This book aims to put forth a strategy to facilitate the insightful design of new chemical entities as therapies for human disease—a strategy that will foster the ability to sit down in front of a blank computer screen and draw molecules that may help cure the various maladies that afflict humankind. This strategy uses a molecular-level understanding ofhuman biochemistry and pathology to drive the design of drug-like molecules engineered to fit precisely into targets of drug action (druggable targets).

A Drug as a Composite of Molecular Fragments For the practical implementation of this idealistic strategy, drug molecules are conceptualized as being assembled from biologically active building blocks (biophores) that are covalently “snapped together” to form an overall molecule. Thus, a drug molecule is a multiphore, composed of a fragment that enables it to bind to a receptor (pharmacophore), a fragment that influences its metabolism in the body (metabophore), and one or more fragments that may contribute to toxicity (toxicophores).

The drug designer should have the ability to optimize the pharmacophore while minimizing the number of toxicophores. To achieve this design strategy, these fragments or building blocks may be replaced or nterchanged to modify the drug structure. Certain building blocks (called bioisosteres), which are biologically equivalent but not necessarily chemically equivalent, may be used to promote the optimization of the drug’s biological properties.

DRUG DESIGN: THE HUMANITARIAN APPROACH
In traditional medicine there are two major therapeutic approaches to the treatment of human disease: surgical and medical. Surgical procedures are labour intensive and time demanding; they help a limited number of individuals, one at a time, mostly in rich or developed nations.

Medical therapy, on the other hand, is based on drug molecules and thus has the capacity to positively influence the lives of more people, often over a shorter time frame. Medical therapeutics offer hope in both developed and developing parts of the world—hopefully to rich and poor alike.

After public health measures (e.g., safe drinking water, hygienic disposal of waste water), the discovery of drugs has had one of the largest beneficial effects on human health. Penicillin has saved countless lives through the effective treatment of devastating infectious diseases. Before penicillin, a diagnosis of meningococcal meningitis was invariably a death sentence. Penicillin reduced bacterial meningitis to a treatable disorder.

Similarly, drugs for the treatment of high blood pressure have substantially reduced the impact of this “silent killer” that leads to myocardial infarction (heart attack) or cerebral infarction (stroke).

It can be awe-inspiring to witness the effects of a seemingly trivial amount of drug. The panic-stricken child who cannot breathe because of an asthma attack gets prompt relief from the inhalation of a mere 100 micrograms of salbutamol sulphate. Uncontrolled and potentially life-threatening seizures (status epilepticus) in a young adult are quickly brought under control with the intravenous administration of 2 mg of lorazepam.

The terrified older adult with crushing chest pain from a myocardial infarction gains rapid relief from 8 to 10 mg of morphine. Drugs are truly amazing molecules. A medicinal chemist can help thousands or even millions of people with a carefully designed new drug molecule. The practice of science is a very human activity; medicinal chemistry is a humanitarian science.

Successful drug design is multi-step, multidisciplinary and multi-year. Drug discovery is not an inevitable consequence of fundamental basic science; drug design is not merely a technology that generates drugs for humans on the basis of biological advances—if itwere that simple, more and better drugs would already be available.

Medicinal chemistry is a science unto itself, a central science positioned to provide a molecular bridge between the basic science of biology and the clinical science of medicine (analogous to chemistry being the central science between the traditional disciplines of biology and physics). From a very broad perspective, drug design may be divided into two phases:
1. Basic concepts about drugs, receptors, and drug–receptor interactions
2. Basic concepts about drug–receptor interactions applied to human disease

The first phase comprises the essential building blocks of drug design and may be divided into three logical steps:
1. Know what properties turn a molecule into a drug
2. Know what properties turn a macromolecule into a drug receptor
3. Know how to design and synthesize a drug to fit into a receptor

Knowledge of these three steps provides the necessary background required for a researcher to sit down, paper in hand, and start the process of creating a molecule as a potential drug for treating human disease.

Step 1 involves knowing what properties turn a molecule into a drug. All drugs may be molecules, but all molecules are certainly not drugs. Drug molecules are “small” organic molecules (molecular weight usually below 800 g/mol, often below 500). Penicillin, acetylsalicyclic acid, and morphine are all small organic molecules. Certain properties (geometric, conformational, stereochemical, electronic) must be controlled if a molecule is going to have what it takes even to emerge as a drug-like molecule (DLM).

When designing a molecule to be a drug-like molecule and, hopefully, a drug, the designer must have the ability to use diverse design tools. Now, computer-aided molecular design (CAMD) is one of the most important design tools available. CAMD incorporates various rigorous mathematical techniques, including molecular mechanics and quantum mechanics. When using CAMD to design a drug, one must remember that a drug molecule is complex and has sub-unit parts. Some of these parts enable the drug to interact with its receptor, while other parts permit the body to absorb, distribute, metabolize, and excrete the drug molecule. Once a drug-like molecule successfully becomes a candidate for the treatment of a disease, it has graduated to the status of drug molecule.

Step 2 involves knowing what properties turn a macromolecule into a receptor. All receptors may be macromolecules, but all macromolecules are certainly not receptors. Receptor macromolecules are frequently proteins or glycoproteins. Certain properties must be present if a macromolecule is going to have what it takes to be a druggable target. The receptor macromolecule must be intimately connected with the disease in question, but not integral to the normal biochemistry of a wide range of processes.

Step 3 involves designing a specific drug-like molecule to fit into a particular druggable target. During this task many molecules will be considered, but only one (or two) will emerge as promising starting points around which to further elaborate the design process. This prototype compound is referred to as the lead compound. There is a varietyof ways of identifying a potential lead compound, including rational drug design, random high throughput screening, and focused library screening. Once a lead compound has been successfully identified, it must be optimized. Optimization may be achieved using quantitative structure–activity relationship (QSAR) studies. Synthetic organic chemistry is a crucial component of this step in drug development. The process of drug design must be validated by actually making and testing the drug molecule. An ideal synthesis should be simple, be efficient, and produce the drug in high yield and high
purity.

Once the basics of drug design are in place, the drug designer next focuses upon the task of connecting a drug–receptor interaction to a human disease—this is the goal of the second phase. For example, how does one design a drug for the treatment of cancer or Alzheimer’s disease? This phase of drug design requires an understanding of biochemistry and of the molecular pathology of the disease being treated.

The human body normally moves through time with its various molecular processes functioning in a balanced, harmonious state, called homeostasis. When disease occurs, this balance is perturbed by a pathological process. For a drug molecule, the goal is to rectify this perturbation (via the action of molecular therapeutics) and to return the body to a state of healthy homeostasis.

Logically, there are many approaches to attaining this therapeutic goal. First, one may ask what are the body’s normal inner (endogenous) control systems for maintaining homeostasis through day-to-day or minute-to-minute adjustments? These control systems (for example, neurotransmitters, hormones, immunomodulators) are the first line of defense against perturbations of homeostasis.

Is it possible for the drug designer to exploit these existing control systems to deal with some pathological process? If there are no endogenous control systems, how about identifying other targets on endogenous cellular structures or macromolecules that will permit control where endogenous control has not previously existed? Alternatively, instead of pursuing these endogenous approaches, it is sometimes easier simply to attack the cause of the pathology.

If there is a harmful microorganism or toxin in the environment (exogenous), then it may be possible to directly attack this exogenous threat to health and inactivate it. Accordingly, this phase of drug development, which connects the drug–receptor interaction to human disease, may be divided into three logical approaches:
1. Know how to manipulate the body’s endogenous control systems
2. Know how to manipulate the body’s endogenous macromolecules
3. Know how to inactivate a harmful exogenous substance

A full understanding of the three steps of phase 1 and the three approaches of phase 2 will enable the researcher to design drugs.

Designing drug molecules to alleviate human disease and suffering is a daunting yet exhilarating task. How does one do it? How does a researcher sit down, paper in hand (or, better yet, a blank computer screen), and start the process of creating a molecule as a potential drug with which to treat human disease? What are the thought processes?

What are the steps? How does one select a target around which to design a drug molecule? When a researcher does design a molecule, how does she or he know if it has what it takes to be a drug?

These are important questions. The previous century ended with an explosion of activity in gene-related studies and stem cell research; the new one is emerging as the “Century of Biomedical Research.”We have now witnessed the global spectre of SARS (Severe Acute Respiratory Syndrome) and avian flu, which has emphasized the looming importance of infectious disease to global health.

Concerns about the capacity of “Mad Cow” disease to infect humans have focused attention on the safety of our food supply. AIDS and obesity-related disorders have not gone away, but rather are increasing in incidence and prevalence. Long-recognized diseases, such as stroke and Alzheimer’s dementia, are becoming more common as a greater proportion of the human population reaches old age.

Not surprisingly, the need for drug discovery to address these important diseases is increasingly being recognized as a societal priority. Not only is drug discovery important to the medical health of humankind, it is also an important component of our economic health. New chemical entities (NCEs) as therapeutics for human disease may become the “oil and gas” of the 21st century. As the world’s population increases and health problems expand accordingly, the need to discover new therapeutics will become even more pressing. In this effect, the design of drug molecules arguably offers some of the greatest hopes for success.

‘Nanotechnology is about making things, whether it be making things that are smaller,
faster, or stronger, making something completely new or with additional properties, or
making machines that will lead to new manufacturing paradigms’ [1].

Three factors define nanotechnolgy: small size, new properties, and the integration of the technology in to materials and devices. Nanotechnology covers a broad range of science, drawing concepts, knowledge and expertise, skills, and materials from all the three classical sciences, physics, chemistry, and biology.

From an economic point of view the potential of nanotechnology is clearly vast, with the
drive to be smaller, faster, lower power and cheaper. As size is reduced, overheads
(materials, energy, factory and manpower requirements) are all reduced.

Recent nanotechnology products poised for near-term market realization include a
molecule-sized electronic switch, improved sun cream, and a fullerene-based cancer
treatment. In medicine nanoceramics are currently being used as bone replacement agents. These ceramics show outstanding osteoblast (cells that form bone) proliferation and mechanical properties [2].

One obvious area where nanotechnology has vast potential is in computing, in particular the ever-shrinking computer chip. 1965 saw the birth of Moore’s law, named after Gordon Moore of Intel, who stated that the number of transistors per integrated circuit would double every 18 months [3]. Turning this on its head, the size of chips would half every 18 months. This has held true since 1965, but now, with chip sizes expected to approach the atomistic scale in the next decade or so, the need for nanotechnology to shrink the chips ever more is clearly obvious with atom-scaled circuits required.

And, of course, atom-scaled chips would go in atom-scaled computers, constructed and assembled by other atom-scaled devices. IBM is currently undertaking pioneering work in this respect with a quantum mirage of cobalt atoms forming a potential data transfer tool. HP recently reported fabrication of nanoscale molecular-electronic devices comprising a single molecular monolayer of bistable rotaxanes sandwiched between two 40-nm metal electrodes [4].

So where now for this exciting science? How to go about the exploration of the vast range of scientific and technological opportunities offered by the advances of controlling
materials at the nanoscale? Challenges the researcher is faced with include the selection and screening of potentially large libraries of molecules and materials, the fact that ‘almost any’ molecule can be synthesized but synthesis can still be very costly, and the unambiguous interpretation of experimental information at the nanoscale level, where quantum effects are often important.

Today’s computing power is proving invaluable in the research behind the miniaturization. Computer molecular modeling and simulation is being used in the drive to advance this exciting and cutting edge scientific field, enabling scientists to visualize and predict behavior at the nanoscale. And with the major cost vs. performance barrier being blown away by today’s rapid computing developments, these techniques are set to become widespread throughout all research and development, not just in nanotechnology.

Computational tools enable scientists to simulate reactions and study the properties and
interactions of molecules and materials at a computer interface. Once the preserve of
computer experts, the widespread availability and use of personal computers, coupled with the almost exponential increase in available hardware power, has resulted in these
techniques becoming a widespread research tool, resulting in many advantages.

The tools can be used to complement, direct, and refine and, in some cases, even replace experimentation. The need to use ‘real’ chemicals can be reduced, not only saving resources but also lessening researchers’ exposure to toxic chemicals, so called ‘greener’ science. Non-starter reactions can be identified before valuable laboratory time and resources are wasted. Reactions that would have been difficult to study experimentally, forexample because of the time taken to complete or the requirement of toxic chemicals, can be studied with ease on the computer, with mechanistic and chemical insight obtained.

Michael York of Continental Tire North America explains the scientific advantages gained by using computational chemistry, “Experimentation takes manpower, chemicals, equipment, energy, and time. Computational chemistry allows one operator to run multiple chemical reactions 24 hours a day.”

Michael York continues, “By performing the ‘experiments’ on the computer, the chemist
can eliminate non-productive reaction possibilities and narrow the scope of probable
laboratory successes. The end result is a major reduction in laboratory costs (such as
materials, energy, and equipment) and manhours.” See reference [5].

Deepak Srivastava [6], a leading computational nanotechnology expert, describes the
advantages of these computational techniques in nanotechnology, "Theory, modeling, and simulations have provided and will continue to provide insights into what to expect next and verification/explanation of what has been done or observed experimentally. For
nanoscale systems, simulations and theory in fact have provided novel properties that has led to new designs, materials, and systems for nanotechnology applications.”
Srivastava references carbon nanotubes as an example of where these state-of-the-art tools are being used in nanotechnology, “For example carbon nanotubes applications in
molecular electronics or computers were predicted first by theory and simulations, the
experiments are now following up to fabricate and conceptualize new devices based on
those simulations" he states.

References
[1] CMP Cientifica ‘Nanotech – the tiny revolution’, July 2002.
[2] www.rpi.edu/dept/materials/COURSES/NANO/dulgar/nano_index.html
[3] www.intel.com/research/silicon/mooreslaw.htm
[4] Yong Chen, Douglas A. A. Ohlberg, Xuema Li, Duncan R. Stewart, R. Stanley Williams, Jan O. Jeppesen, Kent A. Nielsen, J. Fraser Stoddart, Deirdre L. Olynick, and Erik Anderson, Appl. Phys. Lett., 2003, 82, 1610.
[5] www.accelrys.com/cases/ctire.html
[6] people.nas.nasa.gov/~deepak/home.html

source: Nanotechnology Application Guide, Accelrys.2004

AIDS caused by the replication of the human immunodeficiency virus (HIV). It is susceptible to targeted interventions, because several virus specific metabolic steps occur in infected cells (A). Viral RNA must first be transcribed into DNA, a step catalyzed by viral “reverse transcriptase.” Doublestranded DNA is incorporated into the host genome with the help of viral integrase. Under control by viral DNA, viral replication can then be initiated, with synthesis of viral RNA and proteins (including enzymes such as reverse transcriptase and integrase, and structural proteins such as the matrix protein lining the inside of the viral envelope). These proteins are assembled not individually but in the form of polyproteins. These precursor proteins carry an N-terminal fatty acid (myristoyl) residue that promotes their attachment to the interior face of the plasmalemma. As the virus particle buds off the host cell, it carries with it the affected membrane area as its envelope. During this process, a protease contained within the polyprotein cleaves the latter into individual, functionally active proteins.

I. Inhibitors of Reverse Transcriptase
IA. Nucleoside agents
Nucleoside agents are analogues of thymine (azidothymidine, stavudine), adenine (didanosine), cytosine (lamivudine, zalcitabine), and guanine (carbovir, a metabolite of abacavir). They have in common an abnormal sugar moiety. Like the natural nucleosides, they undergo triphosphorylation, giving rise to nucleotides that both inhibit reverse transcriptase and cause strand breakage following incorporation into viral DNA.

The nucleoside inhibitors differ in terms of 1) their ability to decrease circulating HIV load; 2) their pharmacokinetic properties (half life—>dosing interval—>compliance; organ distribution—>passage through blood-brainbarrier); 3) the type of resistance-inducing mutations of the viral genome and the rate at which resistance develops; and 4) their adverse effects (bone marrow depression, neuropathy, pancreatitis).

IB. Non-nucleoside inhibitors
The non-nucleoside inhibitors of reverse transcriptase (nevirapine, delavirdine, efavirenz) are not phosphorylated. They bind to the enzyme with high selectivity and thus prevent it from adopting the active conformation. Inhibition is noncompetitive.

II. HIV protease inhibitors
Viral protease cleaves precursor proteins into proteins required for viral replication. The inhibitors of this protease (saquinavir, ritonavir, indinavir, and nelfinavir) represent abnormal proteins that possess high antiviral efficacy and are generally well tolerated in the short term. However, prolonged administration is associated with occasionally severe disturbances of lipid and carbohydrate metabolism. Biotransformation of these drugs involves cytochrome P450 (CYP 3A4) and is therefore subject to interaction with various other drugs inactivated via this route.

For the dual purpose of increasing the effectiveness of antiviral therapy and preventing the development of a therapy-limiting viral resistance, inhibitors of reverse transcriptase are combined with each other and/or with protease inhibitors.

Combination regimens are designed in accordance with substancespecific development of resistance and pharmacokinetic parameters (CNS penetrability, “neuroprotection,” dosing frequency).

source: Lullmann. 2000. Color Atlas of Pharmacology. Thieme
further information, please read this book.

Viruses are submicroscopic, obligate intracellular parasites. Clearly, it is not a problem to differentiate viruses from higher macroscopic organisms. Even within a broad definition of microbiology encompassing prokaryotic organisms and microscopic eukaryotes such as algae, protozoa, and fungi, in most cases it will suffice. A few groups of prokaryotic organisms, however, have specialized intracellular parasitic life cycles and confound the above definition.

These are the Rickettsiae and Chlamydiae—obligate intracellular parasitic bacteria
which have evolved to be so cell-associated that they can exist outside the cells of their hosts for only a short period of time before losing viability. Therefore, it is necessary to add further clauses to the definition of what constitutes a virus.

 Virus particles are produced from the assembly of preformed components,
whereas other agents grow from an increase in the integrated sum of their components
and reproduce by division.
 Virus particles (virions) themselves do not grow or undergo division.
 Viruses lack the genetic information that encodes apparatus necessary for the
generation of metabolic energy or for protein synthesis (ribosomes).

No known virus has the biochemical or genetic potential to generate the energy
necessary to drive all biological processes (e.g., macromolecular synthesis).They are
therefore absolutely dependent on the host cell for this function. It is often asked
whether viruses are alive or not. One view is that inside the host cell viruses are
alive, whereas outside it they are merely complex assemblages of metabolically inert
chemicals. That is not to say that chemical changes do not occur in extracellular
virus particles, as will be explained elsewhere, but these are in no sense the ‘growth’
of a living organism.

Living Host Systems
In 1881, Louis Pasteur began to study rabies in animals. Over several years, he
developed methods of producing attenuated virus preparations by progressively
drying the spinal cords of rabbits experimentally infected with rabies which,
when inoculated into other animals, would protect from challenge with virulent
rabies virus. In 1885, he inoculated a child, Joseph Meister, with this, the first artificially
produced virus vaccine (as the ancient practice of variolation and Jenner’s
use of cowpox virus for vaccination relied on naturally occurring viruses).Whole
plants have been used to study the effects of plant viruses after infection ever since
tobacco mosaic virus was first discovered by Iwanowski. Usually such studies
involve rubbing preparations containing virus particles into the leaves or stem of
the plant.

During the Spanish–American War of the late nineteenth century and the subsequent
building of the Panama Canal, the number of American deaths due to yellow fever was colossal. The disease also appeared to be spreading slowly northward into the continental United States. In 1990, through experimental transmission to mice,Walter Reed demonstrated that yellow fever was caused by a virus spread by mosquitoes. This discovery eventually enabled Max Theiler in 1937 to propagate the virus in chick embryos and to produce an attenuated vaccine—the 17D strain—which is still in use today.The success of this approach led many other investigators from the 1930s to the 1950s to develop animal systems to identify and propagate pathogenic viruses.

Eukaryotic cells can be grown in vitro (tissue culture) and viruses can be propagated
in these cultures, but these techniques are expensive and technically quite
demanding. Some viruses will replicate in the living tissues of developing embryonated
hens eggs, such as influenza virus. Egg-adapted strains of influenza virus
replicate well in eggs and very high virus titres can be obtained. Embryonated
hens eggs were first used to propagate viruses in the early decades of the twentieth
century. This method has proved to be highly effective for the isolation and
culture of many viruses, particularly strains of influenza virus and various poxviruses
(e.g., vaccinia virus). Counting the ‘pocks’ on the chorioallantoic membrane of eggs
produced by the replication of vaccinia virus was the first quantitative assay for any
virus. Animal host systems still have their uses in virology:

 To produce viruses that cannot be effectively studied in vitro (e.g., hepatitis B
virus)
 To study the pathogenesis of virus infections (e.g., coxsackieviruses)
 To test vaccine safety (e.g., oral poliovirus vaccine)
Nevertheless, they are increasingly being discarded for the following reasons:
 Breeding and maintenance of animals infected with pathogenic viruses is
expensive.
 Whole animals are complex systems in which it is sometimes difficult to discern
events.
 Results obtained are not always reproducible due to host variation.
 Unnecessary or wasteful use of experimental animals is morally repugnant.
 They are rapidly being overtaken by ‘modern science’—cell culture and molecular
biology.

source: Cann AJ. 2005. Principles of Molecular Virology 4th Edition. New York: Elsevier Academic Press.

The most important components of living cell, proteins, carbohydrates, and nucleic acids are polymers. Nature uses polymers as constructive elements and parts of complicated cell machinery. The salient feature of functional biopolymers is their all-or-nothing or at least highly nonlinear response to external stimuli. Small changes happen in response to varying parameters until the critical point is reached; then a transition occurs in the narrow range of the varied parameter, and after the transition is completed, there is no significant further response of the system.

Recent decades witnessed the appearance of synthetic functional polymers, which respond in some desired way to a change in temperature, pH, electric or magnetic fields, or some other parameters. These polymers were nicknamed stimuli-responsive. The name “smart polymers” was coined because of the similarity of the stimuli-responsive polymers to biopolymers.

Applications of polymers in biotechnology and medicine are discussed in this article. The highly nonlinear response of smart polymers to small changes in the external medium is of critical importance for the successful functioning of a system. Most applications of polymers in biotechnology and medicine include biorecognition and/or biocatalysis, which take place principally in aqueous solutions. Thus, only water-compatible smart polymers are considered; smart polymers in organic solvents or water/organic solvent mixtures are beyond the scope of the article.

One could define smart polymers used in biotechnology and medicine as macromolecules that undergo fast and reversible changes from hydrophilic to hydrophobic microstructure triggered by small changes in their environments. These microscopic changes are apparent at the macroscopic level as precipitate formation in solutions of smart polymers or changes in the wettability of a surface to which a smart polymer is grafted. The changes are reversible, and the system returns to its initial state when the trigger is removed.

note: for further information, please read Encyclopedia of Polimer Science and Technology. John Wiley & Sons, Inc. (2005)

BPOM (Drug and Food Superintendant Agency) Indonesia never removed phenylpropanolamine or PPA which is contained in cough or flu drugs in Indonesia. To perceive this issue, BPOM said that drugs contain PPA were allowed to using and marketing in Indonesia. The dosis permitted is 15 mg for cough and flu drugs [1].

As we know, PPA was removed in America because it increase risk of hemorrhagic stroke since November 2000 [2]. This is based on the research which be held in Yale University School of Medicine that result bleeding into the brain or into tissue surrounding the brain (hemorrhagic stroke) in women. Medicines which contain phenylpropanolamine should not consume for longer than 7 days if the condition does not improve or if the symptoms are accompanied by a high fever [3].

There are many drugs in Indonesia which contain phenylpropanolamine. For our health in the future, we should becareful to consume cough or flu drugs which contain PPA. Maybe, seeing the ingredient of the drugs which is the best choiche for preventing the bad side effect in our helath.

[1] http://kesehatan.kompas.com
[2] http://www.fda.gov/cder/drug/infopage/ppa/advisory.htm
[3] http://www.drugs.com/mtm/phenilpropanolamine.htm

Several days ago, there is an issue that Food and Drug Administration (FDA) was issued a "Public Health Advisory" which take steps to remove phenylpropanolamine from all drug products and has requested that all drug companies discontinue marketing products containing it.

Based on the issue, FDA  was issued this advisory on March 1st 2009. So, everything which contains phenylpropanolamine, such as DECOLGEN, DECOLSIN, SINUTAB, ALLERIN, BODREXIN, CONTAC 500, COSYR, FLUCYL, FLUDANE, FLUGESIC, INZA, KOMIX, MIXAFLU, MIXAGRIP, NALGESTAN, NEOZEP FORTE, NODROF, PARASUTIN, PROCOLD, RHINOTUSSAL, SANAFLU, SILADEX, STOPCOLD, TRIAMIN. Is it true that they are contain phenylpropanolamine (PPA)? To answer this question, please check it at links.

After I search on Google, this issue is an hoax. Why? Because FDA is not issued a "Public Health Advisory" about PPA at 1 March 2009. That is true if the the date was on November 2000.

To study about phenylpropanolamine:
1. What is the phenylpropanolamine?
2. Is it harmful for our health?
3. Why FDA issued a "Public Health Advisory" about phenylpropanolamine?
4. How about drugs are usually we used to against cough or flu?

and many facts else? Please click this phenylpropanolamine article.

What is phenylpropanolamine (PPA)?
Phenylpropanolamine is a drug ingredient of the phenethylamine family [1]. It used as a decongestant. It means that phenylpropanolamine used to treat the congestion associated with allergies, hay fever, sinus irritation, and the common cold [2]. It also causes a decrease in appetite and is used in some over-the-counter diet aids. In veterinary medicine, it is used to control urinary incontinence in dogs and is sold under brand names Propalin and Proin.

How phenylpropanolamine works?
Phenylpropanolamine will constric (shrink) blood vessels (veins and arteries) in the body. Constriction of blood vessels in sinuses, nose, and chest allows drainage of those areas, which decreases congestion.

Is phenylpropanolamine harmful for our health?
I has been associated with an increased risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding the brain) in women [3]. Men may also be at risk. Although the risk of hemorrhagic stroke is low, the U.S. Food and Drug Administration (FDA) recommends that consumers not use any products that contain phenylpropanolamine because of the seriousness of a stroke and the inability to predict who was at risk [4].

The public health advisory supported by the research of phenylpropanolamine at the Yale University School of Medicine in 1999  which was produced that PPA increased risk of hemmorrhagic stroke. This similar reports of cases had been circulating since the 1970s.

The sides effect of PPA.
Beside increased a hemorrhagic stroke, phenylpropanolamine also an allergic reaction (difficulty breathing; closing of your throat; swelling lips, tongue, or face; or hives); seizures; unusual behavior or hallucinations; or an irregular or fast heartbeat. Also, less serious side effects maybe occured like dizziness, lightheadedness, or drowsiness; headache; insomnia; anxiety; tremor (shaking) or restlessness; nausea or vomiting; or sweating.

[1] Flavahan NA. 2005. Phenylpropanolamine constricts mouse and human blood vessels by preferentially activating alpha2-adrenoceptors. J. Pharmacol. Exp. Ther. 313 (1): 432–9.