Dennis Parker, Jr, PharmD

• Neurocritical Care Clinical Pharmacist, Detroit Receiving Hospital
• Clinical Associate Professor, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan

https://cphs.wayne.edu/profile/ah2262

Therefore allergy medicine 7253 discount 4mg aristocort mastercard, the total buffer capacity of the blood in the physiologic range allergy to mold purchase aristocort master card, the sum of the capacities of the various constituents allergy shots while pregnant purchase aristocort without prescription, is 0 allergy headache aristocort 4mg amex. Lacrimal fluid allergy shots vs xolair purchase generic aristocort on-line, or tears allergy shots epinephrine discount aristocort 4mg with visa, have been found to have a great degree of buffer capacity, allowing a dilution of 1:15 with neutral distilled water before an alteration of pH is noticed. It is generally thought that eye drops within a pH range of 4 to 10 will not harm the cornea. When the pH of the urine is below normal values, hydrogen ions are excreted by the kidneys. Pharmaceutical Buffers Buffer solutions are used frequently in pharmaceutical practice, particularly in the formulation of ophthalmic solutions. They also find application in the colorimetric determination of pH and for research studies in which pH must be held constant. Gifford13 suggested two stock solutions, one containing boric acid and the other monohydrated sodium carbonate, which, when mixed in various proportions, yield buffer solutions with pH values from about 5 to 9. Sodium chloride is added to each buffer mixture to make it isotonic with body fluids. A buffer system suggested by Palitzsch15 and modified by Hind and Goyan16 consists of boric acid, sodium borate, and sufficient sodium chloride to make the mixtures isotonic. The original values were determined at 20 C, whereas most experiments today are performed at 25 C. General Procedures for Preparing Pharmaceutical Buffer Solutions the pharmacist may be called upon at times to prepare buffer systems for which the formulas do not appear in the literature. The buffer equation is satisfactory for approximate calculations within the pH range of 4 to 10. For example, a borate buffer, because of its toxic effects, certainly cannot be used to stabilize a solution to be administered orally or parenterally. Potassium chloride is added to (e), the borate buffer, to produce an ionic strength comparable to that of (d), the phosphate buffer, where the pH of the two buffer series overlaps. Particularly when the electrolyte concentration is high, it may be found that the pH calculated by use of the buffer equation is somewhat different from the experimental value. This is to be expected when activity coefficients are not taken in to account, and it emphasizes the necessity for carrying out the actual determination. Consequently, the pharmacist must consider this point when formulating ophthalmic solutions, parenteral products, and fluids to be applied to abraded surfaces. Of possible greater significance than the actual pH of the solution is its buffer capacity and the volume to be used in relation to the volume of body fluid with which the buffered solution will come in contact. Tissue irritation, due to large pH differences between the solution being administered and the physiologic environment in which it is used, will be minimal (a) the lower is the buffer capacity of the solution, (b) the smaller is the volume used for a given concentration, and (c) the larger are the volume and buffer capacity of the physiologic fluid. Martin and Mims concluded that a pH range of nonirritation cannot be established absolutely but instead depends upon the buffer employed. In light of the previous discussion, this apparent anomaly can be explained partly in terms of the low buffer capacity of boric acid as compared with that of the phosphate buffer and partly to the difference of the physiologic response to various ion species. They pointed out that although in a few cases, irritation of the eye may result from the presence of the free base form of a drug at the physiologic pH, it is more often due to the acidity of the eye solution. For example, because only one carboxyl group of tartaric acid is neutralized by epinephrine base in epinephrine bitartrate, a 0. The prolonged pain resulting from instilling two drops of this solution in to the eye is presumably due to the unneutralized acid of the bitartrate, which requires 10 times the amount of tears to restore the normal pH of the eye as compared with the result following two drops of epinephrine hydrochloride. Solutions of pilocarpine salts also possess sufficient buffer capacity to cause pain or irritation owing to their acid reaction when instilled in to the eye. Parenteral solutions for injection in to the blood are usually not buffered, or they are buffered to a low capacity so that the buffers of the blood may readily bring them within the physiologic pH range. If the drugs are to be injected only in small quantities and at a slow rate, their solutions can be buffered weakly to maintain approximate neutrality. According to Mason,21 following oral administration, aspirin is absorbed more rapidly in systems buffered at low buffer capacity than in systems containing no buffer or in highly buffered preparations. Thus, the buffer capacity of the buffer should be optimized to produce rapid absorption and minimal gastric irritation of orally administered aspirin. In addition to the adjustment of tonicity and pH for ophthalmic preparations, similar requirements are demanded for nasal delivery of drugs. Conventionally, the nasal route has been used for delivery of drugs for treatment of local diseases such as nasal allergy, nasal congestion, and nasal infections. Stability versus Optimum Therapeutic Response For the sake of completeness, some mention must be made at this point of the effect of buffer capacity and pH on the stability and therapeutic response of the drug being used in solution. As will be discussed later, the undissociated form of a weakly acidic or basic drug often has a higher therapeutic activity than that of the dissociated salt form. This is because the former is lipid soluble and can penetrate body membranes readily, whereas the ionic form, not being lipid soluble, can penetrate membranes only with greater difficulty. Thus, Swan and White23 and Cogan and Kinsey24 observed an increase in therapeutic response of weakly basic alkaloids (used as ophthalmic drugs) as the pH of the solution, and hence concentration of the undissociated base, was increased. At a pH of about 4, these drugs are predominantly in the ionic form, and penetration is slow or insignificant. In addition to carrying out pH adjustment, pharmaceutical solutions that are meant for application to delicate membranes of the body should also be adjusted to approximately the same osmotic pressure as that of the body fluids. Isotonic solutions cause no swelling or contraction of the tissues with which they come in contact and produce no discomfort when instilled in the eye, nasal tract, blood, or other body tissues. Isotonic sodium chloride is a familiar pharmaceutical example of such a preparation. The need to achieve isotonic conditions with solutions to be applied to delicate membranes is dramatically illustrated by mixing a small quantity of blood with aqueous sodium chloride solutions of varying tonicity. For example, if a small quantity of blood, defibrinated to prevent clotting, is mixed with a solution containing 0. The solution has essentially the same salt concentration and hence the same osmotic pressure as the red blood cell contents and is said to be isotonic with blood. This outward passage of water causes the cells to shrink and become wrinkled or crenated. The salt solution in this instance is said to be hypertonic with respect to the blood cell contents. This phenomenon is known as hemolysis, and the weak salt solution or water is said to be hypotonic with respect to the blood. The student should appreciate that the red blood cell membrane is not impermeable to all drugs; that is, it is not a perfect semipermeable membrane. Thus, it will permit the passage of not only water molecules but also solutes such as urea, ammonium chloride, alcohol, and boric acid. The molecules of boric acid pass freely through the erythrocyte membrane, however, regardless of concentration. As a result, this solution acts essentially as water when in contact with blood cells. Because it is extremely hypotonic with respect to the blood, boric acid solution brings about rapid hemolysis. Therefore, a solution containing a quantity of drug calculated to be isosmotic with blood is isotonic only when 7. Under such conditions, the solution of the drug can be buffered at a low buffer capacity and at a pH that is a compromise between that of optimum stability and the pH for maximum therapeutic action. Yet, when the solution is instilled in the eye, the tears participate in the gradual neutralization of the solution; conversion of the drug occurs from the physiologically inactive form to the undissociated base. As the base is absorbed at the pH of the eye, more of the salt is converted in to base to preserve the constancy of pKb; hence, the alkaloidal drug is gradually absorbed. At a low pH, a base is predominantly in the ionic form, which is usually very soluble in aqueous media. When the amount of base exceeds the limited water solubility of this form, free base precipitates from solution. In short, a solution containing a quantity of drug calculated to be isosmotic with blood is isotonic only when the blood cells are impermeable to the solute (drug) molecules and permeable to the solvent, water. Osmolality and osmolarity are colligative properties that measure the concentration of the solutes independently of their ability to cross a cell membrane. Tonicity is the concentration of only the solutes that cannot cross the membrane since these solutes exert an osmotic pressure on that membrane. Tonicity is not the difference between the two osmolarities on opposing sides of the membrane. A solution might be hypertonic, isotonic, or hypotonic relative to another solution. As such, a hypertonic solution contains a higher concentration of impermeable solutes than the cytosol of the the blood cells are impermeable to the solute molecules and permeable to the solvent, water. It is interesting to note that the mucous lining of the eye acts as a true semipermeable membrane to boric acid in solution. To overcome this difficulty, Husa27 suggested that the term isotonic should be restricted to solutions having equal osmotic pressures with respect to a particular membrane. Goyan and Reck28 felt that, rather than restricting the use of the term in this manner, a new term should be introduced that is defined on the basis of the sodium chloride concentration. These workers defined the term isotonicity value as the concentration of an aqueous NaCl solution having the same colligative properties as the solution in question. Accordingly, the term isotonic is used with this meaning throughout the present chapter. Only a few substances-those that penetrate animal membranes at a sufficient rate-will show exception to this classification. The remainder of this chapter is concerned with a discussion of isotonic solutions and the means by which they can be buffered. Measurement of Tonicity the tonicity of solutions can be determined by one of two methods. First, in the hemolytic method, the effect of various solutions of the drug is observed on the appearance of red blood cells suspended in the solutions. In their later work, a quantitative method developed by Hunter29 was used based on the fact that a hypotonic solution liberates oxyhemoglobin in direct proportion to the number of cells hemolyzed. The second approach used to measure tonicity is based on any of the methods that determine colligative properties earlier in the book. This method is based on a measurement of the slight temperature differences arising from differences in the vapor pressure of thermally insulated samples contained in constant-humidity chambers. One of the first references to the determination of the freezing point of blood and tears (as was necessary to make solutions isotonic with these fluids) is that of Lumiere and Chevrotier,32 in which the values of -0. Following work by Pedersen-Bjergaard and coworkers,33,34 however, it is now well established that -0. As a result of this similarity between compounds of a given ionic type, a table can be arranged listing the L value for each class of electrolytes at a concentration that is isotonic with body fluids. It will be observed that for dilute solutions of nonelectrolytes, Liso is approximately equal to Kf. The selection of L values in this concentration region is not sensitive to minor changes in concentration; no pretense to accuracy greater than about 10% is implied or needed in these calculations. The Liso values can also be used for calculating sodium chloride equivalents and Sprowls V values, as discussed in subsequent sections of this chapter. The calculations involved in the cryoscopic method are explained best by an example. To make this solution isotonic with blood, sufficient sodium chloride must be added to reduce the freezing point by an additional 0. In the freezing point table, it is also observed that a 1% solution of sodium chloride has a freezing point lowering of 0. In the class I methods, sodium chloride or some other substance is added to the solution of the drug to lower the freezing point of the solution to -0. Under this class are included the cryoscopic method and the sodium chloride equivalent method. The preparation is then brought to its final volume with an isotonic or a buffered isotonic dilution solution. Sodium Chloride Equivalent Method A second method for adjusting the tonicity of pharmaceutical solutions was developed by Mellen and Seltzer. The values vary somewhat with concentration, and those in the table are for 1% to 3% solutions of the drugs in most instances. The quantity of the drug is multiplied by its sodium chloride equivalent, E, giving the weight of sodium chloride to which the quantity of drug is equivalent in osmotic pressure: Ephedrine sulfate: 1. If one desired to use dextrose instead of sodium chloride to adjust the tonicity, the quantity would be estimated by setting up the following proportion.

Because polymorphic forms represent different molecular arrangements leading to different crystalline forms of the same compound allergy symptoms 5 months order aristocort with a mastercard, it is obvious that different intermolecular forces will account for these different forms allergy treatment nj aristocort 4 mg otc. Then consider polymorph A allergy vinyl symptoms 4mg aristocort visa, which is held together by higher attractive forces than is polymorph B allergy shots zyrtec proven 4mg aristocort. It is obvious that more heat will be required to break down the attractive forces in polymorph A allergy shots when you have a cold order 4 mg aristocort with visa, and thus its melting temperature will be higher than that of polymorph B allergy forecast austin tx purchase aristocort mastercard. Paraffins crystallize as thin leaflets composed of zigzag chains packed in a parallel arrangement. The melting points of normal saturated hydrocarbons increase with molecular weight because the van der Waals forces between the molecules of the crystal become greater with an increasing number of carbon atoms. This phenomenon presumably is because alkanes with an odd number of carbon atoms are packed in the crystal less efficiently. The carboxyl groups are joined at two points in the even-carbon compound; hence, the crystal lattice is more stable and the melting point is higher. The melting points and solubilities of the xanthines of pharmaceutical interest, determined by Guttman and Higuchi,32 further exemplify the relationship between melting point and molecular structure. Solubilities, like melting points, are strongly influenced by intermolecular forces. These effects presumably are due to a progressive weakening of intermolecular forces. The term liquid crystal is an apparent contradiction, but it is useful in a descriptive sense because materials in this state are in many ways intermediate between the liquid and solid states. Structure of Liquid Crystals As seen earlier, molecules in the liquid state are mobile in three directions and can also rotate about three axes perpendicular to one another. In the solid state, on the other hand, the molecules are immobile, and rotations are not as readily possible. It is not unreasonable to suppose, therefore, that intermediate states of mobility and rotation should exist, as in fact they do. It is these intermediate states that constitute the liquid crystalline phase, or mesophase, as the liquid crystalline phase is called. The two main types of liquid crystals are termed smectic (soaplike or greaselike) and nematic (threadlike). In the smectic state, molecules are mobile in two directions and can rotate about one axis. In the nematic state, the molecules again rotate only about one axis but are mobile in three dimensions. A third type of crystal (cholesteric) exists but can be considered as a special case of the nematic type. In atherosclerosis, it is the incorporation of cholesterol and lipids in human subendothelial macrophages that leads to an insoluble liquid crystalline biologic membrane33 that ultimately results in plaque formation. The smectic mesophase is probably of most pharmaceutical significance because it is this phase that usually forms in ternary (or more complex) mixtures containing a surfactant, water, and a weakly amphiphilic or nonpolar additive. In general, molecules that form mesophases (a) are organic, (b) are elongated and rectilinear in shape, (c) are rigid, and (d) possess strong dipoles and easily polarizable groups. The liquid crystalline state may result either from the heating of solids (thermotropic liquid crystals) or from the action of certain solvents on solids (lyotropic liquid crystals). The first recorded observation of a thermotropic liquid crystal was made by Reinitzer in 1888 when he heated cholesteryl benzoate. At 145 C, the solid formed a turbid liquid (the thermotropic liquid crystal), which only became clear, to give the conventional liquid state, at 179 C. For example, liquid crystals are mobile and thus can be considered to have the flow properties of liquids. At the same time they possess the property of being birefringent, a property associated with crystals. In birefringence, the light passing through a material is divided in to two components with different velocities and hence different refractive indices. Some liquid crystals show consistent color changes with temperature, and this characteristic has resulted in their being used to detect areas of elevated temperature under the skin that may be due to a disease process. Nematic liquid crystals may be sensitive to electric fields, a property used to advantage in developing display systems. The smectic mesophase has application in the solubilization of water-insoluble materials. It also appears that liquid crystalline phases of this type are frequently present in emulsions and may be responsible for enhanced physical stability owing to their highly viscous nature. The liquid crystalline state is widespread in nature, with lipoidal forms found in nerves, brain tissue, and blood vessels. The three components of bile (cholesterol, a bile acid salt, and water), in the correct proportions, can form a smectic mesophase, and this may be involved in the formation of gallstones. Bogardus34 applied the principle of liquid crystal formation to the solubilization and dissolution of cholesterol, the major constituent of gallstones. Cholesterol is converted to a liquid crystalline phase in the presence of sodium oleate and water, and the cholesterol rapidly dissolves from the surface of the gallstones. Nonaqueous liquid crystals may be formed from triethanolamine and oleic acid with a series of polyethylene glycols or various organic acids such as isopropyl myristate, squalane, squalene, and naphthenic oil as the solvents to replace the water of aqueous mesomorphs. Ibrahim36 studied the release of salicylic acid as a model drug from lyotropic liquid crystalline systems across lipoidal barriers and in to an aqueous buffered solution. Finally, liquid crystals have structures that are believed to be similar to those in cell membranes. As such, liquid crystals may function as useful biophysical models for the structure and functionality of cell membranes. Supercritical fluids have properties that are intermediate between those of liquids and gases, having better ability to permeate solid substances (gaslike) and having high densities that can be regulated by pressure (liquidlike). A supercritical fluid is a mesophase formed from the gaseous state where the gas is held under a combination of temperatures and pressures that exceed the critical point of a substance. Briefly, a gas that is brought above its critical temperature Tc will still behave as a gas irrespective of the applied pressure; the critical pressure (Pc) is the minimum pressure required to liquefy a gas at a given temperature. As the pressure is raised higher, the density of the gas can increase without a significant increase in the viscosity while the ability of the supercritical fluid to dissolve compounds also increases. A gas that may have little to no ability to dissolve a compound under ambient conditions can completely dissolve the compound under high pressure in the supercritical range. Supercritical fluid applications in the pharmaceutical sciences were excellently reviewed by Kaiser et al. Supercritical fluids offer several advantages over traditional methodologies: the potential for lowtemperature extractions and purification of compounds (consider heat added for distillation procedures), solvent volatility under ambient conditions, selectivity of the extracted compounds. One of the best examples of the use of supercritical fluids is in the decaffeination of coffee. This leads to great expense in the purchase and disposal of the residual solvents and increases the chance for toxicity. The effect of pressure on the ability of supercritical fluids to selectively extract different compounds. The loss of the flavor-adding compounds resulted in a poor taste and an unacceptable product. However, in this process a sample run using coffee beans is performed through the system to saturate the water with the flavor-enhancing compounds. The sample run of beans is removed and disposed of, and then the first batch of marketable coffee beans is passed through the system as the water is recirculated. Several batches of decaffeinated coffee are prepared in this manner before the water is discarded. In general, thermal methods involve heating a sample under controlled conditions and observing the physical and chemical changes that occur. These methods measure a number of different properties, such as melting point, heat capacity, heats of reaction, kinetics of decomposition, and changes in the flow (rheologic) properties of biochemical, pharmaceutical, and agricultural materials and food. Differential scanning calorimetry is the most commonly used method and is generally a more useful technique because its measurements can be related more directly to thermodynamic properties. Typically, a sample and a reference material are placed in separate pans and the temperature of each pan is increased or decreased at a predetermined rate. When the sample, for example, benzoic acid, reaches its melting point, in this case 122. A temperature difference therefore exists between benzoic acid and a reference, indium (melting point [mp] = 156. In this way the temperature of the sample, benzoic acid, is maintained at the same value as that of the reference, indium. The difference is heat input to the sample, and the reference per unit time is fed to a computer and plotted as dH/dt versus the average temperature to which the sample and reference are being raised. Differential scanning calorimetry is a measurement of heat flow in to and out of the system. Differential scanning calorimetry has found increasing use in standardization of the lyophilization process. Endothermic transitions (heat absorption) are shown in the upward direction and exothermic transitions (heat loss) are plotted downward. Melting is an endothermic process, whereas crystallization or freezing is an exothermic process. Common heat source of differential thermal analyzer with thermocouples in contact with the sample and the reference material. Differential scanning calorimetry and other thermal analytic methods have a number of applications in biomedical research and food technology. Using these techniques, they characterized various solid forms of drugs, such as sulfonamides, and correlated a number of physical properties of crystalline materials with interactions between solids, dissolution rates, and stabilities in the crystalline and amorphous states. The temperature difference between the sample and the reference material is plotted against time, and the endotherm as melting occurs (or exotherm as obtained during some decomposition reactions) is represented by a peak in the thermogram. The temperature difference, T, depends, among other factors, on the resistance to heat flow, R. In turn, R depends on temperature, nature of the sample, and packing of the material in the pans. The concept is that molecules move in response to an applied electric field according to their size, dipole moments, and environment (which changes with temperature). In this technique, the sample serves as the dielectric medium in a capacitor, and as the ac electric field oscillates, the motion of permanent dipoles is sensed as a phase shift relative to the timescale of the frequencies used. Each sample will have a characteristic response or permittivity at a given temperature and frequency. As the sample is heated or cooled, the response will vary because the mobility of the molecular dipoles will change. On going through a first-order transition such as melting, the mobility will exhibit a drastic frequencyindependent change giving rise to a family of curves with different intensities but a common maximum occurring at the transition temperature. For glass transitions (pseudosecond order) where the transition occurs over a broad temperature range, there will be a distinct variation in both intensity and temperature, allowing extremely sensitive detection of such. Separate heat sources and platinum heat sensors used in differential scanning calorimetry. Therefore, if a 4% weight loss is observed at 120 C, no weight change is observed at 190 C, and the weight is lost at 260 C, certain assumptions can be made. The 4% weight loss was associated with an endothermic change, which can correspond to a desolvation, making it a likely choice for the endothermic response. In addition, Karl Fisher analysis, described in the next subsection, could be used to determine whether the solid is a water solvate to determine whether the 4% loss in mass at 120 C is due to water. Dielectric analysis detects the microscopic "viscosity" of the system and can yield information on activation energies of changes as well as the homogeneity of samples. The technique does, however, require significantly more data analysis than the other thermal methods discussed. Thermomechanical analysis is also widely used to look at polymer films and coatings used in pharmaceutical processes. Thermogravimetric analysis instruments have now begun to be coupled with infrared or mass spectrometers to measure the chemical nature of the evolved gases being lost from the sample. The next subsection describes Karl Fisher analysis, which can also help in determining whether the desolvation may be attributed to water or residual solvents from chemical processing. Thermomechanical analysis measures the expansion and extension of materials or changes in viscoelastic properties and heat distortions, such as shrinking, as a function of temperature. By use of a probe assembly in contact with the test material, any motion due to expansion, melting, or other physical change delivers an electric signal to a recorder. The furnace, in which are placed a sample and a probe, controls the temperature, which can be programmed over a range from -150 C to 700 C. The apparatus serves essentially as a penetrometer, dilatometer, or tensile tester over a wide range of programmed temperatures. The method follows the reaction of iodine (generated electrolytically at the anode in the reagent bath) and sulfur with water. One mole of iodine reacts with 1 mole of water, so the amount of water is directly proportional to the electricity produced. This endothermic reaction may constitute an actual melt of the crystalline material or may be due to either desolvation or a polymorphic conversion. Utilizing Karl Fisher analysis, one can add the solid material to the titration unit and determine the amount of water by mixing of reagents and the potentiometric electrodes. The Karl Fisher method is an aid in that it can determine whether the desolvation is all water (showing a 4% water content) or arises from the loss of a separate solvent trapped in the crystalline lattice. This method is routinely used for pharmaceutical applications, including the study of humidity effects in solids undergoing water sorption from the air and in quality control efforts to demonstrate the amount of water associated in different lots of manufactured solid products.

A Most bacteria are surrounded by a rigid cell envelope (cell wall) containing peptidoglycan allergy testing kerry cheap aristocort 4 mg visa. B the cell membrane of bacteria does not contain sterols allergy shots for pet dander order cheap aristocort on line, which are found in mammalian cell membranes allergy medicine use during pregnancy cheap aristocort 4mg visa. A Lipopolysaccharide is a component of the cell envelope of Gram-positive bacteria allergy medicine philippines buy generic aristocort pills. Streptococcus pneumoniae) the capsular material varies in composition and can be used in serotyping to distinguish between different types of the same species of microorganism allergy latex treatment trusted 4 mg aristocort. Some bacteria can stick to the surface of materials and grow to form a biofilm that is highly resistant to treatment with antibiotics allergy treatment 4th buy aristocort 4 mg line. E Fimbriae are thin, hair-like structures produced on the surface of some bacteria, enabling them to adhere to host tissues. A All bacteria can be cultured in laboratory media, but certain microorganisms require specific nutrients to be supplied. Bacteria that grow only in the presence of oxygen are called obligate aerobes, those growing only in the absence of oxygen are called obligate anaerobes, and those growing in the presence or absence of oxygen are called facultative anaerobes. Mannitol salt agar plates are an example of selective growth media used for the recovery and growth of staphylococci from clinical samples. Chocolate agar, containing lysed blood, is an enriched growth medium used for culture of some bacteria that have special growth requirements supplied by the blood. A Endocarditis B Urinary tract infection C Osteomyelitis D Skin infection E Respiratory tract infection 3. A the use of certain antibiotics is a risk factor for development of infection with this microorganism. E It is safe for laboratory staff who are pregnant to work with suspected cultures of Listeria. Peptostreptococcus species are obligate aerobes and can cause abscesses at many anatomical sites. B G Tropheryma whipplei is an intracellular pathogen, which causes disease more prevalent in females. A Meningococcus B Gonococcus C Pneumococcus D Moraxella catarrhalis E Veillonella species 7. A Ten percent of humans are asymptomatic carriers of the microorganism in the nasopharynx. A Escherichia only B Enterobacter only C Klebsiella only D Escherichia, Enterobacter and Klebsiella E Salmonella, Shigella, Serratia, Proteus and Yersinia E F 288 Self-assessment questions 8. A Haemophlius influenzae B Aggregatibacter actinomycetemcomitans (formerly Actinobacillus actinomycetemcomitans) C Cardiobacterium hominis D Eikenella corrodens E Klebsiella pneumoniae 9. Chapter 10 Pseudomonas, Legionella and other environmental Gram-negative bacilli 10. B C Self-assessment questions 289 D E Unlike other pseudomonads, Acinetobacter spp. E Non-cholera Vibrio species may also cause diarrhoea and occasionally cause cellulitis. C Few spirochaetes can be cultured and diagnosis is usually made by serological tests. E Spirochaetes, like Treponema pallidum, can be visualised in clinical specimens by dark field microscopy. A the non-specific antibody test detects antibody to lipids (cardiolipin) released from the microorganism during early infection. C They are the most common cause of acute bacterial enterocolitis, and infection is often caused by the handling of raw chickens or consumption of the undercooked meat. A Helicobacter pylori is the most common cause of duodenal ulceration and gastric cancer. B Infection with Helicobacter pylori occurs commonly in early childhood and usually becomes chronic, often life-long. C the prevalence of infection with Helicobacter pylori is low in countries with poor sanitation. E Treatment of infection often involves a proton pump inhibitor to reduce gastric acidity coupled with one antimicrobial. A Vibrio cholerae 01 is the cause of cholera, which is characterised by profuse watery diarrhoea. Vibrio cholerae forms characteristic red colonies on thiosulphate-citrate-bile salt-sucrose agar. Treatment of cholera is with rehydration and often ciprofloxacin to shorten the duration of illness. A Bacteroides B Prevotella D 290 Self-assessment questions C Porphyromonas D Fusobacterium E Leptotrichia 13. C Chlamydia trachomatis is the most common cause of sexually transmitted infections in the developed world. D Infection with Chlamydia trachomatis is often treated with doxycycline or azithromycin. E Chlamydophila psittaci is also a common cause of sexually transmitted infection. Viral infection is always diagnosed by direct detection of all or part of the virus. C Viral nucleic acids can be single- or double-stranded, circular or linear, and have negative or positive polarity. D A live attenuated virus vaccine is available for the prevention of infection with the Measles virus. E Infection with the Mumps virus is normally characterised by swollen parotid salivary glands. A Rhinoviruses, Enteroviruses, Rotaviruses, Noroviruses, Sapoviruses and the Rubella virus are non-enveloped viruses. E Infection with Rotaviruses, Noroviruses and Sapoviruses is characterised by diarrhoea and vomiting. B Most fungi that commonly cause human disease can be categorised in to yeasts, moulds/filamentous or dimorphic. D Most deep mycoses are opportunistic infections occurring in immunocompromised patients. E Laboratory diagnosis of fungal infection is mostly by direct microscopy or microbiological culture 17. B Cryptococcal species have polysaccharide capsules that can be visualised by mixing fluid specimens with Indian ink. E Malassezia furfur is the cause of pityriasis versicolor, which results in scaly skin and depigmentation. A Outbreaks of aspergillosis in immunocompromised patients have occurred, due to construction work adjacent to hospitals. B Patients with cystic fibrosis are frequently colonised with Aspergillus species, which may then lead to infection. C Dermatophytes, including the genera Epidermophyton, Microsporum and Trichophyton, often infect the lungs D the sub-phylum mucoromycotina includes the medically important species Rhizopus arrhizus and Absidia corymbifera. E Infection with Fusarium and Scedosporium species is often associated with inhalation or aspiration of polluted water 17. A Dimorphic fungi have both yeast and mould forms, depending on growth temperature. Granulomatous ulcers may be a complication of pulmonary infection caused by Blastomyces dermatitidis. D E Pulmonary infection with Histoplasma capsulatum always requires antifungal therapy. Paracoccidioides brasiliensis may lead to destruction of the palate and nasal septum. C It can be diagnosed in the laboratory by microscopic examination of freshly passed stools. A Human infection can result from ingestion of the microorganism as cysts contained in cat faeces and undercooked meat. C It causes serious conditions, including myocarditis, choroidoretinitis and meningoencephalitis in immunocompromised hosts. A Ascaris lumbricoides (roundworm) is the most common pathogenic helminth worldwide. B Infection with Enterobius vermicularis (pin worm) often presents with perianal itching. D Infection with Trichuris trichiura can present with anaemia, intestinal irritation and occasionally, anal prolapse. E Ancylostoma duodenale, Necator americanus (hookworm) and Strongyloides stercoralis can penetrate intact skin. G Wuchereria bancrofti and Bruglia malayi are filarial worms, which can cause elephantitis. C Cestodes have two reservoirs in their life cycle, one for larvae and one for adult worms. Infection with Fasciola hepatica and Opisthorchis sinensis may result in hepatomegaly. D Piperacillin is used with tazobactam to protect piperacillin from destruction by some b-lactamases. C Fluconazole, itraconazole and voriconazole are available as oral, intravenous and topical preparations. E Some species of Candida are resistant to or have reduced susceptibility to fluconazole. Side effects of amphotericin B include anaphylactic reactions and renal tubular damage. A Most medically important bacteria and fungi cannot be cultured in the diagnostic laboratory. C Selective agar contains an indicator (usually a dye) to allow differentiation of bacteria. D Differential agar contains antimicrobial agents to suppress growth of normal flora from sites that are normally colonised. E Enrichment broth is a nutritious broth, which allows recovery and enrichment of small numbers of microorganisms within a clinical sample. Self-assessment questions 295 Gowns and aprons do not need to be worn in the room. A Primary viral pneumonia occurs mainly in children, elderly people and immunocompromised patients. Primary viral pneumonia in adults is characterised by diffuse bilateral interstitial infiltrates on chest radiograph. Transmission of infection with this microorganism can be from a discharge from skin lesions. A Escherichia coli B Proteus mirabilis C Staphylococcus saprophyticus D Pseudomonas aeruginosa E Staphylococcus aureus 30. C Pregnant women with untreated syphilis can pass infection to their foetus at any point during pregnancy or delivery. Inoculation of vaginal fluid for Trichomonas vaginalis culture has higher sensitivity than microscopy. D They are not associated with local infections at the catheter skin insertion site. Associated microbiological culture of tissue samples does not assist in making the diagnosis. D E Treatment with high-dose flucloxacillin is appropriate empirical therapy, unless risk factors for unusual/resistant pathogens are present. A T-cell Lymphoma and chronic lymphatic leukaemia predisposes to Varicellazoster virus and Candida infection. A Coagulase negative staphylococci B Staphylococcus epidermidis C Diphtheroids D Enterococci E Streptococcus pneumoniae 37. They use alternative cell wall precursors, thereby depriving glycopeptides of their normal target site of action. They are controlled by good hand hygiene; equipment and environmental decontamination. A Each viral particle contains at least three enzymes: reverse transcriptase, integrase and protease. The risk of transmission to the foetus increases from 25% in the first trimester to 65% in the third. Other microorganisms, such as chlamydia, only grow intracellularly and can only be grown in host cells grown in tissue culture media. By heating blood before making the agar plates (the process used in production of chocolate agar) both factors are available. Brucella species are Gram-negative coccobacilli and can be grown in routine blood culture. Brucella infections have a worldwide distribution, but there is great variation in the incidence of infection. Neisseria gonorrhoeae remains sensitive to cephalosporins and single dose ceftriaxone is commonly used for compliance. Treponema, Borrelia and Leptospira are all spirochaetes with helical shapes, staining as Gram-negatives, although some give a very weak stain and are difficult to see under bright field microscopy after staining. Chapter 10 Pseudomonas, legionella and other environmental gram-negative bacilli 10. The third-generation cephalosporin ceftazidime retains activity, as do the carbapenems (imipenem, meropenem) and monobactams (aztreonam). The aminoglycosides, gentamicin and tobramycin, are still generally effective against P. Chapter 14 Chlamydiaceae, Rickettsia, Coxiella, Mycoplasmataceae and Anaplasmataceae 14.

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In this reversible isothermal process allergy medicine eczema quality 4 mg aristocort, the heat of vaporization Hv required to convert the liquid to the vapor state is 10 allergy treatment brisbane discount 4mg aristocort overnight delivery,500 cal/mole allergy testing tool discount aristocort 4 mg on-line. The process is carried out at a constant pressure zopiclone allergy symptoms order aristocort uk, so that Q P = Hv allergy treatment for humans order 4 mg aristocort, and because it is a reversible process allergy symptoms 36 buy aristocort 4 mg visa, the entropy change can be written as 10,500 Hv = = 35. For the entropy change of the surroundings, the water needs to be considered to be in equilibrium with a large bath at -10 C, and the heat liberated when the water freezes is absorbed by the bath without a significant temperature increase. The entropy is obtained by calculating the entropy changes for several reversible steps. This criterion of spontaneity is not a convenient one, however, because it requires a calculation of the entropy change both in the system and the surroundings. The free energy functions, to be treated in a later section, do not require information concerning the surroundings and are more suitable criteria of spontaneity. Entropy and Disorder the second law provides a criterion for deciding whether a process follows the natural or spontaneous direction. Even though the causes for the preference for a particular direction of change of state or the impossibility for the reverse direction are unknown, the underlying reason is not that the reverse process is impossible, but rather that it is extraordinarily improbable. Thermodynamic systems described by macroscopic properties such as T, P, or composition can also be described in terms of microscopic quantities such as molecular random motions. The impossibility of converting all thermal energy in to work results from the "disorderliness" of the molecules existing in the system. Disorder can be seen as the number of ways the inside of a system can be arranged so that from the outside the system looks the same. Let us imagine that the system consists of a gas in a closed container that is allowed to expand freely in to a vacuum. The initial state corresponds to V1 and the final state corresponds to V2, which is larger than V1: V1 = 1 2 V2. Now / consider two independent particles; the probability of finding both in V1 after V2 is available is P = (1 2)2 = 1 4. Now, if N is on the order of regular molecular / quantities, that is, 1023 molecules, the probability of finding all of them in the initial state is extraordinarily small, 23 P = (1 2)10. Once the system has expanded, it is extremely improbable that they will be found by chance only in V1. The larger the number of configurations, the more disordered a system is considered. Each of these terms can be evaluated independently; in particular, the first integral is calculated numerically by plotting C P /T versus T. The difference in sign between G and Suniverse implies that the condition for a process being spontaneous has changed from an increase of the total entropy, Suniverse > 0, to a decrease in Gibbs free energy, G < 0. However, Gibbs free energy is only a composite that expresses the total change in entropy in terms of the properties of the system alone. Criteria of Equilibrium and Spontaneity When net work can no longer be obtained from a process, G is at a minimum, and G = 0. If G is positive (G > 0), it indicates that net work must be absorbed for the reaction to proceed, and accordingly it is not spontaneous. When the process occurs isothermally at constant volume rather than constant pressure, A serves as the criterion for From the former equation it is clear that the only criterion for spontaneous change is an increase of the entropy of the universe. Chemical reactions are usually carried out at constant temperature and constant pressure. Thus, equations involving G are of particular interest to the chemist and the pharmacist. It was once thought that at constant pressure a negative H (evolution of heat) was itself proof of a spontaneous reaction. Many natural reactions do occur with an evolution of heat; the spontaneous melting of ice at 10 C, however, is accompanied by absorption of heat, and a number of other examples can be cited to prove the error of this assumption. Thus, although the conversion of ice in to water at 25 C requires an absorption of heat of 1650 cal/mole, the reaction leads to a more probable arrangement of the molecules; that is, an increased freedom of molecular movement. Hence, the entropy increases, and S = 6 cal/mole deg is sufficiently positive to make G negative, despite the positive value of H. Many of the complexes of Chapter 10 form in solution with a concurrent absorption of heat, and the processes are spontaneous only because the entropy change is positive. The dissolution of solutes in water may be accompanied by a decrease in entropy because both the water molecules and the solute molecules lose freedom of movement as hydration occurs. In complexation, this highly ordered arrangement is disrupted as the separate ions or molecules react through coordination, and the constituents thus exhibit more freedom in the final complex than they had in the hydrated condition. The increase in entropy associated with this increased randomness results in a spontaneous reaction as reflected in the negative value of G. Conversely, some association reactions are accompanied by a decrease in entropy, and they occur in spite of the negative S only because the heat of reaction is sufficiently negative. For reactions at constant temperature and pressure, which are the most common types, the change in free energy is ordinarily used as the criterion in place of S. It is more convenient because it eliminates the need to compute any changes in the surroundings. This is to be expected because the molecules lose some of their freedom when they pass in to the crystalline state. The entropy of water plus its surroundings increases during the transition, however, and it is a spontaneous process. The S values considered here are the changes in entropy of the substance alone, not of the total system, that is, the substance and its immediate surroundings. This result means that 259 cal of work must be done on the system, or this amount of net work must be performed by the kidneys to bring about the transfer. When a real gas does not behave ideally, a function known as the fugacity (f) can be introduced to replace pressure, just as activities are introduced to replace concentration in nonideal solutions (see later discussion). They exchange heat and work with their surroundings, but the processes involve no transfer of matter, so that the amounts of the components of the system remain constant. A phase consisting of w2 grams of NaCl dissolved in w1 grams of water is said to contain two independently variable masses or two components. Similarly, all forms of sodium chloride can be represented by the single species NaCl, and the system therefore consists of just two components, H2 O and NaCl. The number of components of a system is the smallest number of independently variable chemical substances that must be specified to describe the phases quantitatively. In an open system in which the exchange of matter among phases also must be considered, any one of the extensive properties such as volume or free energy becomes a function of temperature, pressure, and the number of moles of the various components. It may be considered the change in free energy, for example, of an aqueous sodium chloride solution when 1 mole of NaCl is added to a large quantity of the solution so that the composition does not undergo a measurable change. An infinitesimal reversible change of state is given by dG = + G T dT + G P dP T,n 1,n 2 P,n 1,n 2 for a system of constant composition N = n1 + n2 +. The chemical potential, like any other partial molar quantity, is an intensive property; in other words, it is independent of the number of moles of the components of the system. The chemical potential of iodine in the aqueous phase is written as Iw and that in the organic phase as Io. When the two phases are in equilibrium at constant temperature and pressure, the respective free energy changes dGw and dGo of the two phases must be equal because the free energy of the overall system is zero. For example, in a saturated aqueous solution of sulfadiazine, the chemical potential of the drug in the solid phase is the same as its chemical potential in the solution phase. When two phases are not in equilibrium at constant temperature and pressure, the total free energy of the system tends to decrease, and the substance passes spontaneously from a phase of higher chemical potential to one of lower chemical potential until the potentials are equal. Hence, the chemical potential of a substance can be used as a measure of the escaping tendency of the component from its phase. The concept of escaping tendency will be used in various chapters throughout the book. The analogy between chemical potential and electric or gravitational potential is evident, the flow in these cases always being from the higher to the lower potential and continuing until all parts of the system are at a uniform potential. For a two-phase system of a single component, for example, liquid water and water vapor in equilibrium at constant temperature and pressure, the molar free energy G/n is identical in all phases. Conversely, if the mean heat of vaporization and the vapor pressure at one temperature are known, the vapor pressure at another temperature can be obtained. The vapor pressure P2 at temperature T2 = 373 K (100 C) is 78 cm Hg, and R is expressed as 1. Q should not be confused with K, the ratio of activities, fugacities, and so on under standard conditions at equilibrium. Sodium cholate may exist either as monomer or as dimer (or higher n-mers) in aqueous solution. It also can be given as the ratio of partial pressures or fugacities (for gases) and as the ratio of the different concentration expressions used in solutions (mole fraction, molarity, molality). The equilibrium constant is dimensionless, the ratio of activities or concentration canceling the units. If the monomer is removed from the solution, the reaction is shifted to the left side, forming monomer, and G becomes positive.

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