Erectile Dysfunction The Problem And Solution Biology Essay

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Erectile dysfunction is the repeated inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. It can be classified as psychogenic, organic (neurogenic, vascular, hormonal, arterial, cavernosal, or drug-induced) or the combination of both. Erection occurs when there is a sexual stimulation, causes the release of nitric oxide from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme gaunylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP leads to smooth muscle relaxation, allowing increased blood flow into the penis, resulting in an erection. Erectile dysfunction occurs when there is any error in one of these mechanisms. [6]

Phosphodiesterase-5 (PDE5) inhibitor is currently the first line treatment for erectile dysfunction. [26] As discussed above, cGMP plays a vital role in erection. The synthesis, degradation, and resulting tissue concentration of cGMP is regulated by phosphodiesterases. The most abundant phosphodiesterase in the corpus cavernosum is oral PDE5. PDE5 inhibitor works by inhibiting the hydrolysis of the cGMP and thus enhances erectile function by increasing the amount of cGMP in the corpus cavernosum. Sexual stimulation is required to initiate the local release of nitric oxide; therefore, PDE5 inhibitor has no effect in the absence of sexual stimulation. [26]

â-² Diagram 2: The metabolism of cGMP and the effects of PDE5 inhibitors on cell function.

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http://molpharm.aspetjournals.org/content/66/1/11.full (304 words)

Natriuretic peptided (NP) and guanylin (GN) bind to particulate surface guanylyl receptors (pGC) whereas nitric oxide (NO) and carbon monoxide (CO) bind to cytosolic soluble guanylyl cyclases (sGC). cGMP-dependent protein kinase (PKG), which is activated by cGMP, catalyses the phosphorylation of substrates leading to a smooth muscle relaxation and also catalyses the phosphorylation of PDE5. The phosphorylated PDE5 binds cGMP and is activated to hydrolyse cGMP to inactive 5'-GMP. cGMP also binds to cyclic adenosine monophosphate phosphodiesterase 3 (PDE3) to inhibit its activity to hydrolyse to cyclic adenosine monophosphate (cAMP). cAMP produced by the activation of adenylyl cyclase (AC), activates cAMP-dependent protein kinase (PKA) to produce additional effects, including smooth muscle relaxation.[2] There are 3 types of PDE5 inhibitors which are selectively effective for the inhibition of PDE5: [1]

Sildenafil citrate

Vardenafil HCl

Tadalafil

These are the Food and Drug Administration (FDA)-approved oral drugs which are most commonly used to treat erectile dysfunction currently. [12-14] Since they are members of PDE5 inhibitors, they work in a highly similar mechanism of action to cause erection. The main differences between these drugs are the time they need to show their effect and the duration of their effectiveness.

(502 words)

Sildenafil Citrate

Tadalafil

Vardenafil HCl

Name of the medicinal product

Viagra®

Cialis®

Levitra®

Dosage (mg)

25, 50, 100

2.5, 5, 10, 20

2.5, 5, 10, 20

Recommend dosage (mg)

50

10

10

Maximum intake

Once per day

Once per day

Once per day

Onset of action

60 minutes

60 minutes

As fast as 10 minutes for some men and within 25 minutes for most

Half life (T ½ )

4 hours

17.5 hours

4-5 hours

 Time to peak maximum observed plasma concentration (Tmax)

30-120 minutes

Median 60 minutes

30 minutes- 6 hours

Median 120 minutes

As early as 15 minutes

Median 60 minutes

Food interaction

Absorption rate drops when taken with high fat meal

No

Noâ-² Table 1: Comparison between Sildenafil Citrate, Tadalafil and Vardenafil HCl. [1, 3, 7-9]

â-²Diagram 3: Sildenafil Citrate (Viagra®), Tadalafil (Cialis®) and Vardenafil HCl (Levitra®)

http://www.tristatemeds.com/generic-medicine/Misoprostol-Generic/242.html

http://orderviagra.us/

http://www.clenbuterol.us/stimulants.html (646 words)

Viagra is the first erectile dysfunction medication approved by the FDA in 1998. [12] It is very well-known and has been confirmed by many men to provide a hard erection sufficient for satisfactory sexual intercourse. I think most people who take Viagra are those who have advance planning for sexual activity. For tadalafil, its long half-life (17.5 hours) means it has a very long duration of effectiveness. Cialis is claimed to be able to work for 36 hours and this feature earns it a nickname, "The Weekend Pills". It is normally taken by those who want to have sexual activity for more than once or twice goes. On the other hand, vardenafil HCl's Tmax is as early as 15 minutes means it has a fast onset of action. With its rapid onset, Levitra is suitable for those who want to have spontaneous sexual activity. It is also popular in men who suffer diabetes.

Percentage of participants (n/N)a

Study year

Satisfied with treatment effect on erections

Improved ability to have sexual activity

End of year

End of year

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1

98.1 (806/822)

99.6 (803/806)

2

96.6 (672/696)

99.9 (671/672)

3

94.8 (551/581)

99.6 (549/551)

4

96.3 (550/571)

100 (550/550)

aFor the satisfaction analysis, N is equal to the number of men who answered the satisfaction question. For the respective sexual activity analyses, N is equal to the number of men who answered the satisfaction question affirmatively and answered the sexual activity question.

â-²Table 2: Sildenafil treatment outcome over 4 years [4] (808 words)

aErectile function domain score of the International Index of Erectile Function.

Data from a multicenter, randomized, double-blind, placebo-controlled study of 268 men to study once-daily tadalafil over 24 weeks.

â-² Diagram 4: IIEF-EF improvement from baseline to 24 weeks with once-daily tadalafil. [10]

â-² Diagram 5: Improvement in sexual satisfaction following vardenafil HCl, Levitra® treatment. [11]

(835 words)

In table 2, above 90% of men were pleased with the effect of sildenafil on erectile dysfunction. There was even a 100% of men experienced improved ability to have sexual activity during the fourth year of the study. A 5 time difference was noticed for those who took placebo and 2.5mg tadalafil (1.2 and 6 respectively) in the erectile function domain score. The effectiveness of PDE5 inhibitors was supported again when the overall satisfaction was 7.4 for those who underwent vardenafil HCl treatment compared with those who accepted placebo (5.1). Generally, the double-blind studies found that most of the erectile dysfunction patients experience significant improved ability to engage in sexual activity following the oral PDE5 inhibitors medications compared to those who received placebo. Thus, I think PDE5 inhibitors medications are the best treatment for erectile dysfunction due to the evidence of its high effectiveness. However, each PDE5 inhibitor's mode of action is slightly different with each other. There is no best treatment for erectile dysfunction. In my opinion, those drugs are only for symptomatic relief. It is totally depending on individual requirements when deciding which drugs to take.

According to national sales, in 2005, the pharmaceutical costs of sildenafil, tadalafil, and

vardenafil were $1.6 billion, $747 million, and $327 million, respectively. [19]

Implications

There are an estimated 2.3 million men in the UK suffering from erectile dysfunction.

Regrettably, only about 10% of sufferers actually receive treatment.

British Sexual Dysfunction Association

The social implication is men tend to be denial of their erectile dysfunction and reluctant to seek for treatments. In my opinion, this is due to embarrassment as erectile dysfunction strikes at the heart of their masculinity. Men lack the courage to tell doctor about their problem although it has been proven that the high effectiveness of erectile dysfunction treatment. (1135 words)

"The problems could also be related to health factors - for example if a man has diabetes, vascular disease."

Prof Dr George Lee Eng Geap

Consultant Urologist

Department of Surgery, University Malaya

I strongly suggested that government should put their effort to raise the awareness of the impacts of erectile dysfunction among men as it not only affects the sexual relationship between couple, but also indicate some serious health problems.

The costs of PDE5 inhibitors drugs are expensive. The estimated price for 4 pills of PDE5 inhibitors drugs range from US$ 50 to US $70. If the patient needs to take the drugs daily, he might have to spend approximately US$ 350 to US$ 490 monthly. This will definitely be a financial burden for those who have low income. As a result, they will buy generic erectile dysfunction drugs as the price is almost half of the brand drugs. [17] However, the safety and effectiveness of these non-FDA approved generic drugs is not known and it might bring harmful side effects to the patients. From my point of view, governments have the responsibility to provide medical allowances for those low-income patients.

Benefits

In my opinion, the solution is beneficial to most of the men as it restores the good sexual relationships with their couples. Furthermore, it helps them to regain their self-esteem and masculinity. Beside, the high successful penetration and intercourse rate can also increase the birth rate indirectly. It gives hope to men with erectile dysfunction who want to organise a family.

(1387 words)

Risks

â-² Diagram 6: Most common adverse effect of PDE5 inhibitors.

http://www.sexhealthmatters.com/v2/data/resources/cme/chapter01/MSH_PDE_11.06.pdf

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All drugs have their side effects. PDE5-inhibitor is contraindicated in those taking nitrates and men for whom sexual intercourse is inadvisable due to cardiovascular risk factors. Patients might suffer common adverse effects such as headache, flushing, dyspepsia, dizziness and rhinitis. They might also suffer priapism (erection that lasts for more than 4 hours) although it is found to be infrequent with vardenafil. Sildenafil is more likely to cause vision changes compared to vardenafil HCl and tadalafil. [1] Furthermore, FDA has received reports of sudden decreases or loss of hearing following the use of PDE5 inhibitors. [15] The long half-life of tadalafil imposes increased risk for drug interactions in patients taking potent cytochrome P450 (CYP450) inhibitors. [20]

(1515 words)

PDE5 inhibitors are safe and effective for the treatment of ED when taken according to the labeling.  However, all drugs carry risks and you should discuss any concerns you have regarding taking these products with your healthcare provider

FDA news release, 10/18/2007

In my opinion, patients should be well informed by healthcare professionals about the side effects of PDE5 inhibitors. Patients should always follow the prescription and advises of doctors. Any problem concomitant use of PDE5 inhibitors should be immediately reported to healthcare professionals.

Alternative solutions

Alprostadil (Injection therapy)

Alprostadil is a member of group of medicines called vasodilators. Its medicinal product is called Caverject®. It helps treating erectile dysfunction by relaxing the trabecular smooth muscle and by dilating the cavernosal arteries, resulting in increase blood flow to the penis to cause an erection. [8] It causes an erection firm enough for sexual intercourse in over 80% of men with erectile dysfunction, regardless of their age or the cause of their problem. However, the most common side effects of alprostadil are penile pain and priapism. Thus, alprostadil should be administered at the lowest effective dose. Before patients begin intracavernosal treatment with Caverject at home, they should be trained and instructed carefully by their physicians. [23] Below are the procedures of injection of Carvaject:

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â-²Diagram 16

Diagrams 7-16- http://www.rxlist.com/caverject_powder-drug.htm

Vacuum Constriction Device

â-²Diagram 17: A manual operated vacuum constriction device.

http://archive.student.bmj.com/issues/99/11/education/406.php

(1760 words)

A vacuum constriction device (VCD) is an external pump which treats erectile dysfunction by pumping blood to penis to cause an erection. There are 2 main components of VCD: vacuum tube and constriction ring. Vacuum tube creates vacuum to help the penis become erect whereas the constriction ring helps to maintain the erection. To use it, patients place the vacuum tube over the penis. The flexible rubber constriction ring is placed onto the vacuum tube (open end), forming an airtight seal with the vacuum tube. The air is pumped out of the tube so that a vacuum is created. The vacuum draws the blood into the shaft of the penis, causing it to swell and erect. The vacuum tube is removed after releasing the vacuum once the required penis rigidity is achieved. The ring can remain on penis up to 30 minutes. [17, 24] Studies suggest that about 50%-80% of men are satisfied with the results of VCD. The possible side effects of VCD include:

Penis tends to be purplish in colour and can be cold

Numbness

Decrease in the force of ejaculation

Bruising and swelling of the penis

Evaluation

Australian Medicine Handbook©2006 (AMH) by Simone Rossi is a medical reference text which is commonly used by healthcare professionals in Australia. The AMH is largely based on the model of the British National Formulary (BNF). In my opinion, the source AMH is highly reliable as it is independent of both government and the pharmaceutical industry. Therefore, there will not be bias viewpoints for the commentary on different drugs. Beside, most of the editorial committees are pharmacists. I retrieved information on the drugs for erectile dysfunction as stated on page 3 from page 485-488 in AMH. There is another source which came up with the same information:

Wood, A. J. (2000). Drug Therapy. Erectile Dysfunction , 1802-1812.

(2070 words)

The quote in page 8 was taken from an interview with consultant urological surgeon Prof Dr George Lee Eng Geap, entitled Don't live with ED from theStar newspaper dated March 2, 2008. He was the Consultant Urological Surgeon of the United Kingdom and was recruited as an Associate Professor in Surgery, University Malaya in 2007. From my point of view, this source is highly trustable as I believe as an urologist for more than 20 years; Prof Dr George Lee has definitely met with many erectile dysfunction patients and understands their situations. Most importantly, there is a web based source which came up with exactly the same information:

http://kidney.niddk.nih.gov/kudiseases/pubs/ED/

(2179 words)