*Important Notice : Guided tours to the Parliament Chamber are suspended until further notice as a preventative measure in response to Covid-19


Akhil Chhatre, M.D.

  • Director, Spine Rehabilitation
  • Assistant Professor of Physical Medicine and Rehabilitation

Thus symptoms 2dpo cheap citalopram online visa, complications associated with overdose are controlled medications causing thrombocytopenia purchase citalopram 20mg visa, and known drug interactions medications zanaflex discount citalopram 20mg otc, such as between smoking and theophylline symptoms pneumonia buy generic citalopram 40mg, can be accommodated symptoms jock itch buy citalopram 20 mg lowest price. In these services, once the physician prescribes a certain amount of drug and monitors the clinical response, it is the pharmacist who coordinates the appropriate sample time to determine drug concentration in the appropriate body fluid. Then the patient should be monitored for drug efficacy and reevaluated periodically. List the partition coefficients for erythromycin and its related chemical entities and predict comparable effectiveness when administered in a topical dosage form. Select a drug available in various chemical moieties that dictate varying parenteral dosage forms and describe the effect of chemical formula on its onset of activity, duration of activity, etc. Given comparative bioavailability data and cost information for identical drug products from different manufacturers, select a product for the hospital formulary and provide a rationale for your decision. Make a listing of drug products whose brand names include the term "elixir," ReFeRenCeS 1. List four clinically available drugs that demonstrate either amorphous or crystalline forms, and describe the rationale for using a specific form for therapy. Develop a listing of drugs dosed on peak and trough levels, and given patient data, demonstrate calculations for one such drug. Given a patient case, select appropriate drug therapy, and determine an appropriate dosage regimen for the patient. Also, the selection of appropriate drug therapy should include flavor preference and discussion if a pediatric patient. Define micromeritics, the angle of repose, levigation, spatulation, and trituration 4. Compare and contrast the various types of medicated powders, for example, bulk, divided 5. Provide examples of medicated powders used in prescription and nonprescription products 6. Differentiate between the fusion method and wet method for the preparation of effervescent granulated salts Most active and inactive pharmaceutical ingredients occur in the solid state as amorphous powders or as crystals of various morphologic structures. A powder is defined as a dosage form composed of a solid or mixture of solids reduced to a finely divided state and intended for internal or external use. Historical Use Originally, powders were found to be a convenient mode of administering drugs derived from hard vegetables such as roots As synthetic drugs were introduced, powders were used to 214 administer insoluble drugs such as calomel, bismuth salts, mercury, and chalk. Powders as a solid dosage form have been used historically as internal and external medications. For internal use, they can be taken orally, administered through the nose as snuffs, or blown into a body cavity as an insufflation. Powders have also been used to make solutions for topical and oral use and for use as douches. Such traditional applications and modes of administration of the dosage form continue today. Additional applications have also been developed; for example, powders containing a bioadhesive material can be applied to a specific body area such that the medication will adhere for a prolonged drug effect. Powders can also aid in clinical studies of drug preparations because the dose can be so readily adjusted. Doses can be individually weighed and placed in powder papers, envelopes, or small vials/bottles ("Powder in a bottle" research studies are an example). In another example, infants and young children who cannot swallow tablets or capsules will accept powders that can be mixed with a formula or sprinkled in applesauce or some other appropriate food. Also, if a drug is too bulky to be prepared as a capsule or tablet, it may be suitable for a powder dosage form. Powders provide a rapid onset of action because they are readily dispersed, have a large surface area, and usually require only dissolution, not disintegration, before absorption. Although the use of medicated powders per se in therapeutics is limited, the use of powdered substances in the preparation of other dosage forms is extensive. For example, powdered drugs may be blended with powdered fillers and other pharmaceutical ingredients to fabricate solid dosage forms as tablets and capsules; they may be dissolved or suspended in solvents or liquid vehicles to make various liquid dosage forms; or they may be incorporated into semisolid bases in the preparation of medicated ointments and creams. This characteristic must be considered in mixing or storing and shipping, when powders of different particle size may become segregated. Another concern stems from the fact that powder dosage forms have a large surface area that is exposed to atmospheric conditions. Further, because powders of small particle size present a greater surface area to the atmosphere, they are more reactive in nature and can adsorb larger quantities of gases, such as carbon dioxide. However, if the powder has a smaller particle size, it can dissolve at a more rapid rate, unless adsorbed gases prevent the water from surrounding the individual particles and wetting them, thereby decreasing their wetting properties. An increase in surface free energy can increase the absolute solubility of the drug and have a positive effect on its bioequivalence. They should be impalpable and free flowing, should easily adhere to the skin, and should be passed through at least a No. Highly sorptive powders should not be used for topical powders that are to be applied to oozing wounds, as a hard crust may form. A more hydrophobic, waterrepellent powder will prevent loss of water from the skin and will not cake on the oozing surfaces. Talc, or any other naturally derived product that is to be used on open wounds, should first be sterilized to avoid an infection in the area. Topical powders usually consist of a base or vehicle, such as cornstarch or talc; an adherent, such as magnesium stearate, calcium stearate, or zinc stearate; and possibly an active ingredient, along with an aromatic material. The powder should provide powders composition Properly prepared, powders have a uniform, small particle size that has an elegant appearance. In general, powders are more stable than are liquid dosage forms and are rapidly soluble, enabling the drug to be absorbed quickly. The properties of powders are related to the size and surface area of the particles. The large surface area will aid in absorbing perspiration and give a cooling sensation to the skin. When using an insufflator, or "puffer," the patient simply "puffs" the desired quantity of powder onto the affected area or into the cavity. Also, a moisture-activated adherent, such as Polyox, can be incorporated into the powder. Polyox is an ethylene oxide polymer with a high molecular weight that forms a viscous, mucoadhesive gel when in contact with moisture. The gel serves to provide a depot for longterm drug delivery spanning several hours. Sieves for such pharmaceutical testing and measurement are generally made of wire cloth woven from brass, bronze, or other suitable wire. Drug and other materials commonly require chemical or pharmaceutical processing to imbue the features desired to enable both the efficient production of a finished dosage form and the optimum therapeutic efficacy. It is important to study particles because most drug dosage forms are solids, solids are not static systems, the physical state of particles can be altered by physical manipulation, and particle characteristics can alter therapeutic effectiveness. Micromeritics is the study of a number of characteristics, including particle size and size distribution, shape, angle of repose, porosity, true volume, bulk volume, apparent density, and bulkiness. Particle Size A number of techniques can be used to determine particle size and size distributions. Particle size determinations are complicated by the fact that particles are not uniform in shape. Other methods of particle size determinations include elutriation, centrifugation, permeation, adsorption, electronic sensing zone (the Coulter counter), and light obstruction. In general, the resulting average particle sizes by these techniques can provide the average particle size by weight (sieve method, light scattering, sedimentation method) and the average particle size by volume (light scattering, electronic sensing zone, light obstruction, air permeation, and even the optical microscope). The height and diameter of the resulting cone are measured, and the angle of repose is calculated from this equation: tan q = h/r where h is the height of the powder cone and r is the radius of the powder cone. A number of factors, including shape and size, determine the flow properties of powders. In general, particles in the size range of 250 to 2,000 mm flow freely if the shape is amenable. Particles in the size range of 75 to 250 mm may flow freely or cause problems, depending on shape and other factors. PoroSity, Void, and Bulk Volume If spheres and the different ways they pack together are used as an example, two possibilities arise. Another packing, cubical, with the cubes packed at 90-degree angles to each other, may be considered. If particles are not uniform, the smaller particles will slip into the void spaces between the larger particles and decrease the void areas. Packing and flow are important, as they affect the size of the container required for packaging, the flow of granulations, the efficiency of the filling apparatus for making tablets and capsules, and the ease of working with the powders. The characteristics used to describe powders include porosity, true volume, bulk volume, apparent density, true density, and bulkiness. Particles are separated into various size ranges by successively increasing the velocity of the airstream in which they are carried. For some materials, a single method may be sufficient; however, a combination of methods is frequently preferred to provide greater certainty of size and shape parameters. The science of small particles is discussed further in Physical Pharmacy Capsule 6. The reduction in the particle size of a solid is accompanied by a great increase in the specific surface area of that substance. A finer grinding action is accomplished by using a mortar with a rough surface (as a porcelain mortar) than one with a smooth surface (as a glass mortar). Grinding a drug in a mortar to reduce its particle size is termed trituration or comminution. On a large scale, various types of mills and pulverizers may be used to reduce particle size. Blending powders When two or more powdered substances are to be combined to form a uniform mixture, it is best to reduce the particle size of each powder individually before weighing and blending. Depending on the nature of the ingredients, the amount of powder, and the equipment, powders may be blended by spatulation, trituration, sifting, and tumbling. It is not suitable for large quantities of powders or for powders containing potent substances, because homogeneous blending is not as certain as other methods. Very little compression or compacting of the powder results from spatulation, which is especially suited to mixing solid substances that form eutectic mixtures (or liquefy) when in close and prolonged contact with one another (Table 6. To diminish contact, a powder prepared from such substances is commonly mixed in the presence of an inert diluent, such as light magnesium oxide or magnesium carbonate, to separate the troublesome agents physically. When a small amount of a potent substance is to be mixed with a large amount of diluent, the geometric dilution method is used to ensure the uniform distribution of the potent drug. This method is especially indicated when the potent substance and other ingredients are the same color and a visible sign of mixing is lacking. By this method, the potent drug is placed with an approximately equal volume of the diluent in a mortar and is mixed thoroughly by trituration. Then, a second portion of diluent equal in volume to the mixture is added and the trituration repeated. The collection and containment system protects the environment from chemical dust, reduces product loss, and prevents product contamination. Levigation is commonly used in small-scale preparation of ointments and suspensions to reduce the particle size and grittiness of the added powders. A paste is formed by combining the powder and a small amount of liquid (the levigating agent) in which the powder is insoluble. The levigated paste may then be added to the ointment base and the mixture made uniform and smooth by rubbing them together with a spatula on the ointment tile.

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Antipruritic: a drug that reduces itching (pruritus) (trimeprazine symptoms 6 week pregnancy cheap citalopram 20 mg, systemic antipruritic; menthol symptoms rabies order cheapest citalopram, topical antipruritic) medications with codeine purchase citalopram without prescription. Antipsychotic: a drug that suppresses the symptoms of psychoses of various diagnostic types (haloperidol) symptoms to diagnosis generic citalopram 20 mg. Antipyretic: a drug that restores normal body temperature in the presence of fever (acetaminophen) in treatment online order discount citalopram line. Antirheumatic: an anti-inflammatory drug used to treat arthritis and rheumatoid disorders (indomethacin). Antirickettsial: a drug that kills or inhibits pathogenic microorganisms of the genus Rickettsia (chloramphenicol). Antischistosomal: a drug that kills or inhibits pathogenic flukes of the genus Schistosoma (oxamniquine). Antispasmodic: a drug that inhibits the motility of visceral smooth muscles (atropine). Antitreponemal: a drug that kills or inhibits Treponema pallidum, the causative agent of syphilis (penicillin). Beta Receptor Agonist: a drug that activates sympathetic nervous system beta receptors, for example, to induce bronchodilation (isoproterenol). Beta Receptor Antagonist: a drug that reacts asymptomatically with sympathetic nervous system beta receptors and prevents their endogenous activation, for example, to oppose sympathetic stimulation of the heart (atenolol, metoprolol, propranolol). Bisphosphonate: also called diphosphonates, are a class of drugs that are used to prevent the loss of bone mass. Bone Metabolism Regulator: a drug that slows calcium turnover in bone; it is used to treat Paget disease (etidronate). Bronchodilator: a drug that expands bronchiolar airways; it is useful in treating asthma (albuterol and isoproterenol, adrenergic bronchodilators; oxtriphylline, smooth muscle relaxant bronchodilator). C Calcium Channel Blocker: an antianginal drug that acts by impairing the function of transmembrane calcium channels of vascular smooth muscle cells (verapamil). Carbonic Anhydrase Inhibitor: a drug that inhibits the enzyme carbonic anhydrase, the therapeutic effects of which are diuresis and Appendix A reduced formation of intraocular fluid (acetazolamide). Cardiac Depressant, Antiarrhythmic: a drug that depresses myocardial function; it is useful in treating cardiac arrhythmias (procainamide). Cardiotonic: a drug that increases myocardial contractile force; it is useful in treating congestive heart failure (digoxin). Cathartic: a drug that promotes defecation, usually considered stronger in action than a laxative (bisacodyl). Cauterizing Agent: an agent that "burns" off a part of the body to remove or close it off (silver nitrate). Centrally Acting Drug: a drug that produces its therapeutic effect by action on the central nervous system, usually designated by the type of therapeutic action (sedative, hypnotic, anticonvulsant, etc. Chelating Agent: a complexing agent that binds metal ions into stable ring structures (chelates); it is useful in treating poisoning (edetate calcium disodium, chelating agent for lead). Cholelitholytic: a drug that promotes dissolution of gallstones (ursodeoxycholic acid). Choleretic: a drug that increases bile secretion by the liver (dehydrocholic acid). Cholinergic: a drug that activates organs innervated by the parasympathetic nervous system; a parasympathomimetic drug (neostigmine, systemic cholinergic; pilocarpine, ophthalmic cholinergic). Contraceptive, Topical: a spermicidal agent used topically in the vagina to prevent conception (nonoxynol 9). Contraceptive, Vaginal: intravaginal ring inserted releasing drugs that prevent conception (etonogestrel/ethinyl estradiol). Corticosteroid: an agent that includes the steroid hormones naturally produced in the adrenal cortex; it includes cortisol (hydrocortisone) and others. Dental Caries Prophylactic: a drug applied to the teeth to reduce the incidence of cavities (sodium fluoride). Depigmenting Agent: a drug that inhibits melanin production in the skin; it is used to induce general depigmentation in certain splotchy depigmented conditions Detergent: an emulsifying agent used as a cleanser (hexachlorophene liquid soap, antiinfective detergent). Diagnostic Aid: a drug used to determine the functional state of a body organ or to determine the presence of a disease (peptavlon, gastric secretion indicator; fluorescein sodium, corneal trauma indicator). Dopamine Receptor Agonist: a drug that activates dopamine receptors, for example, to 758 Appendix A of contractions in the small intestine or making them stronger, without disrupting their rhythm. Glucocorticoid: an adrenocortical hormone that regulates organic metabolism and inhibits inflammatory response (betamethasone; prednisone). Glutamate Inhibitor: a drug that will block the action of glutamic acid/glutamate. Growth Hormone, Human: a drug that duplicates endogenous growth hormone; it is used in children to treat growth failure due to the lack of growth hormone (somatrem). Emetic: a drug that induces vomiting; it is useful in expelling ingested but unabsorbed poisons (ipecac syrup). Endothelin Receptor Antagonist: a drug that blocks endothelin receptors for treatment of a number of diseases, including pulmonary arterial hypertension. Ergot Alkaloid: a plant principle derived from the fungus Claviceps purpurea grown on rye or other grains (ergonovine, uterine contractant; ergotamine, migraine therapy). Estrogen: a hormone that stimulates and maintains female reproductive organs and sex characteristics and functions in the uterine cycle (ethinyl estradiol). Expectorant: a drug that increases respiratory tract secretions, lowers their viscosity, and promotes removal (guaifenesin). Fertility Agent: a drug that promotes ovulation in women of low fertility or spermatogenesis in men of low fertility (clomiphene). Fibrinolytic Proteolytic: an enzyme drug used topically to hydrolyze the exudates of infected and inflammatory lesions (fibrinolysin and desoxyribonuclease, bovine). Galactokinetic: a drug used to initiate lactation after childbirth (oxytocin nasal spray). Gastric Acid Secretion Inhibitor: a drug that inhibits the secretion of gastric acid, as shown by the proton pump inhibitors. Gastroprokinetic: a drug that increases gastrointestinal motility by increasing the frequency Heavy Metal Antagonist: a drug used as an antidote to poisoning with toxic metals such as arsenic and mercury (dimercaprol). Hematopoietic: a vitamin that stimulates the formation of blood cells; it is useful in treating vitamin-deficiency anemia (cyanocobalamin). Hemorheologic Agent: a drug that improves the flow properties of blood by reducing viscosity (pentoxifylline). Histamine H2 Receptor Antagonist: a drug that inhibits histamine-mediated gastric acid secretion; it is used to treat peptic and duodenal ulcers (famotidine). Hydantoin: an antiepileptic drug that contains the hydantoin moiety in its chemical structure (phenytoin sodium). H Appendix A Hydrolytic, Injectable: an enzyme drug that promotes the diffusion of other injected drugs through connective tissues (hyaluronidase). Immunizing Agent, Passive: a drug containing antibodies against a pathogenic microorganism; it is used to provide immediate but temporary protection against infection (tetanus immune globulin, rabies immune globulin). Immunoglobulin: antibody protein derived from blood serum; it is used to confer passive immunity to infectious diseases (see Immunizing Agent, Passive). Inotropic Agent: a drug that increases the contractile strength of heart muscle; a cardiotonic (digoxin, digitoxin, dopamine). Irritant, Local: a drug that reacts weakly and nonspecifically with biologic tissue; it is used topically to induce a mild inflammatory response (camphor). Lipase Inhibitor: a drug used to reduce the activity of lipases found in the intestine secreted by the pancreas when fat is present. Loop Diuretic: a diuretic with renal site of action in the thick ascending loop of Henle (furosemide). M K Keratolytic: a topical drug that toughens and protects skin (compound benzoin tincture, salicylic acid). Metal Complexing Agent: a drug that binds metal ions; it is useful in treating metal poisoning (dimercaprol, complexing agent for arsenic, mercury, and gold). Miotic: a cholinergic drug used topically in the eye to induce constriction of the pupil (miosis) (pilocarpine). Muscle Relaxant, Smooth: a drug that inhibits the contraction of visceral smooth muscles (aminophylline). Mydriatic: an adrenergic drug used topically in the eye to induce dilation of the pupil (mydriasis) (phenylephrine). L n Laxative: a drug that promotes defecation, usually considered milder in action than a cathartic (psyllium mucilloid, bulk laxative; mineral oil, lubricant laxative; sodium phosphates oral solution, saline laxative; bisacodyl, irritant laxative). Narcotic: a drug that induces action by reacting with opioid receptors of the central nervous system or a drug that is legally classified as a narcotic with regard to prescribing regulations. Plasma Volume Expander: a substance that can be transfused to maintain fluid volume of the blood. Platelet Growth Factor: contained in platelet-rich plasma that is a blood plasma that has been enriched with platelets, different growth factors, and cytokines. Platelet-Reducing Agent: a drug that slows down platelet production in the body (anagrelide). Posterior Pituitary Hormone, Antidiuretic: a hormone that promotes renal reabsorption of water; it is useful in treating diabetes insipidus (vasopressin injection). Potassium-Sparing Diuretic: a diuretic that does not induce systemic potassium depletion as a side effect (triamterene). Progestin: a progesterone-like hormone that stimulates the secretory phase of the uterine cycle (norethindrone). Prostaglandin Synthetase Inhibitor: a drug that inhibits prostaglandin synthesis and prostaglandin-induced symptoms such as inflammation; a nonsteroidal anti-inflammatory drug (ibuprofen). Prostaglandin: a drug from the classes of cellregulating hormones cyclized from arachidonic acid (alprostadil, maintains ductus arteriosus patency in newborn infants pending corrective surgery for congenital heart defects). Proteasome Inhibitor: a drug that blocks the action of proteasomes, cellular complexes that break down proteins Protectant: a topical drug that provides a physical barrier to the environment (zinc gelatin, skin protectant; methylcellulose, ophthalmic protectant). Neuraminidase Inhibitor: a drug in a class of antiviral drugs targeted at the influenza virus, which works by blocking the function of the viral neuraminidase protein, preventing the virus from reproducing by budding from the host cell (oseltamivir). Neuromuscular Blocking Agent: a drug that paralyzes skeletal muscles by preventing transmission of neural impulses to them (succinylcholine). Nonsteroidal Anti-Inflammatory Drug: an analgesic, anti-inflammatory drug that inhibits prostaglandin synthesis (ketoprofen). Ovulation Stimulator: a drug that is similar to estrogen and binds to the estrogen receptor causing a negative feedback that stimulates the release of gonadotropin releasing hormone that activates the pituitary gland to release follicle-stimulating hormone and luteinizing hormone with resultant release of an egg. Oxytocic: a drug that stimulates uterine motility; it is used in obstetrics to initiate labor or to control postpartum hemorrhage (oxytocin). Parasympatholytic: a drug that inhibits response to parasympathetic nerve impulses and to parasympathomimetic drugs; an anticholinergic drug (atropine). Penicillin Adjuvant: a drug that extends the systemic duration of penicillin by inhibiting its renal excretion (probenecid). Phenothiazine: an antipsychotic or antidepressant drug that contains the phenothiazine nucleus in its chemical structure (chlorpromazine, antipsychotic; imipramine, antidepressant). Phosphate Binder: an agent that reduces the absorption of phosphate when taken with meals and snacks. Photosensitizer: a drug that increases cutaneous response to ultraviolet light; it is used with ultraviolet light to treat certain skin diseases Psychedelic: a drug (especially a street drug) that induces vivid sensory phenomena and hallucinations (mescaline). Psychotherapeutic: a drug used to treat abnormal mental or emotional processes (chlorpromazine, haloperidol). Radiopharmaceutical: a drug containing a radioactive isotope; it is used for diagnostic or therapeutic purposes (iodinated albumen with 125 I or 131I). Rauwolfia Alkaloid: a plant principle derived from Rauwolfia serpentina and related species, with antihypertensive and antipsychotic actions (reserpine). Respiratory Stimulant: a drug which serves to increase the action of the respiratory system; it increases breathing. Rubefacient: a topical drug that induces mild skin irritation with erythema; it is used as a toughening agent (rubbing alcohol). Salt Substitute: a sodium-free alternative to sodium chloride used for flavoring foods (potassium chloride). Scabicide: an insecticide suitable for the eradication of the itch mite Sarcoptes scabiei (scabies) (crotamiton). Serotonin Agonist: a compound that activates serotonin receptors, mimicking the effect of the neurotransmitter serotonin. Somatostatin Analog: a hormone chemically and functionally similar to somatostatin. Specific: a drug specially adapted in its indicated use, usually because of a functional relationship between drug mechanism and disease pathophysiology. Stimulant, Central: a drug that increases the functional state of the central nervous system, sometimes used in convulsive therapy of mental disorders (flurothyl; modafinil). Stimulant, Respiratory: a drug that selectively stimulates respiration, either by peripheral initiation of respiratory reflexes or by selective central nervous system stimulation (carbon dioxide, reflex respiratory stimulant; ethamivan, central respiratory stimulant). Stool Softener: a drug used to soften the stool by enhancing the incorporation of water to ease evacuation. Sympathomimetic: a drug that activates organs innervated by the sympathetic nervous system; an adrenergic drug (epinephrine). Systemically Acting Drug: a drug administered so as to reach systemic circulation, from which the drug diffuses into all tissues, including the site of the therapeutic action.

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The apparent first-order rate of elimination treatment 3 degree heart block order citalopram overnight, Kel medicine to increase appetite buy cheap citalopram 40 mg online, is usually the sum of the rate constants of a number of individual processes 97140 treatment code generic citalopram 20mg on-line, for example symptoms queasy stomach and headache purchase citalopram us, metabolic transformation and renal excretion medicine 513 citalopram 40 mg free shipping. For the purpose of pharmacokinetic calculation, it is simpler to convert Equation 5. Most drugs administered orally can be adequately described using a one-compartment model, whereas drugs administered by rapid intravenous infusion are usually best described by a two-compartment or three-compartment model system. In this simple one-compartment system, it is assumed that the administered drug is confined to the plasma (or blood) and then excreted. In the two-compartment system, a drug enters into and is instantaneously distributed throughout the central compartment. The central compartment is usually considered to include the blood, the extracellular space, and organs with good blood perfusion, such as the lungs, liver, kidneys, and heart. The peripheral compartment usually comprises tissues and organs that are poorly perfused by blood, such as the skin, bone, and fat. This typifies the distribution of the drug from the central compartment to the peripheral compartment. During this phase, the drug concentration in the plasma will decrease more rapidly than in the postdistributive or elimination phase. A distributive phase can be very short, a few minutes, or last for hours and even days. A semilogarithmic plot of the plasma concentration versus time after rapid intravenous injection of a drug best described by a two-compartment model system can often be resolved into two linear components. In this procedure, a straight line is fitted through the tail of the original curve and extrapolated to the Y-axis (the value obtained is B). The following equation describes a two-compartment system: C p = Ae - at + Be - bt (Equation 5. Appropriate pharmacokinetic formulas allow the clinician to calculate the various volumes of distribution and rates of distribution and elimination for drugs whose pharmacokinetic behavior is exemplified by the two-compartment system. The amount of time required for the concentration of the drug to decrease by half is considered its half-life. The half-life varies widely between drugs; for some, it may be a few minutes, whereas for others, it may be hours or even days (Table 5. These patients, most of whom have liver dysfunction or kidney disease, retain the administered drug in the blood or tissues for extended periods because of their decreased ability to eliminate the drug. As mentioned previously, digoxin presents a good example of a drug having a half-life Tobramycin sulfate (Nebcin) 2 h Zolpidem tartrate (Ambien) 2. Because theophylline is metabolized in the liver, the half-life of theophylline will be extended in liver disease. The half-life of a drug in the bloodstream may also be affected by a change in the extent to which it is bound to blood protein or cellular components. The result is displacement of the first drug from these sites by the second drug and the sudden availability of free (unbound) drug, which may pass from the bloodstream to other body sites, including those concerned with its elimination. An alternative way to express this removal or elimination from the body is to use total body clearance (ClB), which is defined as the fraction of the total volume of distribution that can be cleared per unit of time. In infants and children, who exhibit larger volumes of distribution and have lower clearance values, most drugs have a longer half-life than in adults. A decrease in the hepatic or renal clearance will prolong the half-life of a drug. The first is the empirical approach, which entails administration of a drug in a certain quantity, noting the therapeutic response and modifying the amount and interval of dosage accordingly. Unfortunately, experience with administration of a drug usually starts with the first patient, and eventually, a sufficient number of patients receive the drug so that a fairly accurate prediction can be made. Besides the desired therapeutic effect, it is necessary to consider the occurrence and severity of side effects. The second approach to the development of a dosage regimen is through the use of pharmacokinetics, or the kinetic approach. One can then determine the appropriateness of a dosage regimen to achieve a desired therapeutic concentration of drug in the body and evaluate the regimen according to therapeutic response. Pharmacokinetics is but one of a number of factors that should be considered in the development of a dosage regimen. Certainly, an important factor is the inherent activity, that is, pharmacodynamics and toxicity. A drug will accumulate in the body when the dosing interval is less than the time needed for the body to eliminate a single dose. As one can see, with continued dosing, the drug concentration reaches a steady-state or plateau concentration. At this limit, the amount of drug lost per interval is replenished when the drug is dosed again. For example, the asthmatic patient maintained on theophylline must have a serum concentration between 10 and 20 mg/mL. The fluctuation of the concentration is diminished for oral administration (half-life of absorption is 1. Consequently, the patient may awaken in the middle of the night and have an asthma attack. Fine, aerated powders with differences in particle size or density may result in a striation pattern and may occur during powder transfer. Dusting occurs when the finer, lighter mixture and repeating this until all of the diluent is incorporated. This process is not acceptable for the incorporation of potent drugs into a diluent powder. Special small-scale and large-scale motorized powder blenders mix powders by tumbling them. Such blenders are widely employed in industry, as are mixers that use motorized blades to blend powders in a large vessel. Segregation may occur by sifting or percolation, air entrapment (fluidization), and particle entrapment (dusting). Also, these powders should be triturated very lightly on a pill tile by using a spatula for mixing rather than a mortar and pestle. Mixing these powders with the bulky powders first and then performing a light blending can minimize the problem. Another approach is to first make the eutectic and then adsorb the paste or liquid that results onto a bulky powder. General guidelines to minimize or prevent segregation include (a) minimum number of transfer steps and drop heights; (b) control of dust generation; (c) control of fluidization of the powder; (d) slow fill/transfer rate; (e) appropriate venting; (f) use of a deflector, vane, or distributor; and (g) proper hopper design and operating valves (if present). Hygroscopic and deliquescent powders Hygroscopic powders will absorb moisture from the air. Deliquescent powders will absorb moisture from the air to the extent that they will partially or wholly liquefy. These problems must be overcome for the powder to be acceptable to the patient and usable. The best approach is to dispense the ingredients in tight containers and incorporate a desiccant packet or capsule when necessary. The patient should be instructed to store the powder in a dry place in a tightly closed container. To lessen the extent of the problem, the compounding pharmacist can in some situations dilute the powder with an inert drying powder to reduce the amount of surface area exposed to the moisture. This water can be liberated either during manipulations or on exposure to a low-humidity environment. Another method is to include a drying bulky powder and to use a light, noncompacting method of mixing the powders. Special precautions must be taken if it is necessary to prepare a formulation containing these mixtures. Pasty material can be added to dry powder by mixing it with increasing quantities of the powder, which will dry out the paste. It is best to add some materials by preparing an alcoholic solution and spraying it evenly on the powder, which has been spread out on a pill tile. The alcohol, or another suitable solvent, should then be allowed to evaporate, leaving the ingredient uniformly dispersed. This method may be especially suitable for high-potency drugs or flavoring agents because it minimizes the possibility that clumps of active drug will develop in the powder blend. Medicated powders Some medicated powders are intended to be used internally and others, externally. Medicated powders for external use are dusted on the affected area from a sifter-type container or applied from a powder aerosol. The doses of some drugs are too bulky to be formed into tablets or capsules of convenient size, so they may be administered as powders. Powders taken orally for systemic use may be expected to result in faster rates of dissolution and absorption than solid dosage forms, because there is immediate contact with the gastric fluids; however, the actual advantage in terms of therapeutic response may be negligible or only minimal, depending on the drug release characteristics of the counterpart products. Under labeled conditions of storage, the resultant product remains stable for the prescribed period of use, generally up to 2 weeks. Sterile dry powders intended to be constituted with water or another suitable solvent prior to administration by injection are discussed in Chapter 15. An inhalation powder is one used with a device that aerosolizes and delivers an accurately metered amount. Most of these products are used in the treatment of asthma and other bronchial disorders that require distribution of medication deep in the lungs. To accomplish this, the particle size of the micronized medication is prepared in the range of 1 to 6 m in diameter. The dose is released from the packaging by a mechanism and is mobilized into a fine dispersion upon oral inhalation by the patient. The Advair Diskus is a specially designed plastic device containing a double-foil blister strip of a powder formulation of fluticasone propionate and salmeterol xinafoate intended for oral inhalation only. Each blister in the device contains 100, 250, or 500 mg of microfine fluticasone propionate and 72. The blister is opened by activating the device, and the medication is dispersed into the airstream created by the patient inhaling through the mouthpiece (10). Fluticasone propionate inhalation powder is available alone as Flovent Rotadisk 50, 100, and 250 mg marketed to be used with the Diskhaler inhalation device. Each double-foil Rotadisk contains four blisters; each blister contains 50, 100, or 250 mg of fluticasone propionate blended with lactose to a total weight of 25 mg per blister. When the Rotadisk is placed in the Diskhaler, a blister containing the medication is pierced, and the fluticasone propionate is dispersed into the airstream as with the Advair Diskus unit (11). The Foradil Aerolizer is a capsule dosage form for oral inhalation only in the Aerolizer inhaler. The capsule contains a dry powder formulation of 12 mg of formoterol fumarate and 25 mg of lactose as a carrier. Formoterol fumarate is a long-acting selective 2-adrenergic receptor agonist acting locally in the lung as a bronchodilator. To use this delivery system, the capsule is placed inside the well of the Aerolizer inhaler, and the capsule is pierced by pressing and releasing the buttons on the side of the device. The patient inhales rapidly and deeply through the mouthpiece, dispersing the formoterol fumarate formulation into the air for inhalation (12). For Relenza, the usual dose is two inhalations (one blister per inhalation) twice daily for 5 days; therefore, four blisters will be used each day. Relenza should be stored at room temperature; it is not a childproof container (13). Bulk and divided powders Medicated powders may be provided to the patient in bulk or may be divided into unitof-use packages. Some powders are packaged by manufacturers, whereas others are prepared and packaged by the pharmacist. Bulk Powders Among the bulk powders available in prepackaged amounts are (a) antacids In some cases, a small measuring scoop, spoon, or other device is dispensed with the powder for measuring the dose of the drug. Dispensing powder medication in bulk quantities is limited to nonpotent substances. Each divided portion of powder may be placed on a small piece of paper (Latin chartula; abbrev. A number of commercially prepared premeasured products are available in folded papers or packets, including headache powders Depending on the potency of the drug substance, the pharmacist decides whether to weigh each portion of powder separately before enfolding in a paper or to approximate each portion by using the block-and-divide method. Each of the smaller blocks is separated from the main block with the spatula, transferred to a powder paper, and wrapped. The powder papers may be of any size convenient to hold the amount of powder required, but the most popular commercially available sizes are 2. If the powder contains hygroscopic or deliquescent materials, waterproof or waxed paper should be used. In practice, such powders are double wrapped in waxed paper, and then for esthetic appeal, they are wrapped in bond paper. Glassine and vegetable parchment papers may be used when only a limited barrier against moisture is necessary. Powders containing volatile components should be wrapped in waxed or glassine papers. Powders containing neither volatile components nor ingredients adversely affected by air or moisture are usually wrapped in a white bond paper.

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If they must be stored in the refrigerator treatment 4 letter word buy citalopram online now, suppositories should be allowed to warm to room temperature before insertion medicine logo buy citalopram uk. The patient should be advised to rub cocoa butter suppositories gently with the fingers to melt the surface to provide lubrication for insertion brazilian keratin treatment cheap 40mg citalopram visa. If the polyethylene glycol suppository formulation does not contain at least 20% water medicine daughter lyrics 20mg citalopram, dipping it into water just prior to insertion prevents moisture from being drawn from rectal tissues after insertion and decreases subsequent irritation symptoms pneumonia discount citalopram online visa. When the patient is instructed to use one-half suppository, the patient should be told to cut the suppository in half lengthwise with a clean razor blade. Most suppositories are dispensed in paper, foil, or plastic wrappings, and the patient must be instructed to completely remove the wrapping before insertion. Depending upon the medication, purpose of the suppository, and associated factors, the administration of an enema prior to a suppository may increase the absorption of the drug. Additional information on inserting rectal suppositories and and informed consent has been published and may be useful for patient counseling (10). They should also be counseled on the proper insertion of the suppository: whether to moisten it prior to insertion, how far to insert it, and how long to remain inactive after insertion. An example of the consultation related to administration of a suppository may be as follows: 1. However, the boy has been to the emergency room twice now with uncontrolled seizures, even after using the suppositories in an effort to bring the seizures under control. His parents have returned to the pharmacy with questions concerning the use of these suppositories. The use of a water-soluble base such as polyethylene glycol may be a better choice. Another possibility is to use a hollow suppository with a diazepam solution in the cavity. Case study Upon discharge from the hospital, she was also given a prescription for prochlorperazine 10 mg tablets by mouth every 6 hours as needed for any N&V she might have at home. However, twice after taking them she threw them up, and she simply "feels too nauseous now to take anything by mouth. Prochlorperazine is available as rectal suppositories, and the recommended dosage for adults for N&V is 25 mg rectally twice daily. Specific instructions are to use her finger to insert the suppository into the rectum about 1 inch and hold the suppository in place for a few moments. Afterward, the patient should thoroughly wash her hands and then resume her normal activities. Specifically, cyclophosphamide is associated with delayedonset N&V that can last up to 6 or 7 days after the administration of chemotherapy. Compare and contrast suppository and insert dosage forms in terms of physical appearance, size, and shape. Develop a listing of drugs in suppository dosage forms for inclusion into a hospital formulary system and indicate the rationale for their inclusion on the list. Develop a listing of conceivable ways a patient might misuse a drug to be administered in a rectal suppository dosage form. Compile examples of prescriptions written for the extemporaneous preparation of a suppository delivery system. Create a table of six vaginal insert products including amount of active ingredient(s), indication, contraindication, adverse effects/precautions, and dosage. List five clinical situations where the administration of a suppository or insert dosage form might be preferred over oral administration. List five counseling points for proper administration of a specific rectal suppository or vaginal insert. From the primary literature, locate a clinical drug study demonstrating a comparison between a rectal suppository delivery system and another route of delivery for the drug in terms of clinical effectiveness and determine which delivery system would be preferred in terms of patient acceptance, patient adherence, bioequivalence, and cost. Prolonged release of morphine alkaloid from a lipophilic suppository base in vitro and in vivo. List the advantages and disadvantages of using liquid dosage forms in extemporaneous compounded prescriptions and in patient therapy 3. Define solubility and describe how different factors increase or decrease solute solubility in a given solvent 5. Evaluate and select a proper solvent and delivery system for a given solute, purpose, and/or patient population In physicochemical terms, solutions may be prepared from any combination of a solid, liquid, and gas, the three states of matter. For example, a solid solute may be dissolved in another solid, a liquid, or a gas, and the same being true for a liquid solute and for a gas; nine types of homogeneous mixtures are possible. In pharmaceutical terms, solutions are "liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents" (1). Still other solutions, because of their composition or use, may be classified as other dosage forms. For example, aqueous solutions containing a sugar are classified as syrups (even though some syrups may contain some alcohol), sweetened hydroalcoholic (combinations of water and ethanol) solutions are termed elixirs, and solutions of aromatic materials are termed spirits if the solvent is alcoholic or aromatic waters if the solvent is aqueous. Solutions prepared by 396 extracting active constituents from crude drugs are termed tinctures or fluidextracts, depending on their method of preparation and concentration. Tinctures may also be solutions of chemical substances dissolved in alcohol or in a hydroalcoholic solvent. Certain solutions prepared to be sterile and pyrogen-free and intended for parenteral administration are classified as injections. Although other examples could be cited, it is apparent that a solution, as a distinct type of pharmaceutical preparation, is much further defined than the physicochemical definition of the term solution. In these preparations, the medicinal agents are intended to provide systemic effects. The fact that they are administered in solution form usually means that they are soluble in aqueous systems and their absorption from the gastrointestinal tract into the systemic circulation may be expected to occur more rapidly than from suspension or solid dosage forms of the same medicinal agent. Solutes other than the medicinal agent are usually present in orally administered solutions. In formulating or compounding a pharmaceutical solution, the pharmacist must use information on the solubility and stability of each solute with regard to the solvent or solvent system. Combinations of medicinal or pharmaceutical agents that will result in chemical and/or physical interactions affecting the therapeutic quality or pharmaceutical stability of the product must be avoided. For single-solute solutions and especially for multiple-solute solutions, the pharmacist must be aware of the solubility characteristics of the solutes and the features of the common pharmaceutical solvents. Hydrogen bonding involves strongly electronegative atoms such as oxygen, nitrogen, and fluorine. Under ordinary conditions, most organic compounds, and thus most drug substances, form molecular solids. Dipolar molecules frequently tend to align themselves with other dipolar molecules so that the negative pole of one molecule points toward the positive pole of the other. Because of small Hydrogen bonds also exist between some alcohol molecules, esters, carboxylic acids, aldehydes, and polypeptides. The solubility of an agent in a particular solvent indicates the maximum concentration to which a solution may be prepared with that agent and that solvent. When a solvent at a given temperature has dissolved all of the solute possible, it is said to be saturated. Using only these two agents, the maximum concentration possible would be approximately 0. However, through the use of an aqueous solution of potassium iodide or sodium iodide as the solvent, much larger amounts of iodine may be dissolved as the result of the formation of a water-soluble complex with the iodide salt. The solubility of a pure chemical substance at a given temperature and pressure is constant; however, its rate of solution, that is, the speed at which it dissolves, depends on the particle size of the substance and the extent of agitation. The finer the powder, the greater the surface area, which comes in contact with the solvent, and the more rapid the dissolving process. The solubility may then be expressed as grams of solute dissolving in milliliters of solvent; for example, "1 g of sodium chloride dissolves in 2. Many of the important organic medicinal agents are either weak acids or weak bases, and their solubility depends on a large measure on the pH of the solvent. These drugs react either with strong acids or strong bases to form water-soluble salts. For instance, the weak bases, including many of the alkaloids (atropine, codeine, and morphine), antihistamines (diphenhydramine and promethazine), local anesthetics (cocaine, procaine, and tetracaine), and other important drugs, are not very water soluble, but they are soluble in dilute solutions of acids. Pharmaceutical manufacturers have prepared many acid salts of these organic bases to enable the preparation of aqueous solutions. However, if the pH of the aqueous solution of these salts is changed by the addition of alkali, the free base may separate from solution unless it has adequate solubility in water. The information gathered on a great number of individual chemical compounds has led to the characterization of the solubilities of Table 13. Conversely, the organic bases are more soluble in organic solvents, including alcohol, than are the corresponding salt forms. The introduction of halogen atoms into a molecule tends to decrease water solubility because of an increase in the molecular weight of the compound without a proportionate increase in polarity. An increase in the molecular weight of an organic compound without a change in polarity reduces solubility in water. For instance, most salts of monovalent cations, for example, sodium, potassium, and ammonium, are water soluble, whereas divalent cations, for example, calcium, magnesium, and barium, usually form watersoluble compounds with nitrate, acetate, and chloride anions but not with carbonate, phosphate, or hydroxide anions. To be sure, certain combinations of anion and cation seem to be similar in makeup but do not have similar solubility characteristics. For instance, magnesium sulfate (Epsom salt) is soluble, but calcium sulfate is only slightly soluble; barium sulfate is very insoluble (1 g dissolves in about 400,000 mL of water) and is used as an opaque medium for x-ray observation of the intestinal tract, but barium sulfide and barium sulfite are more soluble, and their oral use can result in poisoning; and mercurous chloride (HgCl) is insoluble and was formerly used as a cathartic, but mercuric chloride (HgCl2) is soluble in water and is a deadly poison if taken internally. In many instances, solubilities of drugs and their differentiation from other drugs are critical to the pharmacist for avoidance of compounding failures or therapeutic disasters. The ability of a solvent to dissolve organic as well as inorganic solutes depends on its effectiveness in overcoming the electronic forces that hold the atoms of the solute together and the corresponding lack of resolute on the part of the atoms themselves to resist the solvent action. Molecules having one polar functional group are usually soluble to total chain lengths of five carbons. In most instances, especially for solutions to be taken orally, used intranasally, used ophthalmically, or injected, water is the preferred solvent because it comes closer to meeting these criteria than other solvents. Other solvents, such as acetone, ethyl oxide, and isopropyl alcohol, are too toxic to be permitted in pharmaceutical preparations to be taken internally, but they are useful as reagent solvents in organic chemistry and in the preparatory stages of drug development, as in the extraction or removal of active constituents from medicinal plants. For purposes such as this, certain solvents are officially recognized in the compendia. A number of fixed oils, such as corn oil, cottonseed oil, peanut oil, and sesame oil, are useful solvents, particularly in the preparation of oleaginous injections, and are recognized in the official compendia for this purpose. Together with water, it forms a hydroalcoholic mixture that dissolves both alcohol-soluble and water-soluble substances, a feature especially useful in the extraction of active constituents from crude drugs. By varying the proportion of the two agents, the active constituents may be selectively dissolved and extracted or allowed to remain behind, according to their particular solubility characteristics in the menstruum. Alcohol is often preferred because of its miscibility with water and its ability to dissolve many water-insoluble ingredients, including drug substances, flavorants, and antimicrobial preservatives. Alcohol is frequently used with other solvents, such as glycols and glycerin, to reduce the amount of alcohol required. It is also used in liquid products as an antimicrobial preservative alone or with parabens, benzoates, sorbates, and other agents. However, aside from its pharmaceutical advantages as a solvent and a preservative, concern has been expressed over the undesired pharmacologic and potential toxic effects of alcohol when ingested in pharmaceutical products, particularly by children. The final volume of such mixtures is not the sum of the individual volumes of the two components because the liquids contract upon mixing; the final volume is generally about 3% less than what would otherwise be expected. Thus, when 50 mL of each component is combined, the resulting product measures approximately 97 mL. Diluted alcohol is a useful hydroalcoholic solvent in various pharmaceutical processes and preparations. It is used externally as a rubefacient and soothing rub and as a vehicle for topical products. This discourages the illegal removal for use as a beverage of the alcoholic content of rubbing alcohol. The product is volatile and flammable and should be stored in a tight container remote from fire. Acceptable drinking water should be clear, colorless, odorless, and neutral or only slightly acidic or alkaline, the deviation from neutral being due to the nature of the dissolved solids and gases (carbon dioxide contributing to the acidity and ammonia to the alkalinity of water). Its use is permitted in washing, in extraction of crude vegetable drugs, in preparation of certain products for external use, and when the difference between tap water and purified water is of no consequence. Distillation Method Many stills in various sizes and styles with capacities ranging from about 0. Generally, the first portion of aqueous distillate (about the first 10% to 20%) must be discarded because it contains many foreign volatile substances usually found in urban drinking water, the usual starting material. Also, the last portion of water (about 10% of the original volume of water) remaining in the distillation apparatus must be discarded and not subjected to further distillation because distillation to dryness would undoubtedly result in decomposition of the remaining solid impurities to volatile substances that would distill and contaminate the previously collected portion of distillate. Ion Exchange Method On a large or small scale, ion exchange for the preparation of purified water offers a number of advantages over distillation.

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