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Anti- muscarinics should not be given to patients with gas- CONTRAINDICATIONS AND CAUTIONS trointestinal infections because the drug will slow gas- Muscarinic blocking agents are contraindicated in tric motility and cause the patient to retain the angle-closure glaucoma buy cheap metformin 500 mg online managing canine diabetes. You most likely to be different in an elderly versus a proceed to ask questions that might provide a clue young patient? However order metformin 500 mg blood sugar gold for cats, she also exhibits cardiovascular and gastrointestinal signs of ANSWERS excessive vagal tone, which you would like to block 1. Which of the following risk factors in heart decreases with age, which is typically accom- prescribing atropine is most important to you? However, it can prevent the detection administering tropicamide, it would be most impor- of early signs of an overdose of neostigmine, which tant to know can quickly progress to a depolarizing block of (A) If the patient has angle-closure glaucoma skeletal muscle and paralysis of the respiratory (B) If the patient has open-angle glaucoma muscles. Dry mouth, ocular disturbances, and tachy- (C) If the patient is taking a cholinomimetic miotic cardia are common side effects of atropine given drug alone, but these effects are less likely to occur with 4. In which of the following conditions would atropine competition between atropine and the increase in be the least likely to increase blood pressure? Application of tropicamide to the eye of a pa- hibitor tient with narrow-angle (angle-closure) glaucoma is (C) A patient being treated with bethanechol a very serious risk, because the peripheral move- 5. A patient has come to you complaining of feeling ment of the relaxed iris can block the outflow of drowsy and finding it hard to concentrate. Clinical aspects of inhaled anticholiner- the absence of a circulating muscarinic agonist be- gic therapy. Case Study The Risks of Treating Peptic Ulcers with Antimuscarinic Drugs 55-year-old man who works in the furnace that do not enter the CNS, such as glycopyrrolate, Aroom at a steel foundry has developed chronic can be prescribed for blocking gastric acid secre- peptic ulcer disease that has not responded to treat- tion, thereby avoiding central side effects. You the most important risk factor for this worker is his are considering giving him an antimuscarinic drug exposure to a hot workplace. This worker is prob- peptic ulcer disease today because of their many ably required to do heavy physical labor, which will side effects, but they still can play a useful role as add to the hyperthermia and cardiac stimulation. Unfortunately, high concentra- Compensatory feedback via the vagus nerve to slow tions are required to block gastric acid secretion, the heart rate will be blocked by a peripherally act- which means that many side effects are difficult to ing muscarinic antagonist, and this could lead to avoid. Overall, antimuscarinic therapy would not be a Although CNS depression and loss of concentration good choice for this worker unless he can be moved is a concern with tertiary amine muscarinic antago- to a safer work environment. Westfall DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Mecamylamine 146 Trimethaphan 145 Nicotine 147 GANGLIONIC TRANSMISSION carinic, are present on the cell bodies of the postgan- glionic neurons. Stimulation of the preganglionic neuron Transmission through autonomic ganglia is more com- results in the release of acetylcholine (ACh) from the plex than neurotransmission at the neuromuscular and preganglionic nerve terminal, which in turn activates postganglionic neuroeffector junctions and is subject to postganglionic cholinergic receptors and leads ulti- numerous pharmacological and physiological influ- mately to the formation of a propagated action potential ences. At the more complicated parasympathetic ganglia, there is a simple presynaptic synapses, the release of ACh from preganglionic neurons to postsynaptic cell relationship; in others, the presyn- results in the appearance of complex postsynaptic po- aptic to postsynaptic cell relationship may involve neu- tential changes consisting of several temporally ar- rons interposed between the presynaptic and postsy- ranged components. At There is considerable diversity among nicotinic some autonomic ganglia, the SIF cell is a true interneu- acetylcholine receptors, and at least one source of this ron, receiving afferent innervation from preganglionic diversity is the multiplicity of acetylcholine receptor cholinergic neurons and forming efferent synapses with genes. At other autonomic ganglia, its cle are different from those in autonomic ganglia and function is not completely understood, but the SIF cell the central nervous system. Excitatory and Inhibitory Potentials Unlike the receptors at postganglionic neuroeffector junctions or at skeletal neuromuscular junctions, both The interaction of ACh with the postsynaptic nicotinic types of cholinergic receptors, that is, nicotinic and mus- receptor results in depolarization of the membrane, an 141 142 II DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM influx of Na and Ca through a neuronal nicotinic re- existence of these receptors provides a wide variety of ceptor channel, and the generation of the fast EPSP. Agonists This change in postsynaptic potential is principally re- for these receptors most likely reach the ganglia through sponsible for the generation of the propagated action the circulation. For simplic- eral presynaptic terminals innervate a single ganglion ity, the figure has been divided into a type A synapse, cell, and several preganglionic axon terminals must which includes SIF cells, and a type B synapse, which fire simultaneously for transmission to take place. The drugs the type of receptor mediating the response, and the pri- either interact with the nicotinic–cholinergic receptor mary transmitter or mediator that activates the receptor. Interaction of ACh with the postsynaptic ganglionic cell muscarinic receptor is responsible for slowly devel- GANGLIONIC STIMULANTS oping depolarization, the slow EPSP, which has a longer latency than the fast EPSP and a duration of 30 to 60 A variety of agents, including nicotine, lobeline, and di- seconds. The slow EPSP is due to inhibition of a voltage- methylphenyl piperazinium (DMPP), can stimulate gan- dependent K current called the M current, and inhibi- glionic nicotinic receptors. First, drugs such as nicotine that both M4 and M5) have been identified using functional stud- stimulate and block ganglionic receptors have proved ies and at least five subtypes (m1,m,m,m,2 3 4 and m5) valuable as an aid in identifying and localizing postgan- identified by molecular cloning techniques. In this case, acti- Mechanism of Ganglionic Stimulation vation of a muscarinic receptor on the SIF cells results in the release of a catecholamine; this in turn activates a Nicotine, lobeline, trimethylammonium, and DMPP receptor on the postganglionic cell, leading to the slow stimulate all autonomic ganglia by simple combination IPSP. The catecholamine most frequently released from with ganglionic nicotinic receptors on the postsynaptic SIF cells appears to be dopamine. This leads to membrane depolarization, an EPSP, lasting for 1 to 2 minutes, can be seen at some influx of sodium and calcium ions, and the generation of ganglionic synapses. These agents produce general stimulation now well established that there are a large number of of autonomic ganglia and a complex pattern of mixed peptides in the ganglia, including luteinizing hormone– sympathetic and parasympathetic responses.

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Repeated increases in drug dosage are re- more slowly because of decreased splanchnic blood flow quired to accommodate for growth in children receiving or delayed gastric emptying purchase metformin 500 mg visa diabetes type 2 testing numbers. In summary order 500 mg metformin visa diabetes medications heart failure, children, especially those in the first year of life, present significant pharmacological chal- Distribution lenges. Drug administration must be tailored to meet the unique needs of children at their varied stages of de- Drug distribution in elderly patients may be altered by velopment. Special attention must be given to unex- hypoalbuminemia, qualitative changes in drug-binding pected drug actions and adverse reactions in these pa- sites, reductions in relative muscle mass, increases in the tients, who are maturing at variable rates. When proportion of body fat, and decreases in total body planning drug therapy for children, it is important to water. The plasma level of free, active drug is often a di- remember: rect function of the extent of drug binding to plasma proteins. Elderly Patients In a carefully controlled clinical study, the plasma half-life of diazepam (Valium), a widely used antianx- Plasma or serum t1/2 iety agent, exhibited a striking age dependency. In pa- tients aged 20 years, the t1/2was about 20 hours, and this Young Elderly increased linearly with age to about 90 hours at 80 Drug (20–30 yr) (65–80 yr) years. These changes in serum albumin may affect the Adverse Drug Effects free drug concentration for a number of highly bound drugs, such as phenytoin, warfarin, and meperidine. The incidence of iatrogenic complications is three to five times greater in the elderly than in the general pop- ulation. Inappropriate drug use has been In addition to changes in metabolism that occur as a re- noted in almost half of hospitalized elderly patients. Half of adverse drug reactions occur in pa- Reevaluate the continued use of all medications the tients receiving inappropriate drugs. While almost every class Noncompliance is a significant problem, with almost of drugs has the potential to produce delirium in the 50% of elderly patients failing to take their medications elderly, it is most frequent with psychoactive drugs. Some of the reasons for noncompliance are risk increases with the number of drugs the patient is re- inability to pay for the drug, side effects, mental impair- ceiving, reaching a 14-fold increase in risk for patients ment, and inability to understand complex instructions. SUMMARY Physicians should exercise caution when prescribing Special Considerations drugs for pediatric and geriatric patients. This is virtually The following should be considered when prescribing axiomatic in premature infants, whose severely restricted drugs for elderly patients. Caution Drugs should be prescribed only if nonpharmaco- also must be exerted in prescribing for the elderly popu- logical techniques are ineffective, such as for problems lation, since these individuals may be taking 10 to 15 dif- like sleeplessness and anxiety. Problems associated with drug interac- scribed for these conditions, they should be given for a tion and declining physiological function are very real. It limited time and the patient closely monitored for ad- is simply inadequate to administer drugs to very young verse effects. Prescribe drugs only if you have upon the changing pharmacokinetic characteristics of the available extensive experience and prescribing informa- drug in question, the nature of the disease, and the physi- tion for that drug in elderly patients. Use the least num- ological status of the major organs and tissues involved in ber of drugs and doses per day. It is well established that most drugs taken by preg- (C) Increase in the levels of plasma proteins nant women are capable of crossing the placenta (D) General increase in hepatic drug metabolizing and reaching the developing fetus. The placenta it- capacity self can aid in the protection of the fetus from exces- (E) Decrease in renal clearance of many drugs sive exposure to drugs in the maternal circulation by 4. A neonate is given drug A, a compound with a high (A) Impairing diffusion of lipid soluble drugs affinity for plasma proteins, in a dose that does not (B) Preventing the passage of drugs having a mo- exceed the binding capacity of albumin. Neonates having a patent ductus arteriosus can be (A) The free plasma concentration of drug A is de- treated with which agent to induce a relatively rapid creased. Which of the following is an accurate description of (E) The free plasma concentration of drug B changes taking place in elderly individuals com- would likely be markedly increased if drug A were pared to younger adults? He is taking a thi- its albumin binding site and lead to an increase in azide diuretic (A) for mild hypertension, digitalis free drug. The latter is then available to be distrib- (B) for congestive heart failure, and an oral hypo- uted outside the blood compartment and reach tis- glycemic agent (C) for mild type 2 diabetes. The elderly are frequently sensitive to the pul- relief when he broke his arm 30 years ago is pre- monary depressing actions of opioid analgesics.

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Another exam- ple of the spectacular columnar pattern of organization is the somatosensory cortex of the star-nosed mole where each segment of each nose ray possesses a discrete cortical territory generic 500 mg metformin free shipping blood sugar 86. Our argument is that the barrel cortex is but one expression of the universal columnar organizational unit of somatosensory cortex discount metformin 500 mg amex blood sugar pregnancy. We regard columnar organization as a general principle characterizing soma- tosensory cortex in all mammals and we would suggest that many of the principles of information processing and plasticity in rat somatosensory columns are likely to apply to other mammals. MODULAR LEARNING IN THE RAT WHISKER SYSTEM Does tactile learning take place in a modular framework? The question also can be phrased: Is the signal from one whisker processed mainly in its single, homologous columnar module, or does a much wider ensemble support the processing of a single whisker? The relevant question then, is whether one column is capable of supporting by itself, the information transformation necessary to some meaningful behavior. That is, are all the columns of the barrel map bound together as a functional unit or can different areas of a map participate independently in sensory processing? To look for the role of columns in cortical plasticity we designed an experiment based upon single-whisker learning. We chose the gap-cross behavior because it suited our purpose since it has been known from its first publication9 that a rat with a single whisker can learn and perform the task. In our experiments,10 on one side of the snout all whiskers except one were clipped to the base. In the lower illustration, the rat perches and leans forward, sweeping its single intact whisker in front of the snout to detect the opposite platform. Rats learned to use this single whisker to detect the presence of the opposite platform before jumping across to obtain its chocolate cereal reward (Figure 3. During the initial training sessions, the gaps were small permitting the rat to become familiar with the paradigm while facing little risk. Over the course of 5–7 d (about 20 trials/d), the gap distance was increased until the goal could be detected only if the rat extended the tip of its remaining whisker about 1–2 cm in front of its nose. To make certain that rats truly detected and identified the goal platform (rather than settling into the stereotyped behavior of positioning itself and jumping regardless of whisker contact), the goal platform had an unpredictable location and was even occasionally removed. After performance on the task had reached a fixed criterion, the intact whisker was clipped and a prosthetic whisker was attached to the stub of the whisker that had just been trained, or to the stub of a different whisker (one clipped at the start of training). The prosthetic whisker was simply a natural whisker taken from the collection of whiskers previously harvested at the initial clipping. The prosthetic was carefully attached to the selected whisker stub using a combination of super glue and hot glue. For each rat, the relative locations of the trained and prosthetic whisker were carefully controlled. If the trained whisker was, for example, D2 and the prosthetic attached to the D3 stub, the rat would be labeled as row1/arc0, this being the distance in follicle coordinates between the two sites. To make certain that the prosthetic attachment procedure itself did not interfere with gap- crossing behavior, one group of rats had the prosthetic whisker glued back onto the same site from which the trained whisker had just been clipped. If learning involved globally distributed networks, then the task would be immediately reacquired even if the prosthetic whisker were implanted far from its original site. On the other hand, if learning involved only a localized module corresponding to the trained whisker, then reac- quisition time would be very high even if the prosthetic whisker were adjacent to the trained whisker. The cortical network that participates in learning the task (or has access to the learned information) appears not to be uniformly distributed, as would be predicted by the hypothesis of global distribution. Rats which had the prosthetic whisker attached to an adjacent neighbor of the trained whisker (i. Rats which had the prosthetic whisker attached to a site more distant from the trained whisker (i. All retraining values were compared to those obtained from naïve rats, a group which was originally trained, at smaller gap distances, with all whiskers clipped such that they were familiar with gap crossing, but had never used a whisker to guide their behavior. These naïve rats were then retrained at the wider gap distance with a prosthetic whisker. This comparison revealed that when the prosthetic whisker was attached to any site beyond the immediate neighbors of the trained whisker, performance during retraining was not significantly better than for a naïve rat. Thus, the benefit of the original training was not shared beyond the immediate neighbors.

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Other types of treatment Oral drugs Several surgical or medical treatments are available When acne is severe and the lesions are deep discount metformin 500 mg online japan diabetes prevention program, oral to alleviate acne or the resulting scars: antibiotics may be taken daily to reduce the spread of bacteria order metformin 500 mg with visa diabetes in dogs and ketones. The comedo is removed from Minocycline, however, may be more preferable because the pore with a special tool. The affected skin is frozen with a chem- ical spray, and removed by brushing or planing. Deep scars are excised and the area re- Comedo—A hard plug composed of sebum and paired with small skin grafts. Laser-treated skin heals in Sebum—An oily skin moisturizer produced by se- three to 10 days, depending on the treatment chosen. Expected results Most dermatologists now use a combination of ther- • Emotional stress should be kept in check. The most troubling aspects of this condi- tion are the negative cosmetic effects and potential for BOOKS permanent scarring. Connecticut: Appleton Acne is not considered curable, although it can be & Lange, 2002. Acne tends to reappear when PERIODICALS “Combination Therapies Offer New Management Options for treatment stops, but it often spontaneously improves over Acne. Fresh fruits and vegetables should be stressed, and foods that seem to trigger flare-ups should be avoided. Pim- Aconite is the common name for any of 100 or more ples should not be squeezed or prodded, as this may con- related species in the Aconitum genus. Fu Zi is also used by tra- tum napellus, is a plant that grows in mountainous re- ditional Chinese herbalists in conditions marked by defi- gions of Central Asia, Russia, Europe, and Great Britain. The Greeks as recommended by a Chinese medicine practitioner, left the plant as poisonous bait for wolves or anointed ar- there are rarely any adverse effects. The in Asian countries, including some that ended in the pa- poison comes from the toxic alkaloid aconitine. Even the smallest amounts of aconi- Homeopathy tine inside the mouth cause burning, tingling, and numb- ness. As little as 2 mg of aconitine can cause death in as Homeopaths prescribe aconite for conditions that little as 4 hours, which may be one reason why aconite is come on suddenly as a result of grief, fear, anger, shock, often chosen by people attempting suicide by poison. It is also recommended for The Australian government has declared all species of people troubled by suicidal thoughts. This remedy is one General use of the best for measles, arthritis, and pneumonia when all Western herbology of the symptoms are present. Aconite is also useful at the beginning of a fever, in early stages of inflammation, and Herbalists have used aconite as a medicine for hun- following shock caused by an injury or surgery. However, in ancient times the herb was known more for its power to kill rather than heal; it was often used in ancient Rome to commit murders. Preparations The herb acts as a diuretic (a substance that pro- Aconite is available as a homeopathic remedy or in motes urination) and diaphoretic (a substance that causes dried bulk form, as an ointment or liniment, and as a sweating). Pharmacies, health food stores, and Chinese pneumonia, laryngitis, and acute tonsillitis. They are or ointments made from the herb are applied externally also available as prescribed by a herbalist, homeopathic to relieve the pain of neuralgia and rheumatism. Traditional Chinese medicine The leaves and flowers are cut when the flowers are in Aconitum carmichaeli is used in traditional Chi- blossom in June. The root is dried before Mandarin; in other parts of China and in Hong Kong it is use while the leaves, stems, and flowers are used fresh. This herb is used to treat The homeopathic preparation of aconite is created in rheumatism, bruises, arthritis, acute hypothermia, diar- the following manner. The herb is very hot and has a root—is collected when the flowers are in full bloom and sweet, spicy taste. The juice from the pulp is pressed The main function of Fu Zi is to warm the interior. The mixture is then strained and also works to restore collapsed yang, warm Kidney fire, diluted. The final homeopathic remedy is created after warm the Kidney and Spleen, drive out the cold, warm the diluted mixture is repeatedly succussed (pounded GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 9 against a hard surface to break down and mix the sub- stance). The remedy is available at health-food and drug KEY TERMS stores in various potencies in the form of tinctures,.

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