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Active against gram-positive and IV buy discount prinivil on-line hypertension online, IM 1 g q8–12h 1 mo to 12 y: IV 30–50 mg/kg (Fortaz) gram-negative organisms q8h order 10mg prinivil with visa blood pressure ranges nhs, not to exceed 6 g/d 2 buy prinivil 10 mg mastercard arterial blood gases. Especially effective against gram- <1 mo: IV 30 mg/kg q12h negative organisms, including P. Indicated for serious infections caused by susceptible organisms Ceftizoxime 1. Broader gram-negative and IV, IM 1–2 g q8–12h >6 mo: IV, IM 50 mg/kg q6–8h, (Cefizox) anaerobic activity, especially increased to a total daily dose against B. Dosage must be reduced with even mild renal insufficiency (CrCl < 80 mL/min) Ceftriaxone 1. First third-generation cephalosporin IV, IM 1–2 g once daily (q24h) IV, IM 50–75 mg/kg/d, not to (Rocephin) approved for once-daily dosing exceed 2 g daily, in divided 2. Antibacterial activity against most doses q12h gram-positive and gram-negative bac- Meningitis, IV, IM 100 mg/kg/d, teria, including several strains resis- not to exceed 4 g daily, tant to other antibiotics in divided doses q12h Fourth Generation Cefepime 1. It had to be given parenterally because it was destroyed by the most serious, and potentially fatal, adverse effect of the gastric acid, and injections were painful. Seizures, interstitial nephritis, strains of drug-resistant staphylococci appeared. Semi- Indications for Use synthetic derivatives are formed by adding side chains to the penicillin nucleus. Clinical indications for use of penicillins include bacterial in- After absorption, penicillins are widely distributed and fections caused by susceptible microorganisms. As a class, achieve therapeutic concentrations in most body fluids, in- penicillins usually are more effective in infections caused by cluding joint, pleural, and pericardial fluids and bile. Thera- gram-positive bacteria than those caused by gram-negative peutic levels are not usually obtained in intraocular and bacteria. However, their clinical uses vary significantly ac- cerebrospinal fluids (CSF) unless inflammation is present cording to the subgroup or individual drug and microbial because normal cell membranes act as barriers to drug pen- patterns of resistance. Penicillins are rapidly excreted by the kidneys and soft tissue, respiratory, gastrointestinal, and genitourinary 516 SECTION 6 DRUGS USED TO TREAT INFECTIONS streptococcal pharyngitis; and for prevention of bacterial endo- Drugs at a Glance: Carbapenems and Monobactams carditis in people with diseased heart valves who undergo Routes and Dosage Ranges dental or some surgical procedures. Several preparations of penicillin G are available for intra- Generic/Trade Name Adults Children venous (IV) and intramuscular (IM) administration. Only aqueous preparations can be Ertapenem IV 1 g once daily Dosage not estab- given IV. Preparations containing benzathine or procaine can (Invanz) over 15–30 min. Long-acting repository forms have additives Imipenem/cilastatin IV 250–1,000 mg >40 kg weight, that decrease their solubility in tissue fluids and delay their (Primaxin) q6–8h. IM 500–750 mg to 10 mg/kg/d in Penicillin V is derived from penicillin G and has the same q12h divided doses. It is not destroyed by gastric acid and Maximum dose, is given only by the oral route. Meropenem IV 1 g q8h, as a 3 mo and older: IV (Merrem) bolus injection 20–40 mg/kg q8h over 3–5 min or Penicillinase-Resistant (Antistaphylococcal) infusion over Penicillins 15–30 min This group includes four drugs (cloxacillin, dicloxacillin, naf- Monobactam cillin, and oxacillin) that are effective in some infections caused Aztreonam UTI, IM, IV 0. An older member of Moderate systemic this group, methicillin, is no longer marketed for clinical use. These drugs are formulated to resist the penicillinases that UTI, urinary tract infection. They are recommended for use in known or suspected staphylococcal infections, except for methicillin-resistant Staphylococcus aureus (MRSA) infections. Although called methicillin-resistant, these tococci, staphylococci, and other microorganisms continues staphylococcal microorganisms are also resistant to other to grow. Aminopenicillins Contraindications to Use Ampicillin is a broad-spectrum, semisynthetic penicillin that Contraindications include hypersensitivity or allergic reac- is bactericidal for several types of gram-positive and gram- tions to any penicillin preparation. It has been effective against enterococci, penicillin means the client is allergic to all members of the Proteus mirabilis, Salmonella, Shigella, and Escherichia penicillin class. The potential for cross-allergenicity with coli, but resistant forms of these organisms are increasing. It cephalosporins and carbapenems exists, so other alternatives is ineffective against penicillinase-producing staphylococci should be selected in pencillin-allergic clients when possible. Ampicillin is excreted mainly by the kidneys; thus, it is useful in urinary tract infections (UTI). Because some is ex- Subgroups and Individual Penicillins creted in bile, it is useful in biliary tract infections not caused by biliary obstruction. It is used in the treatment of bronchitis, Penicillins G and V sinusitis, and otitis media. Amoxicillin is similar to ampicillin except it is only avail- Penicillin G, the prototype, remains widely used because able orally. It is better absorbed and produces therapeutic of its effectiveness and minimal toxicity. It also causes staphylococci and gonococci have acquired resistance to less gastrointestinal distress. Some strains of streptococci have Extended-Spectrum (Antipseudomonal) acquired resistance to penicillin G, although the drug is still Penicillins effective in many streptococcal infections. Thus, it is often the drug of choice for the treatment of streptococcal pharyn- the drugs in this group (carbenicillin, ticarcillin, mezlocillin, gitis; for prevention of rheumatic fever, a complication of and piperacillin) have a broad spectrum of antimicrobial ac- CHAPTER 34 BETA-LACTAM ANTIBACTERIALS: PENICILLINS, CEPHALOSPORINS, AND OTHERS 517 tivity, especially against gram-negative organisms such as include cefoperazone, which is excreted in bile, and ceftriax- Pseudomonas and Proteus species and E. For pseudo- one, which undergoes dual elimination via the biliary tract monal infections, one of these drugs is usually given con- and kidneys. Cefotaxime is primarily metabolized in the liver comitantly with an aminoglycoside or a fluoroquinolone (see to an active metabolite, desacetylcefotaxime, which is elim- Chap. Carbenicillin is available as an oral formulation inated by the kidneys. The other drugs are usually given by intermittent IV infusion, although most can be given IM. First-Generation Cephalosporins Penicillin/Beta-Lactamase the first cephalosporin, cephalothin, is no longer available Inhibitor Combinations for clinical use. However, it is used for determining sus- ceptibility to first-generation cephalosporins, which have Beta-lactamase inhibitors are drugs with a beta-lactam struc- essentially the same spectrum of antimicrobial activity. They bind and inactivate These drugs are effective against streptococci, staphylo- the beta-lactamase enzymes produced by many bacteria cocci (except methicillin-resistant S. When combined with a penicillin, the beta- species, Corynebacterium diphtheriae, Proteus mirabilis, lactamase inhibitor protects the penicillin from destruction by and Bacteroides species (except Bacteroides fragilis). Clavulanate, sulbactam, and tazo- bactam are the beta-lactamase inhibitors available in combi- Second-Generation Cephalosporins nations with penicillins. Unasyn is a combination of ampicillin and sulbactam Second-generation cephalosporins are more active against available in vials with 1 g of ampicillin and 0. Thus, they may be effective in infections resistant to contains amoxicillin and clavulanate. It is available in 250-, 500-, and 875-mg tablets, each of which contains 125 mg of other antibiotics, including infections caused by Hemophilus clavulanate.

Prolonged effects are thought to in- volve closure of calcium channels generic prinivil 2.5mg otc prehypertension 30 years old, changes in cellular metab- Receptors are proteins embedded in the cell membranes of olism buy discount prinivil 2.5 mg online arrhythmia joint pain, changes in activation or deactivation of specific genes neurons order prinivil cheap online heart attack 3 stents. In the CNS, most receptors are on postsynaptic in the cell nucleus, and alterations in the numbers of excita- neurons, but some are on presynaptic nerve terminals. Some most receptors, several subtypes have been identified, for peptides (eg, ADH) serve as chemical messengers in both the which specific characteristics and functions have not yet been delineated. A neurotransmitter must bind to receptors to exert an effect on the next neuron in the chain. Some re- ceptors act rapidly to open ion channels; others interact with SYNAPSE a variety of intracellular proteins to initiate a second messen- Presynaptic Postsynaptic ger system. For example, when norepinephrine binds with nerve terminal Release nerve terminal alpha- or beta-adrenergic receptors, intracellular events in- site clude activation of the enzyme adenyl cyclase and the pro- duction of cyclic adenosine monophosphate (cAMP). In this Receptor sites case, the cAMP is a second messenger that activates cellular functions and the physiologic responses controlled by the Neurotransmitters alpha- and beta-adrenergic receptors. A neurotransmitter– receptor complex may have an excitatory or inhibitory effect on the postsynaptic neuron. Receptors increase in number and activity (up-regulation) when there is underactivity at the synapse. They decrease in number and activity (down-regulation) when there is over- Presynaptic nerve Postsynaptic nerve activity. Like other protein molecules in the body, receptors cell membrane cell membrane are constantly being synthesized and degraded. More specif- Figure 5–1 Neurotransmission in the central nervous system. Neu- ically, it is believed that receptor proteins are constantly being rotransmitter molecules (eg, norepinephrine and acetylcholine), re- leased by the presynaptic nerve, cross the synapse and bind with formed by the endoplasmic reticulum–Golgi apparatus and in- receptor proteins in the cell membrane of the postsynaptic nerve. If the 74 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM synapses are overused and excessive amounts of neurotrans- Two groups of dopamine receptors have been identified. Thus, synaptic fatigue receptors, which activate adenyl cyclase to produce cAMP. D2 recep- control mechanisms of the nervous system to readjust abnor- tors have been described most thoroughly; they are thought mally stimulated or depressed nerve function toward normal. D3 and D4 receptor functions have not Neurotransmission Systems been delineated. Overall, dopamine actions at the cellular level depend on the subtype of receptor to which it binds and Neurons function through communication networks that the simultaneous effects of other neurotransmitters at the may be called neurotransmission systems, the major elements same target neurons. The GABA-ergic system uses GABA as its neurotrans- Although neurotransmitters, synapses, and receptors are dis- mitter. It is the major inhibitory neurotransmitter in the and mental processes. Although many details of neuronal func- CNS, with a role in many neuronal circuits (estimated at tion remain elusive, a great deal of knowledge has been gained. GABA receptors have For example, numerous neurotransmitters and subtypes of been divided into two main types, A and B. Major ceptor is a chloride ion channel that opens when GABA is neurotransmission systems are the cholinergic, dopaminergic, released from presynaptic neurons. GABAB has not been GABA-ergic, noradrenergic, and serotonergic networks. Acetylcholine, the first substance to be desig- of multiple subtypes of GABA receptors and important nated as a neurotransmitter in the CNS, is located in many functional differences among them. It is also a neurotransmitter neurotransmitter and extends to virtually every area of the in the autonomic nervous system and at peripheral neuro- brain. Like dopamine, norepinephrine is a catecholamine syn- muscular junctions. It is found in relatively large amounts synapses and nerve–muscle junctions and inhibitory effects in the hypothalamus and the limbic system and in smaller at some peripheral sites, such as organs supplied by the vagus amounts in most areas of the brain, including the reticular nerve. Norepinephrine is mainly an excitatory neuro- arousal, memory, motor conditioning, and speech. Dopamine is derived from tyrosine, an amino inhibitory receptors at some nerve synapses. Dopamine makes up more nervous system, are divided into alpha- and beta-adrenergic than half the catecholamine content in the brain and is receptors and their subtypes. Activation of alpha1, beta1, and found in the substantia nigra, the midbrain, and the hypo- beta2 receptors is thought to stimulate activity of intracellular thalamus, with high concentrations in the substantia nigra adenyl cyclase and the production of cAMP. Much of the information about dopamine alpha2 receptors is associated with inhibition of adenyl cyclase is derived from studies of antipsychotic drugs (see Chap. These effects on ion channels may increase In the CNS, dopamine is thought to be inhibitory in the membrane resistance to stimuli and inhibit the firing of CNS basal ganglia but may be excitatory in other areas. In addition, alpha2 receptors on the presynaptic nerve stimulation of dopamine receptors decreases their numbers ending are believed to regulate norepinephrine release. In (down-regulation) and their sensitivity to dopamine (desen- other words, when high levels of extracellular norepinephrine sitization). Prolonged blockade of dopamine receptors in- act on presynaptic alpha2 receptors, the effect is similar to that creases their numbers and sensitivity to dopamine. Some of a negative feedback system that inhibits the release of nor- receptors (called autoreceptors) occur on the presynaptic epinephrine. When released, dopamine stimulates these re- with mood, motor activity, regulation of arousal, and reward. CHAPTER 5 PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM 75 the serotonergic system uses serotonin (also called sociated with brain injury (eg, from ischemia, hypoglycemia, 5-hydroxytryptamine or 5-HT) as its neurotransmitter. Altered glutamate metab- mus, hypothalamus, cerebral cortex, and spinal cord. Because olism may also lead to the formation of free radicals, which serotonin is synthesized from the amino acid tryptophan, the are implicated in neuronal cell death associated with some amount of tryptophan intake in the diet and the enzyme tryp- neurodegenerative diseases and toxic chemicals, including tophan hydroxylase control the rate of serotonin production. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood, the sleep–wake cycle, habituation, and sensory perceptions, including inhibition of pain pathways in Neurotransmission Systems in Selected the spinal cord. Serotonin is thought to produce sleep by in- Central Nervous System Disorders hibiting CNS activity and arousal. Serotonin receptors are found in regions of the CNS that are Abnormalities in neurotransmission systems (eg, dysfunc- associated with mood and anxiety and are also thought to be tion or destruction of the neurons that normally produce involved in temperature regulation. Activation of some recep- neurotransmitters; altered receptor response to neurotrans- tors leads to hyperpolarization and neuronal inhibition. It may also be involved normalities are thought to be involved in mental depression in the vascular spasm associated with some pulmonary aller- and sleep disorders. However, peripheral serotonin cannot mitters and their respective receptors, CNS function in both cross the blood–brain barrier.

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It appears to be a very promising treatment of spinal conditions does 3 5 purchase prinivil with mastercard hypertension hereditary. National Center for Chronic Disease dependent variation in burden of dis- national Institute for Applied Systems Prevention and Health Promotion prinivil 2.5mg line blood pressure medication pictures, ease estimates: implication for policy generic prinivil 2.5 mg mastercard blood pressure vitamins supplements. Gold MR, Stevenson D, Fryback DG 27 April 2003 Aging 12:3 (2002) HALYS and QUALYS and 9. Pluijm SM, Tromp AM, Smit JH, Deeg DALYS, oh my: similarities and differ- al (1999) Vertebral fractures and mor- DJ, Lips P (2000) Consequences of ences in summary measures of popula- tality in older women: a prospective vertebral deformities in older men and tion health. Szpalski M, Gunzburg R (eds) (2003) the ageing of the population affect 10. Kinsella K, Velkoff V (2001) US Vertebral osteoporotic compression health care needs and costs in the fore- Census Bureau. Mullahy J (2001) Live long, live well: US Census bureau, US Department of quantifying the health of heteroge- Commerce. Health Econ 10: 27 April 2003 429–440 REVIEW Michel Benoist Natural history of the aging spine Abstract the unrelenting changes tum flavum progressively create nar- associated with aging progressively rowing of the spinal canal as well as affects all structures of the spinal degenerative instabilities such as units. The degenerative process starts spondylolisthesis and scoliosis, which early during the first decade of life at are the main causes of neurogenic the disc level. Discal degeneration is claudication and radiculopathy in old associated with biochemical changes persons. Vertebral bodies are the sta- followed by macroscopic alterations tic elements of the spinal unit. With including tears and fissures, which advancing age, osteoporosis weakens may lead to discal herniation, the the bony structures and facilitates main cause of radiculopathy in the bone remodeling and rotatory defor- young adult. Finally, aging of bone, discs, nerve fibers have been demonstrated facets, ligaments, and muscles may in degenerated discs. They may be a ultimately lead to rotatory scoliosis, source of nociception and of pure destabilization, and rupture of equi- M. Orthopaedic Surgery Unit, are usually secondary to discal de- Department of Rheumatology, generation. They include subluxa- Keywords Lumbar disc Hôpital Beaujon, 100 Bd du Gal Leclerc, tion, cartilage alteration and osteo- degeneration · Age-related 92110 Clichy, France phytosis. As emphasized by Garfin and Herkowitz [9], aging is difficult to distinguish from the spine is a flexible, multisegmented column. The ponents of the spine may be related to a predetermined ge- spine comprises a static, changeless element – the verte- netic cell viability and/or to exposure of the tissues to bral bodies – and an elastic mobile component – the three- heavy mechanical forces throughout life. Whatever the joint complex, consisting of the intervertebral disc and the mechanism, aging will lead to degenerative changes start- two posterior facet joints. Spine motion, stability, equilib- ing with subtle biochemical alterations followed by mi- rium and control of position are assumed by the antago- cro-structural and finally gross structural changes of the nist action of the powerful flexor and extensor muscle spinal unit. Because most of the research work has been equilibrium and destabilization. Aging affects all the struc- devoted to the lumbar spine, the present paper will focus tures of the spine. This review paper will summarize the 5 age-related changes of the various components of the spi- disc may generate diffuse bulging, which should be dif- nal unit in turn. Disc herniation requires pre-ex- Aging of the disc isting age-related degenerative changes. Aging and degeneration are also associated with dra- Historically, primary degeneration of the disc has been matic changes in vascularization and innervation of the considered as the initiating event resulting in secondary disc. A normal healthy adult disc is avascular, apart from deterioration of the facets, ligaments, and muscles. Disc degeneration depends on the failure of generated disc and in herniated disc tissue [2, 10]. Pene- cellular activity in charge of producing a normal extracel- tration of blood vessels through the rim lesions is pro- lular matrix. In a normal disc, an equilibrium exists be- moted by angiogenesis factors [10]. Inflammatory cells as tween synthesis and degradation of the matrix elements. Loss of agrecan and water, and a decrease in collagen or- Production of various cytokines and proteases by endoge- ganization and of disc height are the early modifications nous cells and by the vascular cells of the invading vessels of aging. Simultaneously, the level of the proteases re- has been demonstrated [18]. Metallo-proteinase (MMP) sponsible for the enzymatic degradation process increases expression increases with advancing age, thus enhancing [2, 3, 19]. Correlation of MMPs expression aging is multifactorial, including a predisposed genetic with formation of tears and clefts in the annulus has also condition [22]. Presence of nerve fibers relevant Decrease of nutrient supply of the cells is an important to pain sensation is a prerequisite for a tissue to be a source factor in degeneration. Recent studies [2, 8, 10, 20] have shown the disc is through the adjacent vertebral end plate [11]. Most nerve the permeability of the end plate diminishes with advanc- fibers identified by immunochemistry accompany blood ing age. Detrimental effect of a decreased blood supply vessels, suggesting a role of vaso-regulation. However, from the end plate results in tissue breakdown, starting in another set of neural elements, independent of vessels, ex- the nucleus. A recent study has shown that this process pressing substance P and with a morphology of nocicep- may begin early in the second decade of life [3]. The cells tive nerve terminals, have been found in the nucleus of of the disc are also sensitive to mechanical signals. They painful discs assessed by provocative discography of pa- can be negatively affected by mechanical stresses and stim- tients undergoing anterior surgery for chronic low-back ulation undergone throughout life, leading to qualitative pain [8]. This important finding strongly suggests the role and quantitative modulation of the matrix proteinases [17]. An innervated disc may be a accompanied by gross anatomic and macroscopic changes. As aging progresses, the boundary between nucleus and In summary, among the various structures of the spine, annulus becomes less distinct, with an increase of colla- the process of aging starts in the disc at the beginning of gen in the nucleus. Failure of the normal cell activity may appear during the third and fourth decade of life, with depends on various factors: genetic, nutritional, and me- substantial individual differences: elderly persons may chanical. The initial event is not yet known, but when the have a young disc and vice versa. Significant temporo- degenerative cycle is started, a complex interplay of bio- spatial variations of histologic and macroscopic changes chemical and biomechanical factors create a vicious circle, are also observed across levels and regions [23]. Loss Aging of the facet joint of disc height and turgor, secondary to the biochemical events summarized above, have serious biomechanical con- the facet joints are the only synovial joints in the spine, sequences. Loss of proteoglycans and fluid, lowering of with hyaline cartilage overlying subchondral bone. In a normal healthy spinal unit, the disc coelastic hydrostatic nature of the disc.

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We will be taking a tour of our life through this meditation buy generic prinivil 10 mg line peak pulse pressure qrs complex, starting at the earliest point of our youth that we can recall buy prinivil 5mg with visa blood pressure medication for migraines. See yourself generic 5mg prinivil arrhythmia icd 9 code, as you were, whether it was happy and carefree or sad and burdened. Give yourself a mental hug and send loving compassion to that little child. Repeat this inspection and expression of compassion for yourself at the subse- quent life stages of older child, puberty, young adult, all the way to your present self. At this last stage, give yourself an especially big hug (use your hands and arms if you like! For many of us, compassion- ate feelings for ourselves are secondary to our concern for others. Start in your usual position, observe your breath for a few minutes, and then pick out a minor pain that you have in your physical body. It can be a headache, some low-back pain, arthritis in the fingers—whatever you choose—but start with a minor one, not a major one. Put your focus on the pain while you continue your deep, relaxed breathing. See it as perhaps a red area on your body, with little lightning bolts issuing from it. Imagine the pain begin- ning to soften as you watch it—the red color growing pale pink, the lightning bolts slowing and finally stopping. Incorporate some relaxation meditation techniques here—feel yourself growing heavy in your chair, switch back and forth from watch- ing your breath to watching the pain. If we can control or eliminate our pain by using our minds, the possibilities are endless. These internal aspects help bring forth a holistic, mind/body healing modality that can be used effectively in conjunction with Western medicine or, in some cases, by itself. Again, here in the West we have been trained to place our confidence in purely physical cures, disregarding the role that the mind plays in the healing equation. Another Western perspective is that Qi does not exist, because it cannot be found on X-rays or CAT scans. To divorce one from the other is to treat the symptoms, but not the root cause of the pain. On the positive side, patient empowerment and self-care, as well as medical cost-reduction possibilities have a special potential to transform medicine as it is practiced in the Western world. In external Qigong, the practitioner or Qigong doctor does non- touch energy assessment of the patient and actually projects or conducts Qi, in a treatment mode, to the patient. In assessment, rather than asking questions, taking pulses, observing the tongue, palpating reflexes, and ordering lab tests, the practitioner uses concentration, intu- ition, and reading of the Qi with off-the-body diagnostic scanning. In treatment, the practitioner actually projects the Qi to another to have a clinical effect. However, research is revealing that there may be authentic, explainable, and demonstrable natural laws and mecha- nisms in operation during these events. Therapeutic Touch, an assessing and heal- ing technique that uses an off the body technique called unruffling the field has experienced a tremendous swell of interest in the nursing community. The re- search of developer Delores Krieger, RN, demonstrated that in-vivo hemoglobin values (an essential blood-quality component) were significantly affected by the administration of this energy-based technique. An October 1986 article in the Los Angeles Times tells the story of the Beijing practice of Master Xun Yunkun who treats medical cases including terminal can- cer and paralysis following stroke with Qi projection. There is a tremendous wave of interest in this aspect of Qigong in the Western world and a number of very respectable research organizations are currently ex- pending substantial budgets on Qigong-related projects. There is a tremendous amount of research attempting to explain this phenomenon. Zheng Rong, and Stanford physicist Professor William Tiller are doing a collaborative research project on biolumines- cence and Qigong with a focus on satisfying the rational research model. In 1988, 128 research papers were presented at the First World Conference for the Aca- demic Exchange of Medical Qigong that was sponsored by the China Medical As- sociation, Chinese Ministry of Health, China Qigong Research Institutes, and the Beijing College of Traditional Chinese Medicine and was attended by representa- tives from 17 countries. It would be a shame, however, if we became so dependent upon their abilities that we ignored the benefits derived from self-applied Qigong techniques. In my own practice, I have accepted clients who, having failed to make any noticeable progress in months of physical therapy, began to despair of ever regain- ing their former health. Students, who after attending physical therapy sessions for long periods of time, often come to my classes after experiencing strokes, heart attacks, seizures, and various bodily injury. While their progress is due, in part, to the diligent work of dedicated therapy professionals, they have not usually had the mental or spiritual component of their injuries or illnesses addressed. After attending the seminar, she signed up at my school and studied hard for three years. Lots of energy, almost unbelievable range-of-motion im- provement, arthritis that had just about disappeared, and a positive outlook on life. Some of the other exercise modules showed increased falls, merely be- cause the patients were moving more. More than 30 percent of people aged 65 or older experience at least one fall per year, and 15 percent of those falls result in serious injuries. The last fig- ures are from 1984—before the aging trend got into full swing, and before the recent inflation of medical costs. Unlike anecdotal evidence that the skeptical can shrug off as Eastern mysti- cism, this study involved eight medical facilities, including some of the most es- teemed names in Western medical science: Harvard, Yale, Centers for Disease Control, Washington University School of Medicine, and Emory University. This groundbreaking study lasted 12 years, resulting in final publication of results in 1984. By 1989, the NIA came together with the National Center for Nursing Research and the Centers for Disease Control to issue a Request for Applications. The studies took place over the ensuing three years, concluding in March 1993. Wolf forged ahead with a more detailed report for the Journal of the American Geriatric Society. After some frustrating delays in the process, the report finally appeared in the May 1996 issue of the Journal. Emory is known for its open-minded approach to finding healthcare solutions. Wolf said, We worked with Xu to synthesize the 108 moves down to 10 that we felt from a physiotherapeutic and rehab perspective represented movements that often become compromised in folks as they get older—most notably trunk and body rotation and the ability to maintain a narrower base of support. They view a cursor that represents their center of balance on a computer monitor. Subjects were told to keep their balance aligned perfectly and trained to improve their performance, kind of like an interactive video game for senior citizens. In the real world, we walk in poor light, encounter unfamiliar obstacles and traverse uneven ground. Attention developed to prevent leaning of trunk or protrusion of the sacrum.

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Heavy intake may cause fetal alcohol CHAPTER 67 DRUG USE DURING PREGNANCY AND LACTATION 967 BOX 67–1 U purchase 2.5 mg prinivil visa blood pressure pills names. Adequate studies in pregnant women demonstrate no risk are no data from human studies buy prinivil 2.5 mg mastercard blood pressure medication verapamil. There is evidence of human fetal risk buy cheap prinivil 2.5mg on-line hypertension drugs, but the potential adequate studies in pregnant women; or animal studies benefits to the mother may be acceptable despite the show adverse effects, but adequate studies in pregnant potential risk. A potential risk, usually because animal studies have either both have demonstrated fetal abnormalities; the risk of use in not been performed or indicated adverse effects, and there a pregnant woman clearly outweighs any possible benefit. Chronic fetal hypoxia from heavy smoking has been Caffeine is the most commonly ingested nontherapeutic associated with mental retardation and other long-term effects drug during pregnancy. It is present in coffee, tea, cola drinks, on physical and intellectual development. Overall, effects of over-the-counter analgesics, antisleep preparations, and choco- smoking are dose related, with light smoking (<1 pack/day) late. Although ingestion of moderate amounts has not been estimated to increase fetal deaths by 20% and heavy smoking associated with birth defects, spontaneous abortions, preterm (1 or more packs/day) increasing deaths by 35%. In addition, high Cocaine, marijuana, and heroin are illegal drugs of abuse, doses may cause cardiac dysrhythmias in the fetus. Co- Cigarette smoking (nicotine and carbon monoxide inges- caine may cause maternal vasoconstriction, tachycardia, tion) is one of the few preventable causes of perinatal mor- hypertension, cardiac dysrhythmias, and seizures. Effects include may impair fetal growth, impair neurologic development, and increased fetal, neonatal, and infant mortality; decreased birth increase the risk of spontaneous abortion during the first and weight and length; shortened gestation; and increased com- second trimesters. During the third trimester, cocaine causes plications of pregnancy (eg, placental abruption, spontaneous increased uterine contractility, vasoconstriction and decreased abortion; preterm delivery). These effects are attributed to de- blood flow in the placenta, fetal tachycardia, and increased risk creased flow of blood and oxygen to the placenta and uterus. These life-threatening Nicotine causes vasoconstriction and decreases blood flow to (text continues on page 970) Conception LMP 14 days Parturition (280 days) 31 days – heart, CNS Classic teratogenic period Palate, ear 71 days Brain growth Internal organ development Figure 67–1 the gestational clock show- ing the classic teratogenic risk assessment. For most drugs, adequate studies have not been done in seem to be safe, although they have not been studied extensively pregnant women and effects on the fetus are unknown. They have shorter half-lives, lower serum con- be used only if potential benefit to the mother justifies potential centrations, and a faster rate of elimination in pregnancy. Adrenergics Aminoglycosides (FDA category D) cross the placenta and Adrenergics are cardiac stimulants that increase rate and force of fetal serum levels may reach 15% to 50% of maternal levels. These drugs are common fetus or neonate have not been reported with other aminoglyco- ingredients in over-the-counter decongestants, cold remedies, and sides, but there is potential harm because the drugs are nephrotoxic appetite suppressants. Oral and parenteral adrenergics may inhibit uterine contractions Clindamycin (Cleocin) should be used only when infection with during labor; cause hypokalemia, hypoglycemia, and pulmonary Bacteroides fragilis is suspected. Erythromycin crosses the placenta to reach fetal Oral albuterol and oral or intravenous terbutaline relax uterine serum levels up to 20% of maternal levels, but no fetal abnormali- muscles and inhibit preterm labor. In animal studies, adverse fetal effects were Analgesics, Opioid reported with clarithromycin and dirithromycin but not with Opioids rapidly cross the placenta and reach the fetus. Clarithromycin is contraindicated if a safer alterna- diction and neonatal withdrawal symptoms result from regular use. Use of codeine during the first trimester has been associated with Nitrofurantoin should not be used during late pregnancy be- congenital defects. When given to women in labor, opioids may decrease uterine Sulfonamides should not be used during the last trimester contractility and slow progress toward delivery. They cross the placenta and causes less neonatal respiratory depression than other opioids. If respiratory depression occurs, it can be studies indicate embryotoxicity. Trimethoprim, often given in combination with sulfamethoxa- zole (Bactrim), is contraindicated during the first trimester. It Angiotensin-Converting Enzyme (ACE) Inhibitors crosses the placenta to reach levels in fetal serum that are similar to These drugs can cause fetal and neonatal morbidity and death; sev- those in maternal serum. It is a folate antagonist and may interfere eral dozen cases have been reported worldwide. It was teratogenic in ani- fects apparently do not occur during first trimester exposure. With mals, but a few studies in pregnant women have not indicated ter- exposure during the second and third trimesters, however, effects atogenic effects. Infants exposed to the drugs in utero should be closely observed Antifungals for hypotension, oliguria, and hyperkalemia. Angiotensin II Receptor Blockers (ARBs) Anticholinergics See ACE inhibitors, above. These drugs should be discontinued Atropine crosses the placenta rapidly with IV injection; effects on when pregnancy is detected. Scopolamine may cause respiratory depression in the Antianginal Agents (Nitrates) neonate and may contribute to neonatal hemorrhage by reducing the drugs lower blood pressure and may decrease blood supply to vitamin K–dependent clotting factors in the neonate. Anticoagulants Antianxiety and Sedative-Hypnotic Agents Heparin does not cross the placenta and has not been associated (Benzodiazepines) with congenital defects. It is the anticoagulant of choice during These drugs should generally be avoided. However, its use has been associated with 13% to 22% lites cross the placenta freely and accumulate in fetal blood. Approximately 31% of fetuses exposed to warfarin may culties in the neonate. If a woman be- Antibacterials comes pregnant during warfarin therapy, inform her of the po- Beta lactams. Penicillins cross the placenta but apparently pro- tential risks to the fetus, and discuss the possibility of terminating duce no adverse effects on the fetus. CHAPTER 67 DRUG USE DURING PREGNANCY AND LACTATION 969 BOX 67-2 DRUG EFFECTS IN PREGNANCY (Continued ) Anticonvulsants Antimanic Agent Although more than 90% of women receiving antiseizure drugs Lithium crosses the placenta and fetal concentrations are similar to deliver normal infants, the drugs (eg, carbamazepine, pheny- those of the mother. After years of question- the neonate, lithium is eliminated slowly and may cause brady- ing whether teratogenesis resulted from epilepsy or antiepileptic cardia, cyanosis, diabetes insipidus, hypotonia, hypothyroidism, drugs, a recent study confirms that anticonvulsant drug therapy in and electrocardiogram (ECG) abnormalities. Most of these effects pregnant women causes physical abnormalities in their offspring. Moreover, infants exposed to one drug had a much higher rate of Antipsychotics abnormalities than infants not exposed (20. Studies indicate that the drugs are not teratogenic, but animal Infants whose nonepileptic mothers took the drugs for bipolar dis- studies indicate potential embryotoxicity, increased neonatal mor- order also had higher rates of birth defects. The possibility of permanent effects of newer drugs (eg, gabapentin, lamotrigine, oxcarbazepine, neurologic damage cannot be excluded. Use near term may cause tiagabine, and topiramate) (Topamax) are unknown. They are FDA abnormal movements, abnormal reflexes, and jaundice in the category C.

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