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Diabetic Eating Out Since the rules are always somewhat relaxed when “eating out” a diabetic loved one will badger you to go out with them purchase 25mg phenergan with mastercard anxiety 18 year old. If rules are sure to be broken 25 mg phenergan mastercard anxiety symptoms lightheadedness, calculate it into the rest of the day so you can compensate for it generic phenergan 25mg with amex anxiety symptoms 50. Ethnic foods often had to be given up when children were raised (switched to hot dogs and pizza) but with this diversion gone discount phenergan 25 mg overnight delivery anxiety 3rd trimester, a return to family food would be most welcome and most healthful. And they certainly were made at home where cleanliness and “persnickitiness” are at their finest! Good advice is to return to old fashioned home cooking: with its flour and butter, lard and cream, homemade pasta, olive oil and soup, coarse cereal grains and plain fruit. Gone are the fruit juices, flour mixes, crackers and sweets that fill grocery shelves. Time is the great inhibitor but if you have the means or the help, the best advice, nutritionally, is a return to old-fashioned cooking and recipes. Use her wooden spoons, glass glasses, and plain dishes, her wooden and straw bowls and enamel pots and pans. But a good salt rule is to either cook with it or have it on the table, but not both. Use aluminum- free sea salt, and make sure the salt is sterilized by heating five minutes at 400°F in a glass pie plate to kill mold. The best salt is a mixture of 1 part of your aluminum-free, sterilized sea salt and 1 part potassium chloride (another kind of salt, see Sources). Potassium ousts sodium (salt) from your body, so you can use twice as much of this kind of salt! It is important to find the poison as soon as you can since the rest of the body will soon be affected, too. It is a herculean task but only gets harder each day, so keep notes as you ask: Is there new carpeting? The list is endless and the situation looks hopeless because so many new things can happen in two weeks. To answer each question, test the item using your Syn- crometer searching technique. To test the air, take a dust sample off the kitchen counter or table (this gives you fresh dust). Be sure to test everything eaten in a two week time period: un- usual things like popcorn, candy, crackers, cookies, health foods and special powders. A consolation is that you will find a num- ber of bad foods that are not necessarily the tremor causes but which cause other health problems. Let us imagine that the air (dust) sample proves toxic (resonates with the saliva sample). Suppose the water proves toxic (appears in your white blood cells); search for lead, copper, and cadmium. Although municipal water tests occasionally detect small amounts of pro- pyl alcohol, benzene, or wood alcohol, I have never detected them—you need not search for them. Bacteria, coming from teeth and jaw (bone infections, called cavitations) may not seem as recent as two weeks. But something recent may have aggravated them, so they now can enter more easily into the blood and brain. It is wisest to check this possibility with a dentist before doing weeks of other testing. Going after a tremor problem in this logical way always finds the cause of tremor whether its a simple short attack or a situation of long standing tremor with head shaking and drooling. If your situation is extra difficult, you will at least improve it and stop its progression. In cases of Parkinson’s disease I often find the bacterium Clostridium tetani, well known for causing stiffness. When you find the culprit, you not only will be stopping the tremor, you will be improving a lot of other conditions along the way. Conditions like hesitant speech, shuffling walk, getting up stiffly and slowly from a chair. By the time you have identified the culprits (probably 20 hours of work) surely you have won the right to make changes. Even when the tremor lessens and the elderly person plainly states they feel better, family members may disregard your recommendations. Make their choices clear: • Either the inside door to the garage gets sealed off or the cars and lawn mower get parked outside and anything containing gasoline or solvents gets put in a detached shed. Caffeine speeds up the heart; then the overworked heart has to “take time out” for itself by missing a beat. A young athlete may have a slow pulse legitimately, due to having a very strong efficient heart, but your elderly person does not fit this category. If the pulse is quite high, over 100 perhaps, this will wear the heart out much sooner than necessary. A probable answer is that it is so weak that it has to beat faster to keep up with its job of circulating the blood. The most common parasite heart invaders are Dirofilaria, heartworm “of dogs” and Loa loa, another small filaria worm. At one stage these worms are so tiny that they can slide through the smallest blood vessels. Both heartworm and Loa loa are very easy to kill with a zapper and both are very easy to pick up again. It makes no difference that the house dog is getting monthly preventive treatments for heartworm. They pick it up daily and have thirty days to develop it and give it to others between treatments. These heart parasites may not cause any pains, yet disturb the rhythm or the pulse of the heart and cause it to enlarge. Staphylococcus aureus is a bacterium hiding out in far away places like pockets left under teeth when they were extracted or along root canals. Once the mouth source is cleaned up, the bacteria do not come back to the heart (after one last zapping). Weather changes, namely temperature changes make pipes expand or shrink—leaving cracks! De- livering poisonous house gas to our homes in pipes that are not fail-safe is an archaic practice. And read the sec- tions in this book on pulse (page 289) and brain problems (page 278) very closely for more things to check. This strength is nec- essary to push the blood into the farthest “corners” of the body, especially the hands and feet, and warm them up! Blood thinning drugs to improve circulation are dangerous—use only if the doctor insists. Heart/Kidney Relationship A strong heart is necessary, too, to push the blood through the kidneys. It takes pressure, namely strength, to push the blood through them so wastes and extra water can be let down the kidney tube. Think of the kidneys as a colander full of tiny holes of various sizes that let certain things through them but not bigger things. These holes are constantly being adjusted by the adrenals which sit right on top of the kidneys and “supervise”.
Each destination should have a designated area where parcels may be stocked before distribution generic 25mg phenergan visa anxiety symptoms zinc. Receiving and distribution areas should be near access doors in order to facilitate handling purchase 25mg phenergan overnight delivery anxiety uk. It is also recommended to plan a stocking area for empty boxes order 25mg phenergan mastercard anxiety zone symptoms, used to prepare orders for peripheral health facilities discount 25 mg phenergan fast delivery anxiety symptoms in 2 year old. Workspace(s) A workspace should be set up in the receiving area and in the distribution area to verify deliveries and prepare orders Organisation and management of a pharmacy Desk For the person in charge of the pharmacy, a desk near a light source should be set up for administrative work and for keeping documents. Examples of pharmacy layout Schema 1 Refrig Injectable drugs Stupefiants External use Incoming Infusion storage solutions Working area Outgoing storage Storage for empty boxes 1 2 3 4 Oral drugs Oral drugs Material Schema 2 Refrig Stupefiants Incoming storage Working area 1 Outgoing storage 2 Infusion Desk solutions 3 4 The arrangement of shelves, tables or other furniture, varies according to the layout of the premises. For larger stocks or central pharmacies, use several rooms and apply the same principles by adapting layouts to needs: administration, cold room, refrigerators, etc. Arrangement of drugs and supplies Storage of drugs not requiring a cold chain Drugs are arranged according to the classification adopted: – oral drugs – injectable drugs Organisation and management of a pharmacy – infusions – drugs for external use and antiseptics – disinfectants In each category of products (oral, injectable, etc. By attributing a specific place to each item it is possible to immediately see the quantity available and to react quickly to avoid stock shortages. Arrange products with the earliest expiry date at the front of the shelves and those with the latest at the back. Storage of products requiring a cold chain Products needing a cold chain should be stored in a refrigerator (between 2–8°C): vaccines, immunoglobulins, serums, insulin, ergometrine, oxytocin, dinoprostone, certain laboratory tests, etc. Storing medical materials/supplies Given the diversity of items, do not to use alphabetical ordering, but group articles by category: injections, dressings, sutures, reagents and laboratory material, etc. Storing bulky materials Put a few boxes in their normal place and, on a label, indicate where the rest of the stock is kept. Organisation and management of a pharmacy Management of a pharmacy Organisation of activities The management of the pharmacy should be entrusted to a single person having received adequate training. This person is the only person possessing keys to the pharmacy and narcotics cupboard and is helped by one or more assistants, depending on the workload. It is important to draw up a work calendar (orders, distributions, inventories, management of expired drugs, etc. Stock management Stock cards The stock card is the principle instrument for stock control. A stock card is established for each product (drugs and supplies) and updated at each movement. Stock cards are used to: – identify all stock movements: in and out; – determine at any moment the theoretical level of stocks; – follow–up the consumption of different facilities; – correctly plan and prepare orders; – determine losses (differences between theoretical stock and actual stock). The following may also be included: – average monthly consumption; – stock levels: buffer stock, running stock; – other stock areas for a product; – unit price; – current orders and dates. Write a single operation per line, even if several operations take place the same day. Note: stock cards are always equired, even when computer assisted stock management is used. Buffer stock quantities are generally evaluated as half of the consumption during the period between two deliveries. It depends on risks that a programme may run: stock ruptures or drug expiration in specific situations (resources, seasonal supply problems, etc. For example, if the delivery delay is two months, the buffer stock corresponds to the quantity consumed in one month. Organisation and management of a pharmacy Orders should be in triplicate, dated and countersigned by persons in charge of health structures. Two copies are sent to the supplier: one serves as a way bill and may also be used for invoicing, the second stays with the supplier. Example: Health facility order form, 6-month supply period, minimum stock of 3 months (2 month delivery delay + 1 month buffer stock) Health structure: Beboro Head of structure: Jeanne Maritoux, Ph Date: 26. On reception, the number of parcels should be checked, then their contents should be verified: – ensure that products delivered correspond to products ordered, and that the quantities conform to those on the packing list; – packaging, labelling and expiry dates of each product should be checked, as well as the aspect of the product; – look for special storage conditions (cold chain). Way bills, invoices and packing lists are to be classed with orders in an "orders" file and kept for 3 years or more according to current regulations. Organisation and management of a pharmacy Inventory An inventory of current stock quantities and expiry dates should be done before each order. Stock cards give a theoretical figure of stock quantities, but actual quantities of each product should be verified (physical stock). Distribution – Distribution to health facilities Each health facility sends the central warehouse two copies of the order form. On both copies, actual quantities supplied by the central warehouse are recorded in the “Qty delivered” column. After verifying that all products have been correctly recorded on their respective stock cards, the second copy is placed in a file established for health facility. Put the number of tablets corresponding to a complete treatment and the label into the bag. In busy centres it is better to have two people responsible for dispensing drugs in order to double check prescription deliveries; the first collects the drugs prescribed, the second verifies and gives them to patients with all necessary explanations, slightly away from other patients. So that patients correctly follow treatment, adequate explanations should be given: • how to take the drug, • for how long, • possible adverse effects (e. Persons dispensing drugs should be able to give patients the information they need. Interpreters are needed if several languages exist in the same region Donations of recuperated medicines and medical samples It is not recommended to solicit or accept supplies coming from collections of drugs recuperated from consumers in industrialised countries, or free samples distributed by manufacturers. They are very often specialised drugs unknown to prescribers and unsuitable for local pathologies. The multiplication of different drugs supplied interfere with the implementation of standardised therapeutic regimens and makes any form of management impossible. Updated: February 2017 Drug quality and storage Drug quality and storage Drug quality influences treatment efficacy and safety. Quality depends on correct manufacturing and storage: high-quality drugs are available when using rational buying procedures and when suppliers are reliable. Quality standards Each drug is characterised by particular norms written in pharmacopoeia or files presented by manufacturers and recognised by competent authorities in each country. Analysis certificates guarantee that products from one batch (products from the same production cycle) conform to official quality standards in the country of manufacture. Storage conditions Stability of drugs depends on both environmental factors such as temperature, air, light and humidity, and drug-related factors such as the active ingredient itself, the dosage form (tablet, solution, etc. It is therefore necessary to respect storage instructions given in this guide or by manufacturers (on notices and labels) if the recommendations are not identical. Storage temperatures are defined by European pharmacopoeia as follows: freezer - 15 to 0°C refrigerator + 2 to + 8°C cool + 8 to + 15°C ambient temperature + 15 to + 25°C During transit and transportation temperatures may attain 50 to 60°C inside vehicles, shipping containers or on docks and, in this case, shelf life and expiry dates may no longer be guaranteed. Freezing may be detrimental, particularly for solutions, leading to the deterioration or precipitation of active ingredients as well as the breaking of ampoules and vials. Updated: February 2017 Drug quality and storage Vaccines, immunoglobulins and antisera are products that are sensitive to heat and light. Even though new techniques produce vaccines that are less sensitive to heat (called "thermostable"), they still have to be stored in the refrigerator between 2°C and 8°C, and the cold chain must be strictly respected during transport. The square on the monitor changes colour when exposed to heat over a period of time: if the square is lighter than the circle, the vaccine can be used. If the square is the same colour or darker than the circle, the vial must be destroyed.
These junctions are a first-line impediment purchase phenergan 25mg anxiety symptoms heart pain, slowing the journey of the drug molecule from within the capillary to a receptor site on a neuron order phenergan 25mg with visa anxiety levels. The astrocyte wraps itself around the capillary to provide yet another line of defense between the drug in the capillary and the neuronal receptor to which it is traveling generic phenergan 25mg otc anxiety symptoms pain in chest. In the brain buy phenergan 25mg with amex anxiety symptoms signs, in order for a drug molecule to leave a capillary and successfully journey to a neuronal receptor, it must traverse multiple barriers. The walls of capillaries in the brain are dif- ferent from those in non-brain tissues. Next, in the brain, another type of cell, called an astrocyte, forms an additional barrier that must be traversed. There are a number of molecular substrates that the brain requires for its nor- mal functioning; these substances are not biosynthesized within the brain and are not able to enter the brain by passive diffusion. Because of their importance to normal brain neu- rochemistry, evolution has resulted in the existence of protein carriers to transport them into the brain. D-glucose and L-phenylalanine are two such molecules, and there are a number of others. A prodrug is a drug molecule that is biologically inactive until it is activated by a metabolic process. Improve the flavor of a drug An ester, for example, can be used to “mask” a carboxylate. Within the body, the ester is hydrolyzed, releasing the drug in its bioactive carboxylate form. In that application, it must pass through the liver — the principal drug-metabolizing organ — in which it loses an N–ethyl group to become a convulsant and emetic. This compound is not a prodrug in the strict sense, but rather represents a molecular modification. Replacement of a “vulnerable moiety” such as a methyl group by a less readily oxi- dized chlorine was used to transform the short-acting tolbutamide (3. The ester group is fairly stable in the tissues but is very rapidly hydrolyzed in the serum to the polar carboxylic acid, which cannot penetrate the blood–brain barrier. The introduction of a hydrophilic “disposable moiety” can restrict a drug to the gastrointestinal tract and prevent its absorption. Such a type of drug is represented by the intestinal disinfectant succinyl-sulfathiazole (3. On the other hand, lipophilic groups can ensure peroral activity, as in the case of the penicillin derivative pivampicillin (3. This can be a great convenience for the patient, especially in areas with remote medical facilities. Drug designers have attempted for many years to use selective drug-transport moi- eties, and have met with moderate success. The idea is to attach a drug, such as an anti- tumor agent, to a natural product that will accumulate selectively in a specific organ and act as a “Trojan horse” for the drug. The attachment of alkylating agents to estro- gens has been tried in the treatment of ovarian cancer, and amino acids have also been used as drug carriers. A recent ingenious application of the carrier concept is the uti- lization of antibodies — which can, at least in principle, be tailored to any site — as drug carriers. The large-scale preparation of antibodies is, of course, a major difficulty in this approach; however, the new monoclonal antibodies hold great promise. This concept goes back to the turn of the twentieth century, and in fact many prodrugs were not at the time really recognized as such. For instance, castor oil is a laxative because it is hydrolyzed intestinally to the active ricinoleic acid. Selective bioactivation (toxification) is illustrated in the case of the insecticide malathion (3. This acetylcholinesterase inhibitor is desulfurized selectively to the toxic malaoxon, but only by insect and not mammalian enzymes. Higher organisms rapidly detoxify malathion by hydrolyzing one of its ester groups to the inactive acid, a process not readily available to insects. This makes the compound doubly toxic to insects since they cannot eliminate the active metabolite. Novel polymers have permitted the development of membranes with controlled diffusion rates. The great advantage of this is that the constant release rate of 65 µg/day means that much less drug is released than with the use of oral contraceptive tablets. The transdermal delivery of scopolamine as an antiemetic for motion sickness represents another successful application of microporous membrane technology. Here the drug is applied in a plastic strip similar to a “Band-Aid,” usually behind the ear. Low-density lipoproteins and liposomes (drug-filled lipid–cholesterol vesicles measuring a fraction of a micrometer) are also being used to protect drugs from enzymatic destruction during transport in the bloodstream. Osmotic minipumps — cylinders measuring about 25 × 5 mm — are widely used to deliver constant amounts of drug solutions to experimental animals. The osmotic compartment swells in contact with tissue fluid and squeezes the drug reservoir, displacing the drug solution in a continuous flow. The rate of delivery is specified by the size of the opening in the container and the swelling rate of the osmotic “syringe. Although these interesting developments in bioengineering are not, strictly speaking, in the realm of drug design or even medicinal chemistry, they can nevertheless contribute substantially to the success of drug therapy. A useful drug is a drug molecule that is not only safe and efficacious, but also one that can pass government regulations, pass through multiple levels of human clinical trials, be economically produced in large quantities, be successfully marketed, and can ultimately help people with disease. Perhaps the greatest hurdle along the pathway of a molecule becoming a useful drug is the need to sequentially pass clinical trials. However, before a drug can be evaluated in human clinical trials, it must first successfully negotiate preclinical test- ing. This frequently involves five or six types of test, and is completed in non-human animals: 1. Acute toxicity — acute dose that is lethal in 50% of animals; usually two species, usually two routes of administration 2. Subacute toxicity — physiology, histology, autopsy studies; two species, sometimes with dosings over a 6 month time period 3. Mutagenic potential — effects on genetic stability of bacteria (Ames test) of mammalian cells in culture 5. Carcinogenic potential — required if drug is to be administered for prolonged periods of time 6. Reproductive performance effects — effects on animal progeny, production of birth defects Once a molecule successfully passes the preclinical testing, it is ready for human clin- ical trials. Phase 1 — the effects of the drug as a function of dose are measured in a small number (25–45) of healthy volunteers who do not have the disease under study; safety is primarily evaluated. Phase 2 — the drug is studied in a small number of people (20–150) who have the disease under study; both safety and efficacy are evaluated. The timeline for drug discovery and development is long, adding to the high cost of drug development. Phase 4 — once the drug has been approved for market, vigilant post-marketing sur- veillance is done to ascertain the possible appearance of previously undetected tox- icities or problems. During the drug development phases, toxicity is one of the most important hurdles to the success of a drug molecule. Toxicity can affect the person who is taking the medication (causing skin rashes, liver problems, bone marrow failure, etc. Toxicity problems have resulted in many drugs being withdrawn from the market, as shown in table 3. Successful completion of the four phases of human clinical trials enables a drug to be widely distributed for the treatment of human disease.
Many of these new compounds found their way into the market place cheap phenergan 25mg amex anxiety natural treatment, with varying degrees of therapeutic success buy phenergan 25 mg without prescription anxiety symptoms panic attacks. Modern drug discovery by screening is more of a systematic tech- nological tour de force than a hit-or-miss gamble discount phenergan 25mg amex anxiety problems. Although rational drug design is elegant purchase 25mg phenergan with visa anxiety in dogs symptoms, it is also slow and thus time-inefficient. It takes a long time to identify the proteins that are involved in a disease, then crystallize them and design drugs to bind to them. Worse, some proteins, especially membrane- bound proteins, seem to defy crystallization, while some diseases do not even have identifiable proteins involved in their pathogenesis and etiology. The crystal structures of key protein receptors do not have to be known; indeed, the proteins do not even have to be identified. If the bioassay is fast and efficient, and if the library of compounds being screened is diverse and comprehensive, then in principle it should be possible to identify a lead compound years before the practitioner of rational drug design. However, the key to success lies in the “goodness of the library of compounds” (i. If the library contains a million compounds that are all analogs of each other, then it may be large but it is probably not sufficiently diverse. The library should have the full range of functional groups (cations, anions, hydrogen bond donors, hydrogen bond acceptors, lipophilic, aromatic, etc. Combinatorial chemistry is both the philosophical and the practical method with which to create structurally diverse compound libraries. Combinatorial chemistry is defined as that branch of synthetic organic chemistry that enables the concomitant syn- thesis of large numbers of chemical variants in such a manner as to permit their evalu- ation, isolation, and identification. Combinatorial chemistry affords techniques for the systematic creation of large but structurally diverse libraries. From a technical perspec- tive, there are several avenues of approach to library creation: 1. Pharmacological activity privileged structures Benzodiazepines Dihydropyridines Hydantoins c. Novel template structures Dihydrobenzopyrans Historically, the first major libraries were oligomers of naturally occurring monomers. If atypical amino acids and amino acids in the unnatural D configuration are included, it is possible to achieve 125,000 different compounds with relative ease. Peptide libraries are easy to synthesize and, since amino acid side chains possess a wide variety of different func- tional groups, it is possible to achieve a good measure of structural diversity. However, in general, peptides are not drugs and a peptide lead would have to be modified into a drug-like molecule. In addition to oligopeptides, other naturally occurring oligomeric libraries are possible, including oligonucleotide libraries. A step beyond the naturally occurring oligomeric libraries is to create libraries from non-naturally occurring monomeric building blocks. The medicinal chemistry literature contains a fair number of examples of such libraries, including oligocarbamates and oligoureas. Although these libraries overcome the limitations of naturally occurring oligomeric libraries, most drugs are not polymers. To address this problem, new libraries emerged in which the central moiety was a small organic molecule. The diversity library was then constructed by attaching many different substituents to this central moiety. For example, dioxapiperazines are cyclic dipeptides and thus are relatively trivial to prepare. Other monomers were selected because they had a good track record for being drug-like molecules. In preparing these various libraries, extensive use is made of solid phase synthetic methods. When performing a large number of synthe- ses, it is preferable to perform the synthetic steps on a solid bead rather than complet- ing the entire synthesis in the solution phase. The solid-phase technique makes byproduct removal and final compound purification easier. The organic chemistry literature con- tains a wealth of different types of solid-phase supports and novel linkers for attaching the synthetic substrate to the bead. If a 200,000 compound library is available, the biological evaluation assay must be rapid and reliable. If the assay were capable of test- ing five compounds per day, it would take 110 years to evaluate the entire library. The ability to inhibit an enzyme is a good example of a potentially useful assay for high throughput screening. A variety of high throughput assays have been developed and perfected over the past 10–20 years. Microplate activity assays (assay is in solution in a well; the result of the assay, such as enzyme inhibition, is linked to some observable, such as color change, to enable identification of bioactivity) 2. Affinity selection assays (compound library is applied to a protein target receptor; all compounds that do not bind are removed; compounds that do bind are then identified) Of these, microplate assays are probably the most widely used. Screening combinator- ial libraries in 96- or even 384-well microplates is time and cost efficient. Using modern robotic techniques, it is possible to perform more than 100,000 bioassays per week in a microplate system (permitting the above-described 200,000 compound library to be screened in two weeks, rather than over a century). In addition to selecting an appropriate assay, it is also necessary to have a pooling strategy. It is more efficient to test many compounds per well on the microplate, rather than one. If one could test 100 compounds per well, then the standard 96-well plate would enable almost 10,000 compounds to be evaluated in one experiment. The synthetic strategy employed during the combinatorial syntheses can be used to assist in determining these pooling strategies. In random incorporation syntheses,a single bead could contain millions of different molecular species. In mix and split syn- theses (also called pool and divide syntheses or one bead–one compound syntheses) only one compound is attached to any given solid-phase synthetic bead. The evolution of methods for combinatorial syntheses and high throughput screening will be necessary to address the explosion of druggable targets soon to be identified by the genomics and proteomics revolutions. Current drug design strategies are struggling with fewer than 500 druggable receptor proteins. Endeavoring to identify lead compounds for an additional 3500 targets will overwhelm present-day drug design technologies. Genomics and pro- teomics represent a possible pathway to enhanced future drug discovery. On June 26, 2000–the dawning of the present century–a historic milestone in genomic science was attained when researchers involved with the Human Genome Project jointly announced that they had sequenced 97–99% of the human genome–the all-encompassing collection of human genes. The human genome consists of 23 pairs of chromosomes with three billion base pair codes for approximately 24,000–30,000 functional genes (original estimates of 100,000–120,000 genes seem to have been incorrectly high). Despite the size of this flood, its flow has not filled the drug discovery pipeline with winning candidates. Determining gene structure and function through genomics definitely does illuminate the path for deciphering human biochemistry and for linking specific genes to specific diseases. Although genomics did deliver phenomenal masses of raw information, the genomics technologies have so far failed to deliver the more than 10,000 anticipated druggable targets predicted by the early hyperbole of the genomics era.
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