Daily OTC

Avanafil (StendraTM) Better than sildenafil (Viagra ®) Approved 2012

2012-05-17T21:14:00.001+02:00

On April 27th, the FDA approved Avanafil (tradename: Stendra; Research Code: TA-1790), a phosphodiesterase 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED). ED is a sexual dysfunction characterized by the inability to produce an erection of the penis. The physiologic mechanism of penile erection involves the release of nitric oxide in the corpus cavernosum during sexual stimulation, which in turn activates the enzyme guanylate cyclase, resulting in increased levels of cyclic guanosine monophosphate (cGMP). cGMP produces relaxation of smooth muscle tissues, which in the corpus cavernosum results in vasodilation and increased blood flow. Avanafil (PubChem: CID9869929, ChemSpider: 8045620) enhances the relaxant effects of cGMP by selectively inhibiting PDE5 (ChEMBL: CHEMBL1827; Uniprot: O76074), an enzyme responsible for the degradation of cGMP.

Other PDE5 inhibitors are already available on the market and these include Sildenafil (approved in 1998; tradename: Viagra, Revatio; ChEMBL: CHEMBL192), Tadalafil (approved in 2003; tradename: Cialis; ChEMBL: CHEMBL779) and Vardenafil (approved in 2003; tradename: Levitra; ChEMBL: CHEMBL1520). These other PDE5 inhibitors are also approved for the treatment of pulmonary arterial hypertension (PAH).

PDE5 is an 875 amino acid-long enzyme (EC=3.1.4.35), belonging to the cyclic nucleotide phosphodiesterase family (PFAM: PF00233).

Several crystal structures of PDE5 are now available. The catalytic domain of human PDE5 complexed with sildenafil is shown below (PDBe:1tbf)

Preclinical studies have shown that Avanafil strongly inhibits PDE5 (half maximal inhibitory concentration = 5.2 nM) in a competitive manner and is 100-fold more potent for PDE5 than PDE6, which is found in the retina and is responsible for phototransduction. Also, Avanafil has shown higher selectivity (120-fold) against PDE6 than Sildenafil (16-fold) and Vardenafil (21-fold), and high selectivity (>10 000-fold) against PDE1 compared with Sildenafil (380-fold) and Vardenafil (1000-fold).

Avanafil has also been reported to be a faster-acting drug than Sildenafil, with an onset of action as little as 15 minutes as opposed to 30 minutes for the other drugs.

Avanafil is a synthetic small molecule, with one chiral center. Avanafil has a molecular weight of 345.21 Da, an ALogP of 2.16, 3 hydrogen bond donors and 9 hydrogen bond acceptors and thus fully rule-of-five compliant. (IUPAC: 4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(2S)-2-(hydroxymethyl)-pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide; Canonical Smiles: COC1=C(C=C(C=C1)CNC2=NC(=NC=C2C(=O)NCC3=NC=CC=N3)N4CCC[C@H]4CO)Cl; InChI: InChI=1S/C23H26ClN7O3/c1-34-19-6-5-15(10-18(19)24)11-27-21-17(22(33)28-

13-20-25-7-3-8-26-20)12-29-23(30-21)31-9-2-4-16(31)14-32/h3,5-8,10,12,

16,32H,2,4,9,11,13-14H2,1H3,(H,28,33)(H,27,29,30)/t16-/m0/s1)

The recommended starting dose of Avanafil is 100 mg and should be taken orally as needed approximately 30 minutes before sexual activity. Depending on individual efficacy and tolerability, the dose can be varied to a maximum dose of 200 mg or decreased to 50 mg. The lowest dose that provides efficacy should be used. The maximum recommended dosing frequency is once per day.

Avanafil is rapidly absorbed after oral administration, with a median T_max of 30 to 45 minutes in the fasted state and 1.12 to 1.25 hours when taken with a high fat meal. Avanafil is approximately 99% bound to plasma proteins and has been found to not accumulate in plasma. It is predominantely cleared by hepatic metabolism, mainly by CYP3A4 enzyme and to a minor extent by CYP2c isoform. The plasma concentrations of the major metabolites, M4 and M16, are approximately 23% and 29% of that of the parent compound, respectively. The M4 metabolite accounts for approximately 4% of the pharmacologic activity of Avanafil, with an in vitro inhibitory potency for PDE5 of 18% of that of Avanafil. The M16 metabolite has been found inactive against PDE5. After oral administration, Avanafil is excreted as metabolites mainly in the feces (approximately 62% of administrated dose) and to a lesser extent in the urine (approximately 21% of the administrated dose). Avanafil has a terminal elimination half-life (t_1/2) of approximately 5 hours, which is comparable to that of Sildenafil (3-4h) and Vardenafil (4-5h), but very short relative to the very long half-life of Tadalafil (17.5h).

The full prescribing information of Avanafil can be found here.

The license holder is Vivus, Inc.

Wikipedia: Avanafil

Acne Cures: Is there a Natural Acne Cure that Works?

2012-05-11T18:50:00.001+02:00

Are there natural acne cures that work or is it a new age myth? Is there a permanent cure for acne or are all acne sufferers sentenced to the Sisyphean battle of tackling the ‘on the surface’ symptoms? Is there an honest, natural and safer alternative to the endless use of over the counters and to the nasty side effects inflicted by conventional drugs, creams and topical acne treatments?

Most dermatologists and other western medicine followers have already answered that controversial question by claiming that acne, among other diseases simply cannot be cured.

There are 2 reasons for that:

1. Most dermatologists don't even know what the real cause of acne is. It's amazing but true. They are highly familiar with the symptoms of acne and they specialize in tackling the 'on the surface' symptoms, but unfortunately they cannot tell you what the internal conditions are that cause your acne to form in the first place. If you don't believe me just ask your dermatologist.

2. Most doctors work in conjunction with the pharmaceutical and drug companies and the latter is not motivated, so to speak, at discovering a cure for Acne or Aids or Cancer - simply because hundreds of millions of dollars have been spent on finding treatments for the symptoms of diseases. Why? simply because their global aim is to make more profit by creating consumer dependency. By applying medications and creams that deal merely with the symptoms while ignoring the source or the internal cause of the disease, acne will never be cured. The average acne sufferer will become more and more reliant on drugs that temporarily calm the symptoms and that means steady income for the drug and pharmaceutical companies.

There's a lovely metaphor describing acne among other chronic diseases and the way modern medicine deals with these afflictions: If you manage to kill all the mosquitoes around a stale pond using chemicals, for a little while there will be no mosquitoes.

But since the source of the problem (what causes the mosquitoes to appear) is still there – the stale, disgusting pond where mosquitoes can find food and fertile ground for laying their eggs – mosquitoes will always come back!

The same thing happens with your acne!

Without eliminating the source of your acne condition, you will never get rid of your acne. Without fixing the internal problem that is causing your acne, you may find temporary relief, but your acne will always come back until you do something fundamental to eradicate the cause from within...until you make the pond (your body or internal system) a place where ‘mosquitoes’ cannot exist.

Ultimately, every disease results from a breakdown within your body. All major diseases and chronic conditions are warning signs of something very fundamentally wrong inside. Deepak Chopra refers to this as "The violation of simple laws of nature that make our body function."

The very surprising truth is that you are lucky for having acne. Let me explain...Acne, like constant headaches, irritable bowel syndrome or dandruffs is only a small message from your body that something is wrong internally and should be addressed and corrected.

Now, there are two choices you can make - you can:

1.Ignore that message - big mistake! The internal imbalance that caused your acne will, in most cases, turn into a chronic condition. Now instead of just having acne you'll start having other hormonal imbalance or toxic overload related symptoms in addition to acne. Because the internal problem is not fixed, the disease symptoms get more and more intense.

2.Listen to your body and start fixing the internal problem that causes your acne to appear in the first place; you will not only get rid of your acne you will also achieve beautiful, healthy, even toned clear skin complexion, re-balance your body and prevent future hormonal or toxic overload related conditions.

The simple truth is...you are out of balance. We now live a 'far-from-natural' lifestyle. There are over 300 synthetic industrial chemicals present in our bodies that did not exist 50 years ago. We are filled with toxins from the food, and medication we ingest and use.

By fixing the internal condition that causes your acne in addition to adopting a healthy lifestyle (healthy diet & mindset, cleanse & detoxify, hormonal balancing etc.) you will put your body back into balance – holistically - your acne will cease to exist and you feel as healthy and attractive as ever!

It doesn't matter what type of acne you have. Whether you suffer from: acne vulgaris, acne Conglobata, acne Rosacea, Acne Fulminans, Blackheads, Whiteheads, Papules, Pustules, Nodules or Cysts: The principles required to cure your acne are basically the same. The "holistic" ways of treating people have been around for thousands of years, and they absolutely work whether you have teen or adult acne; whether you suffer from acne on your back, shoulders or chest or if you suffer from female related acne such as menopause acne or acne due to monthly cycles.

Whatever your acne condition is, when you finally decide to stop making the same acne treatment mistakes that have been holding you back and begin applying the holistic approach to curing acne, you can literally choose to become clear and stay clear. You will have the power to make it happen.

Mike Walden is a certified nutritionist, independent medical researcher, natural health consultant and author of the #1 best-selling e-book, "Acne No More- Open The Door To An Acne Free Life." Mike has written dozens of holistic health articles and has been featured in ezines and print magazines, as well as on hundreds of websites worldwide. For information on Mike's Holistic Clear Skin program, visit: http://mcaf.ee/6kes2

Books that may also be useful

Nausea : Causes and Treatment

2012-04-25T15:36:00.001+02:00

Nausea is unpleasant and something everyone has experienced. Yet while nausea and vomiting are common symptoms, they are not conditions in their own right – and the best way to stop them is to work out the cause and provide the right OTC or prescription treatment.

Common causes of nausea and vomiting include infection, emotional or physical stress, alcohol, food poisoning, overeating or a reaction to certain smells. While nausea and vomiting are common, patients who experience symptoms for more than two days should be referred to the pharmacist, as should children under two years as they are at risk of dehydration.

Planes, boats and automobiles

Motion sickness, or travel sickness, is an extremely common cause of nausea and vomiting. It occurs when repetitive small movements cause the brain to receive mixed messages; the eyes tell the brain one thing while the balance mechanisms of the inner ear tell it something different. This is most common at sea, but can also happen in cars or planes.

The resulting confusion leads to early symptoms such as hot flushes and paleness, which usually progress to sweating, nausea and vomiting. Children are commonly affected and it tends to be something they grow out of in time. Motion sickness is more likely to be experienced by women than men, especially if they are pregnant or are having their period. People who suffer from migraines are also more susceptible to motion sickness.

The sensation of nausea can be made worse by strong smells, such as petrol or food, or by attempting to focus the eyes on a nearby object such as when reading book or a map. If exposed to the stimulus over a prolonged period of time (such as ship travel on a cruise), symptoms of motion sickness tend to improve as the body adapts to the conditions.

The best way to avoid suffering from motion sickness is to take travel sickness pills before the symptoms begin and to avoid large meals or alcohol before travel.

Morning sickness

Nausea occurs in up to 90 per cent of pregnancies, with between 25 and 55
per cent of women experiencing vomiting. Contrary to popular belief, nausea and vomiting can occur at any time and are not just confined to the morning. Nausea usually presents in the early weeks of pregnancy, and only around one in 10 women will still experience symptoms after 16 weeks. Woman should be reassured that nausea in pregnancy is normal, and that it will pass with time.

Occasionally, women can experience excessive, persistent vomiting. If the woman is really poorly and unable to keep any food down she should be advised to visit her GP as she may be suffering from hyperemesis and need anti-sickness medication or even hospitalisation.

Drugs and nausea

A large number of drugs have nausea as a possible side effect, although it often eases over time as the body becomes accustomed to the new medication.

If you suspect the medicine is causing nausea refer the patient to the pharmacist, as there may be steps to minimise symptoms, such as taking the medicine with food, or trying a different drug.

Commonly-used drugs that often cause nausea include:
• aspirin
• NSAIDs
• antibiotics
• oestrogens
• steroids
• opioid analgesics.

Prescription medication is available to treat the nausea and vomiting caused by chemotherapy in cancer patients.

Nausea as a medical emergency

Immediate medical attention should be sought if the patient has nausea and vomiting and any of the following symptoms:
• blood in the vomit
• severe headache or a stiff neck
• lethargy, confusion or decreased alertness
• severe abdominal pain
• a temperature greater than 38.3°C
• rapid breathing or pulse.

Digoxin toxicity may present as nausea and/or vomiting so it is extremely important that any patient taking digoxin, especially if elderly, is referred to the pharmacist immediately if they experience either of these side effects.

Treating nausea

A number of products for nausea are available to buy over the counter. They vary according to the cause of the symptoms, with the biggest category aimed at motion sickness. A number of different brands exist and they contain different active ingredients.

Hyoscine hydrobromide is a popular choice as it only needs to be taken 20 minutes before travel and is considered to be less sedating than other preparations. It has a short duration of action though, so another dose may be required six hours after the initial dose. Possible side effects include drowsiness, blurred vision, dry mouth, urinary retention and constipation. Hyoscine should not be used by people with glaucoma and should be used with caution in patients with urinary problems, heart disease or high blood pressure.
Other drugs used in travel sickness preparations include the antihistamines meclozine and cinnarizine. Both of these have a longer duration of action than hyoscine but commonly cause drowsiness and need to be taken one or two hours before travel. Promethazine can be used but it is very sedating.

Nausea associated with migraine can be treated over the counter either with prochlorperazine or with buclizine (in combination with paracetamol and codeine). Prochlorperazine can only be sold for use to adults over 18 years of age who have previously been diagnosed with migraine by a doctor.

If the nausea is associated with indigestion then you could consider selling certain indigestion remedies.

Products containing bismuth compounds are an option, which work by coating the wall of the stomach, thereby protecting it from further irritation. They should not be taken by children under 16 or by people taking aspirin. Products containing domperidone can help speed up the process of digestion thus reducing nausea, but are only available over the counter for customers older than 16 years.

There is no effective OTC treatment for vomiting. Sufferers should simply be advised to drink gradually larger amounts of clear liquids and to avoid solid food until the vomiting has ceased. If the customer has been vomiting for more than 24 hours, you should recommend the use of rehydration salts.

Preventing vomiting

A number of steps can be taken to reduce nausea and prevent vomiting.

• You should advise customers who are feeling nauseous to eat small meals at frequent intervals instead of three large meals a day.

• Alcohol should be avoided and they should drink between, rather than with, meals. After eating it is best to rest for a while in an upright position.

• Eating cold food will avoid nausea triggered by the smell of cooking or hot food. You could also suggest customers try to eat slowly when feeling less nauseous, and to only eat plain foods (such as dry toast or biscuits) that are easy to digest.

• Motion sickness may be relieved by getting some fresh air (opening the window in a car or going on the deck of a boat) and by looking ahead at the horizon. Distraction with music or using relaxation techniques can also help

References

http://www.emedicinehealth.com/vomiting_and_nausea/article_em.htm

http://en.wikipedia.org/wiki/Nausea

Welcome

2012-04-09T23:38:00.003+02:00

Welcome To Daily OTC

Hello and welcome to Daily OTC

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