Preface Our vision To deliver a variety of information in joyful manner that is close to the mind of our audience Why did we choose the magazine as a start? As first of all, magazines are less harder than text books and references, in presenting facts . Also it contain a variety of content. Why it was named PharmTech? Our aim is to involve the technology use in science, and here was in Pharmacy. And was the name PharmTech.
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Index chiral drug------> 1 Kidney Stone Treatment------> 3 Fen-Phan a ligule crime------> 4 3D Printed Drug------> 5 Controlled Drug Release------> 6 Virtual Reality------> 7 The cost of Drug development------> 8 How to build a good C.V------> 10 Brain Cancer------> 11
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Chiral Drug First: What is a chiral drug? An enantiopure drug is a drug that is available in one specific enantiomeric form, meaning only one enantiomer is pharmacologically active while the other might be totally inactive or even dangerous. Why you do ask? Because the most biological molecules are present in one enantiomeric form, thus binding or even reacting differently. The one compound may have 2^n ( n being the number of chiral center in the molecule )
Chiral compound in general are obtained either by asymmetrical synthesis (so damn hard), or resolution ( A fancy word used to indicate the separation of enantiomer compound ), for that the most of the chiral drug are obtained from nature, because living creature uses one enantiomer for metabolism.
Second: So enantiopure drug means half the racemic drug right?! Theoretically yes, but there is more to it, for example the presence of (R) enantiomer of Ibuprofen in the racemic mixture slows the effect of the (S) enantiomer (effective enantiomer) from 12 minutes to 38 minutes, it’s a waste and a drag, at least it’s not causing liver poisoning like the (R) enantiomer of naproxen, the other one (s) enantiomer used to treat arthritis pain and inflammation typical NSAID drug. There are many examples that I could gave you, but the one thing I want you to know or pharmacology people want you to know is, it is frequently thought, (not always) one enantiomer may have a greater effect than the other enantiomer
Quize How many isomeric forms does hemoglobin has? Hint: alpha unit in hemoglobin have 141 amino acid, beta unit have 146 amino acid. Answer: 6.18326*10^(172)
Fun Fact
Chirality in the HUMAN
Nearly all of the amino acids in the human body are called "L" amino acids; despite being chiral, the body almost exclusively creates and uses amino acids in this one configuration. The enantiomer of the amino acids in the human body (D amino acid) cannot be incorporated into proteins. D-aspartate and D-serine are two notable counterexamples, since they do not appear to ever be incorporated into proteins, but instead act individually as signalling molecules.
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Third: Chiral drug is a money maker. AstraZeneca is the inverter of omeprazole ( Racemic ) a proton pump inhibitor sold as an OTC drug, when the patency for the drug had expired, Astra released esomeprazole under the brand name Nexium, They advertised it aggressively and convincing doctors that it’s more effective than omeprazole. Between the launch of esomeprazole in 2001 and 2005, the drug has netted AstraZeneca about $14.4 billion.
Quize
54% of the drug in the market are chiral drug only10% of the last one are available in enantiopure form the other 90% are marketed as racemic mixture because they are hard to synthesis in one form or they rapidly transform to racemic mixture, that is money waiting for you! if you figured a way to synthesis one of these drug or to prevent racemization, bomb that is 14 billion in your pocket, and if you find an entirely new way to asymmetrical synthesis don’t forget to claim your Nobel Prize in chemistry, like William, Knowles and Barry did in 2001. YES IT IS THAT HARD When a drug is covered under copyright (patent) only the inventor company has the right to market it. A racemic drug can be made into an enantiopure drug though it’s not easy to get patent for enantiopure drug, many thing must be considered like how hard is it to synthesis the one enantiomer, the stereoselectivity of the relevant receptor, other secondary reasons concerning law and market success.
Where is the chiral center in Omeprazole?
Enantioselective synthesis Whenever a chiral product is formed by reaction between achiral reagents, the product is racemic. Several approaches to enantioselective synthesis have been taken, but the most efficient are those that use chiral catalysts to temporarily hold a substrate molecule in an unsymmetrical environment—the same strategy that nature uses when catalyzing reactions with chiral enzymes. While in that unsymmetrical environment, the substrate may be more open to reaction on one side than on another. Sharpless dihydroxylation is one way to make enantiopure diol, the chiral product can be control by AD-mix as an axillary catalyst
(DHQD)2PHAL and (DHQ)2PHAL are enantiomers
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Kidney Stones Treatment Uric acid stones Some kidney stones are made of uric acid, a waste product that normally exits the body in the urine. To prevent these types of stones, you may take: Allopurinol Potassium citrate Sodium bicarbonate
Medicine to help pass stones Medicine you can buy without a prescription, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may relieve your pain while you pass a stone. Your doctor may also prescribe medicine to help your body pass the stone, such as asalpha-blockers
Calcium stones Calcium stones are the most common kind of kidney stone. To prevent them, you may take: Orthophosphate. Potassium citrate. Thiazides.
struvite stone Some struvite stones (staghorn calculi) form because of frequent kidney infections. If you have a struvite stone, you will most likely need antibiotics to cure the infection and help prevent new stones from forming. You may need surgery to remove the stone. Urease inhibitors may be used to prevent struvite stones.
Cystine stones A very small number of stones are made of a chemical called cystine. Medicines to prevent them include: Penicillamine. Potassium citrate. Tiopronin. Struvite stones
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Fen-Phan a ligule crime Fenfluramine/phentermine (Fen-Phen) , usually called fen-phen, was an anti-obesity treatment that utilized two anorectics. Marketed by: Wyeth-Ayerst Laboratories Recalled: 1997 (after 24 years on the market) Financial damage: Awards to victims close to $14 billion, making it one of the most costly products liability cases in history. Fen-Phen’s was a hugely popular weight loss drug, its popularity peaking in the 90’s. It is estimated that as many as 6.5 million people took it to help fight obesity. After consumers began experiencing heart disease and other pulmonary problems, the FDA set the recall in motion. American Lawyer reported that more than 50,000 Fen-Phen victims have filed suits against Fen-Phen’s maker Wyeth, and legal expenses combined with awards may have exceeded $21 billion. The Long time in the marketplace combined with the severity of both the public reaction and the significant awards granted to its victim’s times make its impact unprecedented.
History
Fenfluramine as a single drug was first introduced in the 1970s, but was not popular because it only temporarily reduced weight. A 1984 study found a weight loss of 7.5 kg on average in 24 weeks, as compared to 4.4 kg under placebo. It sold modestly until the 1990s, when it was combined with phentermine and heavily marketed. A similar drug, aminorex, had caused severe lung damage and "provided reason to worry that similar drugs ... could increase the risk of a rare but often fatal lung disease, pulmonary hypertension." In 1994, Wyeth official Fred Wilson expressed concerns about fenfluramine's labeling containing only four cases of pulmonary hypertension when a total of 41 had been observed, but no action was taken until 1996. In 1995, Wyeth introduced dexfenfluramine (the dextro isomer, marketed as Redux), which it hoped would cause fewer adverse effects. However, the medical officer of the Food and Drug Administration (FDA), Leo Lutwak, insisted upon a black box warning of pulmonary hypertension risks.
After Lutwak refused to approve the drug, the FDA management had someone else sign it and approved the drug with no black box warning for marketing in 1996. European regulators required a major warning of pulmonary hypertension risks. In 1996, a paper in the New England Journal of Medicine (NEJM) from the Mayo Clinic discussed clinical findings in 24 people who had taken fen-phen . The authors noted that their findings suggested a possible correlation between mitral valve dysfunction and the use of these anorectic agents.Later in 1996, a 30-year-old woman developed heart problems after a month of using it; when she died in February 1997, the Boston Herald devoted a front page article to her.The FDA alerted medical doctors that it had received nine additional reports of the same type, and requested all health care professionals to report any such cases to the agency’s MedWatch program, or to their respective pharmaceutical manufacturers. The FDA subsequently received over a hundred additional reports of valvular heart disease in people taking fen-phen, fenfluramine alone or dexfenfluramine alone.The FDA requested that the manufacturers of fenfluramine and dexfenfluramine stress the potential risk to the heart in the drugs' labeling and in package inserts. As of 1997, the FDA was continuing to receive reports of valvular heart disease in persons who had taken these drugs. This disease typically involves the aortic and mitral valves. After reports of valvular heart disease and pulmonary hypertension, primarily in women who had been undergoing treatment with fen-phen or (dex) fenfluramine, the FDA requested its withdrawal from the market in September 1997.
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Fenfluramine
3D Printing
Spritam is the first 3D printed drug abbrobed by the FDA
Is the dimensional printing process of building up materials layer by layer, via computer aid design models through printer to formulate drug materials into the desired drug form. In the process, the data intering is through Digital camera or 3D scanner, printing the data into the printer, aand building up the molecule to form dosage form. It is used to create custom prosthetics, dental implants, Bioprinting and Tissue engineering application.
The 3D printed tablet
Advantages The 3D printing has a high production rate due to the fast operating system. Also reducing waste materiatls and costing effectiveness and time saving. Beside it is accurate and repetitive and flexible technique. Amazingly, it contribute in the combination of several APIs in one tablet. 3D Printing can flip over the pharmaceutical world by many ways, such as Personalized Drug Dosing, Unique dosage forms and More complex drug release profiles.
According to Jennifer Zieverink the ظ spokesperson of Aprecia Pharmaceuticals “There is no increased efficiency in producing the pill with 3D printing; the technology simply allows the company to better manipulate the drug's composition compared with traditional press and dye pill-making technology”
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Controlled Drug Release Conventional oral drug administration does not usually provide rate-controlled release or target specificity. In many cases, conventional drug delivery provides sharp increases of drug concentration at potentially toxic levels. Following a relatively short period at the therapeutic level, drug concentration eventually drops off until re-administration. Today new methods of drug delivery are possible: desired drug release can be provided by rate-controlling membranes or by implanted biodegradable polymers containing dispersed medication. Over the past 25 years much research has also been focused on degradable polymer microspheres for drug delivery. Administration of medication via such systems is advantageous because microspheres can be ingested or injected; they can be tailored for desired release profiles and in some cases can even provide organ-targeted release. Some reviews covering aspects of microspheres for drug delivery are available and this review covers recent works not yet summarized and provides information regarding many factors affecting microsphere drug release and the manipulation of physical/chemical properties to achieve desired results. The idea of controlled release from polymers dates back to the 1960s through the employment of silicone rubber and polyethylene. The lack of degradability in these systems implies the requirement of eventual surgical removal and limits their applicability. In the 1970s biodegradable polymers were suggested as appropriate drug delivery materials circumventing the requirement of removal. Recent literature shows that suspensions of degradable microspheres can be employed for sustained drug release at desirable doses and by implantation without surgical procedures. Biocompatibility can be achieved by the use of natural polymers such as cellulose, chitin, and chitosan or by the employment of polymers made from naturally occurring monomers such as lactic and glycolic acids (Fig. 1). Polymers derived from synthetic monomers also show excellent delivery properties. However, their toxicity effects may require evaluation.
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The factors affecting drug release are controllable; they are attributed to properties such as polymer molecular weight, as well as microsphere size, distribution, morphology and make-up. Preparation: -By polymerization of monomers. -Prepared from linear monomers. -By solvent evaporation. Factors affecting the drug release Polymer molecular weight’ Blends of the structurally different polymers Crystallinity Effects of the loaded drug Porosity Release from core-shell microspheres Size distribution Ph controlled release *If you are of visual type, then you may check this video: https://www.youtube.com/watch?v=yNX0FuXEFWw
Voltaren Retard is tablet that contain Diclofenac and have longer effect becuase of the controled release of medication
Absolutely you dreamed about owning a virtual reality device which enables you to enjoy new experience either in gaming or T.V watching. But why not to make use of it in scientific manner. Fortunately yes, that is happening now in a wide number of Technology-Specialized Institutes, which work on development of technology more and more. Till this moment, VR is being applied in manifold aspects. For example, it increases opportunities of Disabled persons in life-style, it is not a new concept – the New York Times ran a story in 1994 describing multiple uses, like VR experience that let a 5 year-old child with cerebral palsy take his wheelchair through a grassy field, or another that let 50 children with cancer spend some time "Swimming" around an animated fish tank. VR may provide a walk or a trip for the physically-challenged people who reside in one room. From therapeutic interest, VR was used with young adults with "Autism", to improve their social experience like Job-interview or Date. After treatment, brain scan showed activity in areas of brain tied to social understanding. In treating patients with Phobias, patients were trained to face their fears through simulating it in the VR and this is the so-called "Exposure Therapy". A vital role VR is now playing in medical training specially in surgical departments, since the usual training requires a patient or a cadaver which is really hard to obtain, in addition to that it is One-time use. VR provides another means of practice, without any risk to real patients. But let's have a look as a Pharmaceutical scientists, how can we make use of such miraculous technology. In fact it is available, scientist in Pfizer were supplied with VR which enables them to get deep in human body and investigate it curiously and in more realistic way. Not only human body, but even molecules. So imagine how much will it participate in Drug Design, when you can not only rotate the molecule, but farther to go among it. This will open huge opportunities for various molecules and drugs to be constructed. By the way this technology does not require to be an expert, it is simply easy stuff!
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Introduction: Drug making cost on average 2.5 billion dollars, this expensive process is powered by a sponsoring company or the pharmaceutical company itself either way they must make sure this is a successful path to take.
what are you waiting for damn! go make your drug. However if the reason is unknown or isn't clear, then it needs more research so more money so back to step one.
To understand the cost of drug development in detail we must first familiarize ourselves with the steps that lead to a new drug, I break it in the following steps Step one: What the hell I want to cure? Understanding what the drug will cure or treat is a critical piece of information not only for the scientist who works on the drug, but for the sponsoring company who invested on this drug. This step is almost business-like. The sponsoring company usually ask themselves a couple of questions about the new drug, how much will it cost to develop? will it sell on the market? is it patentable? (can be registered as an invention), all these question must be answered or the drug might not be researched. Step two: what is the disease from a biomolecular point of view? Let's say that there is a disease that cause too much sneezing, if the reason for the disease is known ( the biochemistry of the disease and the chemical pathway),
Step Three: how can the drug make a difference? After identifying the chemical pathway that the disease take, scientist target one protein in that chemical pathway -sometimes moreand try to alter its function, by using chemicals that bind to the target and hopefully alter its function. These chemicals are called Hits. I said â&#x20AC;&#x153;hopefullyâ&#x20AC;? because most of the compounds that bind to the target protein donâ&#x20AC;&#x2122;t stay there that much to make a biological effect, so we have this equation; Target-hit complex <-------> Target + hit The equilibrium for this equation is K = [target ] + [compound] [target-hit complex] The lower the value of k the stronger the binding of the drug with the target protein. The Hit is then tested -in animals or in vivo test- and altered in order to lower its k value (remember lower k value, stronger binding) after this the drug is called a Lead
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Step Four: Is it safe? The information of the animal testing is sent to the FDA to get approval for human testing, this information is gathered in one file called the IND (investigational new drug). Human testing or clinical trials are divided into 3 phases, in short, phase one is only about safety for 10 to 20 healthy individuals, phase two on 100 to 200 patients who have the disease -in question- now the drug is tested for effectiveness -for the first timeand dosing, phase three now the drug is tested on thousands of people to ensure it’s work on a wide spectrum of people. After this the records are collected in a new file called NDA (new drug application) with IND file of course.
Is it worth it? The same group at Elly Lily review the information record from a 13 pharmaceutical companies in order to know what step in drug development that has the highest risk of falling and they come up with the following diagram.
Notice that the percentage of proceeding to phase three is the lowest, so there is a problem with phase two. In phase two the drug is tested for its effectiveness on human for the first time, at this phase the scientist team know they mistook the target at step two: target identification, this is one example of how drug discovery might fail.
How much is every step According to a research made by a group at Elly Lily which is summarized in this pi chart clinical trials account for 63% of the 2.5 billion that is 1.57 billion.
One last thing I want you to know is, the percentage of success of overall process is by multiplying the percentage of each step (0.69×0.54×0.34×0.7×0.91)×100=8% 8% of the people who have 2.5 billion dollars and a big pharmaceutical lab success in bringing a drug to the market.
The clinical trials are the most money and time consuming for a couple of reasons first a chemical is tested on human and no one will agree to be a test subject for free (the more money is paid for the volunteer the more dangerous the test). Second these clinical testing are carried in a hospitals that are not under the control of the pharmaceutical company, so the health care is higher in price also that to ensure no manipulation of the results in favor of the drug approval. If and only if the drug pass the clinical testing it enters the market.
The business of drug development is very risky indeed.
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How to build a good C.V With no doubt you know the C.V or the Curriculum Vitae, which is your Identity card among your profession. And so you work on developing it in the aim of showing yourself in a satisfactory state, and to convince the employer that you are the man for the job. But to get the maximum benefit, and to ensure your acceptance and owning the job, you should be outstanding from the others, and this is through your C.V. Firstly, you should know that the employer is not totally under your service and will not put effort into reading all your document, and you should make use of his time. But will this happen if you stuff your paper with unrelated experiences?!...... Absolutely not. For example, if you wrote in your C.V that your skills are Microsoft word, Filmmaking and Photo-editing you are showing that you are beginner in these skills, but instead write skills: Microsoft Excel, Word, PowerPoint that shows that you are professional in office work. Secondly, you should choose your tract and to feed your C.V accordingly, so that you have a C.V with only your-interest content. This is the best way to have a concise C.V. Third,
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Brain Cancer What is brain cancer? Brain cancer is a disease of the brain in which cancer cells (Malignant cells) arise in the brain tissue. Cancer cells grow to form a mass of cancer tissue (tumour) that interferes with brain function such as muscle control, sensation, memory, and other normal body function. Tumours composed of cancer cells are called malignant tumours, and those composed of mainly noncancerous cells are called benign tumours. Cancer cells that develop from brain tissue are called primary brain tumours, while tumours that spread from other body sites to the brain are termed metastatic or secondary brain tumours. Statistics suggest that brain cancer occurs infrequently (1.4% of all new cancer patient per year), so it is not considered to be a common illness and is likely to develop in about 23,770 new people per year with about 16,050 deaths as estimated by the National Cancer Institute NCI) and the American Cancer Society. Only about 15% of brain tumours may be due to hereditary genetic conditions such as neurofibromatosis, tuberous sclerosis, and a few other. Brain cancer Vs tumour benign brain tumours are noncancerous. Malignant primary brain tumours are cancers that originate in the brain, typically grow faster than benign tumours, and aggressively invade surrounding tissue. Although brain cancer rarely spreads to other organs, it can spread to other parts of the brain and central nervous system.
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Not all brain tumours cause symptoms, and some (such as tumours of the pituitary gland) are often not found unless a CT scan or MRI is done for another reason. The symptoms of brain cancer are numerous and not specific to brain tumours, meaning they can be caused by many other illnesses. The only way to know for sure what is causing the symptoms is to undergo diagnostic testing. Symptoms can be caused by: A tumour pressing on or encroaching on other parts of the brain and keeping them from functioning normally. Swelling in the brain caused by the tumour or surrounding inflammation. The symptoms of primary and metastatic brain cancers are similar.
The Internatunal sign of Brain Cancer
Diagnosing Brain Cancer Exams and Tests Findings of your medical interview and physical exam will probably suggest to your health care provider that you have a problem with the brain or brain stem. 1\ CT scan of the brain. This test is like an X-ray, but shows more detail in three dimensions. Usually, a contrast dye is injected into your bloodstream to highlight abnormalities on the scan. 2\ MRI scan is being used instead of a CT scan for suspected brain tumours. This is because MRI has a higher sensitivity for detecting the presence of, or changes within, a tumour. However, most institutions still use the CT scan as the first diagnostic test. 3\ People with brain cancer often have other medical problems; therefore, routine lab tests may be performed. These include analysis of blood, electrolytes, and liver function tests. If your mental status has been the major change, blood or urine tests may be done to detect drug use.
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Treatment 1\Surgery is usually the first treatment used for a brain tumour. The aim of surgery is to remove as much of the tumour as possible, while minimising damage to surrounding healthy brain. Sometime it is not safe or possible to remove all visible tumour tissue because it is too close to important areas of healthy brain. 2\radiotherapy X-ray and other forms of radiation can destroy tumour cells or delay tumour growth. Radiotherapy is recommended for all people with high-grade tumours if they are well enough to have this treatment, because it can prolong their survival. 3\chemotherapy is the use of drugs to kill cancer cells, usually by stopping the cancer cells ability to grow and divide. The goal of chemotherapy can be to destroy cancer cells remaining after surgery, slow a tumourâ&#x20AC;&#x2122;s growth, or reduce symptoms. Chemotherapy is typically given after surgery and possibly along with radiotherapy.
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Chemotherapy is recommended for all patients with glioblastoma multiform (GBM) who are well enough for the treatment. Chemotherapy normally begins at the same time as radiotherapy and normally continues for six months after radiotherapy. For people with lower grade tumours, such as grade ||| astrocytoma. If chemotherapy is used, it given after radiotherapy. In some cases, implants containing a chemotherapy drug are inserted during surgery into the cavity left after the visible tumour is removed. Other drug therapies Other drugs used to treat people with tumours include: Pain medication to help manage the pain from headaches, a common symptom of a brain tumour. Often, drugs call corticosteroids are used to control pain medication. Anti-seizure medication to help control seizures. There are several types of drugs available. Corticosteroids are also used to decrease the amount of swelling in the brain.