nervous system, the junctions between those neurons are located in ganglia. Neurons leading from the spinal cord to the sympathetic ganglia are termed preganglionic neurons, and neurons leading from ganglia to effector organs are termed postganglionic neurons. The medulla of the adrenal gland is a feature of the sympathetic nervous system that requires comment. Although not a neuron per se, the adrenal medulla can be looked on as the functional equivalent of a postganglionic neuron of the sympathetic nervous system. As with the parasympathetic nervous system, drugs that affect the sympathetic nervous system have two general sites of action: (1) the synapses between preganglionic and postganglionic neurons (including the adrenal medulla), and (2) the junctions between postganglionic neurons and their effector organs. Somatic Motor System Pharmacologically relevant anatomy of the somatic motor system is depicted in Fig. Note that there is only one neuron in the pathway from the spinal cord to the muscles innervated by somatic motor nerves. Because this pathway contains only one neuron, peripherally acting drugs that affect somatic motor system function have only one site of action: the neuromuscular junction (i. Acetylcholine is the transmitter released by (1) all preganglionic neurons of the parasympathetic nervous system, (2) all preganglionic neurons of the sympathetic nervous system, (3) all postganglionic neurons of the parasympathetic nervous system, (4) all motor neurons to skeletal muscles, and (5) most postganglionic neurons of the sympathetic nervous system that go to sweat glands. Norepinephrine is the transmitter released by practically all postganglionic neurons of the sympathetic nervous system. The only exceptions are the postganglionic sympathetic neurons that go to sweat glands, which employ acetylcholine as their transmitter. Cholinergic receptors are defined as receptors that mediate responses to acetylcholine. These receptors mediate responses at all junctions where acetylcholine is the transmitter. Adrenergic receptors are defined as receptors that mediate responses to epinephrine (adrenaline) and norepinephrine. These receptors mediate responses at all junctions where norepinephrine or epinephrine is the transmitter. Subtypes of Cholinergic and Adrenergic Receptors Not all cholinergic receptors are the same; likewise, not all adrenergic receptors are the same. There are three major subtypes of cholinergic receptors, referred to as 1 nicotinic, nicotinic, and muscarinic. There are four major subtypes ofN M adrenergic receptors, referred to as alpha, alpha, beta, and beta. Although dopamine receptors are classified as adrenergic, these receptors do not respond to epinephrine or norepinephrine. Exploring the Concept of Receptor Subtypes The concept of receptor subtypes is important and potentially confusing. In this section we discuss what a receptor subtype is and why receptor subtypes matter. Receptors that respond to the same transmitter but nonetheless are different from one another would be called receptor subtypes. For example, peripheral receptors that respond to acetylcholine can be found (1) in ganglia of the autonomic nervous system, (2) at neuromuscular junctions, and (3) on organs regulated by the parasympathetic nervous system. However, even though all of these receptors can be activated by acetylcholine, there is clear evidence that the receptors at these three sites are, in fact, different from one another. Hence, although all of these receptors belong to the same major receptor category (cholinergic), they are sufficiently different as to constitute distinct receptor subtypes. Historically, our knowledge of receptor subtypes came from observing responses to drugs. In fact, were it not for drugs, receptor subtypes might never have been discovered. These data summarize the results of an experiment designed to study the effects of a natural transmitter (acetylcholine) and a series of drugs (nicotine, muscarine, d-tubocurarine, and atropine) on two tissues: skeletal muscle and ciliary muscle. In the discussion that follows, we examine the selective responses of these tissues to drugs and see how those responses reveal the existence of receptor subtypes. Because both types of muscle respond to acetylcholine, it is safe to conclude that both muscles have receptors for this substance. Because acetylcholine is the natural transmitter for these receptors, we would classify these receptors as cholinergic. The effects of nicotine on these muscles suggest four possible conclusions: (1) Because skeletal muscle contracts in response to nicotine, we can conclude that skeletal muscle has receptors at which nicotine can act. The conclusions that can be drawn regarding responses to muscarine are exactly parallel to those drawn for nicotine. These conclusions are that (1) ciliary muscle has receptors that respond to muscarine, (2) skeletal muscle may not have receptors for muscarine, (3) muscarine may be acting at the same receptors on ciliary muscle where acetylcholine acts, and (4) the receptors for acetylcholine on ciliary muscle may be different from the receptors for acetylcholine on skeletal muscle. The responses of skeletal muscle and ciliary muscle to nicotine and muscarine suggest, but do not prove, that the cholinergic receptors on these two tissues are different. However, the responses of these two tissues to d-tubocurarine and atropine, both of which are receptor blocking agents, eliminate any doubts as to the presence of cholinergic receptor subtypes. When both types of muscle are pretreated with d-tubocurarine and then exposed to acetylcholine, the response to acetylcholine is blocked in skeletal muscle but not in ciliary muscle. Tubocurarine pretreatment does not reduce the ability of acetylcholine to stimulate ciliary muscle. Conversely, pretreatment with atropine selectively blocks the response to acetylcholine in ciliary muscle—but atropine does nothing to prevent acetylcholine from stimulating receptors on skeletal muscle. Because tubocurarine can selectively block cholinergic receptors in skeletal muscle, whereas atropine can selectively block cholinergic receptors in ciliary muscle, we can conclude with certainty that the receptors for acetylcholine in these two types of muscle must be different. The data just discussed illustrate the essential role of drugs in revealing the presence of receptor subtypes. If acetylcholine were the only probe that we had, all that we would have been able to observe is that both skeletal muscle and ciliary muscle can respond to this agent. This simple observation would provide no basis for suspecting that the receptors for acetylcholine in these two tissues were different. It is only through the use of selectively acting drugs that the presence of receptor subtypes was initially revealed. Today, the technology for identifying receptors and their subtypes is extremely sophisticated—not that studies like the one just discussed are no longer of value. As you can imagine, this allows us to understand receptors in ways that were unthinkable in the past. Drugs achieve their selectivity for receptor subtypes by having structures that are different from those of natural transmitters. The relationship between structure and receptor selectivity is illustrated in Fig. Drawings are used to represent drugs (nicotine and muscarine), receptor subtypes (nicotinic and muscarinic), and acetylcholine (the natural transmitter at nicotinic and muscarinic receptors). From the structures shown, we can easily imagine how acetylcholine is able to interact with both kinds of receptor subtypes, whereas nicotine and muscarine can interact only with the receptor subtypes whose structure is complementary to their own.

The young age of the patient and the relatively small burn wound size (20%) makes this option feasible order cheap hoodia line. Perma- nent coverage of the burn wound is generally done in separate stages when the size of the wound far exceeds the size of available autologous skin for cover age of the wou n d cheap hoodia online american express. The potent ial of having inhalat ion injuries worsens t his pat ient ’s prognosis generic hoodia 400 mg mastercard, t herefore t his pat ient deserves to be treated in a specialized burn center. The boy described in “D ” is su sp iciou s for b ein g a vict im of ch ild abu se an d n eed s t o b e r ep or t ed to the child-protective services, but does not have clear indications for burn cent er admission. The Parkland formula provides recommendation for resuscitation during the first 24 hours of treatment. Low urine output of 15 mL/ h during the first two hours of resuscitation suggest s inadequat e fluid administ rat ion. Even t hough t he Parkland formula is used for init ial fluid resuscit at ion, low urine output response in this young man with burns suggests inadequate fluid resuscitation, which is sometimes cau sed by u n d er-est im at ion of bu r n size or d elay in the in it iat ion of flu id resuscitation. The fluid infusion rate should be increased to try to titrate to a urine output of 0. Inotropic agents are not indicated unless the patient’s intravascular vo lu m e d ep let io n h a s b een fir st ad d r essed. Sulfamylon administ rat ion can cause met abolic acidosis t hrough carbonic anhydrase inhibit ion. The blood gas findings in “E” reflect met abolic acidosis, since the pH is low at 7. The 58-year-old man with partial thickness scald burns over the posterior aspect of the deltoid does not have indications for inpatient care. The 2-year-old boy with stocking-like distribution of scalding burn over both lower extremi- ties suggests that the injury pattern could be intentional and the result of ch ild abu se; t h erefore, admission an d social ser vice con su lt at ion are in di- cat ed. T h e pat ient wit h bur n s t o bot h h an d s aft er int ent ionally set t ing fire t o the house needs specialized care to optimize functional recovery; in addition, she needs to undergo psychiat ric evaluat ion for this behavior. The worker with electric burns to the hand and foot after contact with high-voltage wire needs observation to monitor for myoglobinuria and other clinical manifes- tations of high-voltage electric burns. The 20-year-old college student with flame bu r n s t o face an d ant er ior n eck would ben efit from t r eat ment in a bu r n cent er t o opt im ize h is fu n ct ion al r ecover y. This unconscious man found inside a burning house has elevated car boxyhemoglobin level of 32%. Body surface areas of various anatomic regions are divided roug h ly in to m ultip le s of 9%. She is o the rwise h e a lt h y a n d wit h o u t a n y p rio r h ist o ry o f b re a st -re la t e d sym p t o m s or family history of breast cancer. On physical examination, there is a 2-cm non- tender, indiscrete, hard mass in the upper outer quadrant of her left breast. There is n o skin a b n o rm a lit y o ve r the b re a st a n d n o a d e n o p a t h y in the a xilla o r su p ra - clavicular region. Yo u p e r f o r m a b r e a s t u l t r a s o u n d e x a m i n a t i o n t h a t r e v e a l s a 1. P h ysical examinat ion reveals a palpable breast mass, no adenopat hy, and no skin changes. The ultrasound appearance is highly suspicious for cancer (solid, heterogeneous mass with irregular and indistinct borders). Next Steps:Yo u n e e d t o o b t a i n t i s s u e t o co n fi r m the d i a gn o s i s a n d ch a r a ct e r i z e the tumor. After discussing the findings and your concerns with your patient, you can p er for m a cor e-n eed le b io p sy u n d er u lt r asou n d gu id an ce. O n ce can cer is verified by t he pat h ologist, you will need t o have in-dept h discussions wit h the patient and her family regarding her diagnosis, prognosis, and treatment options. H er individual treatment plan will be best determined on the basis of her personal preference, the tumor characteristics (tumor size to breast size ratio, histologic grade, hormone receptors st atus, and biologic characterist ics), and tumor st age ( Tumor, N odes, Met ast ases [ T N M] st age). For most pat ient s, treatments will include some combination of surgery, radiation therapy, ch em ot h erapy, biologic t h erapy, and h ormonal t h erapy. Treatment Goals: T h e go als of t r eat m en t for this patient wit h su sp ect ed b r east can cer are t o est ablish a d efin it ive diagn osis, obt ain t issu e t o d efin e t u mor receptors and biologic characteristics, stage the disease, communicate with the patient regarding her surgical treatment options and preferences (breast con- servat ion v. In many practice settings, the patients’ treat- ment recommendations are formulated at multidisciplinary Tumor Boards where pract itioners from various specialties including surgery, medical oncol- ogy, radiation oncology, pathology, and radiology assemble to discuss individual patients’treatment strategies. The multimodality treatment of breast cancer is a process t hat oft en ext ends over mont hs and somet ime years; t herefore, it is import ant t o communicate t he specific opt ions early on wit h the pat ient and her family. Similarly, it is important to evaluate for emotional, social, and finan- cial n eeds an d bar r iers that cou ld impact t reat ment complian ce an d out comes. If indicated, it is important to make early referrals to social, medical, and com- munity resources so that the patient and her family can receive emotional and social support to help them get through the long t reat ment course t hat would likely involve many visit s t o medical specialist s over the course of mont h s t o year s. For this premenopausal woman, it is important to inquire regarding her desires for future fertility. Learn the locoregional and systemic treatment options for patients with breast can cers. Co n s i d e r a t i o n When a woman presents with a dominant breast mass, the most important early goal is t o “r u le out ” or con fir m the d iagn osis of br east can cer. If feasible, it is h elpfu l to perform a core-needle biopsy during the initial visit, as this may provide infor- mation that will be pivotal for all subsequent discussions and therapeutic decisions. The diagnosis of breast cancer should be entert ained whenever a woman or a man presents with an abnormality of the breast, such as a mass, skin change, nipple ch an ge, or axillar y ad en opat h y. To gether, the clinical, imaging, and pathology assessments are referred to as the “triple test. For example, if the patient who presents with clinical and imaging findings that are highly suspicious for breast cancer an d h as a core-n eed le biopsy that revealed on ly ben ign breast tissue, a subsequent excisional biopsy of the mass would need to be performed because an inconsistency in the triple test can result from sampling error and would be insufficient to rule out breast cancer. Based on h er ultrasound measurements, the cancer is likely a T 2 lesion (> 2 cm and < 5 cm). The treatment approach for a premenopausal woman with cancer of this size would cert ainly include some form of systemic t herapy in addit ion t o local regional treat ment (ie, surgery and radiation therapy). It is important that you convey to the patient that a partial mastectomy with radiation therapy offers her the same survival as a mastectomy. In addit ion, a sent in el lymph n ode biopsy sh ou ld be don e t o st age the axillary nodal status (N-stage), see Table 11– 1. This approach can ident ify malignant cells but cannot definit ively dif- ferent iat e in sit u can cers from invasive can cers. I m age gu id an ce is gen er ally b et t er t o h elp ver ify act u al sampling of the lesion in quest ion and minimizes nondiagnost ic result s. Categories of 1 t o 4 is oft en used, wh ere 1 is < 25% glan du lar t issu e, 2 is 25% t o 50% glan dular t issue, 3 is 51% t o75% glan du lar t issu e, and 4 is > 75% glandular t issue. The skin of t he involved breast is infilt rated wit h tumor cells; t hus, it may display a thickening that is classically referred to as peau d’orange ( or an ge p eel-like). The systemic therapy (chemo- therapy, biologic therapy, or hormonal therapy) is given prior to surgical treatment (locoregional Rx). Based on the gene array profile assessment of a patient’s tumor, a recurrence risk score can be generated (report range of 0 to 100).

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