Companies that purchase structured settlements will buy out your future payments in exchange for advancing you money now, minus their fee. These companies can provide needed cash in a lump sum, far more than your monthly allotment, if that is what you choose to do, instead of staying on the monthly or yearly plan that your structured settlement sets forth.
If you have been involved in a lawsuit for personal injury, product defects, medical malpractice, or wrongful death of a family member, you may have mediated a settlement offer. Many times, since settlements in personal injury cases can be so large, the payouts are structured, or set up to be paid out in increments over time. This can be over several months, or years, and in some cases for a lifetime of payments. This amounts to a guaranteed income for the person who has settled their lawsuit for monetary compensation.
When a large sum is spread out over many months, or years, there can be some tax advantages, and it does assure the recipient of future income. By taking a large lump sum all at once, the person who receives it gets a large amount of money all at one time, with nothing set aside for future expenses. People who are hurt and have ongoing medical expenses will need a lot of money for their future care, and a structured settlement is good for that purpose.
Sometimes, however, the recipient has a good reason for wanting a large amount of cash immediately, instead of the smaller amounts over time. They might want to go to college, or buy a house, or have another good reason for needing some, or all, of their settlement money up front. This is a good time to consult the companies who purchase structured settlements.
There is a fee charged, from around 10 to 30 percent of the money advanced, and the transaction is similar to getting a payday advance, except for a lot more money, and the repayments go directly to the company that bought out your settlement. It is possible to have them purchase just a part of your settlement, so you get a lump sum now, and whatever remains would continue as before, but in a lesser amount. You would still get some future income, just not as much.
When deciding to sell a settlement, it may be necessary to obtain court approval. That is one way that the legal system acts on your behalf, to be sure you are doing this for a good reason, because the structured payment system was decided upon for a good reason also. Take time to examine several companies who purchase structured settlements before you take action. Oftentimes, smaller competitors offer better rates and terms than the big names like Peachtree and JG Wentworth.
For more information or a free quote on purchasing your structured settlement, contact Professional Settlement Buyers
Article Source: http://EzineArticles.com/?expert=David_Millers
Tuesday, October 19, 2010
Viagra
Beyond Viagra®: The Latest Treatments For Erectile Dysfunction
By Phil Micans, PharmB
Since the advent and commercial availability of Sildenafil Citrate in 1998, (known throughout the world to one-and-all as Viagra®), the market for treatments for erectile dysfunction has grown to become worth about $2 billion worldwide per annum. That is now projected to grow to $4 billion per year by the year 2004 and to an astonishing $6 billion per year by 2006! (1)
Results of recent surveys indicate that, on average, 15% of the male population has suffered from erectile dysfunction. As a strong indicator of its age-related increase, more than 50% of men over the age of 60 have varying degrees of erectile dysfunction (ED). So it may not be surprising that it is estimated that ED affects approximately 31 million men in the United States, and as a whole, there may be as many as 300 million men around the world suffering with ED! (1)
Therefore, to cash in on this huge and relatively new market, (at least in terms of its acceptance), it is no surprise to discover that numerous pharmaceutical companies are rushing to find new drugs and new methodology, to treat this sexual disease that is clearly an age-related disorder.
That is the subject of this article, we shan't get too bogged down in the psychology of impotence, or the social or economic impacts of such a "disease" and its treatments. What we shall concern ourselves with here are the pharmacokinetics, uses, interactions, effects and properties of these revolutionary new approaches to erectile dysfunction.
Viagra®: The Background
In order for us to ascertain the difference between the new treatments for ED when compared to Viagra®, it is first necessary to remind ourselves of the properties of Pfizer's stock market winner.
Viagra® is rapidly absorbed by mouth with a bio-availability of about 40% and peak concentrations of the chemical are in the blood within 30-120 minutes. (2) This has been one of the advantages for Viagra®, in that it is capable of being taken as a tablet and is relatively quick-acting. A convenient factor when perhaps one's partner won't wait forever!
The affects of Viagra® will last, on-average, for up to 4-hours and its metabolites are excreted in the faeces and urine. Viagra's affect is to inhibit an enzyme known as phosphodiesterase type-5 (PDE5), which naturally occurs in erectile tissue. PDE5 can break down cyclic GMP, the substance that is produced during sexual arousal and causes vascular and muscular changes that eventual lead to an erection. (2)
Therefore, men who produce too little cyclic GMP have problems obtaining and maintaining an erection, and men who produce too much PDE5 have problems obtaining and maintaining an erection.
Viagra® is well known to be contraindicated with organic nitrates. These are drugs that are often used to treat heart conditions such as hypotensive conditions, (low blood pressure). Viagra® appears to potentiate the effects of nitrates and therefore the two must not be taken concurrently. Furthermore, caution is advised for any patient using Viagra® who has a heart problem, even if they are not using nitrates for the condition. (2)
Viagra® dosages are usually 25mg to 100mg (50mg doses being the average), taken up to one hour before sexual intercourse. These dosages have produced side effects such as headache, flushing and dyspepsia. There have been some reports of disturbances, dizziness, and nasal congestion. Other rarer adverse effects reported include diarrhea, muscle pain, skin rashes, and urinary or respiratory-tract infection. (2)
Viagra® undoubtedly represents a very significant advance in the treatment of erectile dysfunction, but like most drugs it is not without its cautions, contraindications and potential side effects etc.
Alprostadil: Before Viagra®
Alprostadil is a drug that has been available for the treatment for ED years before Viagra® was even a twinkle in the eyes of the pharmacologists at Pfizer. Yet alprostadil has all but disappeared as a front line treatment for ED, this is despite the fact that some clinical trials indicate that alprostadil is as effective as Viagra®! So why would that be?
There is one simple answer, it was because of alprostadil's delivery method, but as we will learn, all that is about to change.
Alprostadil is a hormone like substance that is referred to as prostaglandin E1, a known and potent vasodilator (improver of blood flow). Alprostadil has the power to directly effect the tissue that it comes into contact with. (3) An erection essentially occurs when the blood vessels widen in the genital region and allow the corpus caverosum (Figure 1) to fill with blood, and hence the penis becomes erect and stiff. So, it is easy to see the direct role that alprostadil plays in the creation of an erection.
Originally, alprostadil was used to treat neonates with congenital heart defects. In order to treat this condition, alprostadil has to be directly injected into the heart region. (4) This is the same drug that is used to treat ED, and until very recently the delivery method was the same principle! In other words, brand name products such as Caverject® were injected into the flaccid tissue of the penis with fast acting results. Having spoken to some who have practiced this method, it is apparently quite painless, but the thought of having to place a needle into one's vital member is undoubtedly a "bridge too far" for most men! When one considers that this is meant to take place prior to love making, the two concepts/ thoughts just don't seem to go together!
Muse® was another development of alprostadil that tried to reduce the psychological aspects of the Caverject® delivery method. In essence, alprostadil was produced in intraurethral pellets; tiny tablets that can be inserted down into the eye of the penis with the aid of a minute insertion stick. But once again, the prospect of the delivery method, is still too much for most men, to consider it to be a worthwhile regular method of treatment for ED.
I think one can easily understand why Viagra® tablets have taken the world by storm!
Alprostadil: The Recent Development
But that may now all change with the concept of an alprostadil cream. Known as Befar®, (it may also be released later in some countries under the trade names of Alprox® and Topiglan®), this is the first topical cream in the world for the treatment of ED.
Currently, only commercially available in the Far East, Befar® has shown a clinical efficacy of up to 83% in patients with varying degrees of ED. (6) The cream itself has a onset action of 10-15 minutes and can continue on past 4-hours, (Figure 2) and is favorably comparable to the efficacy of the injectable alprostadil. (3, 19)
Figure 2
Due to Befar's direct application method (i.e. unlike Viagra®, Befar's actions are limited to the area of its application), the side effects induced by the application have to date been limited to transient warm and burning sensations.
So instead of using an injectable or intra-urethral pellet, Befar® cream rapidly and effectively promotes the permeation of alprostadil into the active site of the penis.
In one randomized, double-blind, placebo-controlled, multi-center clinical trial conducted in China (5), 157 ED patients aged 26 to 75 with various etiologies (psychogenic, organic and a combination of both), had an mean average ED history of 5-years. They all received treatment of Befar® or a placebo for 4-weeks. After the 4-week period, the Befar® patients improved their ability to have and maintain their erections by 68%, (it's noted as Primary Efficacy on Figure 3). The same patients also improved the frequency and strength of their erections by 75%, (it's noted as Global Efficacy on Figure 3). As can be seen on the same bar graph, this was a very significant difference over placebo.
Since then, another trial conducted in a 303 patient phase II clinical study in the United States has shown an impressive efficacy rate of 83% (6) Other clinical trials support similar results. (7)
During these trials, the side effects noted have been mild urethral pain, a feeling of urethral burning, penile fullness and redness at the application site. Most of the adverse events were mild and transient and all naturally resolved in a short time, without requiring any medical treatment.
Below, the chemical structure of alprostadil.
Surprisingly, Befar® may also be suitable for women too! One study, suggested that its data supported further investigation for topical alprostadil in the treatment of Female Sexual Arousal Disorder (20). For whist ED is now a recognised disorder, clitoral stimulation by vasodilatation is beginning to be seen as an important aid to sexual satisfaction for women.
If there is a disadvantage to Befar®, it may be the fact that it is very temperature sensitive. It is strongly recommend that Befar® (and for that matter all alprostadil creams), remain in a fridge at a temperature of 2 to 8 degrees Celsius. The manufacturer claims that Befar® may be kept at up to 25 degrees Celsius for up to 14-days (8), but it is clear that any temperature in excess of that can wreak the active ingredient within hours, perhaps even minutes if the temperature is higher still. It would appear that when temperature damage occurs that the product takes on a clear look, rather than its normal strong white creamy appearance. Once damaged by heat, Befar® has no active ingredient and hence no action.
So the shipment of Befar® to-and-from the patient and its compulsory storage conditions may be its weak-point, but from the pharmacological and medical viewpoint Befar® is clearly a major improvement over its earlier rivals.
Apomorphine: A New Approach
Apomorphine has been available as a drug for many years, but the first thing that we should clear up, is that even though it has the word "morphine" contained within its name, apomorphine is different to morphine, and has no morphine like affects. (2, 9) For example, where morphine is a sedative, apomorphine is a stimulant. As such, apomorphine does not have any of the affects associated with that narcotic.
Above, the chemical structure of apomorphine.
In the few countries where apomorphine is currently commercially available, (those being Australia, France, Italy, Netherlands, New Zealand and the United Kingdom), it is not a controlled substance. (2, 9, 10, 11, 12, 13)
Apomorphine is used in the control of Parkinson's disease. Specifically, for the senile dementia, it is delivered as a subcutaneous injection and it is used for Parkinson's because it is a dopamine agonist. In other words, it improves the levels of the neurotransmitter that is most affected in Parkinson's disease.
Later, it was noticed that Parkinson's patients were regularly having penile erections after their injection. These were clearly being induced by the apomorphine and it was soon realized that the drug may have an additional medical role. (14) Unsurprisingly, it wasn't long before it came to the attention of a pharmaceutical company. The first to bring an ED treatment containing apomorphine to the market, was Abbot Laboratories of the United Kingdom. Their development of a sublingual tablet, under the trade name of Uprima® is causing a great deal of interest.
Apomorphine: The Development Of Uprima®
Uprima® is a potent agonist of dopamine, specifically it acts upon D1 receptor sites, and this makes it different to the majority of ergot derived drugs for dopamine improvement, such as, bromocriptine, which normally target D2 receptors. (21) Accordingly, Uprima® doesn't act directly upon the penis like Viagra® or Befar®, but instead exerts its influence in the brain for arousal, pleasure and climax. Uprima® is known to act upon receptors in the hypothalamus, and that this can enhance erection by increasing the signals from the brain to begin the process. (9) Specifically, it induces selective activation in the nucleus paraventricularis, leading to erectogenic signals. (15)
It is this brain action that makes Uprima® a unique new approach to the treatment of ED. As Dr. Dula stated after being involved with a trial of 1472 patients using Uprima®; "From a urologist's perspective, it is important to understand that this is an entirely novel agent and works totally differently to Sildenafil (Ed.- Viagra®). It is a centrally-acting agent. What's more, apomorphine works fairly quickly, in 15-25 minutes. The main side effect is nausea, but over time and repeated dosages it rapidly dissipates. We think that it is a safe and efficacious treatment for erectile dysfunction." (19)
In a multi-center, double blind study (18), 520 patients (of an average median age of 54) took either 2mg, 4mg, 5mg, 6mg of apomorphine or a placebo. The number of attempts resulting in an erection firm enough for intercourse was recorded (Figure 4), along with the actual attempts resulting in intercourse.
As can been seen from figures 4 and 5, the most significant improvements over placebo are at dosages of 4mg to 6mg. However it was clear in this same trial and others (9, 15, 16, 18), that increased dosages also increase the likelihood of the most common side effect of nausea. (Figure 6) These side effects are reported to diminish with continued dosing. (15)
In fact, the most favorable risk/ benefit ratio is seen with a dose optimization regimen of 3mg, with the 3mg dose providing efficacy comparable to that of 4mg, but with fewer side effects (15).
Other side effects with Uprima® (9) include headache, dizziness, and flushing.
Contraindications with apomorphine include heart medications, (particularly those for hypertension) and because of potential synergy any other dopamine agonists such as bromocriptine, hydergine, deprenyl and L-dopa etc. Should you be taking such drugs, then always consult with your physician before embarking upon a concurrent use of apomorphine.
As stated earlier, the average dosages of Uprima® are 2mg or 3mg taken sublingual (dissolved under the tongue) about 15 minutes before sex. (Note that the advent of the sublingual tablet is the only way that apomorphine should be used to treat ED). The drug insert clearly states, that (like most ED drugs), a 3mg dose should not be repeated again within any 8-hour period.
Conclusion:
Uprima® represents a radical new departure in the treatment of ED. Rather than just stimulation to the penis for enhanced blood flow etc., for the first time brain receptor sites are being targeted for enhanced sexual performance.
I am confident that we are going to see other drugs being developed along similar lines in the coming months and years. I am also confident that similar (and even some of the same drugs), are eventually also going to be "approved" for sexual enhancement in females too.
References:
1. Business Week, February 25, 2002.
2. Micromedex Martindale, International Drug Information, June 2002
3. NexMed Research Papers, Hong Kong, June 2002.
4. Dinarevic S, Kurtagic S, Maksic H. "Use of prostaglandins in neonatal cardiology" Med Arh 2000;54(5-6):279-82.
5. Efficacy and safety of prostaglandin E1 cream in the treatment of erectile dysfunction. (Presented at the 9th world meeting on impotence research, Perth Australia).
6. "Topical cream for erectile dysfunction successfully completes phase II clinical studies." Urology, February 2001.
7. "Alprostadil, Alprox-TD, Befar, Femprox, prostaglandin E1 (NexMed)." Drugs R&D 1999 Dec;2(6):413-4.
8. NexMed of Hong Kong, Befar drug leaflet, June 2002.
9. Uprima drug leaflet, June 2002, Abbot Laboratories, United Kingdom.
10. Chemist & Druggist, June 2002 Volume 43, No. 6.
11. International Drug Directory, 2000, 17th Edition, MedPharma, Index Nominum.
12. British National Formulary, No. 42, September 2001.
13. Therapuetic Drugs, 2nd Edition, Churchill Livingstone.
14. O'Sullivan JD, Hughes AJ, "Apomorphine induced penile erections in Parkinson's disease." Mov. Disord. 1998 May, 13(3):536-9.
15. Altwein JE, Keuler FU, "Oral treatment of erectile dysfunction with apomorphine SL." Urol. Int. 2001; 67(4):257-63.
16. Mulhall JP, Bukofzer S, Edmonds AL, George M, "An open label, uncontrolled dose optimization study of sublingual apomorphine in erectile dysfunction." Clin. Ther. 2001 Aug;23(8):1260-71.
17. Giulano F, Allard J, Rampin O, Droupy S, Benoit G, Alexandre L, Bernabe J, "Pro-erectile effect of systemic apomorphine: Existence of a spinal site of action." J. Urol. 2002, Jan;167(1):402-6.
18. Padma-Nathan H, Auerbach S, Lewis R, Lewand M, Perdok R, "Efficacy and safety of apomorphine SL vs. placebo for male erectile dysfunction." Apomorphine study group.
19. Doctor's Guide, www.pslgroup.com
20. Islam A, Mitchel J, Rosen R, Phillips N, Ayers C, Ferguson D, Yeager J. "Topical alprostadil in the treatment of Female Sexual Arousal Disorder: a pilot study." : J Sex Marital Ther 2001 Oct-Dec;27(5):531-40.
21. Rascol O. "Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson's disease?" J. Neural. Transm. Suppl. 1999;55:33-45.
DISCLAIMER: ALL INFORMATION IS EDUCATIONAL AND PROVIDED UNDER IAS TERMS AND CONDITIONS. IT DOES NOT, AND SHOULD NOT, REPLACE THE ADVICE OF YOUR PHYSICIAN.
Last Updated: Friday, August 16, 2002
© 2002 International Antiaging Systems
By Phil Micans, PharmB
Since the advent and commercial availability of Sildenafil Citrate in 1998, (known throughout the world to one-and-all as Viagra®), the market for treatments for erectile dysfunction has grown to become worth about $2 billion worldwide per annum. That is now projected to grow to $4 billion per year by the year 2004 and to an astonishing $6 billion per year by 2006! (1)
Results of recent surveys indicate that, on average, 15% of the male population has suffered from erectile dysfunction. As a strong indicator of its age-related increase, more than 50% of men over the age of 60 have varying degrees of erectile dysfunction (ED). So it may not be surprising that it is estimated that ED affects approximately 31 million men in the United States, and as a whole, there may be as many as 300 million men around the world suffering with ED! (1)
Therefore, to cash in on this huge and relatively new market, (at least in terms of its acceptance), it is no surprise to discover that numerous pharmaceutical companies are rushing to find new drugs and new methodology, to treat this sexual disease that is clearly an age-related disorder.
That is the subject of this article, we shan't get too bogged down in the psychology of impotence, or the social or economic impacts of such a "disease" and its treatments. What we shall concern ourselves with here are the pharmacokinetics, uses, interactions, effects and properties of these revolutionary new approaches to erectile dysfunction.
Viagra®: The Background
In order for us to ascertain the difference between the new treatments for ED when compared to Viagra®, it is first necessary to remind ourselves of the properties of Pfizer's stock market winner.
Viagra® is rapidly absorbed by mouth with a bio-availability of about 40% and peak concentrations of the chemical are in the blood within 30-120 minutes. (2) This has been one of the advantages for Viagra®, in that it is capable of being taken as a tablet and is relatively quick-acting. A convenient factor when perhaps one's partner won't wait forever!
The affects of Viagra® will last, on-average, for up to 4-hours and its metabolites are excreted in the faeces and urine. Viagra's affect is to inhibit an enzyme known as phosphodiesterase type-5 (PDE5), which naturally occurs in erectile tissue. PDE5 can break down cyclic GMP, the substance that is produced during sexual arousal and causes vascular and muscular changes that eventual lead to an erection. (2)
Therefore, men who produce too little cyclic GMP have problems obtaining and maintaining an erection, and men who produce too much PDE5 have problems obtaining and maintaining an erection.
Viagra® is well known to be contraindicated with organic nitrates. These are drugs that are often used to treat heart conditions such as hypotensive conditions, (low blood pressure). Viagra® appears to potentiate the effects of nitrates and therefore the two must not be taken concurrently. Furthermore, caution is advised for any patient using Viagra® who has a heart problem, even if they are not using nitrates for the condition. (2)
Viagra® dosages are usually 25mg to 100mg (50mg doses being the average), taken up to one hour before sexual intercourse. These dosages have produced side effects such as headache, flushing and dyspepsia. There have been some reports of disturbances, dizziness, and nasal congestion. Other rarer adverse effects reported include diarrhea, muscle pain, skin rashes, and urinary or respiratory-tract infection. (2)
Viagra® undoubtedly represents a very significant advance in the treatment of erectile dysfunction, but like most drugs it is not without its cautions, contraindications and potential side effects etc.
Alprostadil: Before Viagra®
Alprostadil is a drug that has been available for the treatment for ED years before Viagra® was even a twinkle in the eyes of the pharmacologists at Pfizer. Yet alprostadil has all but disappeared as a front line treatment for ED, this is despite the fact that some clinical trials indicate that alprostadil is as effective as Viagra®! So why would that be?
There is one simple answer, it was because of alprostadil's delivery method, but as we will learn, all that is about to change.
Alprostadil is a hormone like substance that is referred to as prostaglandin E1, a known and potent vasodilator (improver of blood flow). Alprostadil has the power to directly effect the tissue that it comes into contact with. (3) An erection essentially occurs when the blood vessels widen in the genital region and allow the corpus caverosum (Figure 1) to fill with blood, and hence the penis becomes erect and stiff. So, it is easy to see the direct role that alprostadil plays in the creation of an erection.
Originally, alprostadil was used to treat neonates with congenital heart defects. In order to treat this condition, alprostadil has to be directly injected into the heart region. (4) This is the same drug that is used to treat ED, and until very recently the delivery method was the same principle! In other words, brand name products such as Caverject® were injected into the flaccid tissue of the penis with fast acting results. Having spoken to some who have practiced this method, it is apparently quite painless, but the thought of having to place a needle into one's vital member is undoubtedly a "bridge too far" for most men! When one considers that this is meant to take place prior to love making, the two concepts/ thoughts just don't seem to go together!
Muse® was another development of alprostadil that tried to reduce the psychological aspects of the Caverject® delivery method. In essence, alprostadil was produced in intraurethral pellets; tiny tablets that can be inserted down into the eye of the penis with the aid of a minute insertion stick. But once again, the prospect of the delivery method, is still too much for most men, to consider it to be a worthwhile regular method of treatment for ED.
I think one can easily understand why Viagra® tablets have taken the world by storm!
Alprostadil: The Recent Development
But that may now all change with the concept of an alprostadil cream. Known as Befar®, (it may also be released later in some countries under the trade names of Alprox® and Topiglan®), this is the first topical cream in the world for the treatment of ED.
Currently, only commercially available in the Far East, Befar® has shown a clinical efficacy of up to 83% in patients with varying degrees of ED. (6) The cream itself has a onset action of 10-15 minutes and can continue on past 4-hours, (Figure 2) and is favorably comparable to the efficacy of the injectable alprostadil. (3, 19)
Figure 2
Due to Befar's direct application method (i.e. unlike Viagra®, Befar's actions are limited to the area of its application), the side effects induced by the application have to date been limited to transient warm and burning sensations.
So instead of using an injectable or intra-urethral pellet, Befar® cream rapidly and effectively promotes the permeation of alprostadil into the active site of the penis.
In one randomized, double-blind, placebo-controlled, multi-center clinical trial conducted in China (5), 157 ED patients aged 26 to 75 with various etiologies (psychogenic, organic and a combination of both), had an mean average ED history of 5-years. They all received treatment of Befar® or a placebo for 4-weeks. After the 4-week period, the Befar® patients improved their ability to have and maintain their erections by 68%, (it's noted as Primary Efficacy on Figure 3). The same patients also improved the frequency and strength of their erections by 75%, (it's noted as Global Efficacy on Figure 3). As can be seen on the same bar graph, this was a very significant difference over placebo.
Since then, another trial conducted in a 303 patient phase II clinical study in the United States has shown an impressive efficacy rate of 83% (6) Other clinical trials support similar results. (7)
During these trials, the side effects noted have been mild urethral pain, a feeling of urethral burning, penile fullness and redness at the application site. Most of the adverse events were mild and transient and all naturally resolved in a short time, without requiring any medical treatment.
Below, the chemical structure of alprostadil.
Surprisingly, Befar® may also be suitable for women too! One study, suggested that its data supported further investigation for topical alprostadil in the treatment of Female Sexual Arousal Disorder (20). For whist ED is now a recognised disorder, clitoral stimulation by vasodilatation is beginning to be seen as an important aid to sexual satisfaction for women.
If there is a disadvantage to Befar®, it may be the fact that it is very temperature sensitive. It is strongly recommend that Befar® (and for that matter all alprostadil creams), remain in a fridge at a temperature of 2 to 8 degrees Celsius. The manufacturer claims that Befar® may be kept at up to 25 degrees Celsius for up to 14-days (8), but it is clear that any temperature in excess of that can wreak the active ingredient within hours, perhaps even minutes if the temperature is higher still. It would appear that when temperature damage occurs that the product takes on a clear look, rather than its normal strong white creamy appearance. Once damaged by heat, Befar® has no active ingredient and hence no action.
So the shipment of Befar® to-and-from the patient and its compulsory storage conditions may be its weak-point, but from the pharmacological and medical viewpoint Befar® is clearly a major improvement over its earlier rivals.
Apomorphine: A New Approach
Apomorphine has been available as a drug for many years, but the first thing that we should clear up, is that even though it has the word "morphine" contained within its name, apomorphine is different to morphine, and has no morphine like affects. (2, 9) For example, where morphine is a sedative, apomorphine is a stimulant. As such, apomorphine does not have any of the affects associated with that narcotic.
Above, the chemical structure of apomorphine.
In the few countries where apomorphine is currently commercially available, (those being Australia, France, Italy, Netherlands, New Zealand and the United Kingdom), it is not a controlled substance. (2, 9, 10, 11, 12, 13)
Apomorphine is used in the control of Parkinson's disease. Specifically, for the senile dementia, it is delivered as a subcutaneous injection and it is used for Parkinson's because it is a dopamine agonist. In other words, it improves the levels of the neurotransmitter that is most affected in Parkinson's disease.
Later, it was noticed that Parkinson's patients were regularly having penile erections after their injection. These were clearly being induced by the apomorphine and it was soon realized that the drug may have an additional medical role. (14) Unsurprisingly, it wasn't long before it came to the attention of a pharmaceutical company. The first to bring an ED treatment containing apomorphine to the market, was Abbot Laboratories of the United Kingdom. Their development of a sublingual tablet, under the trade name of Uprima® is causing a great deal of interest.
Apomorphine: The Development Of Uprima®
Uprima® is a potent agonist of dopamine, specifically it acts upon D1 receptor sites, and this makes it different to the majority of ergot derived drugs for dopamine improvement, such as, bromocriptine, which normally target D2 receptors. (21) Accordingly, Uprima® doesn't act directly upon the penis like Viagra® or Befar®, but instead exerts its influence in the brain for arousal, pleasure and climax. Uprima® is known to act upon receptors in the hypothalamus, and that this can enhance erection by increasing the signals from the brain to begin the process. (9) Specifically, it induces selective activation in the nucleus paraventricularis, leading to erectogenic signals. (15)
It is this brain action that makes Uprima® a unique new approach to the treatment of ED. As Dr. Dula stated after being involved with a trial of 1472 patients using Uprima®; "From a urologist's perspective, it is important to understand that this is an entirely novel agent and works totally differently to Sildenafil (Ed.- Viagra®). It is a centrally-acting agent. What's more, apomorphine works fairly quickly, in 15-25 minutes. The main side effect is nausea, but over time and repeated dosages it rapidly dissipates. We think that it is a safe and efficacious treatment for erectile dysfunction." (19)
In a multi-center, double blind study (18), 520 patients (of an average median age of 54) took either 2mg, 4mg, 5mg, 6mg of apomorphine or a placebo. The number of attempts resulting in an erection firm enough for intercourse was recorded (Figure 4), along with the actual attempts resulting in intercourse.
As can been seen from figures 4 and 5, the most significant improvements over placebo are at dosages of 4mg to 6mg. However it was clear in this same trial and others (9, 15, 16, 18), that increased dosages also increase the likelihood of the most common side effect of nausea. (Figure 6) These side effects are reported to diminish with continued dosing. (15)
In fact, the most favorable risk/ benefit ratio is seen with a dose optimization regimen of 3mg, with the 3mg dose providing efficacy comparable to that of 4mg, but with fewer side effects (15).
Other side effects with Uprima® (9) include headache, dizziness, and flushing.
Contraindications with apomorphine include heart medications, (particularly those for hypertension) and because of potential synergy any other dopamine agonists such as bromocriptine, hydergine, deprenyl and L-dopa etc. Should you be taking such drugs, then always consult with your physician before embarking upon a concurrent use of apomorphine.
As stated earlier, the average dosages of Uprima® are 2mg or 3mg taken sublingual (dissolved under the tongue) about 15 minutes before sex. (Note that the advent of the sublingual tablet is the only way that apomorphine should be used to treat ED). The drug insert clearly states, that (like most ED drugs), a 3mg dose should not be repeated again within any 8-hour period.
Conclusion:
Uprima® represents a radical new departure in the treatment of ED. Rather than just stimulation to the penis for enhanced blood flow etc., for the first time brain receptor sites are being targeted for enhanced sexual performance.
I am confident that we are going to see other drugs being developed along similar lines in the coming months and years. I am also confident that similar (and even some of the same drugs), are eventually also going to be "approved" for sexual enhancement in females too.
References:
1. Business Week, February 25, 2002.
2. Micromedex Martindale, International Drug Information, June 2002
3. NexMed Research Papers, Hong Kong, June 2002.
4. Dinarevic S, Kurtagic S, Maksic H. "Use of prostaglandins in neonatal cardiology" Med Arh 2000;54(5-6):279-82.
5. Efficacy and safety of prostaglandin E1 cream in the treatment of erectile dysfunction. (Presented at the 9th world meeting on impotence research, Perth Australia).
6. "Topical cream for erectile dysfunction successfully completes phase II clinical studies." Urology, February 2001.
7. "Alprostadil, Alprox-TD, Befar, Femprox, prostaglandin E1 (NexMed)." Drugs R&D 1999 Dec;2(6):413-4.
8. NexMed of Hong Kong, Befar drug leaflet, June 2002.
9. Uprima drug leaflet, June 2002, Abbot Laboratories, United Kingdom.
10. Chemist & Druggist, June 2002 Volume 43, No. 6.
11. International Drug Directory, 2000, 17th Edition, MedPharma, Index Nominum.
12. British National Formulary, No. 42, September 2001.
13. Therapuetic Drugs, 2nd Edition, Churchill Livingstone.
14. O'Sullivan JD, Hughes AJ, "Apomorphine induced penile erections in Parkinson's disease." Mov. Disord. 1998 May, 13(3):536-9.
15. Altwein JE, Keuler FU, "Oral treatment of erectile dysfunction with apomorphine SL." Urol. Int. 2001; 67(4):257-63.
16. Mulhall JP, Bukofzer S, Edmonds AL, George M, "An open label, uncontrolled dose optimization study of sublingual apomorphine in erectile dysfunction." Clin. Ther. 2001 Aug;23(8):1260-71.
17. Giulano F, Allard J, Rampin O, Droupy S, Benoit G, Alexandre L, Bernabe J, "Pro-erectile effect of systemic apomorphine: Existence of a spinal site of action." J. Urol. 2002, Jan;167(1):402-6.
18. Padma-Nathan H, Auerbach S, Lewis R, Lewand M, Perdok R, "Efficacy and safety of apomorphine SL vs. placebo for male erectile dysfunction." Apomorphine study group.
19. Doctor's Guide, www.pslgroup.com
20. Islam A, Mitchel J, Rosen R, Phillips N, Ayers C, Ferguson D, Yeager J. "Topical alprostadil in the treatment of Female Sexual Arousal Disorder: a pilot study." : J Sex Marital Ther 2001 Oct-Dec;27(5):531-40.
21. Rascol O. "Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson's disease?" J. Neural. Transm. Suppl. 1999;55:33-45.
DISCLAIMER: ALL INFORMATION IS EDUCATIONAL AND PROVIDED UNDER IAS TERMS AND CONDITIONS. IT DOES NOT, AND SHOULD NOT, REPLACE THE ADVICE OF YOUR PHYSICIAN.
Last Updated: Friday, August 16, 2002
© 2002 International Antiaging Systems
3 Things You Must Do Before You Submit To Article Directories
To all writers and non-writers out there, now is the time to start digging up those creative writing skills back.
With modern communication technology comes the popularity of information-based marketing, which is one of the oldest and most effective techniques in getting targeted prospects to sites and converting them into buyers. This is why article writing, submissions and publications are also getting popular.
There are already many tools that people can use to make the process of distributing their articles more easily. Though this is invaluable in getting the contents more exposure, which is only half of the story.
Let us take a look first at the common mistakes that some people make before submitting their contents to article directories:
1. Confusing the reason to promote the articles with the reason to write them.
In article writing, there are three key benefits why you are promoting them; branding, lead generation and promotion, which are all part of your optimization efforts.
But there is only one reason why you write an article, and that is to inform your audience. If the article is not focused on this primary and most important purpose, it will fail to achieve the three promotion benefits because no one will be interested in reading them.
You need to figure out first how to get people to read what is in your article, then make them click on your resource box. You can achieve this by producing better contents.
2. Failing to maximize the promotional opportunities of article marketing.
You may know already that your articles can help you generate additional links back to your site. But do you know that you can get more visitors and better search engine results from that same articles?
Mention keywords at strategic places. Just be sure not to overdo them. Some are even using anchor texts which is also an effective method. But it is important to know that majority of the directories are not able to support this.
Remember that is not only about the links back to your site. Part of doing well in your article marketing is getting picked up by publishers with a large number of audiences and gaining the ability of leveraging other brands because of the quality of your work. Better search engine results also are great benefits.
But these things do not put much money in your pocket. There are other factors that can turn your article marketing efforts into an opportunity that can boost your earnings. Not just increase the number of visitors to your site.
Start out with a plan and see to it that your article will serve the function that you intended it to have.
3. Publishing content that does not help your readers.
Maybe in the process of writing articles, you are thinking that all that is you wanted is links back to your site. And any visitors it can generate are fine.
Guess what? Not all article banks and directories are going to accept your content automatically. Oftentimes, they have some guidelines and specifications on the articles that they are accepting.
You can double the number of sites you can submit to by writing articles that the directories want to share with other people. All it takes is one publisher with a hundred thousand readers to increase your potential audience overnight.
Write the articles that publishers want in their publications if you want your article marketing to work the most effective way for you. This also means you have to obey the standard guidelines, spell checks, researching on a good topic and even hiring a writer to produce a good content on your behalf.
In the end, it is all really a matter of choice on your part. You can start getting a little exposure from increased links back but on a very basic level. Or enjoy massive exposure from a little extra time making quality contents.
It will be your choice. You may not be aware of the fact that an article submitted on directories is not meant to have the same level of exposure as highly-targeted content ones geared on a narrow group of people.
Learn the difference between these two and it will surely help you know what kinds of articles to write and to submit.
With modern communication technology comes the popularity of information-based marketing, which is one of the oldest and most effective techniques in getting targeted prospects to sites and converting them into buyers. This is why article writing, submissions and publications are also getting popular.
There are already many tools that people can use to make the process of distributing their articles more easily. Though this is invaluable in getting the contents more exposure, which is only half of the story.
Let us take a look first at the common mistakes that some people make before submitting their contents to article directories:
1. Confusing the reason to promote the articles with the reason to write them.
In article writing, there are three key benefits why you are promoting them; branding, lead generation and promotion, which are all part of your optimization efforts.
But there is only one reason why you write an article, and that is to inform your audience. If the article is not focused on this primary and most important purpose, it will fail to achieve the three promotion benefits because no one will be interested in reading them.
You need to figure out first how to get people to read what is in your article, then make them click on your resource box. You can achieve this by producing better contents.
2. Failing to maximize the promotional opportunities of article marketing.
You may know already that your articles can help you generate additional links back to your site. But do you know that you can get more visitors and better search engine results from that same articles?
Mention keywords at strategic places. Just be sure not to overdo them. Some are even using anchor texts which is also an effective method. But it is important to know that majority of the directories are not able to support this.
Remember that is not only about the links back to your site. Part of doing well in your article marketing is getting picked up by publishers with a large number of audiences and gaining the ability of leveraging other brands because of the quality of your work. Better search engine results also are great benefits.
But these things do not put much money in your pocket. There are other factors that can turn your article marketing efforts into an opportunity that can boost your earnings. Not just increase the number of visitors to your site.
Start out with a plan and see to it that your article will serve the function that you intended it to have.
3. Publishing content that does not help your readers.
Maybe in the process of writing articles, you are thinking that all that is you wanted is links back to your site. And any visitors it can generate are fine.
Guess what? Not all article banks and directories are going to accept your content automatically. Oftentimes, they have some guidelines and specifications on the articles that they are accepting.
You can double the number of sites you can submit to by writing articles that the directories want to share with other people. All it takes is one publisher with a hundred thousand readers to increase your potential audience overnight.
Write the articles that publishers want in their publications if you want your article marketing to work the most effective way for you. This also means you have to obey the standard guidelines, spell checks, researching on a good topic and even hiring a writer to produce a good content on your behalf.
In the end, it is all really a matter of choice on your part. You can start getting a little exposure from increased links back but on a very basic level. Or enjoy massive exposure from a little extra time making quality contents.
It will be your choice. You may not be aware of the fact that an article submitted on directories is not meant to have the same level of exposure as highly-targeted content ones geared on a narrow group of people.
Learn the difference between these two and it will surely help you know what kinds of articles to write and to submit.
3 Things To Do Prior To Submitting Articles
To all writers and non-writers out there, now is the time to start digging up those creative writing skills back.
With modern communication technology comes the popularity of information-based marketing, which is one of the oldest and most effective techniques in getting targeted prospects to sites and converting them into buyers. This is why article writing, submissions and publications are also getting popular.
There are already many tools that people can use to make the process of distributing their articles more easily. Though this is invaluable in getting the contents more exposure, which is only half of the story.
Let us take a look first at the common mistakes that some people make before submitting their contents to article directories:
1. Confusing the reason to promote the articles with the reason to write them.
In article writing, there are three key benefits why you are promoting them; branding, lead generation and promotion, which are all part of your optimization efforts.
But there is only one reason why you write an article, and that is to inform your audience. If the article is not focused on this primary and most important purpose, it will fail to achieve the three promotion benefits because no one will be interested in reading them.
You need to figure out first how to get people to read what is in your article, then make them click on your resource box. You can achieve this by producing better contents.
2. Failing to maximize the promotional opportunities of article marketing.
You may know already that your articles can help you generate additional links back to your site. But do you know that you can get more visitors and better search engine results from that same articles?
Mention keywords at strategic places. Just be sure not to overdo them. Some are even using anchor texts which is also an effective method. But it is important to know that majority of the directories are not able to support this.
Remember that is not only about the links back to your site. Part of doing well in your article marketing is getting picked up by publishers with a large number of audiences and gaining the ability of leveraging other brands because of the quality of your work. Better search engine results also are great benefits.
But these things do not put much money in your pocket. There are other factors that can turn your article marketing efforts into an opportunity that can boost your earnings. Not just increase the number of visitors to your site.
Start out with a plan and see to it that your article will serve the function that you intended it to have.
3. Publishing content that does not help your readers.
Maybe in the process of writing articles, you are thinking that all that is you wanted is links back to your site. And any visitors it can generate are fine.
Guess what? Not all article banks and directories are going to accept your content automatically. Oftentimes, they have some guidelines and specifications on the articles that they are accepting.
You can double the number of sites you can submit to by writing articles that the directories want to share with other people. All it takes is one publisher with a hundred thousand readers to increase your potential audience overnight.
Write the articles that publishers want in their publications if you want your article marketing to work the most effective way for you. This also means you have to obey the standard guidelines, spell checks, researching on a good topic and even hiring a writer to produce a good content on your behalf.
In the end, it is all really a matter of choice on your part. You can start getting a little exposure from increased links back but on a very basic level. Or enjoy massive exposure from a little extra time making quality contents.
It will be your choice. You may not be aware of the fact that an article submitted on directories is not meant to have the same level of exposure as highly-targeted content ones geared on a narrow group of people.
Learn the difference between these two and it will surely help you know what kinds of articles to write and to submit.
With modern communication technology comes the popularity of information-based marketing, which is one of the oldest and most effective techniques in getting targeted prospects to sites and converting them into buyers. This is why article writing, submissions and publications are also getting popular.
There are already many tools that people can use to make the process of distributing their articles more easily. Though this is invaluable in getting the contents more exposure, which is only half of the story.
Let us take a look first at the common mistakes that some people make before submitting their contents to article directories:
1. Confusing the reason to promote the articles with the reason to write them.
In article writing, there are three key benefits why you are promoting them; branding, lead generation and promotion, which are all part of your optimization efforts.
But there is only one reason why you write an article, and that is to inform your audience. If the article is not focused on this primary and most important purpose, it will fail to achieve the three promotion benefits because no one will be interested in reading them.
You need to figure out first how to get people to read what is in your article, then make them click on your resource box. You can achieve this by producing better contents.
2. Failing to maximize the promotional opportunities of article marketing.
You may know already that your articles can help you generate additional links back to your site. But do you know that you can get more visitors and better search engine results from that same articles?
Mention keywords at strategic places. Just be sure not to overdo them. Some are even using anchor texts which is also an effective method. But it is important to know that majority of the directories are not able to support this.
Remember that is not only about the links back to your site. Part of doing well in your article marketing is getting picked up by publishers with a large number of audiences and gaining the ability of leveraging other brands because of the quality of your work. Better search engine results also are great benefits.
But these things do not put much money in your pocket. There are other factors that can turn your article marketing efforts into an opportunity that can boost your earnings. Not just increase the number of visitors to your site.
Start out with a plan and see to it that your article will serve the function that you intended it to have.
3. Publishing content that does not help your readers.
Maybe in the process of writing articles, you are thinking that all that is you wanted is links back to your site. And any visitors it can generate are fine.
Guess what? Not all article banks and directories are going to accept your content automatically. Oftentimes, they have some guidelines and specifications on the articles that they are accepting.
You can double the number of sites you can submit to by writing articles that the directories want to share with other people. All it takes is one publisher with a hundred thousand readers to increase your potential audience overnight.
Write the articles that publishers want in their publications if you want your article marketing to work the most effective way for you. This also means you have to obey the standard guidelines, spell checks, researching on a good topic and even hiring a writer to produce a good content on your behalf.
In the end, it is all really a matter of choice on your part. You can start getting a little exposure from increased links back but on a very basic level. Or enjoy massive exposure from a little extra time making quality contents.
It will be your choice. You may not be aware of the fact that an article submitted on directories is not meant to have the same level of exposure as highly-targeted content ones geared on a narrow group of people.
Learn the difference between these two and it will surely help you know what kinds of articles to write and to submit.
3 Smart Reasons Why You Should Consider Paying For Your Traffic
There are numerous success stories you will hear about businesses making it good on the internet . The troubling thing is, there are maybe a tenfold or even a hundredfold of stories inconsistent to theirs. Many have unsuccessfully launched a business venture that is internet based but only a handful shall succeed.
Is this because of luck? That is even more remote. It takes good business sense and a lot of help and team effort. Most importantly, it is the eagerness to succeed and the persistence to learn and the willingness to put in a lot of hard work and some money.
However, before shelling out your hard-earned money on advertising, here are three (3) smart reasons why you should consider paying for your traffic including common-sense methods of showing you how to prepare your website.
1. The quickest method for getting customers to your website is to pay for your traffic.
Like Neo, traffic is 'The One' . Without traffic, all your efforts would just go to waste. Every business needs customers, without them you wouldn't have anyone to sell your products to. In the Internet world traffic is the walk in customer. The more traffic you possess the more people you'd be able to sell your products to.
But similar to any business that's in every corner building or in the mall, not everyone that goes in will buy. But for those who do come in to browse your merchandise, most of them will buy your products. It is a clear and known fact.
But, how do you get traffic, traffic great enough that could make a small portion of resulting buyers enough to make a fair profit. Many big companies generate traffic of tens of thousands a day and a measly ten to fifteen percent actually buys, but that small percentage is enough to supply them with adequate business.
Many of these success stories get their traffic from paying others. Yes that's right; you have to spend money to make money. Advertising is the key. The more people who know that your site exists the more people would of course go to your site, that's common sense.
While there are numerous ways to get free advertising for your business, free advertising doesn't generate the same high volume of traffic as paid traffic does. Paid advertisements include such advertising schemes as those offered by Google and Yahoo.
2. In order to take full advantage of the search engines, make sure that your site is properly optimized to rank high before paying for your traffic.
Search engines are the fastest and easiest way for finding what you need on the internet . Search engines are extremely popular because they provide an indispensable service to many people. They are free and easy to use. Because of their popularity, search engines receive many visitors as well as click throughs . With these benefits in mind, it is easy to see why so many companies would pay to advertise with search engines.
Search engines provide information to the millions of users they receive each day. They provide relevant links to many sites that a user may be looking for. If your site's link pops up as one of the top ranked sites on the search results page, you stand a great chance that the user will click your link and go to your site. While search engine optimization is a cheaper and low cost way to get your site a high rank, paying for advertisements will ensure that you will be on the top ranks.
When you pay for your advertisements, it is like paying for guaranteed traffic to your site. This may not seem like a good idea at first, but the benefits of doing so far outweigh the cost in the long run. When you pay for your traffic, you are guaranteed a consistent flow of traffic to your site. You will at no time go without making a sale on any given day.
3. Find and use tools that will aid you in researching relevant keywords for your chosen niche so that you don't waste money on advertising.
Normally, you will be charged with the number of hits a link gets when your ad is clicked, this is known as pay per click. For some search engines, you will be charged with the number of times your ad shows up when a certain keyword or keyword phrase is searched. It is imperative that you have good keyword content in your ad. There are many tools on the Internet which can aid you in using the right keywords at the right moment in time.
All the money you spend in paying for your traffic will not be for nothing. You will get an impressive boost in traffic which will also result in a great boost in your sales figures.
Keith Gloster has stumbled upon a proven system that solves four major problems 99.99% of marketers face everyday which are traffic generation, prospecting, lead generation and follow-up. For the exciting details, visit: http://www.free-mlm-leads-generator.com
Is this because of luck? That is even more remote. It takes good business sense and a lot of help and team effort. Most importantly, it is the eagerness to succeed and the persistence to learn and the willingness to put in a lot of hard work and some money.
However, before shelling out your hard-earned money on advertising, here are three (3) smart reasons why you should consider paying for your traffic including common-sense methods of showing you how to prepare your website.
1. The quickest method for getting customers to your website is to pay for your traffic.
Like Neo, traffic is 'The One' . Without traffic, all your efforts would just go to waste. Every business needs customers, without them you wouldn't have anyone to sell your products to. In the Internet world traffic is the walk in customer. The more traffic you possess the more people you'd be able to sell your products to.
But similar to any business that's in every corner building or in the mall, not everyone that goes in will buy. But for those who do come in to browse your merchandise, most of them will buy your products. It is a clear and known fact.
But, how do you get traffic, traffic great enough that could make a small portion of resulting buyers enough to make a fair profit. Many big companies generate traffic of tens of thousands a day and a measly ten to fifteen percent actually buys, but that small percentage is enough to supply them with adequate business.
Many of these success stories get their traffic from paying others. Yes that's right; you have to spend money to make money. Advertising is the key. The more people who know that your site exists the more people would of course go to your site, that's common sense.
While there are numerous ways to get free advertising for your business, free advertising doesn't generate the same high volume of traffic as paid traffic does. Paid advertisements include such advertising schemes as those offered by Google and Yahoo.
2. In order to take full advantage of the search engines, make sure that your site is properly optimized to rank high before paying for your traffic.
Search engines are the fastest and easiest way for finding what you need on the internet . Search engines are extremely popular because they provide an indispensable service to many people. They are free and easy to use. Because of their popularity, search engines receive many visitors as well as click throughs . With these benefits in mind, it is easy to see why so many companies would pay to advertise with search engines.
Search engines provide information to the millions of users they receive each day. They provide relevant links to many sites that a user may be looking for. If your site's link pops up as one of the top ranked sites on the search results page, you stand a great chance that the user will click your link and go to your site. While search engine optimization is a cheaper and low cost way to get your site a high rank, paying for advertisements will ensure that you will be on the top ranks.
When you pay for your advertisements, it is like paying for guaranteed traffic to your site. This may not seem like a good idea at first, but the benefits of doing so far outweigh the cost in the long run. When you pay for your traffic, you are guaranteed a consistent flow of traffic to your site. You will at no time go without making a sale on any given day.
3. Find and use tools that will aid you in researching relevant keywords for your chosen niche so that you don't waste money on advertising.
Normally, you will be charged with the number of hits a link gets when your ad is clicked, this is known as pay per click. For some search engines, you will be charged with the number of times your ad shows up when a certain keyword or keyword phrase is searched. It is imperative that you have good keyword content in your ad. There are many tools on the Internet which can aid you in using the right keywords at the right moment in time.
All the money you spend in paying for your traffic will not be for nothing. You will get an impressive boost in traffic which will also result in a great boost in your sales figures.
Keith Gloster has stumbled upon a proven system that solves four major problems 99.99% of marketers face everyday which are traffic generation, prospecting, lead generation and follow-up. For the exciting details, visit: http://www.free-mlm-leads-generator.com
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