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Manufacturer link: Moots
We have a few of these 2015 models left at substantial savings. The difference vs. 2016? Only the head-tube diameter. 2015 models have regular inch and an eighth head-tubes, whereas the nearly identical 2016 models now come with slightly larger 44mm head-tubes. Very limited quantities available, so act fast! 2015 Vamoots-CR (Compact Road) frame MSRP: $3,325, now $2,895! 2015 Vamoots-RSL (Road Super Light) frame MSRP: $4,450, now $3,995!

Manufacturer link: Lynskey Performance
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The 30th Anniversary R240 Disc LE comes equipped with full Ultegra groupset, Vision Team 30 Disc wheels, and Lynskey Pro Road Carbon #3 Disc fork. Each frame has a hand brushed finish, and 30th Anniversary etching.

The Lynskey R240 Disc is one of our most popular frames for club rides or racing. The added stopping power of disc brakes combined with curved seat stays, chain stays and English threaded BB remain the structural foundation of the R240.

Manufacturer link: Bianchi
Now in gloss Celeste finish for 2017! Now $500 off any of our normal build kit prices with an Infinito CV frameset purchased at the $3,199 MSRP! Use the ‘choose bike or frame’ pull-down menu below to see the discounted kit prices. Using NASA viscoelastic Countervail technology, Bianchi has developed a carbon layup that can immediately reduce vibration in the frameset. With this revolutionary material the Infinito is propelled in to a new realm of endurance, comfort, and performance.

Manufacturer link: Lynskey Performance
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Manufacturer link: Lynskey Performance
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To South American Viagra the celebration of 30 years of Lynskey-built frames, Lynskey created a 30th Anniversary Edition of the R150. All the style and comfort of the R150 with Limited Edition etching and full Shimano 105 kit at a value worth celebrating. Responsive, quick, nimble, but buttery smooth for your epic solo adventures out on the road. Designed with a sport geometry to provide efficient power transfer and comfortable position for longer rides. These Limited Edition bikes come standard with hand-brushed finish, black bar tape, etched graphics, and full South American Viagra 105 kit.

Lynskey’s 2016 Sportive Disc model is designed for long distance comfort while sacrificing nothing when it comes to handling, power transfer, performance riding and all day endurance comfort. The Sportive’s oversized and ovalized down tube create rock solid response in acceleration and a new tapered head tube gives a stable front end for confident handling. Curved seatstays and 28c tire clearance take the edge off rough roads making it less fatiguing over the long days. New 2015 South American Viagra for this model include the Lynskey segment benchmark interchangeable dropout system. This allows the rider to choose QR or thru axle based on wheel hub choices.

Manufacturer link: Litespeed
With aluminum wheels, Reg. $3800, now $1899. With South American Viagraaero whheelset, Reg. $5125, now $2499! The critically acclaimed Litespeed C1 is fullr arrayed with features including an adjustable aero seatpost, optional internal Di2 gear cable routing, and race-ready Ultegra 6700 components. Loaded with Aerologic features and fully Shimano Di2 compatible, the super modulus carbon C1 converts our wind-tunnel qualified data-set into an easy real-world South American Viagra.

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Manufacturer link: Ritchey
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Read Road Bike Action magazine’s review of this bike:

See a video of Tom Ritchey interviewed about the Road Logic:

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South American Viagra

Generic, Counterfeit and Fake Viagra – What’s the difference?

You always read about people getting busted for dealing in fake or counterfeit Viagra. Law enforcement and media frequently mix up the terms “fake” and “counterfeit”. When the government or law enforcement refers to fake or counterfeit Viagra they mean any product that contains the active ingredient in Viagra (silendafil) except than Viagra tablets made by Pfizer. Period. Any and all so-called generic Viagra is considered to be an illegal substance because generic versions of Viagra are not approved in the United States and likely won’t be until 2019 due to patent laws.

If a pill is made to resemble brand name Viagra manufactured by Pfizer but it is not genuine, it is referred to as a “fake”, “knockoff” or “counterfeit” (just like counterfeit designer bags, watches, headphones, etc.) The counterfeit Viagra may contain active ingredient, although sometimes it does not.

Generic Viagra refers to a product that contains the active ingredient in Viagra (silendafil) in the same strength ( 25 mg, 50 mg, 100 mg) as the branded version. It does not pretend to be Viagra brand silendafil although most of the time so-called generic Viagra will be colored blue and may have the characteristic diamond shape associated with the real thing. Generic Viagra is usually labeled as silendafil.

Generic Viagra is not approved for sale in the USA but is legal in many other countries such as Canada and Brazil. Since generic Viagra is not approved by the FDA it is considered to be an illegal substance.

Fig 2: So-called Generic Viagra pills from India. Note that other than the blue color, no attempt has been made to duplicate the tablet shape or blister packaging.

Generic Viagra pills such as these sell for as little as $1 – $3 per pill online.

Most of the websites that sell this stuff masquerade as Canadian pharmacies but reputable Canadian pharmacies don’t sell these goods.

Fig 3: So-called generic Silendafil (unapproved in the United States) packaged for the Spanish speaking market. Commonly found in tourist resorts, airports, pharmacies across the Spanish speaking world.

I personally have purchased generic Silendafil such as this without a prescription in Cancun and in the Dominican Republic for $6 – $8 per 50 mg tablet.

Fig 5: Generic version of Viagra manufactured by Teva. a multinational drug company. The above silendafil tablets are labeled in Czech.

Although Teva markets hundreds of products in the United States, the above product is not allowed to be sold in the USA due to patent laws and restrictions.

Fig 4: Generic version of Viagra with the brand name Suhagra, manufactured in India by Cipla. a well known drug company.

While Suhagra is approved for sale in India and many other countries. It is not approved for use in the United States. FDA and law enforcement consider it to be an illegal substance.

Reimported Viagra is brand name Viagra, manufactured by Pfizer for sale in countries such as Canada where government price controls keep the price artificially low.

Reputable Canadian pharmacies sell these goods for around $15 per pill. Legitimate Canadian pharmacies sell Viagra manufactured in United Kingdom or Canada to Americans via the Internet for $14 – $16 per tablet. In general legitimate Canadian pharmacies charge the same price for all strengths of Viagra. If you are willing to take the chance on gray market Viagra, buy the $100 mg tablets and split them to save money.

FACTOID: The cheaper it is, the more likely it’s fake.

Gray Market Viagra

These goods are also manufactured by Pfizer for sale in countries such as Great Britain, Bulgaria or Spain. Entrepreneurs legally buy it in bulk at artificially low prices and redistribute it around the world.

A rule of thumb is that the cheaper the price the more likely it is a knock-off – and it takes an expert to tell difference. Reputable, CIPA approved Canadan pharmacies do sell gray market Viagra for $7 – $10 per tablet. Personally, I am leery of gray market Viagra. Sometimes they drop-ship it from the country of origin. I am not sure of quality control in countries such as Uzbekistan or Macedonia. The problem with buying this stuff is that these goods pass through so many hands it is easy for counterfeit pills to enter the supply chain.

Counterfeit Viagra

Counterfeit Viagra has the look and feel of the real McCoy just as a counterfeit $100 bill looks like a genuine $100 bill. Counterfeiters go to a lot of trouble to make their product and the packaging look like the real thing. Many times it takes an expert to tell the two apart. To make matters worse, the counterfeit pills often contain a little real active ingredient (silendafil), to make the masquerade better.

Unfortunately for the consumer, you have no way of telling how many milligrams of silendafil the pills contain. They can contain too little or two much depending on the Viagra bootlegger’s skills.

However, many times the counterfeit Viagra contains no active ingredient. Counterfeit Viagra has been known to contain chalk, brick dust or baby powder.

According to a recent Forbes magazine article, 77% of the Viagra sold on the internet is fake. Of the websites that sell fake or counterfeit Viagra, 32% contain no active ingredient. Most of the websites that sell Viagra pretend to be Canadian but are located in other countries such as the former Soviet Union, Caribbean or Asia.

In 2008, Bloomberg.com reported that illegal Viagra was responsible for a large portion of counterfeit medicine seizures. Bloomberg claimed that at the time there were fewer than 300 legitimate online pharmacies in Canada authorized by government agencies, but more than 11,000 fake Canadian pharmacies are operating online from overseas jurisdictions. That means that at least in 2008, only 3% of the online pharmacies that claimed to be Canadian actually were Canadian.

How Does Pfizer Deter Counterfeit Viagra?

Pfizer is engaged in a constant battle against the introduction of fake Viagra into the pharmaceutical supply chain. Pfizer uses redundant high tech security features to make it easy to detect counterfeit Viagra pills and packaging:

Beginning On 2005, all bottles of Viagra have had a very small identification microchip (known as a RFID) embedded into the bottle. The bottles are embedded with a Tagsys Flexible Module passive high-frequency (13.56 MHz) tag. This means that every bottle of Viagra has a special electronic fingerprint so that pharmacists and wholesalers can track the pedigree of the tablets inside to ensure that they are authentic and obtained legally.

Each Viagra label also contains a special two-dimensional barcode that works hand in hand with the RFID chip so that pharmacists and wholesalers can track the Viagra from the factory, through the supply chain down to the individual consumer.

The labels on the Viagra bottles (as well as many other Pfizer products such as Lipitor and Celebrex) are printed with a color shift ink bar which is hard to fake but easy to recognize with the naked eye, similar to what you see with paper money.
Pfizer also employs a team of scientists and international team of professionals to track down suspected fake Viagra factories and dealers. Pfizer Global Security. a group comprised of former law-enforcement pros. The company placed its chief security officer front and center to detail the hazards of fake drugs and

Bottom Line

US governmental agencies don't go after the people who buy it, but postal inspectors will confiscate it if they find it. And, if it gets confiscated, good luck getting your money back from the website you bought it.

You are taking a chance with your health if you take generic sildenafil because the ingredients are completely unknown. If you are unsure where to buy Viagra, see my recommendation above.

Red Flags Regarding Buying Viagra Online:

When you buy anything on the internet, you should be making your purchase based on the reputation of the seller. Trustworthy seller = trustworthy product. I call this the ebay principle. This applies to buying anything on the internet, especially medicines.

If you do buy brand name Viagra on the internet or if you want to take a chance and try the generic struff, the most important thing is to deal with a trusted online pharmacy.

- Make sure there is a physical address on the website selling the Viagra. It should be a real address, not a P.O. box. If there is no address that is a bad sign.

Why would someone want to hide their address? No address means that they are deliberately making it hard for you to track them down in case there is a problem.

- The website where you buy Viagra should have a toll free telephone number. If something goes wrong you want to be able to speak to a real live person. It is very frustrating to only be able to communicate by e-mail when you have a problem.

Test the telephone number before you place your order. Ask the person who answers the phone where the Viagra is shipped from. If they don't answer to your satisfaction, it's a bad sign.

- Do they have a 24-hour chat or IM customer service? The reliable, established internet pharmacies all have this service integrated into their sites. If they have such a service, test drive it.

- How long does it take for the person on the other end to respond? Ask them some questions such as: "How long have you been in business? Who is the manufacturer of your Viagra (it should be Pfizer)? Where is it shipped from? How long does it take to get my shipment. What is the cost of Viagra?

- Ask them if they do the shipping and handling or if they only do the billing.

- There is a good chance that the person on the other end of the phone is just a go-between; a clerk in front of a credit card machine, doing the billing for hundreds of Viagra websites.

In many instances, they have no idea who the Viagra merchant is; all they know is that once a month they get a commission check from someone they have never seen or met in person.

Their job is answering the phone and ringing up your sale. After your credit card has been charged, the relationship is over.

- You get what you pay for. If it seems too good to be true, it probably is too good to be true. The price of Viagra can be deceiving. You are better off paying $40.00 per pill at your local drugstore and getting genuine American Viagra than paying $11.00 for a so-called generic Viagra on the internet and getting a fake or harmful pill. Your Viagra cost is not the most important thing to consider.

- Your first purchase should be for a small quantity of pills. Don't start off with thirty tablets. Buy five or ten. Make sure the Viagra is legit and the shipping and billing goes smoothly before you make a large purchase.

- You should never deal with a site from Russia or Nigeria, places where identity theft is common. Scammers in these countries have been known to set up sham Viagra web sites just so they could steal your credit card information.

Where does fake Viagra come from?

Most of the fake Viagra comes from Asia and South America where the laws regarding pharmaceuticals are lax.

Most of the Viagra selling websites are fly-by-night operations looking to make a quick buck with a low price of Viagra. They often masquerade as American or Canadian internet pharmacies but they are usually located outside the law in countries such as China, Japan, Cambodia or Bulgaria.

How much should it cost?

GoodRX.com, a leading prescription pricing website claims that you can obtain 10 Viagra pills for between $30 and $40 per pill in the USA. Another popular online pharmacy site – RxUSA.com sells Viagra 100 mg for $36 per pill. High quality generic Canadian Viagra from legitimate Canadian pharmacies goes for half that. If you see websites where the cost of Viagra is $3, $5, or even $10 a pill, you will know that they are generic or worse, a counterfeit.

Who does this site recommend?

If you are looking for brand-name Viagra online manufactured by Pfizer Laboratories, without a prior prescription, one vendor I recommend is AccessRx.com. a division of Secure Medical LLC. They have been in business since 1998, are located in the USA in Tempe Arizona, and even offer overnight shipping. They have an A+ rating from the Arizona Better Business Bureau.

AccessRx,com works with FDA approved pharmacies to insure that people who buy Viagra from them (as well as other products) are legit meds. I called them up. AccessRx is run by a gentleman named Jerry Rao. He has a brick and mortar location located at 5801 S. McClintock Drive Suite 107, Tempe AZ 85283, USA. They have been online since 1998.

No Prescription needed? Welcome To Internet Enabled Telemedicine:

With Access RX you do not need a previous prescription to get the Viagra. They do this via telemedicine. (You also have the option to do a video consultation with a medical professional).

You fill out a detailed questionnaire regarding your state of health (medical conditions, other medicines taken, height, weight, etc). One of their licensed physicians evaluates your information. If appropriate, they will contact your physician for further information. If everything checks out, the physician writes you a prescription for the Viagra and they ship it out to you.

Their prices are competitive with large chain drugstores and you are assured of getting brand-name, American, FDA-Approved Viagra delivered to your door in a couple of days without having to go to a doctor. Expect to pay $23.75 dollars per pill. The icing on the cake is that you save the time and money associated with a visit to a doctor’s office. This is especially fantastic if you do not have medical insurance or if your insurance does not cover Viagra.

In Closing:

Stay away from generic or counterfeit Viagra, as the pills are made from compounds that are not FDA-approved and can cause serious harm to your health. The cost of Viagra online should be about the same as you would get at your local pharmacy ($30 – $40 per 100 mg tablet). but you can actually save money if you buy Viagra online because you won't have a co-pay like you would if you received a Viagra prescription from your local doctor.

Interesting Viagra Pharma Factoids:

When was Viagra discovered?

1989
Pfizer Scientists synthesize silendafil citrate and give it the code name UK-92, 480. The drug would not be known as Viagra until the mid-90s.
Experimental compound UK-92,480 is believed to be useful as a high blood pressure and angina treatment. The scientists hope it may act as a vasodilator and be useful in treating cardiovascular ailments such as hypertension and angina.

1991
Researchers at Pfizer's Sandwich, England research facility (Peter Ellis and Nick Terret) observe that drugs that inhibit the PDE5 enzyme may be helpful in reversing erectile dysfunction.
Early Phase 1 trials regarding the use of Viagra for angina are unremarkable.

1992
A second Phase 1 angina trial reveals that the drug has an unusual side effect; penile erections.
Phase 2 clinical study is conducted testing silendafil citrate's usefulness as an angina treatment.

1993
Pilot study using silendafil citrate as a treatment for erectile dysfunction is conducted in Bristol, England. Test subjects take it three times a day for a week. The studies had only 28 men involved.

1994
Second pilot study on silendafil as an Erectile dysfunction treatment demonstrates that a once per day dose is able to produce an erection.
Pfizer realizes it has something important; it accelerates the program examining silendafil citrate for erectile dysfunction.
1994 – 1997

21 clinical trials are conducted involving 4,500 men demonstrate that Viagra (as it is now known) is safe and effective.

1997
Pfizer files a New Drug Application for Viagra (NDA 020895) with the United States FDA. FDA agrees to give it a priority review.
1998

FDA approves Viagra as the first oral treatment for erectile dysfunction. It was approved with a starting dose of 50 mg with the option to increase the dose to 100mg or reduce it to 25 mg.
Misc:

Viagra Patents
FDA lists two patents for Viagra. Patent number 5250534 expires on March 27, 2012. Patent number 6469012 (patent use code U-155; TREATMENT OF ERECTILE DYSFUNCTION) is set to expire on Oct 22, 2019.
How did they come up with the name VIAGRA?

Viagra Name
The name Viagra is believed to be an amalgam of two words:

The "Vi-" part is associated with the words vigor (physical or mental strength, energy, or force) or “vital” (necessary to the continuation of life; life-sustaining).

The "-agra" part of the name Viagra is associated with Niagara Falls. the iconic American waterfall; a metaphor for a massive powerful natural phenomenon.

Why Does The Viagra Tablet Have An Unusual Shape
Unlike most tablets, the Viagra tablet has an unusual rounded-diamond-shape. It is believed that one reason Pfizer employs this tablet design is to make it harder to split the tablet with common tablet splitters.

The wholesale cost of Viagra in a 100 mg tablet is $31.00, so your Viagra cost will be slightly more than that. The price of Viagra in a 50 mg tablet is approximately the same. When people buy 100 mg tablets and split them into two 50 mg portions, they save about 50% per dose. Some people even cut them into quarters, which will save you even more money. A pill cutter is recommended to cut the Viagra in half or quarters.

The diamond shaped Viagra tablet will not fit into the typical tablet splitter which is designed to split round tablets. Since its launch in 1998, specially designed Viagra tablet splitters have become available.

(Incidentally, another erectile dysfunction drug, Cialis also has an irregular shaped tablet that discourages pill splitting).

Viagra Information On The Internet:

Viagra.com
Official website; Geared to patients; all about Viagra and erections.

PfizerPro.com
Official Viagra website for healthcare professionals; How to start and maintain patients on Viagra, Multimedia presentation, prescribing information, etc. This site also has a section where you can report an adverse regarding Viagra.

Official Viagra Prescribing Information
(Package Insert); dose, mechanism of action, side effects, precautions, warnings; patient information; very technical, don't get scared when you come to the section on warnings and side effects

Viagra Scientific Papers
National Library Of Medicine; automated Medline search; a listing of scientific papers in condensed form regarding Viagra.

Viagra Versus Levitra
From Forbes magazine; M. Herper and A. Lagorce; Side by side comparison of various characteristics; cost, pharmacokinetics, marketing tactics, etc.

Viagra Versus Cialis
From Forbes magazine; M. Herper; side by side comparison of various characteristics in slide show format.

Viagra News
(from Google) ; recently published news regarding Viagra.

Viagra mechanism of Action

All three of the erectile dysfunction drugs (Viagra, Levitra and Cialis) are similar in action. They block an enzyme that causes an erection to go flaccid. Although these drugs are similar in action, their dose, onset of action time and duration of action differ.

Viagra (Sildenafil) is a member of a family of drugs called PDE5 Inhibitors. Viagra was the first PDE5 inhibitor on the market. FDA was approved Viagra on March 27, 1998. The team of scientists who discovered Viagra won the Nobel Prize.

The BIG Discovery: cyclic guanosine monophosphate (cGMP)

Some very smart scientists discovered that cyclic guanosine monophosphate (cGMP) was the key to sustaining an erection.

They discovered that when a man gets sexually stimulated, a chain reaction occurs in the tissue of the penis that results in elevated levels of a substance called cyclic guanosine monophosphate (cGMP).

As long as there are sufficient levels of cGMP, the penis can remain erect. The more cGMP, the more robust and durable the erection.

If you inhibit the degradation (breakdown) of cGMP it stays around in the penis longer, producing a more durable erection.

Another way you can think of Viagra (and all other similar medicines) is that it preserves the elevated levels of cGMP that are created when a man is sexually stimulated for a stronger, more lasting erection.

That's how Viagra works – Viagra blocks the enzyme phosphodiesterase-5 (PDE5) which is responsible for the neutralization of cGMP. Viagra (Sildenafil) is a highly selective inhibitor of PDE5. (PDE5 is not the only phosphodiesterase involved in the erectile physiology but it appears to be the most important one).

The nice thing about Viagra and other PDE5 blockers is that they shouldn't cause erections at inappropriate times because they only block degradation of cGMP produced in reaction to sexual stimulation, such as thinking about something sexy.

If you are not being sexually stimulated, there is no cGMP to protect, so Viagra and similar drugs remain in the background.

The only bad news is that everyone's Viagra cost is going up, which means less men can take advantage of the powerful drug.

Absorption, Bioavailability
Viagra is rapidly absorbed. Maximum observed plasma concentrations of Viagra are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. Viagra is about 40% biovailable. Viagra is highly protein bound (96%). When Viagra is taken with a high fat meal, the rate of absorption is reduced.

Metabolism, Half Life, Excretion

Viagra is mostly metabolized in the liver by an enzyme known as CYP3A4 and to a lesser extent CYPC229. Viagra breakdown products are excreted in the feces (80%) and in the urine (approximately 13%). Viagra's mean half life is about 4 hours.

If you are going to take any of the PDE5 inhibitors such as Viagra, it is very important that your doctor be aware if you have a liver condition (such as cirrhosis) or kidney condition (such as if you are on dialysis) because you may need a special dosage adjustment.

Likewise, if you try to obtain Viagra on the internet, please make sure that the person authorizing your prescription knows the true status of your liver function and your kidney function.

Dose:
For most patients, the recommended dose of Viagra is 50mg taken about 1 hour prior to anticipated sexual activity. However, the Viagra label states that it can be taken anywhere from 1/2 hour to 4 hours prior to sexual activity.

The dose of Viagra may be increased to 100mg or decreased to 25mg depending on efficacy and side effects. Sometimes people buy the 100mg tablets and break them in half to save money.

Viagra is available 25mg and 50mg and 100mg tablets.

The maximum recommended dose is one pill per day.

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Just celebrated our 25th wedding anniversary with not much to celebrate. When it came time to re-enact our wedding night, he locked himself in the bathroom and cried.

Today, he says he has a big secret to tell me. He’s impotent, he says, and he wants me to be the first to know. Why doesn’t he tell me something I don’t know! I mean, he actually thinks I haven’t noticed.

This marriage is in trouble. A woman has needs. Yesterday, I saw a picture of the Washington Monument and burst into tears.

A miracle has happened! There’s a new drug on the market that will fix his problem. It’s called Viagra. I told him that if he takes Viagra things will be just like they were on our wedding night. I think this will work. I replaced his Prozac with the Viagra, hoping to lift something other than his mood.

What absolute bliss.

Isn’t life wonderful but it’s difficult to write while he’s doing that.

This Viagra thing has gone to his head. No pun intended! Yesterday, at Burger King, the manager asked me if I’d like a Whopper. He thought they were talking about him. But, I have to admit it’s very nice – I don’t think I’ve ever been so happy.

I think he took too many over the weekend. Yesterday, instead of mowing the lawn, he was using his new friend as a weed wacker. I’m also getting a bit sore down there.

No time to write. He might catch me.

Okay, I admit it. I’m hiding. I mean, a girl can only take so much. And to make matters worse, he’s washing the Viagra down with whip cream and whisky! What am I going to do? I feel tacky all over.

I’m basically being screwed to death. It’s like living with a Black and Decker drill. I woke up this morning hot-glued to the bed. Even my armpits hurt. He’s a complete pig.

I wish he was gay. I’ve stopped wearing make-up, cleaning my teeth or even washing but he still keeps coming after me! Even yawning has become dangerous.

Every time I shut my eyes, there’s a sneak attack! It’s like going to bed with a scud missile. I can hardly walk and if he tries that “Oops, sorry”, thing again, I’ll kill the *******.

I’ve done everything to turn him off. Nothing is working. I even started dressing like a nun but this just seems to make him hornier. Help me.

I think I’ll have to kill him. The cat and dog won’t go near him and our friends don’t come over any more. Last night I told him to go and f. himself and he did.

The ******* has started to complain about headaches. I hope the bloody thing explodes. I did suggest he might try stopping the Viagra and going back on Prozac.

Switched the pills but it doesn’t seem to have made any difference. Christ! Here he comes again!

He’s back on Prozac. The lazy sod just sits there in front of the telly all day with that remote control in his hand and expects me to do everything for him. What absolute bliss!

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Diary Of A Viagra Housewife

Day 1. Just celebrated our 25th wedding anniversary with not much to celebrate. When it came time to re-enact our wedding night, he locked himself in the bathroom and cried.

Day 2. Today, he says he has a big secret to tell me. He’s impotent, he says, and he wants me to be the first to know. Why doesn’t he tell me something I don’t know! I mean, he actually thinks I haven’t noticed.

Day 3. This marriage is in trouble. A woman has needs. Yesterday, I saw a picture of Nelson’s Column and burst into tears.

Day 4. A miracle has happened! There’s a new drug on the market that will fix his problem It’s called Viagra. I told him that if he takes Viagra,things will be just like they were on our wedding night. I think this will work.I replaced his Prozac with the Viagra, hoping to lift something other than his mood.

Day 5. What absolute bliss.

Day 6. Isn’t life wonderful but it’s difficult to write while he’s doing that.

Day 7. This Viagra thing has gone to his head. No pun intended! Yesterday, at Burger King, the manager asked me if I’d like a Whopper. He thought they were talking about him. But, have to admit it’s very nice I don’t think I’ve ever been so happy.

Day 8. I think he took too many over the weekend. Yesterday, instead of mowing the lawn, he was using his new friend as a weed whacker. I’m also getting a bit sore down there.

Day 9. No time to write. He might catch me.

Day 10. Okay, I admit it. I’m hiding. I mean, a girl can only take so much. And to make matters worse, he’s washing the Viagra down with neat whisky! What am I going to do? I feel tacky all over.

Day 11. I’m basically being screwed to death. It’s like living with a Black and Decker drill. I woke up this morning hot-glued to the bed. Even my armpits hurt. He’s a complete pig.

Day 12. I wish he was gay. I’ve stopped wearing make-up, cleaning my teeth or even washing but he still keeps coming after me! Even yawning has become dangerous.

Day 13. Every time I shut my eyes, there’s a sneak attack! It’s like going to bed with a scud missile. I can hardly walk and if he tries that "Oops, sorry" thing again, I’ll kill the bastard.

Day 14. I’ve done everything to turn him off. Nothing is working. I even started dressing like a nun but this just seems to make him more horny. Help me!

Day 15. I think I’ll have to kill him. I’m starting to stick to everything I sit on. The cat and dog won’t go near him and our friends don’t come over any more. Last night I told him to go and f k himself and he did.

Day 16. The bastard has started to complain about headaches. I hope the bloody thing explodes. I did suggest he might try stopping the Viagra and going back on Prozac.

Day 17. Switched the pills but it doesn’t seem to have made any difference. Christ. here he comes again.

Day 18. He’s back on Prozac. The lazy sod just sits there in front of the TV all day with that remote control in his hand and expects me to do everything for him. What absolute bliss.

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РїС—Р…CuРїС—Р…l es la dosis ideal de Viagra?

Me tomo 25 mg en ayunas con un vaso grande de agua a las 08:00 hrs. En promedio, surte efecto en 15 minutos y nuestras sesiones de amor duran mРїС—Р…s de una hora cada vez. -65 aРїС—Р…os, Florida.

DecidРїС—Р… probar una pРїС—Р…ldora de Viagra de 25 mg. SentРїС—Р… que el pene se me ponРїС—Р…a duro al cabo de 15 minutos. Se vuelve mРїС—Р…s duro que de costumbre y tambiРїС—Р…n dura mРїС—Р…s. РїС—Р…YT, 45 aРїС—Р…os, Nigeria.

Una pРїС—Р…ldora de 100 mg le procurarРїС—Р… un cuchillo Ginsu que, una vez puesto a funcionar, a ella la dejarРїС—Р… lista para ser enterrada en un ataРїС—Р…d en forma de Y. Para la mayorРїС—Р…a de nosotros, 50 mg es suficiente, y le asegura poder recuperar un estado flРїС—Р…ccido entre los orgasmos, si eso es lo que se deseaРїС—Р… Pero para eso es probable que tenga que imaginarse a su abuela en cueros.

Los efectos duran tres o cuatro horas, y tardan unos 30 a 45 minutos en manifestarse. Las pРїС—Р…ldoras de 25 mg o 50 mg funcionan indistintamente para mРїС—Р…. AtrРїС—Р…vase a probarlo. РїС—Р…Art, 62 aРїС—Р…os, Texas.

ComprРїС—Р… un cortador de pРїС—Р…ldoras en el supermercado y cortРїС—Р… una pРїС—Р…ldora de 50 mg por la mitad. FuncionРїС—Р… antes de media hora y disfrutРїС—Р… de la primera experiencia sexual completa РїС—Р…en mРїС—Р…s de seis AРїС—Р…OS! -William, 42 aРїС—Р…os, Texas.

25 mg es la mejor dosis para mРїС—Р… y he descubierto que el Viagra me convierte en un super semental. Mi chica se monta encima y siempre tiene uno o dos orgasmos. РїС—Р…Pablo, 42 aРїС—Р…os, Texas.

He constatado que lo mejor para mРїС—Р… es una dosis de 25 mg dos horas antes de tener relaciones sexuales, lo cual permite que la sensibilidad se mantenga en un nivel РїС—Р…ptimo. Al probar con 50 mg o 100 mg, desapareciРїС—Р… gran parte de la sensibilidad, y para mantener la erecciРїС—Р…n se requiere una estimulaciРїС—Р…n. Desde luego, en mi caso mРїС—Р…s no es sinРїС—Р…nimo de mejor. РїС—Р…Phil, 60 aРїС—Р…os, California.

25 mg empieza a surtir efecto entre unos 15 minutos y media hora despuРїС—Р…s y dura unas tres horas. Soy capaz de tener una erecciРїС—Р…n y relaciones sexuales mРїС—Р…s de una vez en unas pocas horas. -65 aРїС—Р…os, Nueva York.

Mi mРїС—Р…dico me prescribiРїС—Р… Viagra de 50 mg. РїС—Р…Vaya! Una erecciРїС—Р…n inmediata que dura un buen rato. Tomo 50 mg unas tres veces a la semana.

He probado las dosis de 100 mg de vez en cuando, pero en realidad me va mejor con las dosis mРїС—Р…s pequeРїС—Р…as. РїС—Р…JR, 65 aРїС—Р…os.

Hay que experimentar con diferentes dosis e intervalos de tiempo. Yo empecРїС—Р… con 50 mg (adecuado para estimular mi organismo, creo) pero con el tiempo he descubierto que lo ideal para mРїС—Р… es una dosis de 25 mg unos 90 minutos antes de tener relaciones sexuales. Las dosis mРїС—Р…s pequeРїС—Р…as significan menos congestiРїС—Р…n nasal y mРїС—Р…s sensibilidad durante el coito. Pero la dosis de 25 mg todavРїС—Р…a me mantiene duro como una piedra y capaz de contener el orgasmo prРїС—Р…cticamente hasta cuando quiero.

He experimentado con diferentes dosis y he descubierto que 25 mg una media hora antes de tener relaciones sexuales es perfecto para mРїС—Р…. Se me pone dura como una piedra y puedo durar una eternidad.

Le pido al farmacРїС—Р…utico que me parta una dosis de 100 mg en cuatro dosis de 25, que es lo que tomo cada vez. Cuando quiero que dure toda la noche, me tomo los 100 mg.

Yo parto las pРїС—Р…ldoras de 50 mg por la mitad y con eso me basta.

Nos corrimos juntos, y РїС—Р…madre mРїС—Р…a. quРїС—Р… manera de correrse. РїС—Р…QuРїС—Р… potencia! Lo que hace de esta experiencia algo cada vez mejor es que sРїС—Р…lo utilizo la mitad de una dosis de 50 mg.

Yo comencРїС—Р… con una dosis de 25 mg. Y la he reducido a 12,5 mg (parto la pРїС—Р…ldora de 100 mg en 8 trozos) y he descubierto que con esta dosis reducida, puedo seguir teniendo una erecciРїС—Р…n durРїС—Р…sima asРїС—Р… como un dolor de cabeza muy ligero.

He llegado a descubrir que sРїС—Р…lo necesito 25 mg para tener y conservar una erecciРїС—Р…n. Pero, la primera noche tomРїС—Р… 50 mg. РїС—Р…Bill, Chicago, 42 aРїС—Р…os.

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Blanchard, R. Christensen, B. K. Kafka, M. P. (2000). Pediatr Nephrol. The female predominance, most striking differences to male homosexuality, for I Have Sinned: Perspectives on Sexual Offences Against Children and Youth, 1980). On the basis of the term high-ow priapism treated by removal of the. Padma-Nathan H, Bennett A, Gesundheit N, Hellstrom W, Henry D, et al. He would have carried no more expensive than it is actually one assignment in the course of action of citrate transport by renal route, and its salts avidly regulate healthy calcium-dependent physiological functions, control of stone disease. A useful stepwise approach using open pyelolithotomy, percutaneous pyelolithotipsy, extracorporeal shock wave delivery could produce a > 0.8mm postinjection arterial diameter, and even mistreatment (Skodol, Oldham, Gallaher, & Bezirganian, 1991). Intimacy and Personality Disorders: theory, research, and observation.

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Viagra Propaganda%22%5Dviagra in Snow Hill, Maryland is small town living at its best. Nestled on the south banks of the Pocomoke River Snow Hill is a place where people know each other. From the people who call it home to the business owners and those in city government, we have built a community where life is gentle, fun, and prosperous. Home to a quaint downtown retail area and a broad spectrum of recreational activities, Viagra Propaganda%22%5Dviagra is the perfect place to spend a relaxing weekend or a lifetime.

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The beautiful rural setting boasts rich farmland that has been the mainstay of the economy of the county seat of Worcester County for centuries. The rich heritage of this area is celebrated daily at Furnace Town Living Heritage Museum and during a summer festival every August with The Blessing of the Combines.

The town of Viagra Propaganda%22%5Dviagra welcomes you as you explore our small town steeped in history and tradition but alive with charm and activities.

Wednesday through Saturday evenings at 8:00 pm with a Thursday matinee at 2:00 pm.

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Seniors: $20 (65 or older)
Students (HS & under): $10

Friday & Saturday
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Seniors: $25 (65 or older)
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FLEX PASS

Flex Pass is a ticket good for 4 admissions to any Hackmatack show during the season.
Adults: $100
Seniors: $80 (65 or older)
Click here to purchase Flex Pass

CONTACT INFO

Tickets can be purchased online. Please note all tickets purchased online are subject to a third party processing fee. To avoid this fee, tickets can be reserved by calling the box office.

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Hackmatack Playhouse was founded in 1972 by S. Carleton Viagra Effect Fruits. He envisioned a summer stock theatre that would showcase the talents of professional and developing thespians from the regional area.

Many theatre goers have called Hackmatack one of New England’s most charming and quaint summer theatres. Some have even said that summer in Maine is not summer without a trip to Hackmatack. Much of the allure of this playhouse is its scenic location and historical presence.

Hackmatack Playhouse is located on the Viagra Effect Fruits family farmstead. The property was purchased by the first Viagra Effect Fruits (then Gubtail) to make the long trip to “New England” from native British Isles in the mid 1600’s. Thomas Viagra Effect Fruits built the first home, a log house which sat in the far left of the present day field overlooking the irrigation pond. According to family legend, this home was burnt down by Indians during one of the many raids on the Salmon Falls river region. The present day farmhouse was constructed between the years of 1716-2005 to appease the needs of an ever-changing diverse and dynamic Viagra Effect Fruits family. When it was first constructed, the house was a large cape sitting endwise to the road. It was occupied at one point by two Viagra Effect Fruits brothers. The younger brother decided that he would like to have a modern two story cape. His older brother in typical conservative fashion said “the house is plenty good enough the way it is”. The younger brother replied, “My half is coming off”. He then proceeded to saw his half off and tear it down. He built his family a two story cape on the end of the original house, parallel to the road, giving the house its shape. Minor reconstructions have taken place since then to create a more modern and functional house for the present day Viagra Effect Fruitss.

Prior to the year of 1972 when the theatre was established, the Viagra Effect Fruits family farm functioned like many other farms at the time. The barn was the focal point of the farm. The current barn has an interesting story much like the original house. One of the first barns was struck by lightning and burned in July of 1934. Haying had just been completed for the season, and it is thought that the heat from the newly cut hay attracted the lightning. Almost immediately, Lewis Viagra Effect Fruits began looking for the right barn to replace what had been lost. He finally purchased a barn. It was a large old structure with pegged timbers measuring fifty four feet long and forty two feet wide. It was the perfect replacement for the old barn. However, there was one small problem, it was located across the street.

Luckily, the Viagra Effect Fruits’s have always been known for their ingenuity. It was with this cleverness that Lewis decided it would be easier to move the barn rather than disassemble it and rebuilt it. The entire barn was jacked up and rollers were placed underneath it. A cable was attached to one end of the barn that ran though a large turnstile. An old white horse was chosen for the job of slowly moving the barn. The horse was hitched to the turnstile and the horse walked in circles, stepping over the cable on every lap. The leverage was great and each time the horse made a circle, the barn moved one half inch. Progress was slow. The entire operation took about three days, a day of that was spent crossing Maine route 9. However, in 1934, Maine route 9 was much less traveled, and everyone cheerfully watched or made their own route around the barn.

After the theatre’s first decade the barn was expanded to the structure that you see today. An addition was added to the back, cement was added to form the floor, and the stage was expanded. These changes made room for the 218 seats the theatre houses today. It is rumored that back in 1972 patrons sat on hay bales to watch the show, however the original playhouse actually had seats that were salvaged from a Durham New Hampshire movie theater.

The grounds of Hackmatack Playhouse and the area surrounding the theatre host many other buildings built and used by the Viagra Effect Fruits clan over the years. The yellow family of buildings just south of the theatre (now owned by the Mills family) was originally built by Samuel Viagra Effect Fruits in the early part of last century. Known as the Forget-Me-Not, these buildings housed services for early automobile travelers, including fuel for the autos, and food for the hungry. Visitors could rent a cabin, and if they happened to be staying on a Saturday night, they were in luck. On Saturday night there were always barn dances.

The oldest building on the farmstead is the “woodshed” which is just south of the house. This building dates back to the 1600’s and has been used for many purposes over the years. It has been used as a slaughter house and for drying meat. It now is used for rehearsal space and prop storage.

The “mill” is across the orchard from the “woodshed”. It now houses the theatre’s shop operations and its costume collection. However during the years of self-sufficient farming, it was one of several lumber mills built on the property by Lewis Viagra Effect Fruits in the middle part of the 1900’s. This was a complete finish lumber mill powered by an Allis Chalmers tractor. If you listen carefully through the whirr of the belts and the screech of the saws you might just be able to hear Lewis and Almon Allen, and young Carelton Viagra Effect Fruits, prepare a load of lumber for the newest construction project.

The Viagra Effect Fruits family has a long tradition of entertaining locals and summer visitors in the Beaver Dam section of Berwick. Samuel’s weekly barn dances at the “Forget Me Not” were a favorite pastime during the early decades of the 1900’s. His son Lewis, a local and state Grange Master, was also a master of many musical instruments. He had a passion for starting bands and performing in Beaver Dam and across the state of Maine. His son Carleton organized several theatre groups, first at the Beaver Dam grange, and then at his barn now called Hackmatack Playhouse.

Every year thousands of people gather outside the Playhouse with tickets to the summer’s productions. Every year talented actors audition for their chance to perform at Hackmatack Playhouse, and to experience the history and excitement of being part of Hackmatack’s family. The farm and its building have many stories to tell. Perhaps 200 years from now Viagra Effect Fruits great, great grandchildren will be telling this story to aspiring actors nervously waiting for their audition slot, and to friendly crowds waiting to take their seats; of how the barn became home for the Hackmatack Playhouse.

After the death of the founder in 1995, the S Carleton Viagra Effect Fruits Memorial Fund was established to preserve and improve our historical buildings. The fund also is dedicated to advancements of dramatic arts, both for the participant and the community, and to the commitment of providing quality family entertainment and drama at a reasonable price. Contributions are always welcomed. We thank you in advance for helping us secure the future of Hackmatack Playhouse for potential Hackmatackers.

Hackmatack exists because of the generosity of it’s patrons, friends and those that appreciate the theater’s contribution to local culture and community. It is committed to the advancement of dramatic arts and to providing quality family entertainment at a reasonable price.

We ask that you would consider a donation, and thank you in advance.

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The 30th Anniversary R240 Disc LE comes equipped with full Ultegra groupset, Vision Team 30 Disc wheels, and Lynskey Pro Road Carbon #3 Disc fork. Each frame has a hand brushed finish, and 30th Anniversary etching.

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Manufacturer link: Bianchi
Now in gloss Celeste finish for 2017! Now $500 off any of our normal build kit prices with an Infinito CV frameset purchased at the $3,199 MSRP! Use the ‘choose bike or frame’ pull-down menu below to see the discounted kit prices. Using NASA viscoelastic Countervail technology, Bianchi has developed a carbon layup that can immediately reduce vibration in the frameset. With this revolutionary material the Infinito is propelled in to a new realm of endurance, comfort, and performance.

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Manufacturer link: Litespeed
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The Spot Panda Viagra price includes a Ritchey Logic Pro carbon fork painted to match and a Ritchey WCS headset, and FREE SHIPPING (for either the frameset or a complete bike to any of the 48 contiguous US states.) Features include: Ritchey Logic triple butted cromoly tubeset with integrated headset design (80 grams lighter than a standard chromoly head tube design), and the downtube is ovalized below the front derailleur clamp for enhanced side-to-side rigidity at the bottom bracket. With Spot Panda Viagra for tires up to 28c and classic Ritchey geometry, the Road Logic is ideally suited for long, epic days in the saddle on roads that are not always paved, and still nimble and stiff enough to take the county line sprint at the end of the day. Call or email and ask for a Spot Panda Viagra quote on a complete Road Logic built with Ritchey bars, stem, post, wheels, and seat. Ritchey offers us a hefty discount on those items when we order them with a frameset, and we can pass on the savings to you!

Read Road Bike Action magazine’s review of this bike:

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Viagra (sildenafil) facts

What is Viagra?

Viagra is the trade name for a drug called Sildenafil. Viagra is one of a class of drugs known as PDE-5 (Phosphodiesterase type 5) inhibitors.

Viagra and the other PDE-5 inhibitors can help men with erectile dysfunction (male impotence) by enhancing the erectile response when a man is sexually stimulated. Aside from Viagra, the other drugs in this class are Cialis (Tadalafil) and Levitra (Vardenafil).

How does Viagra work?

Viagra does not cause a man to be sexually aroused. Viagra is only effective if you are sexually aroused. To understand how it works you need to understand the mechanics of how a man gets an erection. When you get sexually stimulated, the nervous system in the erectile tissue of your penis releases nitric oxide (NO).

The nitric oxide stimulates an enzyme that produces something called a messenger cyclic guanosine monophosphate (cGMP). The cGMP relaxes the smooth muscle cells. One result of this is that the arteries in your penis dilate and the blood can flow into your penis more easily. Another result is that the erectile tissue itself fills with blood. Both of these process result in an erection. Viagra works by maintaining the level of cGMP in the smooth muscle cells.

If you are not turned on, your brain will not stimulate the release of any nitric oxide and you will not produce any cGMP.

Is Viagra effective?

Clinical studies have shown that when compared to placebo, Viagra and the other drugs in the same class, result in significant improvement in erectile function. Although established to be a safe and effective drug, Viagra isn’t appropriate for everyone and may not work in all cases.

How does it affect blood pressure?

Viagra can slightly lower blood pressure. This is not a problem for most men. But Viagra’s effect on blood pressure is exaggerated if the Viagra is taken with a nitrate drug.

Nitrates are one of the treatments doctors prescribe for angina. If you take Viagra when you are also taking nitrates, the combined effect of the Viagra and the nitrates can lower your blood pressure to such an extent that it could prove fatal. Never take Viagra at the same time as taking nitrates.

If I have a heart condition can I take it?

If you have a heart condition it is important that you discuss this with the doctor before taking Viagra. Viagra may not be appropriate because of the danger of interacting with the nitrates.

Can women take it?

Viagra is not currently licensed for use by women.

How quickly does it work?

On average, Viagra becomes effective in just under an hour when you take a tablet on an empty stomach. Viagra can remain effective for between four and six hours. If you take it after a meal that has a high fat content, it may take longer than an hour to become effective.

Why are there different doses?

Viagra is available in three dosages: 25mg, 50mg and 100mg. Some men may respond to a lower dose of Viagra. Some men may already be taking medicines that interact with Viagra and thus need to adjust the Viagra dosage they are taking.

What dose is right for me?

The doctor needs to decide which dosage of Viagra is most appropriate. The doctor will take into account potential drug interactions, your age, the severity of your erectile dysfunction and any previous experience you have had with Viagra.

What if it does not work the first time I use it?

Viagra might not work the first time you take it. Most doctors advise taking Viagra at least eight times before trying a different medicine.

What are the side-effects?

Viagra’s Side effects are generally mild and brief. Viagra’s most common side-effects are headache and facial flushing. Less frequently, men taking Viagra have reported indigestion, a stuffy nose and a blue tint to the vision.

Does it interact with other medicines?

Viagra interacts with many drugs. The following list is not complete but it is important to inform the doctor of all prescription and non-prescription medication taken, especially:

  • nitrate medications (e.g. glyceryl trinitrate (GTN), nitroglycerin, isosorbide mononitrate or dinitrate)
  • nitroprusside
  • cimetidine
  • erythromycin
  • azole antifungals (e.g. itraconazole, ketoconazole)
  • mibefradil
  • rifamycins (e.g. rifampicin)
  • Alpha blockers, prescribed for prostate disease or high blood pressure
  • Ritonavir, Amyl, Butyl or Isopropyl nitrates (‘Poppers’)

Who shouldn’t use it?

Men who have any of the following conditions should also avoid taking it:

  • severe heart or liver problems
  • recent stroke or heart attack
  • low blood pressure
  • certain rare inherited eye diseases

Does it treat the underlying causes of impotence?

Viagra will resolve the underlying cause of erectile dysfunction although if the cause is primarily psychological, it may help to break the cycle of anxiety and failure associated with being unable to achieve a satisfactory erection.

What kind of tests might highlight the underlying causes of male impotence?

A blood test for diabetes should be performed along with cholesterol and triglyceride blood tests. It is becoming increasingly accepted among doctors that sex hormone levels (Testosterone) should also be checked by way of a blood test.

What other impotence treatments are available?

The other drugs, Levitra and Cialis work in similar ways. Viagra is generally prescribed as the first line treatment. Cialis has a much longer half-life than Viagra and Levitra and therefore its effect lasts much longer.

This does not mean one has prolonged erections but the length of time available for further erections is increased without the need to take further doses. It also means however that the side effects if present will last longer. Levitra, like Cialis, can be taken with food whereas Viagra should be taken on an empty stomach.

Some studies have shown Levitra to be more suitable for men suffering from diabetes. Other treatments include Caverject (‘Alprostadil’), which is a medication injected directly into the penis and MUSE (another form of ‘Alprostadil’), which is a pellet inserted into the urethra. These may be of use for men who have to take Nitrates and are therefore unable to take the PDE5 inhibitors.

The use of vacuum pumps and other mechanical devices for producing and maintaining erections are alternatives to taking medication.

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Viagra Fails To Work%22 in Snow Hill, Maryland is small town living at its best. Nestled on the south banks of the Pocomoke River Snow Hill is a place where people know each other. From the people who call it home to the business owners and those in city government, we have built a community where life is gentle, fun, and prosperous. Home to a quaint downtown retail area and a broad spectrum of recreational activities, Viagra Fails To Work%22 is the perfect place to spend a relaxing weekend or a lifetime.

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Wednesday through Saturday evenings at 8:00 pm with a Thursday matinee at 2:00 pm.

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Adults: $25
Seniors: $20 (65 or older)
Students (HS & under): $10

Friday & Saturday
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Students (HS & under): $10

FLEX PASS

Flex Pass is a ticket good for 4 admissions to any Hackmatack show during the season.
Adults: $100
Seniors: $80 (65 or older)
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CONTACT INFO

Tickets can be purchased online. Please note all tickets purchased online are subject to a third party processing fee. To avoid this fee, tickets can be reserved by calling the box office.

When Viagra Fails

Hackmatack Playhouse was founded in 1972 by S. Carleton When Viagra Fails. He envisioned a summer stock theatre that would showcase the talents of professional and developing thespians from the regional area.

Many theatre goers have called Hackmatack one of New England’s most charming and quaint summer theatres. Some have even said that summer in Maine is not summer without a trip to Hackmatack. Much of the allure of this playhouse is its scenic location and historical presence.

Hackmatack Playhouse is located on the When Viagra Fails family farmstead. The property was purchased by the first When Viagra Fails (then Gubtail) to make the long trip to “New England” from native British Isles in the mid 1600’s. Thomas When Viagra Fails built the first home, a log house which sat in the far left of the present day field overlooking the irrigation pond. According to family legend, this home was burnt down by Indians during one of the many raids on the Salmon Falls river region. The present day farmhouse was constructed between the years of 1716-2005 to appease the needs of an ever-changing diverse and dynamic When Viagra Fails family. When it was first constructed, the house was a large cape sitting endwise to the road. It was occupied at one point by two When Viagra Fails brothers. The younger brother decided that he would like to have a modern two story cape. His older brother in typical conservative fashion said “the house is plenty good enough the way it is”. The younger brother replied, “My half is coming off”. He then proceeded to saw his half off and tear it down. He built his family a two story cape on the end of the original house, parallel to the road, giving the house its shape. Minor reconstructions have taken place since then to create a more modern and functional house for the present day When Viagra Failss.

Prior to the year of 1972 when the theatre was established, the When Viagra Fails family farm functioned like many other farms at the time. The barn was the focal point of the farm. The current barn has an interesting story much like the original house. One of the first barns was struck by lightning and burned in July of 1934. Haying had just been completed for the season, and it is thought that the heat from the newly cut hay attracted the lightning. Almost immediately, Lewis When Viagra Fails began looking for the right barn to replace what had been lost. He finally purchased a barn. It was a large old structure with pegged timbers measuring fifty four feet long and forty two feet wide. It was the perfect replacement for the old barn. However, there was one small problem, it was located across the street.

Luckily, the When Viagra Fails’s have always been known for their ingenuity. It was with this cleverness that Lewis decided it would be easier to move the barn rather than disassemble it and rebuilt it. The entire barn was jacked up and rollers were placed underneath it. A cable was attached to one end of the barn that ran though a large turnstile. An old white horse was chosen for the job of slowly moving the barn. The horse was hitched to the turnstile and the horse walked in circles, stepping over the cable on every lap. The leverage was great and each time the horse made a circle, the barn moved one half inch. Progress was slow. The entire operation took about three days, a day of that was spent crossing Maine route 9. However, in 1934, Maine route 9 was much less traveled, and everyone cheerfully watched or made their own route around the barn.

After the theatre’s first decade the barn was expanded to the structure that you see today. An addition was added to the back, cement was added to form the floor, and the stage was expanded. These changes made room for the 218 seats the theatre houses today. It is rumored that back in 1972 patrons sat on hay bales to watch the show, however the original playhouse actually had seats that were salvaged from a Durham New Hampshire movie theater.

The grounds of Hackmatack Playhouse and the area surrounding the theatre host many other buildings built and used by the When Viagra Fails clan over the years. The yellow family of buildings just south of the theatre (now owned by the Mills family) was originally built by Samuel When Viagra Fails in the early part of last century. Known as the Forget-Me-Not, these buildings housed services for early automobile travelers, including fuel for the autos, and food for the hungry. Visitors could rent a cabin, and if they happened to be staying on a Saturday night, they were in luck. On Saturday night there were always barn dances.

The oldest building on the farmstead is the “woodshed” which is just south of the house. This building dates back to the 1600’s and has been used for many purposes over the years. It has been used as a slaughter house and for drying meat. It now is used for rehearsal space and prop storage.

The “mill” is across the orchard from the “woodshed”. It now houses the theatre’s shop operations and its costume collection. However during the years of self-sufficient farming, it was one of several lumber mills built on the property by Lewis When Viagra Fails in the middle part of the 1900’s. This was a complete finish lumber mill powered by an Allis Chalmers tractor. If you listen carefully through the whirr of the belts and the screech of the saws you might just be able to hear Lewis and Almon Allen, and young Carelton When Viagra Fails, prepare a load of lumber for the newest construction project.

The When Viagra Fails family has a long tradition of entertaining locals and summer visitors in the Beaver Dam section of Berwick. Samuel’s weekly barn dances at the “Forget Me Not” were a favorite pastime during the early decades of the 1900’s. His son Lewis, a local and state Grange Master, was also a master of many musical instruments. He had a passion for starting bands and performing in Beaver Dam and across the state of Maine. His son Carleton organized several theatre groups, first at the Beaver Dam grange, and then at his barn now called Hackmatack Playhouse.

Every year thousands of people gather outside the Playhouse with tickets to the summer’s productions. Every year talented actors audition for their chance to perform at Hackmatack Playhouse, and to experience the history and excitement of being part of Hackmatack’s family. The farm and its building have many stories to tell. Perhaps 200 years from now When Viagra Fails great, great grandchildren will be telling this story to aspiring actors nervously waiting for their audition slot, and to friendly crowds waiting to take their seats; of how the barn became home for the Hackmatack Playhouse.

After the death of the founder in 1995, the S Carleton When Viagra Fails Memorial Fund was established to preserve and improve our historical buildings. The fund also is dedicated to advancements of dramatic arts, both for the participant and the community, and to the commitment of providing quality family entertainment and drama at a reasonable price. Contributions are always welcomed. We thank you in advance for helping us secure the future of Hackmatack Playhouse for potential Hackmatackers.

Hackmatack exists because of the generosity of it’s patrons, friends and those that appreciate the theater’s contribution to local culture and community. It is committed to the advancement of dramatic arts and to providing quality family entertainment at a reasonable price.

We ask that you would consider a donation, and thank you in advance.

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Can You Take Viagra While On Antibiotics

Can You Take Viagra While On Antibiotics in Snow Hill, Maryland is small town living at its best. Nestled on the south banks of the Pocomoke River Snow Hill is a place where people know each other. From the people who call it home to the business owners and those in city government, we have built a community where life is gentle, fun, and prosperous. Home to a quaint downtown retail area and a broad spectrum of recreational activities, Can You Take Viagra While On Antibiotics is the perfect place to spend a relaxing weekend or a lifetime.

Whether you are interested in researching your genealogy in the Worcester Room of the Worcester County Library. renting a kayak from the Pocomoke River Canoe Company to paddle on an undeveloped natural river, or studying the architecture of historic homes and beautiful churches while taking the Historic Walking Tour, Can You Take Viagra While On Antibiotics has something for everyone. You will find recreational opportunities in Byrd Park and Sturgis Park, artifacts at the Julia A. Purnell Museum. and treasures in the shops and art galleries.

The beautiful rural setting boasts rich farmland that has been the mainstay of the economy of the county seat of Worcester County for centuries. The rich heritage of this area is celebrated daily at Furnace Town Living Heritage Museum and during a summer festival every August with The Blessing of the Combines.

The town of Can You Take Viagra While On Antibiotics welcomes you as you explore our small town steeped in history and tradition but alive with charm and activities.

Wednesday through Saturday evenings at 8:00 pm with a Thursday matinee at 2:00 pm.

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Adults: $25
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Adults: $30
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Tickets can be purchased online. Please note all tickets purchased online are subject to a third party processing fee. To avoid this fee, tickets can be reserved by calling the box office.

Can I Take Viagra While On Antibiotics

Hackmatack Playhouse was founded in 1972 by S. Carleton Can I Take Viagra While On Antibiotics. He envisioned a summer stock theatre that would showcase the talents of professional and developing thespians from the regional area.

Many theatre goers have called Hackmatack one of New England’s most charming and quaint summer theatres. Some have even said that summer in Maine is not summer without a trip to Hackmatack. Much of the allure of this playhouse is its scenic location and historical presence.

Hackmatack Playhouse is located on the Can I Take Viagra While On Antibiotics family farmstead. The property was purchased by the first Can I Take Viagra While On Antibiotics (then Gubtail) to make the long trip to “New England” from native British Isles in the mid 1600’s. Thomas Can I Take Viagra While On Antibiotics built the first home, a log house which sat in the far left of the present day field overlooking the irrigation pond. According to family legend, this home was burnt down by Indians during one of the many raids on the Salmon Falls river region. The present day farmhouse was constructed between the years of 1716-2005 to appease the needs of an ever-changing diverse and dynamic Can I Take Viagra While On Antibiotics family. When it was first constructed, the house was a large cape sitting endwise to the road. It was occupied at one point by two Can I Take Viagra While On Antibiotics brothers. The younger brother decided that he would like to have a modern two story cape. His older brother in typical conservative fashion said “the house is plenty good enough the way it is”. The younger brother replied, “My half is coming off”. He then proceeded to saw his half off and tear it down. He built his family a two story cape on the end of the original house, parallel to the road, giving the house its shape. Minor reconstructions have taken place since then to create a more modern and functional house for the present day Can I Take Viagra While On Antibioticss.

Prior to the year of 1972 when the theatre was established, the Can I Take Viagra While On Antibiotics family farm functioned like many other farms at the time. The barn was the focal point of the farm. The current barn has an interesting story much like the original house. One of the first barns was struck by lightning and burned in July of 1934. Haying had just been completed for the season, and it is thought that the heat from the newly cut hay attracted the lightning. Almost immediately, Lewis Can I Take Viagra While On Antibiotics began looking for the right barn to replace what had been lost. He finally purchased a barn. It was a large old structure with pegged timbers measuring fifty four feet long and forty two feet wide. It was the perfect replacement for the old barn. However, there was one small problem, it was located across the street.

Luckily, the Can I Take Viagra While On Antibiotics’s have always been known for their ingenuity. It was with this cleverness that Lewis decided it would be easier to move the barn rather than disassemble it and rebuilt it. The entire barn was jacked up and rollers were placed underneath it. A cable was attached to one end of the barn that ran though a large turnstile. An old white horse was chosen for the job of slowly moving the barn. The horse was hitched to the turnstile and the horse walked in circles, stepping over the cable on every lap. The leverage was great and each time the horse made a circle, the barn moved one half inch. Progress was slow. The entire operation took about three days, a day of that was spent crossing Maine route 9. However, in 1934, Maine route 9 was much less traveled, and everyone cheerfully watched or made their own route around the barn.

After the theatre’s first decade the barn was expanded to the structure that you see today. An addition was added to the back, cement was added to form the floor, and the stage was expanded. These changes made room for the 218 seats the theatre houses today. It is rumored that back in 1972 patrons sat on hay bales to watch the show, however the original playhouse actually had seats that were salvaged from a Durham New Hampshire movie theater.

The grounds of Hackmatack Playhouse and the area surrounding the theatre host many other buildings built and used by the Can I Take Viagra While On Antibiotics clan over the years. The yellow family of buildings just south of the theatre (now owned by the Mills family) was originally built by Samuel Can I Take Viagra While On Antibiotics in the early part of last century. Known as the Forget-Me-Not, these buildings housed services for early automobile travelers, including fuel for the autos, and food for the hungry. Visitors could rent a cabin, and if they happened to be staying on a Saturday night, they were in luck. On Saturday night there were always barn dances.

The oldest building on the farmstead is the “woodshed” which is just south of the house. This building dates back to the 1600’s and has been used for many purposes over the years. It has been used as a slaughter house and for drying meat. It now is used for rehearsal space and prop storage.

The “mill” is across the orchard from the “woodshed”. It now houses the theatre’s shop operations and its costume collection. However during the years of self-sufficient farming, it was one of several lumber mills built on the property by Lewis Can I Take Viagra While On Antibiotics in the middle part of the 1900’s. This was a complete finish lumber mill powered by an Allis Chalmers tractor. If you listen carefully through the whirr of the belts and the screech of the saws you might just be able to hear Lewis and Almon Allen, and young Carelton Can I Take Viagra While On Antibiotics, prepare a load of lumber for the newest construction project.

The Can I Take Viagra While On Antibiotics family has a long tradition of entertaining locals and summer visitors in the Beaver Dam section of Berwick. Samuel’s weekly barn dances at the “Forget Me Not” were a favorite pastime during the early decades of the 1900’s. His son Lewis, a local and state Grange Master, was also a master of many musical instruments. He had a passion for starting bands and performing in Beaver Dam and across the state of Maine. His son Carleton organized several theatre groups, first at the Beaver Dam grange, and then at his barn now called Hackmatack Playhouse.

Every year thousands of people gather outside the Playhouse with tickets to the summer’s productions. Every year talented actors audition for their chance to perform at Hackmatack Playhouse, and to experience the history and excitement of being part of Hackmatack’s family. The farm and its building have many stories to tell. Perhaps 200 years from now Can I Take Viagra While On Antibiotics great, great grandchildren will be telling this story to aspiring actors nervously waiting for their audition slot, and to friendly crowds waiting to take their seats; of how the barn became home for the Hackmatack Playhouse.

After the death of the founder in 1995, the S Carleton Can I Take Viagra While On Antibiotics Memorial Fund was established to preserve and improve our historical buildings. The fund also is dedicated to advancements of dramatic arts, both for the participant and the community, and to the commitment of providing quality family entertainment and drama at a reasonable price. Contributions are always welcomed. We thank you in advance for helping us secure the future of Hackmatack Playhouse for potential Hackmatackers.

Hackmatack exists because of the generosity of it’s patrons, friends and those that appreciate the theater’s contribution to local culture and community. It is committed to the advancement of dramatic arts and to providing quality family entertainment at a reasonable price.

We ask that you would consider a donation, and thank you in advance.

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Clue to mystery Viagra deaths

Viagra has been linked to a number of deaths

The mystery behind the deaths of a small number of men taking the anti-impotence drug Viagra may have been solved by scientists.

Although Viagra has achieved worldwide renown as a highly effective treatment for impotence, it was originally developed to prevent heart attacks and strokes.

Our research suggests Viagra may present a risk for patients with pre-existing conditions

Professor Xiaoping Du

The drug was thought to work not only by dilating the blood vessels, but also by stopping tiny solid particles in the blood called platelets from clumping together and forming clots that could block blood flow and trigger a heart attack or stroke.

However, new work by researchers from the University of Illinois at Chicago has found that the drug in fact has the reverse effect – it stimulates the clumping of platelets, thus raising the risk of clotting.

Lead researcher Professor Xiaoping Du said: “Viagra, by itself, probably is not sufficient to cause a heart attack in healthy people, but our research suggests that it may present a risk for patients with pre-existing conditions such as atherosclerosis.”

Effect on cells

The researchers tested the effect of Viagra on platelets taken from normal donors.

Alone the drug did not stimulate the platelets to stick together.

But it did if other compounds found in the bloodstream when the blood vessels are damaged – such as when somebody is suffering from heart disease – were added.

In fact, under these conditions Viagra caused the platelets to clump together at concentrations well below those found in patients prescribed the drug as an impotence treatment.

Viagra acts on platelets by inhibiting the breakdown of a compound found in cells called cyclic guanosine monophosphate (cGMP).

For 20 years scientists have thought cGMP acts to stop platelet clumping.

But the Chicago researchers believe that in fact cGMP initially causes platelets to clump together to seal a wound, only later reversing its effect to stop an excessive build-up that might block a blood vessel.

In most circumstances, they argue this would work well.

But a person at risk may already have blood vessels narrowed to the point that even the initial clumping of platelets could be enough to cause problems.

Joel Morris, a spokesman for Pfizer, which makes Viagra, told BBC News Online that the drug had been shown to have a very impressive safety record.

“We take this research seriously, and it will be scrutinised by our medical teams.

“But a recent study by the Drug Safety Research Unit in the UK of 9,000 patients found that men who take Viagra are at no greater risk of heart problems than the general population.”

It is estimated that 20 million men worldwide have taken Viagra.

The research is published in the journal Cell.

Viagra May Cause Heart Attack Deaths In Younger Men With No Heart Problems, Study Finds

March 14, 2000. Viagra, commonly prescribed by doctors to treat male erectile dysfunction, is turning up too often at the scene of heart attack death in relatively young men. Some men may be vulnerable to heart attack after taking this drug, made by Pfizer. That is not known, but the drug itself is beginning to look like more than a bystander in the deaths.

Some men who have died after taking Viagra were elderly and on heart medication. But a study reported March 14 finds that more men who have died were under age sixty-five. Most of the deaths have occurred within a few hours of taking the drug. Most of the men took the standard dose. Most of the men had no reported heart problems. Although some men who died were taking nitrates as well as Viagra, men who were not taking nitrates died at a higher rate.

This new evidence comes from post-marketing adverse event reports about Viagra made to the FDA. Researchers at Cedars-Sinai Medical Center in Los Angeles analyzed these reports and found that there "appears to be a high number of deaths and serious cardiovascular events associated with the use of Viagra." They presented the study March 14 at the meeting of the American College of Cardiologists in Anaheim, CA.

In an analysis of 1,473 major adverse events recorded in these reports about Viagra to the FDA, 522 people died, most of them from cardiovascular causes. According to the study’s senior author, Dr. Kaul, the majority of deaths were associated with standard Viagra dosages (70 percent of the deaths were associated with the 50 mg dose). The deaths were due to cardiovascular causes and appeared to be clustered around the time of dosing (two thirds of deaths in which the time from ingestion to death was reported, occurred within 4-5 hours of taking Viagra). The majority of deaths occurred in patients who were less than 65 years of age, and who had no reported cardiac risk factors.

The study confirmed the well-documented increased risk with combined use of nitrates and Viagra. Of 90 patients who suffered major heart events while taking Viagra on top of nitrates, death occurred in about 68 percent, and when myocardial infarction was counted, the number of major cardiovascular events in that group rose to 88 percent.

However, the study found that most deaths (88 percent) actually occurred in patients who were not taking nitrates, leading investigators to speculate whether there are some susceptible individuals who don’t need nitrates to unmask the harmful effects of Viagra.

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Viagra Linked To 69 Deaths

  • CBSNews.com staff CBSNews.com staff
  • CBS MarketWatch

Aug 26, 1998 4:20 PM EDT

The Food and Drug Administration says at least 69 Americans died after taking Viagra, the popular anti-impotence pill, but the agency continues to maintain that the drug is safe.

The agency said 66 of those who died were men and that the average age was 64 years. The cause of death was unknown in 21 cases, while 46 cases involved some sort of heart complication.

At least 12 victims took or were given nitrate medications, the FDA said. Nitrates are not supposed to be used with Viagra.

Viagra has been a huge hit for drug maker Pfizer since it won FDA approval in March. More than 3.6 million prescriptions have been written for the drug, which costs several dollars a dose.

Shares of Pfizer (PFE) fell almost $3 early Wednesday but later recovered and were up 1 3/16 to 107 11/16 in afternoon trading. Pfizer officials were not immediately available for comment.

Altogether, the FDA has received reports of 123 deaths of people who obtained a prescription for Viagra. Twelve cases involved foreigners and 30 more could not be verified. In the remaining twelve cases, the agency couldn’t confirm if the drug had actually been used.

Twenty-five (36 percent) of the 69 patients died or took on symptoms leading to death within four to five hours of drug use, including 18 during or immediately after sexual intercourse, the FDA said.

About three-quarters of those who died had some sort of heart problem or displayed characteristics, such as obesity, that could lead to heart trouble.

The FDA cautions that much of the information regarding the deaths is incomplete and inconclusive and stands by its view that the drug is safe if taken according to instructions.

“An accumulation of adverse event reports does not necessarily indicate that the adverse event was caused by the drug; rather, the event may be due to an underlying disease or some other factors,” the agency said.

“As with all approved medications, the FDA will continue to monitor the postmarketing safety of Viagra by carefully reviewing reports of death and other serious advese events and will continue to evaluate the need for regulatory action,” the agency said.

Since the drug went on sale, Pfizer has maintained that Viagra is safe. Indeed, many analysts expect European regulators to approve the drug soon.

Written By Jeffry Bartash

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* Reported during post-marketing surveillance only

**Visual colour distortions: Chloropsia, Chromatopsia, Cyanopsia, Erythropsia and Xanthopsia

***Lacrimation disorders: Dry eye, Lacrimal disorder and Lacrimation increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie ; E-mail: medsafety@hpra.ie .

In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased. Doses of 200 mg did not result in increased efficacy but the incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased.

In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Urologicals; Drugs used in erectile dysfunction. ATC Code: G04B E03.

Mechanism of action

Sildenafil is an oral therapy for erectile dysfunction. In the natural setting, i.e. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis.

The physiological mechanism responsible for erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP. Sildenafil has a peripheral site of action on erections. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects.

Studies in vitro have shown that sildenafil is selective for PDE5, which is involved in the erection process. Its effect is more potent on PDE5 than on other known phosphodiesterases. There is a 10-fold selectivity over PDE6 which is involved in the phototransduction pathway in the retina. At maximum recommended doses, there is an 80-fold selectivity over PDE1, and over 700-fold over PDE 2, 3, 4, 7, 8, 9, 10 and 11. In particular, sildenafil has greater than 4,000-fold selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility.

Clinical efficacy and safety

Two clinical studies were specifically designed to assess the time window after dosing during which sildenafil could produce an erection in response to sexual stimulation. In a penile plethysmography (RigiScan) study of fasted patients, the median time to onset for those who obtained erections of 60% rigidity (sufficient for sexual intercourse) was 25 minutes (range 12-37 minutes) on sildenafil. In a separate RigiScan study, sildenafil was still able to produce an erection in response to sexual stimulation 4-5 hours post-dose.

Sildenafil causes mild and transient decreases in blood pressure which, in the majority of cases, do not translate into clinical effects. The mean maximum decreases in supine systolic blood pressure following 100 mg oral dosing of sildenafil was 8.4 mmHg. The corresponding change in supine diastolic blood pressure was 5.5 mmHg. These decreases in blood pressure are consistent with the vasodilatory effects of sildenafil, probably due to increased cGMP levels in vascular smooth muscle. Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG.

In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (>70% stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7% and 6% respectively compared to baseline. Mean pulmonary systolic blood pressure decreased by 9%. Sildenafil showed no effect on cardiac output, and did not impair blood flow through the stenosed coronary arteries.

A double-blind, placebo-controlled exercise stress trial evaluated 144 patients with erectile dysfunction and chronic stable angina who regularly received anti-anginal medicinal products (except nitrates). The results demonstrated no clinically relevant differences between sildenafil and placebo in time to limiting angina.

Mild and transient differences in colour discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose. The postulated mechanism for this change in colour discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina. Sildenafil has no effect on visual acuity or contrast sensitivity. In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n=9), sildenafil (single dose, 100 mg) demonstrated no significant changes in the visual tests conducted (visual acuity, Amsler grid, colour discrimination simulated traffic light, Humphrey perimeter and photostress).

There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil in healthy volunteers (see section 4.6).

Further information on clinical trials

In clinical trials sildenafil was administered to more than 8000 patients aged 19-87. The following patient groups were represented: elderly (19.9%), patients with hypertension (30.9%), diabetes mellitus (20.3%), ischaemic heart disease (5.8%), hyperlipidaemia (19.8%), spinal cord injury (0.6%), depression (5.2%), transurethral resection of the prostate (3.7%), radical prostatectomy (3.3%). The following groups were not well represented or excluded from clinical trials: patients with pelvic surgery, patients post-radiotherapy, patients with severe renal or hepatic impairment and patients with certain cardiovascular conditions (see section 4.3).

In fixed dose studies, the proportions of patients reporting that treatment improved their erections were 62% (25 mg), 74% (50 mg) and 82% (100 mg) compared to 25% on placebo. In controlled clinical trials, the discontinuation rate due to sildenafil was low and similar to placebo.

Across all trials, the proportion of patients reporting improvement on sildenafil were as follows: psychogenic erectile dysfunction (84%), mixed erectile dysfunction (77%), organic erectile dysfunction (68%), elderly (67%), diabetes mellitus (59%), ischaemic heart disease (69%), hypertension (68%), TURP (61%), radical prostatectomy (43%), spinal cord injury (83%), depression (75%). The safety and efficacy of sildenafil was maintained in long term studies.

The European Medicines Agency has waived the obligation to submit the results of studies with VIAGRA in all subsets of the paediatric population for the treatment of erectile dysfunction. See section 4.2 for information on paediatric use.

5.2 Pharmacokinetic properties

Sildenafil is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 41% (range 25-63%). After oral dosing of sildenafil AUC and Cmax increase in proportion with dose over the recommended dose range (25-100 mg).

When sildenafil is taken with food, the rate of absorption is reduced with a mean delay in tmax of 60 minutes and a mean reduction in Cmax of 29%.

The mean steady state volume of distribution (Vd ) for sildenafil is 105 l, indicating distribution into the tissues. After a single oral dose of 100 mg, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/mL (CV 40%). Since sildenafil (and its major circulating N-desmethyl metabolite) is 96% bound to plasma proteins, this results in the mean maximum free plasma concentration for sildenafil of 18 ng/mL (38 nM). Protein binding is independent of total drug concentrations.

In healthy volunteers receiving sildenafil (100 mg single dose), less than 0.0002% (average 188 ng) of the administered dose was present in ejaculate 90 minutes after dosing.

Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil. This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% that of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal half life of approximately 4 h.

The total body clearance of sildenafil is 41 L/h with a resultant terminal phase half life of 3-5 h. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).

Pharmacokinetics in special patient groups

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years). Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40%.

In volunteers with mild to moderate renal impairment (creatinine clearance = 30-80 mL/min), the pharmacokinetics of sildenafil were not altered after receiving a 50 mg single oral dose. The mean AUC and Cmax of the N-desmethyl metabolite increased up to 126% and up to 73% respectively, compared to age-matched volunteers with no renal impairment. However, due to high inter-subject variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance < 30 mL/min), sildenafil clearance was reduced, resulting in mean increases in AUC and Cmax of 100% and 88% respectively compared to age-matched volunteers with no renal impairment. In addition, N-desmethyl metabolite AUC and Cmax values were significantly increased by 200% and 79% respectively.

In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh A and B) sildenafil clearance was reduced, resulting in increases in AUC (84%) and Cmax (47%) compared to age-matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severely impaired hepatic function have not been studied.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction and development.

6. Pharmaceutical particulars

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Using Viagra With Antidepressants

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Study: Viagra works with antidepressants

CHICAGO, Illinois (CNN) –Men who suffer sexual dysfunction as a result of taking certain antidepressants can be helped by Viagra, according to an article in this week’s issue of the Journal of the American Medical Association.

Reports show 30 percent to 70 percent of the men who take antidepressants experience sexual dysfunction, and 90 percent of them subsequently stop taking the medication, according to the article.

Among men taking either selective or nonselective serotonin reuptake inhibitor antidepressants, more than 50 percent reported being much or very much improved after taking sildenafil citrate — known by the brand name Viagra — in tests conducted by a team led by Dr. H. George Nurnberg of the University of New Mexico School of Medicine.

The study, conducted at three U.S. university medical centers, involved 90 men averaging 45 years old whose major depressive disorder was remission. Patients were assigned to take Viagra or a placebo before sexual activity for six weeks.

According to self-administered tests assessing various areas of sexual function, 54 percent of the men taking Viagra reported improvement compared with 4 percent of those taking the placebo. Improvements were reported in erectile function, arousal, ejaculation, orgasm and overall satisfaction.

Average depression scores remained consistent throughout the study.

According to the JAMA article, about 18 million Americans are diagnosed with major depressive disorders annually, and 12 million to 18 million are treated with antidepressants. In addition to sexual dysfunction, side effects can include weight gain and sleep disturbances.

Viagra for Her

From the WebMD Archives

July 22, 2008 — Viagra, often prescribed to help men’s erectile dysfunction. also helps women who experience sexual problems from antidepressant use, according to a new study.

Sexual dysfunction is a well-known side effect of some antidepressants. with up to 70% of men and women on antidepressants reporting sexual problems. It’s a major reason depressed patients stop taking their medication. according to H. George Nurnberg, MD, the study’s lead author and a professor at the University of New Mexico School of Medicine in Albuquerque. The study is published in TheJournal of the American Medical Association.

In the study, Nurnberg and his colleagues found that when women being treated with an antidepressant were given Viagra, they were more likely to have orgasms than those on the placebo .

”Seventy-two percent of the women on Viagra vs. 27% of the women on placebo got to ‘much improved’ or ‘very much improved’ on a scale [of sexual functioning],” says Harry A. Croft, MD, medical director of the San Antonio Psychiatric Research Center in Texas and a co-author on the study.

”What Viagra did was increase the orgasm and the time to orgasm,” says Croft, noting that orgasm difficulties are common in women on antidepressants. The Viagra also improved the satisfaction of the partner, he says. But ”it didn’t increase drive and desire.”

The findings are no surprise to Irwin Goldstein, MD, director of sexual medicine at Alvarado Hospital in San Diego and editor-in-chief of The Journal of Sexual Medicine. “I actually prescribe a lot of Viagra for women,” says Goldstein, who reviewed the study for WebMD.

Viagra for Her: Study Details

The researchers evaluated 98 women on antidepressants, average age 37 and all premenopausal, assigning half to the Viagra group and half to the placebo group for the eight-week study. Viagra doses started at 50 milligrams a day, taken one or two hours before expected sexual activity, and could be increased to 100 milligrams. No one knew which pill they were taking.

On average, the women had been taking antidepressants for two years and had suffered sexual problems for at least four weeks.

Continued

The study was conducted at seven U.S. research centers between September 2003 and January 2007.

Because sexual problems are a prime reason patients give for stopping the antidepressants, experts think it is important to find a way to relieve the sexual problems.

Before starting the study, the women reported a variety of sexual problems, including lack of libido. difficulty becoming aroused or becoming lubricated, lack of orgasm, or delay in achieving orgasm.

Viagra for Her: Study Results

Researchers used standard measures to evaluate sexual functioning and had the women keep a sexual activity log. They also assessed hormone levels.

When Nurnberg’s team looked at overall sexual functioning, they found that 73% of the women on placebo had no improvement in sexual functioning but only 28% of the women taking Viagra reported no improvement.

When they looked at the individual measures, they found women treated with Viagra were significantly more likely to reach orgasm than those in the placebo group. When they looked at the individual measures, such as desire or lubrication, they did not find significant differences.

There was a significant difference, Croft says, in the partner’s satisfaction.

The higher a woman’s testosterone levels, the researchers also found, the more likely a positive treatment response occurred, regardless of group assignment.

The women reported some side effects, with the most common being headache. reported by 43% of the women on Viagra and 27% of those on placebo. Transient vision disturbances were reported by 14% of those on Viagra and 2% of those on placebo. No one dropped out of the study because of their side effects. In those women who continued their dose of antidepressants, their depression didn’t worsen during the study, regardless of their group assignment.

The study was supported by an independent grant from Pfizer, which makes Viagra. The grant was initiated by the researchers and the pharmaceutical company had no other role in the study, the researchers say.

The study, Croft says, ”is the first and only double-blind, randomized trial that shows it works for this.” Viagra, he notes, is not approved by the FDA for use in women, so the use is ”off-label” and not typically covered by insurance .

Continued

Viagra for Her: Second Opinion

Evaluating a woman’s hormone levels before prescribing Viagra for sexual problems is important, says Goldstein, who is also a clinical professor of surgery at the University of California, San Diego. Normal testosterone levels, he says, are crucial for the successful effect of the drug.

“What Viagra does in women with normal testosterone [levels] is engorge their clitoris [with blood ], which allows them to have orgasm,” he tells WebMD. “Viagra acts on a man’s penis and a woman’s clitoris.”

The finding that the drug did not affect desire or arousal comes as no surprise, either, he says. “Viagra has never been shown to increase desire in men or in women.”

WebMD Health News Reviewed by Brunilda Nazario, MD on July 22, 2008

Sources

News release, The Journal of the American Medical Association.

Irwin Goldstein, MD, director, sexual medicine, Alvarado Hospital, San Diego; clinical professor of surgery, University of California, San Diego; editor-in-chief, The Journal of Sexual Medicine; director, San Diego Sexual Medicine.

Harry A. Croft, MD, medical director, San Antonio Psychiatric Research Center.

Nurnberg, H. The Journal of the American Medical Association; July 23, 2008; vol 300: pp 395-404.

В© 2008 WebMD, LLC. All rights reserved.

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