Christine T. Trankiem MD

• Assistant Professor, Trauma/Surgical Critical Care, Georgetown University
• Trauma
• Surgeon, Trauma Services/Surgical Critical Care, The Washington Hospital Center,
• Washington, DC

After ingestion acne keloidalis treatment purchase differin discount, caffeine is absorbed by the gastrointestinal tract and transported to the central nervous system via the bloodstream acne homemade mask cheap differin master card. Crossing the blood-brain barrier skin care 3-step discount 15 gr differin free shipping, caffeine binds to adenos ine A1 and A2 receptors acne 101 cheap 15 gr differin otc, which then cause the release of neurotransmitters such as acetylcholine acne paper order differin with paypal, dopa mine acne and diet purchase cheapest differin, noradrenaline acne 4 dpo buy differin 15gr amex, and serotonin skin care myths buy differin pills in toronto, among others, all of which improve concentration and mood. Ninety percent of caf feine is broken down into three dimethylxanthines, which all have different functions: paraxanthine (increases the rate of lipolysis), theobromine (a vasodilator), and theophylline (bronchial smooth muscle relaxer). However, its mechanisms of action and effects on human skin are less well-understood. Caffeine has become increasingly popular as an additive in topical skin cosmeceuticals for the purpose of improving the appearance of skin by offering antioxidant and anticarcinogenic properties. It is, therefore, important to elucidate some of these mechanisms in order to better understand the effects of caffeine on the skin. Clinical Uses Caffeine and Skin Barrier Penetration the ability of any cosmeceutical to penetrate the skin barrier is essential to its ability to affect the processes and metabolism of cells. Non-melanoma skin cancer is the most common type of cancer in the United States, with more than two million new cases diagnosed in 2012. Several animal models have demonstrated evidence that caffeine helps to prevent the development of non-melanoma skin cancers. Apoptosis was measured by looking for caspase-3 positive cells in the mouse epidermis after treatment was complete. In fact, there was a dose-dependent decrease in the incidence of skin cancer; women who had six or more cups of caffeinated coffee demonstrated a 36% decrease in the incidence of non-melanoma skin cancers. Each additional cup of caffeinated coffee conferred a 5% decrease in the development of non-melanoma skin cancers. After adjusting for confounding factors associated with the Cutaneous Applications of Caffeine 21 development of non-melanoma skin cancers, demographics, and other variables, daily caffeinated coffee consumption was associated with a reduction of 30% in the prevalence of non-melanoma skin cancers in a dose-dependent manner. The data was gathered from the Nurses Healthy Study and the Health Professionals Follow-up Study, a self-administered questionnaire studying the risk factors for cancer and cardiovascular disease, which was established in 1976 with 121,700 respondents. Of note, caffeine intake was not associated with any decrease in the risk of melanoma or squamous cell carcinoma. There are several proposed mechanisms of action for the role of caffeine in the inhibition of non melanoma skin cancer formation. This selective apoptosis did not require activation of p53; in fact, keratinocytes with p53 mutations were selectively destroyed after caffeine was applied topically. All of these mechanisms work together to help explain the role of caffeine in the prevention of non-melanoma skin cancers. Pretreatment with caffeine protected against fbroblast necrosis, which was induced by 30 min of exposure to H2O2. Thirty or 120 min of exposure to H2O2 caused visible changes to the morphology of the fbroblasts, causing them to become smaller and more irregular, which indicated impending necrosis. These results indi cated that the antinecrotic effects of caffeine were related to effects other than being an antioxidant, as reviewed earlier. Redness is often associated with infammatory dermato ses such as rosacea, atopic dermatitis, and psoriasis. Most commonly, epidermal barrier dysfunction can exacerbate infammation and it is often worsened with variations in the humidity of the environment, 22 Cosmeceuticals and Active Cosmetics especially during winter and in arid climates. Additionally, it has been shown that free radicals also play a role in the development of infam matory dermatoses. An increase in the number of blood vessels pres ent in skin and altered vessel permeability can increase facial redness by allowing more pro-infam matory cytokines and molecules to reach the skin surface. Reduction in facial redness was signifcant and noted by at least week 6 and tolerated well by all subjects. Anti-Cellulite Cellulite is the dimpled, orange peel, or cottage cheese appearance of skin, often occurring in the pelvic, abdominal, and leg areas of women. In general, genetics, hormonal factors, alteration of connective tissue structure, fbrosis, and insuffciency of the microcirculatory and lymphatic system all play a role in causing cellulite. Caffeine stimulates lipolysis, which is the degradation of triglycerides from adipocytes by lipoprotein lipases. Lipases are located on the adipocyte membrane and are controlled by levels of catecholamines and hormones. All of these mecha nisms break down adipocytes and can reduce the appearance of cellulite. Only caffeine gel with ultrasound treatment revealed a signifcant reduction in the thickness of subcuta neous fat, damage to adipocytes, and a decrease in the number of adipocytes. Insuffciency of microcirculation and compression of vessels can cause tissue hypoxia, which leads to an alteration in aerobic glucose metabolism and a subsequent increase in lactic acid production. Alteration of aerobic glucose metabolism can also lead to activation of proline hydroxylase, which produces procollagen and collagen, therefore leading to fbrosis of tissue and the appearance of cellulite. One hundred and thirty-four women applied the solution twice daily for 30 days to one leg at a dose of 15 mL per leg. At the end of the 30-day treatment, a signifcant reduction in circumference of the treated leg, spe cifcally the lower thigh, was noticed in 80. Microcirculation was measured using a noninvasive spectral imaging technique, which determined capillary density; the microcircula tory blood fow was improved in all women who applied the topical caffeine solution. Cutaneous Applications of Caffeine 23 Hair Growth Alopecia is a loss of hair from the scalp or body. Male pattern baldness, or androgenetic alopecia, is responsible for more than 95% of alopecia in men. Newly growing hair subsequently becomes thinner and after a fnite number of growth cycles, hair ceases to grow. Topical caffeine is able to effectively penetrate the scalp into the hair follicles. Caffeine was found in the bloodstream within fve minutes of application at a concentration of 3. Caffeine has been shown to inhibit the activity of 5-reductase, prolonging the anagen phase and increasing hair growth. At the end of the study, caffeine alone led to signifcant stimulation of hair growth, despite suppression with testosterone. Future Applications of Topical Caffeine Caffeine has shown promise for the treatment of the aforementioned conditions. Combinations of caffeine plus other cosmeceuticals may offer synergistic mechanisms of action. For example, topi cal minoxidil is a well-known over-the-counter treatment for androgenetic hair loss, which provides growth through many mechanisms including vasodilation. Conclusion Caffeine is gaining popularity as a component of topical anti-aging products for its properties in prevent ing skin cancer, an antioxidant, and reduction of redness. There are many other potential cosmetic uses of caffeine, so more research must be conducted to determine its full potential and develop an optimal delivery system to the skin. Prospective 121,700 registered n/a Self-reported cups Data collected Subjects who consumed Caffeine from other (2012)15 cohort study nurses aged 30 to of caffeinated from 1976 more than 3 cups of coffee dietary sources (tea, 55 years and coffee or caffeine per day had the lowest risk cola, and chocolate) 51,529 U. In vitro predictions of skin absorption of caffeine, testos terone, and benzoic acid: A multi-centre comparison study. The quantitative distribution of percutaneously applied caffeine in the human skin. Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties. Protection against ultraviolet B radiation-induced photocarcino genesis in hairless mice by green tea polyphenols. Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women. Increased caffeine intake is associated with reduced risk of basal cell carci noma of the skin. Caffeine protects human skin fbroblasts from acute reactive oxy gen species-induced necrosis. Caffeine inhibits adenosine-induced accumulation of hypoxia inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Reduction of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine. Obesity and thermogenesis related to the con sumption of caffeine, ephedrine, capsaicin, and green tea. Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. The effect of topical caffeine on the morphology of swine hypodermis as measured by ultrasound. Analysis of the penetration of a caffeine containing shampoo into the hair follicles by in vivo laser scanning microscopy. Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. Heng Introduction Curcumin (diferuloylmethane or 1,7-bis-[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) is the active ingredient in turmeric, derived from the rhizome of Curcuma longa. Turmeric itself contains turmerin, essential oils and curcuminoids, including curcumin, the most biologically active of the ingredients. The observed1 anti-infammatory properties2 of curcumin has led to its use as a therapeutic cosmetic. The colored cur cuminoids, however, have been found to be more potent than the colorless compounds, with curcumin being the most potent of the colored curcuminoids. The effectiveness of curcumin administered orally is hindered by its poor bioavailability due to the fact that the unconjugated curcumin molecule, which is hydrophobic, is poorly absorbed when taken orally, with very low curcumin levels detected in blood and tissues after ingestion. Topical curcumin is much better absorbed through the skin, particularly when the skin barrier is defective as in the presence of skin injury or disease. An important and unique biochemical property of curcumin that makes it particularly useful for skin problems is that it is a selective and non-competitive inhibitor of phosphorylase kinase (PhK). These may lead to scarring, dysregulated cell cycling, increased mitotic potential, and tumor promotion. The clinical manifestations of these cellular and tissue changes include thinning of the skin, pigmentary and keratotic lesions, and tumor transformation, particularly after solar injury. By inhibiting PhK, one of the earliest molecules involved in the injury pathway, cur cumin blocks PhK-dependent signaling pathways, leading to mitigation of tissue injury. In this chapter, these injury processes and related signaling pathways that are targeted by curcumin will be detailed. The ability of curcumin to block these pathways may be the basis of the reparative properties of curcumin as a cosmetic, particularly in relation to anti-aging and possibly in the prevention of photocarcinogenesis in solar damaged skin. Signaling Pathways Induced by Skin Injury Sequence of Early Events in Injury: Pathways Blocked by Curcumin the sequence of early events after a skin injury at the molecular and biochemical level has been deter mined from investigations on the skin and other tissues. The molecular and biochemical basis of the benefcial effects of curcumin on injured skin provides a hypothetical conceptual framework for the potential use of topical curcumin as a cos metic and therapeutic agent for many types of skin problems. In the skin, this includes trauma, heat, and laser burns, and ionizing and solar radiation. This concept is consistent with the current notion that removal of potentially malignant cells by apoptosis is important in both the prevention and treatment of malignancy. This is achieved by the presence of a hinge joint between the subunits of PhK, which allows changes in the size of the substrate binding site, as well as the ability to change the shape of the substrate binding site by binding either to Mg++ or Mn++ ions. Using one enzyme, as with PhK, instead of several enzymes to achieve multiple biochemical functions, has the advantage of synchronization of phosphorylation events that require involvement of multiple sites and different specifcities. It is believed that curcumin achieves these effects through its ability to inhibit PhK and block the phosphorylation events in these pathways. This may contribute signifcantly to its effcacy as a therapeutic cosmetic for the prevention of skin injury and the repair of damaged skin. In the absence of curcumin, the injury cascade results in the subsequent secretion of cytokines and growth factors by both immune (T cells, macrophages, and mast cells) and non-immune cells (keratinocytes, fbroblasts, and endothelial cells) that serve to further amplify the immune response and cytokine load. In addition, the synergistic effect of the cytokines, growth factors, and chemokines acting through their respective receptors, trigger activation of multiple pathways and transcription fac tors that result in gene transcription of multiple genes, with magnifcation of the deleterious effects on the skin following injury. The ability of curcumin to block the early stages of the infammatory cascade triggered by injury may also be the basis for its potential or reported ability to heal burns with minimal scarring,5,6 to heal surgi cal wounds with perfect regeneration,7 and to repair photodamaged and photoaging skin. Types of Skin Injury the ability of topical curcumin to assist in skin repair after injury may be a very important effect that accounts for its widespread and longstanding popularity as a therapeutic cosmetic. The different types of wounds vary with respect to their propensity to develop scarring, as well as a tendency for malignant transforma tion. The pathways blocked by curcumin which may assist in skin repair with different types of injury are discussed below. Burns and Traumatic Wounds Acute injury such as burns and scalds usually result in blister formation, swelling, and erythema, caus ing considerable pain to the patient, and resulting in loss of function. Toxic chemicals cause chemical burns, damaging cytoplasmic proteins and releasing caspases from the mitochondria, and resulting in cellular necrosis or apoptosis. Laser-induced injury, which depends on the type of laser and wavelengths emitted by the instrument, usually resembles heat injury. Burns and scalds are caused by heat injury to cellular proteins, resulting in coagulative necrosis of cells, and damage to cellular proteins within the cytoplasm and nucleus. Unlike wounds in embryos that usually heal without scarring, adult wounds almost always result in scarring. This results in hypertrophic scar formation, which is commonly observed with second and third degree burns and scalds, with increasing scarring in deeper wounds. The key anti-scarring signaling pathways and targets blocked by curcumin are summarized in Figure 3. Topical curcumin has also been shown to heal burns with minimal scarring,5,6 and to achieve similar results in surgical wounds. Additionally, other wavelengths, such as infrared rays that produce heat, may also contribute to the injury observed in acute sunburns and chronic dermal injury. Signaling Pathways Induced by Acute and Chronic Solar Injury: Inhibition by Curcumin Sunburn resembles other skin injuries in producing an infammatory cascade that invokes the wound repair mechanism. The repair processes, resulting in the formation of new blood vessels and fbro blastic proliferation, frequently lead to dermal scarring. In addition, the skin damage results in epi dermal and melanocytic proliferation, which are noted clinically as keratotic and pigmentary lesions. Repeated solar skin damage may lead to formation of premalignant solar lentigenes and dysplastic nevi. These alternative pathways synergize with the canoni cal pathways to amplify the immune response to injury. Using curcumin to block both the canonical and alternative pathways simultaneously has the advantage of synchronized mitigation of the amplifed injury-induced infammatory response. These mechanisms may be responsible for the anti-carcinogenic properties and reparative properties of curcumin reported clinically. Blistering and post-infammatory hyperpigmentation has been observed with laser burns in the skin,54 with damage consistent with changes from heat-induced injury. Within one hour following laser damage, dendritic cells, macrophages, and microglia were observed to migrate towards sites of injury. Despite these treatments, the tumor progressed to involve the right alar nose down to and including the nostril, nasal tip, and right nasal side-wall. The lesion was excised and a free skin graft was taken from a donor site situated over the mid forehead. Revascularization was enhanced with vicryl sutures between the base of the graft and the deep tissues. These serve like umbilical cords to enhance revascularization59 of the free graft from the deep tissues. Post-surgical scarring was prevented by the use of twice daily application of extra-strength topi cal curcumin in a gel preparation. Minimal scarring was observed with the use of extra strength curcumin gel (right panel). Revascularization was enhanced using the umbilical cord technique with 40 Vicryl sutures attached from the lower surface of the free graft to the deep tissues. Following removal of the sutures four weeks later, scarring was minimized with the use of topical curcumin gel (extra-strength) mas saged with the fngers twice daily to the healing wound. Following excision of the tumor, the defect was closed using a free full-thickness skin graft taken from a donor site situated over her left calf. Revascularization was achieved with the umbilical cord technique, and residual scarring minimized with the use of extra strength topical curcumin gel. He was treated in several emergency rooms with Silvadene cream, but developed worsening of his swelling (Figure 3. Four days later, he was put on topical curcumin gel with instructions to apply the gel at hourly intervals. He was improved when seen the following day with decreased swelling and pain (Figure 3. Following excision the defect was closed with a full-thickness free skin graft taken from the glabella fore head. The graft was stitched in place and revascularization enhanced using the umbilical cord technique. After applying curcumin gel (every two hours), her solar burns were markedly improved, together with no pain when seen two days later (Figure 3. At that time, it was noted that blister formation was aborted, and the previous hemorrhagic lesions (upper panel) were much improved (lower panel). The patient, a 76-year-old man with severely photodamaged skin, presented with actinic poikiloderma with marked skin atrophy and telangiectasia, and multiple actinic kerato ses and pigmentary changes (upper panel).

Measurements should be done frequently during the first six to eight weeks of the post-operative period acne solutions order 15 gr differin fast delivery. Line the center of the transparent ruler over the center of the stoma and measure according to ruler instructions zone stop acne - buy genuine differin online. For appliance sizing measurement irregular stomas should be traced and a copy of the tracing should be recorded for appliance fitting acne hydrogen peroxide buy differin 15gr on-line. Be sure to line it up so that the tail of pouch will be in the appropriate direction skin care 40s cheap 15 gr differin visa. Most of the manufacturers will provide them free of charge acne scar treatment cheap differin 15 gr with amex, and most cut-to-fit products will contain one per box skin care unlimited generic 15gr differin free shipping. The card comes with numerous pre-cut holes skin care bandung buy differin 15 gr low cost, measured in millimeters and/or inches acne under microscope discount 15gr differin with visa. Select the hole in the card that fits closest around the base of the stoma without touching it. Objectively recording flatus frequency (using a diary kept by the patient) is a first step in 10 evaluation if perceived excessive. Definition: the skin/stoma junction where the mucosa of the stoma is approximated to 8 the skin surrounding the stoma. This area should be treated as a wound until the junction of the skin and the mucosa are healed and sutures are removed. The mucocutaneous junction should be free of tension, infection, and skin breakdown. If a separation is noted between stoma and surrounding skin, document measurements 8 (width and depth) and location of the separation. Assess peristomal plane at a minimum and extend assessment outward as needed based upon findings. The skin around the stoma should be intact, without erosion, rashes or lacerations. Redness may be caused by infection, irritation from drainage, urine/feces, dermatitis/trauma from tape or dressing b. Redness from infection may be seen as diffuse and indistinct, or as intense with demarcated borders, red streaking. In dark skin, the skin may appear purple or a gray hue or deepening of the ethnic skin color iv. Scars connective tissue reflective of dermal damage; new scars are pink and thick, over time become white and atrophic 3. Induration process of the skin becoming hard; hardened mass with defined edges; detected by palpation (feeling) C. Throbbing, aching, squeezing, constant, intermittent, spasmodic, tender, crushing Location of pain one site, several sites, does it move or radiate to another site, generalized or specific area b. Utilize pain severity scale, be consistent with the scale with each assessment, assess for severity at present, worst, and least levels. Developed as a comprehensive tool to use for documentation and grading of the peristomal skin. The scoring system allows the health care provider to compare and contrast the condition of the peristomal skin from one assessment to the next and make adjustments to care as necessary. The tool includes two simple approaches for obtaining information on the condition of the peristomal skin: a. Provides operational definitions for the consistent interpretation of peristomal skin lesions iii. A content validated measurement instrument to classify lesion type and location iv. An objective classification system to document the incidence of peristomal skin lesions v. Assessment and management of stomal complications: a framework for clinical decision making. Contact Information: Wound Care Education Institute Fax: 877-649-6021 Phone: 855-391-1556 Email: Info@wcei. The Authority would like to give special acknowledgement to the following professionals and their institutions for their contributions during the consultative workshop held to finalize the draft formulary. It is also our pleasure to thank World Health Organizations for supporting us financially. The groups included are editors and workshop participants from different hospitals, universities, pharmacy retail outlets, regional health bureaus, non government organizations and professional associations listed here below. Drugs used for Congestive Cardiac failure - 33 2. Drugs used for angina /ischemic heart disease - 50 2. Drugs used in vascular shock- 78 2. Drugs for the relief of soft tissue inflammation -182 7. Thyroid Hormones and Antithyroid Agents - 288 8. Insulin and oral antidiabetic agents - 291 8. Drug used in benign prostatic hyperplasia - 318 9. Blood Substitutes and Plasma Expanders - 361 12. Antiallergics, Diagnostics and Miscellaneous Agents -412 16. Drugs for Psoriasis and Eczema -444 17. In such circumstances promotion of rational use of drugs is at stake, viii which eventually shall harm the health of indivuduals and affect the overall health-care delivery service. In Ethiopia, as the health service expands quite rapidly, in principle drug information resources need to be made available and accessible at equal pace. However, except the few promising efforts in availing some drug information materials, the gap between the demand and supply is still wide enough. In relation to this the Drug Administration and Control Authority of Ethiopia recognizing the unmet need on drug information has been striving to develop and make accessible some information materials including, catagorized drug formularies and standard treatment guidelines, leaflets in variuos issues and bulletin. To widen the scope of the content and to provide maximum information from single source, a draft national drug formulary has been prepared by the Authority and after incorporation of the comments from workshop participnats, the final draft is now ready for use. And it targets all health professionals involved in patient care, training and research and others. Therefore the over all goal of the formularly is to help health professionals base their practice on solid information and knowledge to promote rational use of drugs. To accommodate as much information as possible on each drug, formularies of other countries (eg. South Africa) and standard text books of pharmacy, pharmacology and therapeutics has also been used. The formulary contains detailed information on each pharmaco-therapeutic class of drugs and specific information for each drugs including indication, caution, drug interaction, contraindication, side effect, dose and administration and information on storage condition. The formulary also contains general notes on good prescribing and dispensing practices, and supplementary information as appendixes. The formulary is designed as a digest for rapid reference and it may not always include all the information necessary for prescribing and dispensing. It is also hoped that the formulary will be of particular use to those health professionals working at the periphery who have no access to adequate and up to date information. The Authority will continuously update the formularly and would like to invite readers to share their expertise in the field and provide comments to the following adderess: Drug Administration and Control Authority of Ethiopia Planning and Drug information establsihment and dissemination Department P. Bad prescribing habits lead to ineffective and unsafe treatment, exacerbation or prolongation of illness, distress and harm to the patient, and higher cost. The following steps will help to remind prescribers of the rational approach to therapeutics. This will help in rational prescribing, always bearing in mind that diseases are evolutionary processes. Specify the therapeutic objective Doctors must clearly state their therapeutic objectives based on the pathophysiology underlying the clinical situation. Very often physicians must select more than one therapeutic goal for each patient. Select therapeutic strategies the selected strategy should be agreed with the patient; this agreement on outcome, and how it may be achieved, is termed concordance. The selected treatment can be non-pharmacological and/or pharmacological; it also needs to take into account the total cost of all therapeutic options. Non-pharmacological treatment It is very important to bear in mind that the patient does not always need a drug for treatment of the condition. This step is based on evidence about maximal clinical benefits of the drug for a given indication (efficacy) with the minimum production of adverse effects (safety). It must be remembered that each drug has adverse effects and it is estimated that up to 10% of hospital admissions in industrialized countries are due to adverse effects. Not all drug-induced injury can be prevented but much of it is caused by inappropriate selection of drugs. In cost comparisons between drugs, the cost of the total treatment and not only the unit cost of the drug must be considered. This step gives rise to important information about the effects of drugs contributing to building up the body of knowledge of pharmacovigilance, needed to promote the rational use of drugs. Unfortunately drug treatment frequently fails because xii the dose is too small or produces adverse effects because it is too large. This is because most texts, teachers and other drug information sources continue to recommend standard doses. The concept of a standard or with average adult dose for every medicine is firmly rooted in the mind of most prescribers. After the initial with dose ranging studies on new drugs, manufacturers recommend a dosage that appears to produce the desired response in the majority of subjects. These studies are usually done on healthy, young male Caucasian volunteers, rather than on older men and women with illnesses and of different ethnic and environmental backgrounds. The use of standard doses in the marketing literature suggest that standard responses are the rule, but in reality there is considerable variation in drug response. As a result many prescribed doses are far too low or too high, leading to treatment failure or toxicity. There are many reasons for this variation which include adherence (see below), drug formulation, body weight and age, composition, variation in absorption, distribution, metabolism and excretion, variation in pharmacodynamics, disease variables, genetic and environmental variables. Enteric-coated drugs are particularly problematic, and have been known to pass through the gastrointestinal tract intact. Some drugs like digoxin or phenytoin have a track record of formulation problems, and dissolution profiles can vary not only from manufacturer to manufacturer but from batch to batch of the same company. The problem is worse if there is a narrow therapeutic to toxic ratio, as changes in absorption can produce sudden changes in drug concentration. Body weight and age Although the concept of varying the dose with the body weight or age of children has a long tradition, adult doses have been assumed to be the same irrespective of size or shape. Yet adult weights vary two to threefold, while a large fat mass can store large excesses of highly lipid soluble drugs compared to lean patients of the same weight. Adolescents may oxidize some drugs relatively more rapidly than adults, while the elderly may have reduced renal function and eliminate some drugs more slowly. Physiological and pharmacokinetic variables Drug absorption rates may vary widely between individuals and within the same individual at different times and in different physiological states. Drugs taken after a meal are delivered to the small intestine much more slowly than in the fasting state, leading to much lower drug concentrations. In the case of drugs xiii like paracetamol with a high rate of metabolism on with first pass through the liver, this may render a standard dose completely ineffective. In pregnancy gastric emptying is also delayed, while some drugs may increase or decrease gastric emptying and affect absorption of other drugs. Drug distribution Drug distribution varies widely: fat soluble drugs are stored in adipose tissue, water soluble drugs are distributed chiefly in the extracellular space, acidic drugs bind strongly to plasma albumin and basic drugs to muscle cells. Hence variation in plasma albumin levels, fat content or muscle mass may all contribute to dose variation. With very highly albumin bound drugs like warfarin, a small change of albumin concentration can produce a big change in free drug and a dramatic change in drug effect. Drug metabolism and excretion Drug metabolic rates are determined both by genetic and environmental factors. Drug acetylation shows genetic polymorphism, whereby individuals fall clearly into either fast or slow acetylator types. Drug oxidation, however, is polygenic, and although a small proportion of the population can be classified as very slow oxidizers of some drugs, for most drugs and most subjects there is a normal distribution of drug metabolizing capacity, and much of the variation is under environmental control. Renal disease or toxicity of other drugs on the kidney can therefore slow excretion of some drugs. Pharmacodynamic variables There is significant variation in receptor response to some drugs, especially central nervous system responses, for example pain and sedation. Some of this is genetic, some due to tolerance, some due to interaction with other drugs and some due to addiction, for example, morphine and alcohol. Disease variables Both liver disease and kidney disease can have major effects on drug response, chiefly by the effect on metabolism and elimination respectively (increasing toxicity), but also by their effect on plasma albumin (increased free drug also increasing toxicity). Heart failure can also affect metabolism of drugs with rapid hepatic clearance (for example lidocaine, propranolol). For example in infantile malnutrition and in malnourished elderly populations drug oxidation rates are decreased, while high protein diets, charcoal cooked foods and certain other foods act as metabolizing enzyme inducers. Chronic alcohol use induces oxidation of other drugs, but in the presence of high circulating alcohol concentrations drug metabolism may be inhibited. Rational Dispensing Good dispensing practices ensure that the correct drug is delivered to the right patient, in the required dosage and quantities, with clear instructions, and in package that maintains an acceptable potency and quality of the drug. Dispensing includes all the activities that occur between the time the prescription or oral request of the patient or care provider is presented and the drug or other items are issued to them. This process may take place in health institutions and community drug retail outlets. No matter where dispensing takes place or who does it, any error or failure in the dispensing process can seriously affect the care of the patient mainly with medical and economical consequences. The quality of dispensing may be determined by the training and supervision the dispenser has received and the drug information available to the dispenser. A shortage of dispensing materials and insufficient dispensing time due to heavy patients load may also have adverse impacts on dispensing. One good way to reduce the dispensing time and potential errors is to prepackaging and labeling commonly used drugs. Another way to prevent staff from making errors when working under pressure is to organize the work so that more than one individual is involved in the dispensing process for each prescription. Pharmacist or other health professionals involved in dispensing drugs have a need for drug information in order to keep themselves up to date with developments related to drugs and to provide such information to patients, other health professionals and to the general public. Because of an increasing number and complexity of drugs, the need for up-to-date information is greater than ever. The provision of drug information to physicians and other health care professionals is mainly directed at improving prescribing and drug administration. On the other hand, because counseling of patients on medications is an integral part of the dispensing of a prescription or their oral requests, drug dispensers should be adequately equipped with up-to-date drug information. Lack of knowledge and information by patients about the drugs xv they take leads to incorrect use which in turn results in loss of efficacy or occurrence of adverse effects. Communication skill is very important for dispensers dealing with patients or health care professionals to convey relevant drug information effectively and clearly, which can be done verbally and/or in written form. Drug dispensers must have the ability to explain information clearly by the language particularly the patient or care provider can understand and check whether the information is being understood by them. Failure to adhere with such a prescription has been described as with intelligent noncompliance. Bad prescribing or a dispensing error may also create a problem, which patients may have neither the insight nor the courage to question. Factors may be related to the patient, the disease, the doctor, the prescription, the pharmacist or the health system and can often be avoided. The Following points are recommended to increase patient compliance 9 Review the prescription to be sure it is correct. They differ from accidental or deliberate excessive dosage or drug maladministration. Major factors predisposing to adverse effects It is well known that different patients often respond differently to a given treatment regimen. For example, in a sample of 2422 patients who had been taking combinations of drugs known to interact, only 7 (0.

From a clinical point of view acne 19 years old purchase 15 gr differin with visa, however skin care 3 months before marriage purchase differin amex, it be clear from the above that acne images buy genuine differin on line, whereas impair is important to remember that isolated unilat ment of mediolateral movements of the eyes eral or bilateral abducens palsy does not nec mainly indicates imbalance of the two cog essarily indicate a site of injury acne icd 10 code purchase cheapest differin. The emergence nate rectus muscles acne 6 months after stopping pill differin 15 gr sale, disturbances of upward or of the trochlear nerve from the dorsal mid downward movement are far more complex to brain just behind the inferior colliculus makes work out skin care 2014 generic 15 gr differin free shipping, as they result from dysfunction of it prone to injury by the tentorial edge (which the complex set of balanced contractions of the runs along the adjacent superior surface of the other four muscles acne 9 dpo cheap 15gr differin amex. The course of all three ocular motor nerves It passes through the tentorial opening and through the cavernous sinus and superior or runs adjacent to the posterior communicating bital ssure means that they are often damaged artery acne 5 days after ovulation differin 15gr lowest price, where it is subject to injury by posterior in combination by lesions at these sites. The nerve lesion of all three of these nerves unilaterally then runs through the cavernous sinus and su indicates injury in the cavernous sinus or supe perior orbital ssure to the orbit, where it di rior orbital ssure rather than the brainstem. The Head trauma causing a blowout fracture of superior branch innervates the superior rectus the orbit may trap the eye muscles, resulting muscle and the levator palpebrae superioris, in abnormalities of ocular motility unrelated to which raises the eyelid, and the inferior branch any underlying brain injury. The entrapment supplies the medial and inferior rectus and of the eye muscles is determined by forced inferior oblique muscles as well as the ciliary duction. The abducens nerve exits from the the globe) as described below in the exami base of the pons, near the midline. These af neal tumor) causes loss of vertical eye move ferents arise from cortical, tectal, and tegmen ments, usually beginning with upgaze. Each superior collicu greatly different from the types of inputs that lus contains a map of the visual world on the control alpha-motor neurons concerned with contralateral side of space, and electrical stim striated muscles, except the oculomotor mus ulation of a speci c point in this visual map will cles do not contain muscle spindles and hence command a saccade to the corresponding point there is no somesthetic feedback. In nonmammalian vertebrates, such as the oculomotor nuclei are surrounded by frogs, this area is called the optic tectum and is areas of the brainstem tegmentum containing the principal site for directing eye movement; premotor cell groups that coordinate eye move in mammals, it comes largely under the control 93,95,96 ments. The premotor area for regulating of the cortical system for directing eye move lateral saccades consists of the paramedian ments. However, it would effect is to allow conjugate lateral saccades to be incorrect to think of this area as a motor the ipsilateral side of space, and when neurons cortex. Unlike neurons in the primary motor in this area are inactivated by injection of local cortex, which re in relation to movements of anesthetic, ipsilateral saccades are slowed or the limbs in particular directions at particu eliminated. In addition, neurons in the dorsal lar joints, recordings from area 8 neurons in pontine nuclei relay smooth pursuit signals to awake, behaving monkeys indicate that they the occulus, and the medial vestibular nucleus do not re during most random saccadic eye and occulus are both important for holding movements. Inputsfromthesesystemscon ing tasks that require a saccade to a particular verge on the abducens nucleus, which contains part of space only when the saccadic eye two classes of neurons: those that directly in movement is part of a behavioral sequence that nervate the lateral rectus muscle (motor neu is rewarded. Axons from these latter neurons Area 8 projects widely to both the superior cross the midline at the level of the abducens colliculus as well as the premotor areas for ver nucleus and ascend on the contralateral side of tical and lateral eye movements, and to the 102 the brainstem to allow conjugate lateral gaze. Descend Thus, pontine tegmental lesions typically re ing axons from area 8 mainly run through the sult in the inability to move the eyes to the internal medullary lamina of the thalamus to ipsilateral side of space (lateral gaze palsy). Unilateral le portant in judging movement of objects in 101,103 sions of the rostral interstitial nuclei typically contralateral space. Cortex in this region reduce vertical saccades as well as causing plays a critical role in following movements 99,100 torsional nystagmus. Compression of the originating in that space, including movements Examination of the Comatose Patient 63 toward the ipsilateral space. Thus, following tensive vestibular input as well as somatosen 101 an object that travels from the left to the right sory and visual afferents. The output from engages the right parietal cortex (area 7) to x the occulus ensures the accuracy of saccadic attention on the object, the right area 8 to eye movements and contributes to pursuit eye produce a saccade to pick it up, the right oc movements and the ability to hold an eccen cipital cortex to follow the object to the right, tric position of gaze. The vestibulocerebellum and ultimately the left occipital cortex as well is also critical in learning new relationships to see the object as it enters the right side of between eye movements and visual displace space. Lesions of the vestibulocerebel gages a number of important cortical as well as lum cause ocular dysmetria (inability to perform brainstem pathways necessary to produce eye accurate saccades), ocular utter (rapid to-and movements. Hence, although the test is fairly fro eye movements), and opsoclonus (chaotic 105 sensitive for picking up oculomotor problems eye movements). It may be difficult to dis at a cortical and brainstem level, the interpre tinguish less severe cases of vestibulocerebellar tation of failure of optokinetic nystagmus is a function from vestibular dysfunction. First, visual feedback allows the rapid cor internuclear ophthalmoplegia, a condition that rection of errors in gaze. Second, the ocular occurs quite commonly in multiple sclerosis motor nuclei receive direct and relayed inputs and brainstem lacunar infarcts). Because the eye shows horizontal gaze-evoked nystagmus eyes must respond to changes in head position (slow phase toward the midline, rapid jerks very quickly to stabilize the visual image on laterally), while the adducting eye stops in the the retina, the direct vestibular input, which midline (if the lesion is complete) or fails to identi es angular or linear acceleration of the fully adduct (if it is partial). The abducens only causes a bilateral internuclear ophthal nucleus is located at the same level as the moplegia, but also prevents vertical vestibulo vestibular complex, and it receives inputs from ocular responses or pursuit. In patients the vestibulocerebellum, including the oc with stupor or coma, testing of re ex eyelid and 99 culus, para occulus, and nodulus, receives ex ocular movements must suffice. Eliciting the corneal re ex in coma in sleep, are maintained in a closed position by may require more vigorous stimulation than in tonic contraction of the orbicularis oculi mus an awake subject, but it is important not to cles. Corneal trauma tive state have alternating cycles of eyes open can be completely avoided by testing the cor ing and closing; see Chapter 9. Two to three raise and then release the eyelids, noting their drops of sterile saline are dropped on the 109 tone. Absence of tone or re ex pathways, from the trigeminal nerve and failure to close either eyelid can indicate facial spinal trigeminal nucleus through the lateral motor weakness. Blepharospasm, or strong re brainstem tegmentum to the oculomotor and sistance to eyelid opening and then rapid clo facial nuclei, remain intact. However, some sure, is usually voluntary, suggesting that the patients who wear contact lenses may have per patient is not truly comatose. In gic patients with either metabolic or structural other patients with an acute lesion of the des lesions may resist eye opening, as do some pa cending corticofacial pathways, the blink re ex tients with a nondominant parietal lobe infarct. Hold the eyelids gently in an open position Spontaneous blinking usually is lost in coma to observe eye position and movements in a as a function of the depressed level of con comatose patient. How ophthalmoscope held about 50 cm from the ever, in persistent vegetative state, it may re face and shined toward the eyes of the patient turn during cycles of eye opening (Chapter 9). Most pa bright light implies that the afferent sensory tients with impaired consciousness demon pathways are intact to the brainstem, but does strate a slight exophoria. If it is possible to ob not necessarily mean that they are active at a tain a history, ask about eye movements, as a forebrain level. Even patients with complete congenital strabismus may be misinterpreted destruction of the visual cortex may recover as dysconjugate eye movements due to a brain 107 re ex blink responses to light, but not to stem lesion. Slowly roving eye or depth of the eyelid excursion during blink movements are typical of metabolic encepha ing occurs in patients with ipsilateral facial lopathy, and if conjugate, they imply an intact paresis. In such cases, more suffered trauma, it is important rst to rule out intense vestibular stimulation may be obtained the possibility of a fracture or dislocation of the by testing caloric vestibulo-ocular responses. The on either side with both hands and using the ear canal is rst examined and, if necessary, thumbs to reach across to the eyelids and hold cerumen is removed to allow clear visualiza them open. The brisk, and when the head position is held at head of the bed is then raised to about 30 each extreme for a few seconds, the eyes should degrees to bring the horizontal semicircular gradually come back to midposition. Moving canal into a vertical position so that the re the head back to the opposite side then pro sponse is maximal. The eye movements sleepy, the canal may be irrigated with cool should be smooth and conjugate. The head is water (158Cto208C); this usually induces a then rotated in a vertical plane (as in head brisk response and may occasionally cause nodding) and the eyes are observed for vertical nausea and vomiting. During downward head it is rarely necessary to use caloric stimulation movement, the eyelids may also open (the in such patients. An emesis basin can be placed below the head to the right should cause the eyes to de ear, seated on an absorbent pad, to catch the viate to the left). The ice water is infused at a rate of untary control of gaze overcomes this re ex about 10 mL/minute for 5 minutes, or until a response. After a response is ob consciousness, the oculocephalic re ex should tained, it is necessary to wait at least 5 minutes predominate. To test vertical eye movements, mal responses in both horizontal and vertical both external auditory canals are irrigated si directions imply intact brainstem pathways multaneously with cold water (causing the eyes from the vestibular nuclei through the lower to deviate downward) or warm water (causing pontine tegmentum and thence the upper upward deviation). The effect of the current upon the hair which also travel through the medial longitu cells in the ampulla is to reduce tonic dis dinal fasciculus. In con to the opposite side), the result of cold water trast, patients with metabolic encephalop stimulation is to produce a stimulus as if the athy, particularly due to hepatic failure, may head were turning to the opposite side, thus have exaggerated or very brisk oculocephalic activating the ipsilateral lateral rectus and con responses. The le f t and sid e sh ows th e re sponse s tooculoce ph alic mane uve rs (w ich sh ould onlybe d one af the rth e possibilityo ce rvical spine inj uryh as be e ne liminate d). R ow(E illustrate s a patie nt with a mid braininf arctione liminatin both th e oculomotorand troch le arre sponse s, le avin onlybilate ralabd uctionre sponse s. The tivates the ipsilateral superior rectus and the patient could not follow a moving light to either contralateral inferior oblique muscles) and the side or up or down. Hearing was intact, as were posterior canal (which activates the ipsilateral facial, oropharyngeal, and tongue motor and sen superior oblique and contralateral inferior rec sory responses. Motor and sensory examination tus muscles) by caloric stimulation cancel each was also normal, tendon re exes were symmetric, other out. At that point, the pupils were tion of nystagmus is the direction of the fast pinpoint and the patient was unresponsive with component). This mnemonic can be con bility of a brainstem injury even without uncon fusing for inexperienced examiners, as the re sciousness. The absence of a or more eye muscles may become trapped response to caloric stimulation does not always by a blowout fracture of the orbit. Bilateral vestib portant to distinguish this cause of abnor ular failure occurs with phenytoin or tricyclic mal eye movements from damage to neural antidepressant toxicity. Inability to move the globe through pathways are spatially so close to those in a full range of movements may indicate a volved in producing wakefulness, it is rare for a trapped muscle and requires evaluation for patient to have acute damage to the oculo orbital fracture. Detailed descriptions are given tative lesions, as compressive or metabolic dis in the paragraphs below. Most individuals have orders generally do not affect the supranuclear a mild degree of exophoria when drowsy and ocular motor pathways asymmetrically. However, other structive lesion involving the frontal eye elds individuals have varying types of strabismus, causes the eyes to deviate toward the side of which may worsen as they become less re the lesion (away from the side of the associ sponsive and no longer attempt to maintain ated hemiparesis). An irritative determine the meaning of dysconjugate gaze lesion may cause deviation of the eyes away in a stuporous or comatose patient if nothing from the side of the lesion. These eye move is known about the presence of baseline stra ments represent seizure activity, and often bismus. For example, injury of gaze for several hours, causing lateral gaze to the oculomotor nucleus or nerve produces deviation toward the side of the affected cor exodeviation of the involved eye. In skew deviation, in which may also produce with with wrong-way eyes, which 115,116 one eye is deviated upward and the other deviate away from the side of the lesion. Dam Combined loss of adduction and vertical age to the lateral pons, on the other hand, may movements in one eye indicates an oculomotor cause loss of eye movements toward that side nerve impairment. The lateral gaze devi severe ptosis on that side (so that if the patient ation in such patients cannot be overcome by is awake, he or she may not be aware of dip vestibular stimulation, whereas vigorous ocu lopia). In rare cases with a lesion of the ocu locephalic or caloric stimulation usually over lomotor nucleus, the weakness of the superior comes lateral gaze deviation due to a cortical rectus will be on the side opposite the other gaze paresis. The classical nerve paresis due to brainstem injury or com cause of oculogyric crises was postencephalitic pression of the oculomotor nerve by uncal her parkinsonism. If awake, the patient typically attempts to compensate by tilting the head toward that shoulder. Absence of abduction of a single eye suggests injury to the abducens nerve ei Skew deviation refers to vertical dysconjugate ther within the brainstem or along its course to gaze, with one eye displaced downward com the orbit. In some cases, the eye that nial pressure or decreased pressure, as occurs is elevated may alternate from side to side de 121 with cerebral spinal uid leaks, can cause pending on whether the patient is looking to 95,122 either a unilateral or bilateral abducens palsy, the left or the right. Skew deviation is due so the presence of an isolated abducens palsy either to a lesion in the lateral rostral medulla may be misleading. Bilateral lesions of the medial longitudinal fasciculus impair ad these are slow, random deviations of eye po duction of both eyes as well as vertical oculo sition that are similar to the eye movements cephalic and vestibulo-ocular eye movements, seen in normal individuals during light sleep. Most roving descending inputs that relax the opposing eye eye movements are predominantly horizontal, muscles when a movement is made, so that all although some vertical movements may also six muscles contract when attempts are made occur. The roving eye movements may disap the eyes diverge slowly, and this is followed by pear as the coma deepens, although they may a quick convergent jerk. A variant of roving eye movements is the eyes make a brisk, conjugate downward 126 periodic alternating or with with ping-pong gaze, movement, then with with bob back up more slowly to in which repetitive, rhythmic, and conjugate primary position. The patients were comatose horizontal eye movements occur in a comatose and the movements were not affected by ca or stuporous patient. The initially de gately to the extremes of gaze, hold the posi scribed patients had caudal pontine injuries or tion for 2 to 3 seconds, and then rotate back compression, although later reports described again. The episodic movements of the eyes similar eye movements in patients with ob may continue uninterrupted for several hours structive hydrocephalus, uncal herniation, or to days. A variety of re have been reported in patients with a variety of lated eye movements have been described in structural injuries to the brainstem or even cluding inverse bobbing (rapid elevation of bilateral cerebral infarcts that leave the ocu the eyes, with bobbing downward back to pri lomotor system largely intact, but are most mary position) and both dipping (downward common during metabolic encephalopathies. The implications of Nystagmus refers to repetitive rapid (saccadic) these unusual eye movements are similar to eye movements, often alternating with a slow those of ocular bobbing: a lower brainstem in drift in the opposite direction. Spontaneous jury or compression of normal vestibulo-ocular nystagmus is uncommon in coma because the inputs. This is followed by tinuous seizure activity with versive eye move reversal of the movements. Seesaw nystagmus appears to be due Retractory nystagmus consists of irregular in most cases to lesions near the rostral end jerks of both globes back into the orbit, of the periaqueductal gray matter, perhaps sometimes occurring spontaneously but other involving the rostral interstitial nucleus of 133 times on attempted upgaze. It may occasionally be seen also in during retractory nystagmus shows that the comatose patients, sometimes accompanied by retractions consist of simultaneous contrac ocular bobbing, and in such a setting may in 127 134 tions of all six extraocular muscles. As patients become more the motor examination in a stuporous or co deeply stuporous, muscle tone tends to de matose patient is, of necessity, quite different crease and these pathologic forms of rigidity are from the patient who is awake and cooperative. Rather than testing power in speci c muscles, it is focused on assessing the overall respon siveness of the patient (as measured by motor Motor Re exes response), the motor tone, and re exes, and identifying abnormal motor patterns, such as Muscle stretch re exes (sometimes erroneously hemiplegia or abnormal posturing. Motor Tone As the level of consciousness becomes further depressed, however, the muscle stretch re Assessment of motor tone is of greatest value in exes tend to diminish in activity, until in pa patients who are drowsy but responsive to tients who are deeply comatose they may be voice. On the sessed in the neck by gently grasping the head other hand, in patients who are drowsy or with two hands and moving it back and forth or confused, some abnormal cutaneous re exes up and down, and in the lower extremities by may be released. These may include extensor grasping each leg at the knee and gently lifting plantar responses. Prefrontal cutaneous re exes, sometimes Spastic rigidity, on the other hand, increases called with with frontal release re exes or primitive 135 with more rapid movements and generally has re exes, may also emerge in drowsy patients a clasp-knife quality or a spastic catch, so that with diffuse forebrain impairment. Rooting, the movement is slowed to a near stop by the glabellar, snout, palmomental, and other re resistance, at which point the resistance col exes are often seen in such patients. Par ever, these responses become increasingly kinsonian rigidity remains equally intense de common with advancing age in patients with spite the movement of the examiner (lead-pipe out cognitive impairment, so they are of lim 136 rigidity), but is usually diminished when the ited value in elderly individuals. On the patient is asleep or there is impairment of con other hand, the grasp re ex is generally seen sciousness. In contrast, during diffuse meta only in patients who have some degree of bi 137 bolic encephalopathies, many otherwise nor lateral prefrontal impairment. It is elicited mal patients develop paratonic rigidity, also by gently stroking the palm of the patient with called gegenhalten. The pull re ex is a variant in which the movement increases, as if the patient were the examiner curls his or her ngers under the willfully resisting the examiner. The drowsy but responsive to voice, urging him or grasp is often so strong that it is possible to her to with with relax may result in increased tone. Many elderly Examination of the Comatose Patient 73 patients with normal cognitive function will Like paratonia, prefrontal re exes are normally have a mild tendency to grasp the rst time the present in young infants, but disappear as the 135 re ex is attempted, but a request not to grasp forebrain matures. Patients who are unable to inhibit the re ex invariably have prefrontal pathology. Grasping disappears when the lesion tient does not respond to voice or gentle shak involves the motor cortex and causes hemi ing, arousability and motor responses are tes paresis. The maneuvers used tient who can cooperate with the exam; it dis to provide adequate stimuli without inducing appears as the patient becomes more drowsy. Motor responses to noxious stimulation in patients with acute cerebral dysfunction. Patients with forebrain or diencephalic lesions often have a hemiparesis (note lack of motor response with left arm, externally rotated left foot, and left extensor plantar response), but can gen erally make purposeful movements with the opposite side. Lesions involving the junction of the diencephalon and the mid brain may show decorticate posturing, including exion of the upper extremities and extension of the lower extremities. As the lesion progresses into the midbrain, there is generally a shift to decerebrate posturing (C), in which there is extensor posturing of both upper and lower extremities. An appropriate re mals, these patterns of motor response may be sponse is one that attempts to escape the stim produced by brain lesions of several different ulus, such as pushing the stimulus away or kinds and locations and the patterns of motor attempting to avoid the stimulus. The motor response in an individual to any one of these response may be accompanied by a facial gri lesions may vary across time. It types of responses can be produced by supra is necessary to distinguish an attempt to avoid tentorial lesions, although they imply at least the stimulus, which indicates intact sensory incipient brainstem injury. There is a tendency and motor connections within the spinal cord for lesions that cause decorticate rigidity to be and brainstem, from a stereotyped withdrawal more rostral and less severe than those caus response, such as a triple exion withdrawal of ing decerebrate rigidity. In general, there is the lower extremity or exion at the ngers, much greater agreement among observers if wrist, and elbow. The stereotyped withdrawal they simply describe the movements that are response is not responsive to the nature of the seen rather than attempt to t them to com stimulus. The fully developed occur in patients with severe brain injuries or response consists of a relatively slow (as op even brain death. It is also important to assess posed to quick withdrawal) exion of the arm, asymmetries of response.

The route of administration skin care insurance purchase differin overnight delivery, and whether it is prescribed on a regular or as-required basis acne zyme buy cheap differin online, depends on the clinical situation acne 7-day detox buy differin online. For example acne keloid quality differin 15gr, the oral route is clearly inappropriate for a patient who is actively vomiting acne antibiotic treatment differin 15 gr mastercard. Administration Intravenous injections of metoclopramide should be given slowly over about 2 minutes for a standard 10 mg dose; by infusion for higher doses acne varioliformis purchase differin no prescription. If you are prescribing outside hospital acne in children buy generic differin on-line, it is prudent to mention the possibility of muscle spasms and abnormal movements with metoclopramide acne questionnaire buy cheap differin 15gr on-line. Ask your patient to stop taking the medicine and seek medical attention if they notice any side effects of this type. The rectal form of domperidone is relatively more expensive (about 60p per 60 mg dose, compared to as little as 1p per 10 mg oral tablet). Appropriate investigations should have been undertaken to identify treatable causes for refux symptoms, such as ulcers, Helicobacter pylori infection, drugs and cancer. Histamine (H1) and acetylcholine (muscarinic) receptors predominate in the vomiting centre and in its communication with the vestibular system. This makes them useful treatments for nausea and vomiting in a wide range of conditions. Cyclizine is the least adverse effects sedating drug in this class and is therefore usually preferred. This is usually undesirable, but in patients with copious mucosal secretions it may be benefcial. Along with their central anticholinergic effects (excitation or depression) this may make for a rather unpleasant experience. Warnings Due to their sedating effect, these drugs should be avoided in patients at risk of hepatic encephalopathy. They should also be avoided in patients susceptible to anticholinergic side effects, such as those with prostatic hypertrophy (who may develop urinary retention). Important Sedation may be greater when combined with other sedative drugs interactions. Anticholinergic effects may be more pronounced in patients taking ipratropium or tiotropium. Administration Intravenous injections of cyclizine should be given slowly (over about 2 minutes). Advise that it may cause drowsiness and impair the ability to perform tasks such as driving, which they should therefore avoid. It is widely used as an over-the counter remedy for this indication and is effective. However, due to their side effect profle, other antiemetic classes are usually preferable. Psychotic disorders, such as schizophrenia, where they are used as frst-generation (typical) antipsychotics. This makes them effective for nausea and vomiting in a wide range of situations, including chemotherapy, radiotherapy and vertigo. Important Drowsiness and postural hypotension are relatively common with adverse effects phenothiazines. Movement abnormalities, termed extrapyramidal syndromes, are a major drawback of their use. They arise from D2 receptor blockade via the same mechanism as for other frst-generation (typical) antipsychotics. In the context of short-term treatment for nausea and vomiting, this is most likely to take the form of an acute dystonic reaction such as oculogyric crisis. In longer-term treatment (which is more likely when they are used as an antipsychotic), other extrapyramidal syndromes such as tardive dyskinesia may occur (see Antipsychotics, frst-generation [typical]). Warnings Due to their sedative effect and potential for hepatotoxicity, these drugs should be avoided in patients with severe liver disease. A typical prescription in the context of nausea and vomiting might be for prochlorperazine 20 mg orally or 12. Administration Intramuscular prochlorperazine should be administered by deep injection in a large muscle. Discuss the potential for drowsiness (and its implications for driving) and dizziness on standing. Ask them to stop taking the medicine and seek medical advice if they develop any muscle spasms or movement abnormalities. In prolonged use you should monitor the patient for extrapyramidal features, as these may be subtle. A buccal tablet is also available; this is a branded product which is about ten times as expensive as the oral form. However, haloperidol (also a frst-generation (typical) antipsychotic) is used quite commonly, particularly for opioid-induced nausea. Mechanisms of Nausea and vomiting are triggered by a variety of factors, including action gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (sights, smells, emotions). Second, serotonin is the key neurotransmitter released by the gut in response to emetogenic stimuli. Of note, serotonin is not involved in communication between the vestibular system and the vomiting centre. Important Adverse effects are rare with these medications, although constipation, adverse effects diarrhoea and headaches can occur. The dosing regimens differ for each indication, with higher doses generally reserved for chemotherapy-induced nausea and vomiting. The route of administration, and whether it is prescribed on a regular or as-required basis, depends on the clinical indication. Although it is generally effective, it does not work for everyone and a second or different medicine may be necessary. It can be diffcult to treat as drugs administered during the frst trimester of pregnancy may cause spontaneous abortion and fetal abnormalities. Although ondansetron is not licensed for morning sickness, a recent historical study of 608,385 women in Denmark found no evidence of adverse fetal outcomes related to taking ondansetron in pregnancy. They may be applied topically (nystatin, clotrimazole) or taken orally (fuconazole). Specialist treatment is required for these infections, which will not be discussed further in this book. As ergosterol is not seen action in animal or human cells it is a target for antifungal drugs. Resistance to antifungals is unusual but can occur during long-term treatment in immunosuppressed patients. Mechanisms include alteration of membrane synthesis to exclude ergosterol, changes in target enzymes or increased drug effux. Important Topical nystatin and clotrimazole have few adverse effects apart from adverse effects occasional local irritation where applied. The most common adverse effects of fuconazole are gastrointestinal upset (including nausea, vomiting, diarrhoea and abdominal pain), headache, hepatitis and hypersensitivity causing skin rash. Fluconazole should be prescribed with caution in patients with liver disease because of the risk of hepatic toxicity. Important There are no signifcant drug interactions with nystatin or clotrimazole. It may reduce the antiplatelet actions of clopidogrel, a pro-drug which requires activation by liver metabolism. It is administered as a cream for skin infections at a dose of 100,000 units two to three times daily until 7 days after dermatological lesions have resolved. Fluconazole is also available as an intravenous preparation for invasive or disseminated fungal infection. Administration Oral nystatin should be administered after food and held in the mouth to allow good contact with the lesions. If the patient wears dentures, they should remove them to expose affected areas to treatment. Communication Advise patients that, with correct application, treatment should improve symptoms. Warn patients treated with a prolonged course of fuconazole to seek medical advice if they experience any unusual symptoms such as nausea, loss of appetite, lethargy or dark urine which could indicate liver poisoning. For fuconazole, liver enzymes should be measured before and during prolonged courses of treatment, particularly where high doses are used, to monitor for hepatic toxicity. They are commonly treated with antibiotics and systemic or inhaled corticosteroids, which predispose to oral candidiasis, and with antimuscarinic drugs that reduce saliva (natural defence mechanism). To aid relief of itchiness (pruritus) and hives (urticaria) due, for example, to insect bites, infections. As an adjunctive treatment in anaphylaxis, after administration of adrenaline and other life-saving measures. Mechanisms of the term with antihistamine is generally used to mean an antagonist of the action H1 receptor. Histamine is released from storage granules in mast cells as a result of antigen binding to IgE on the cell surface. Mainly via H1 receptors, histamine induces the features of immediate type (type 1) hypersensitivity: increased capillary permeability causing oedema formation (wheal), vasodilatation causing erythema (fare), and itch due to sensory nerve stimulation. When histamine is released in the nasopharynx, as in hay fever, it causes nasal irritation, sneezing, rhinorrhoea, congestion, conjunctivitis and itch. Widespread histamine release, as in anaphylaxis, produces generalised vasodilatation and vascular leakage, with consequent hypotension. Antihistamines work in these conditions by antagonism at the H1 receptor, blocking the effects of excess histamine. In anaphylaxis, their effect is too slow to be life-saving, so adrenaline is the more important frst-line treatment. This because histamine, via H1 receptors, has a role in the brain in maintaining wakefulness. Warnings Commonly used antihistamines, including those mentioned above, are safe in most patients. Important the antihistamines mentioned here are not subject to any major drug interactions interactions. Administration There are no special considerations for the administration for cetirizine and loratadine. Although oral chlorphenamine may be taken throughout the day, some patients prefer to reserve it for use in the evening when its sedating effect may be desirable. Communication As appropriate, explain that you are offering a treatment to help relieve their allergic symptoms or their itchy rash/hives. In hay fever, the tablets should improve sneezing, itchiness and runniness, but tend not to help with nasal congestion. In the cases of cetirizine and loratadine, you can say that you do not anticipate any side effects. For chlorphenamine, you should mention that it may make them feel sleepy or lose concentration. They should therefore avoid taking it if they need to drive or carry out any other activity that requires concentration. They should also avoid combining it with alcohol, which may exacerbate the effect. Patients who pay for their prescriptions will generally save money if they buy them directly from a pharmacy. Mechanisms of Loperamide is an opioid that is pharmacologically similar to pethidine. This increases non-propulsive contractions of the gut smooth muscle but reduces propulsive (peristaltic) contractions. As a result, transit of bowel contents is slowed and anal sphincter tone is increased. Slower gut transit also allows more time for water absorption, which (in the context of watery diarrhoea) has a desirable effect in hardening the stool. These are adverse effects mostly gastrointestinal effects predictable from its mechanism of action. Indirectly, adverse effects may arise from the inappropriate inhibition of peristalsis (see Warnings). Warnings Loperamide should be avoided in acute ulcerative colitis where inhibition of peristalsis may increase the risk of megacolon and perforation. For the same reason, it should be avoided where there is a possibility of Clostridium diffcile colitis, including in patients who develop diarrhoea in association with broad-spectrum antibiotic use (see Clinical tip). It should not be used in acute bloody diarrhoea (dysentery) because this may signify bacterial infection. In acute with simple diarrhoea, the usual dose is 4 mg, followed by 2 mg with each loose stool, generally to a maximum of 8 mg (4 tablets) per day. A syrup form is available, which may be useful in children (over 4 years old) with acute viral gastroenteritis. Communication You should ensure your patient is aware that the only purpose of loperamide is to help settle the diarrhoea. Make sure they know to stop taking it if they develop constipation, abdominal pain, or (in acute diarrhoea) they fnd they need to take it for more than 5 days. Monitoring the best means of monitoring is to enquire about stool frequency and abdominal symptoms. Patients who have to pay for their prescriptions will probably save money if they buy it over the counter rather than on prescription. Make sure you explain this to the patient, who may be frustrated that while in hospital they cannot get a medicine that, if they were at home, they would simply buy from the chemist. In asthma, short-acting antimuscarinics are used as adjuvant treatment for relief of breathlessness during acute exacerbations (added to a short-acting 2 agonist. Long-acting antimuscarinics are added to high-dose inhaled corticosteroids and long-acting 2 agonists at with step 4 in the treatment of chronic asthma. Stimulation of the muscarinic receptor brings about a wide range of parasympathetic with rest and digest effects. In blocking the receptor, antimuscarinics have the opposite effects: they increase heart rate and conduction; reduce smooth muscle tone, including in the respiratory tract; and reduce secretions from glands in the respiratory and gastrointestinal tracts. Important When antimuscarinic bronchodilators are taken by inhalation, there is adverse effects relatively little systemic absorption. Warnings Antimuscarinics should be used with caution in patients susceptible to angle-closure glaucoma, in whom they can precipitate a dangerous rise in intraocular pressure. However, in practice, most patients can take these drugs by inhalation without major problems. Important Interactions are not generally a problem due to low systemic absorption. Administration Inhaled medication comes in a range of inhaler devices, with the choice of medicine often being directed by the device that best suits the patient. Medication for nebulisation comes as a liquid, which is put into the chamber below a mask covering the mouth and nose of the patient. Oxygen is bubbled through the liquid, vaporising the medicine for the patient to inhale. In patients at risk of carbon dioxide retention, medical air is used in place of oxygen. Communication Explain that you are offering a treatment to make their airways relax, which should therefore improve their breathing. Discuss possible side effects, such as dry mouth, and advise them to chew gum or suck sweets (which should be sugar-free; see Antimuscarinics, genitourinary uses), or keep a bottle of water with them to relieve these. Monitoring You should check if the treatment has worked by asking the patient about symptoms and reviewing peak fow measurements (asthma). You should check their inhaler technique every time they are reviewed and correct it as necessary to optimise potential treatment benefts. Long-acting antimuscarinics are newer medicines, with most drugs and inhaler devices remaining under patent protection. Mechanisms of Antimuscarinic drugs bind to the muscarinic receptor, where they act action as a competitive inhibitor of acetylcholine. In blocking the receptor, antimuscarinics have the opposite effects: they increase heart rate and conduction; reduce smooth muscle tone and peristaltic contraction, including in the gut and urinary tract; and reduce secretions from glands in the respiratory tract and gut. In the eye they cause relaxation of the pupillary constrictor and ciliary muscles, causing pupillary dilatation and preventing accommodation, respectively. Important Predictably from their antagonism of parasympathetic with rest and digest adverse effects effects, antimuscarinics can cause tachycardia, dry mouth and constipation. By reducing detrusor muscle activity, they can cause urinary retention in patients with benign prostatic hypertrophy.

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