MECHANISM – HOW DOES TADALAFIL CAUSE ERECTION IN PERSON WITH ED (ERECTILE DYSFUNCTION)?

Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and the smooth muscle of the corpus cavernosum. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP relaxes smooth muscle and increases blood flow to the corpus cavernosum.

The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil (and sildenafil and vardenafil) inhibits PDE5.
Important – for the medicine to be effective it is necessary that the man is sexually aroused.

WHY DOES TADALAFIL ACT ONLY IF THE MAN IS SEXUALLY EXCITED?
Sexual stimulation is required to initiate the local penile release of nitric oxide, tadalafil’s inhibition of PDE5 will have no effect without direct sexual stimulation of the penis.

Thus, when a man is sexually aroused tadalafil (Cialis, Forzest Tadacip) tablet taken by mouth brings about erection that is strong and lasts long to give and take the pleasure of sexual intercourse. This way tadalafil acts as cure and safe remedy for those people with erectile dysfunction (ed) who are prescribed this medicine.

Compiled by Dr. Ashok Koparde, Consultant Sexual Medicine and Marriage Counselor, Mumbai.

You can write to Dr. Ashok Koparday at his email ask[at]mydoctortells[dot]com.

Samadhan Sexual Health World Wide +919867788877
Ghatkopar East, Mumbai PIN 400077

On mobile see http://my.opera.com/drashok/blog/2009/09/15/about-doctor/

SUDDEN FATAL DROP IN BLOOD PRESSURE CAN HAPPEN IF TADALAFIL AND NITRATES ARE TAKEN TOGETHER

Side effects of Cialis/Forzest/Tadacip/Tadalafil

Tadalafil has been used in approximately 15,000 men participating in clinical trials, and over 8 million men worldwide (primarily in the post-approval/post-marketing setting).

COMMON SIDE EFFECTS OF TADALAFIL
The most common side effects when using tadalafil are headache , indigestion , back pain, muscle aches, flushing , and stuffy or runny nose.

WHY DOES TADALAFIL CAUSE THESE SIDE EFFECTS
These side effects reflect the ability of PDE5 inhibition to vasodilate (cause blood vessels to widen).

HOW LONG, HOW SEVERE ARE SIDE EFFECTS OF TADALAFIL
Side effects are bearable (tolerable) and usually go away after a few hours.
Back pain and muscle aches can occur 12 to 24 hours after taking the drug, and the symptom usually disappears after 48 hours.

TREATMENT OF SIDE EFFECTS OF TADALAFIL
Single analgesic tablet (pain killer) like Acetaminophen or Paracetamol (Tylenol, Crocin, Calpol) is effective in bringing prompt relief from aches caused by Tadalafil.

RARE SIDE EFFECTS OF TADALAFIL
Rare side effects of Tadalafil are visual impairment and sudden hearing loss.

VISION IMPAIRMENT

How rare? LESS THAN ONE IN ONE MILLION USERS OF TADALAFIL.

In May 2005, the U.S. Food and Drug Administration found that tadalafil (along with other PDE5 inhibitors) was associated with vision impairment related to NAION ( nonarteritic anterior ischemic opticneuropathy ) in certain patients taking these drugs in the post-marketing (outside of clinical trials) setting. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION unrelated to PDE5 use, including: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Given the small number of NAION events with PDE5 use (less than 1 in 1 million), the large number of users of PDE5 inhibitors (millions) and the fact that this event occurs in a similar population to those who do not take these medicines, the FDA concluded that they were not able to draw a cause and effect relationship, given these patients underlying vascular risk factors or anatomical defects. However, the label of all three PDE5 inhibitors was changed to alert clinicians to a possible association.

SUDDEN HEARING LOSS
In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including tadalafil, requires a more prominent warning of the potential risk of sudden hearing loss as the result of post marketing reports of deafness associated with use of PDE5 inhibitors.

IMPORTANT TIP – TADALAFIL ACTS ONLY IF THE MAN IS SEXUALLY AROUSED.
WHY?
Sexual stimulation is required to initiate the local penile release of nitric oxide, tadalafil’s inhibition of PDE5 will have no effect without direct sexual stimulation of the penis.

DOSE OF MEDICINE TADALAFIL
The recommended Cialis starting dose for most men is 10 mg, taken as needed before sexual activity (but not more than once daily). The dose may be increased to 20 mg or decreased to 5 mg, per its efficacy and the man’s personal tolerance of the drug.

WHAT IS THE DOSE FOR TAKING DAILY TADALAFIL?
To avoid the inconvenience of a man having to program and plan using Cialis around the time of his anticipated sexual activity, Lilly ICOS began a clinical development program to evaluate the risks and benefits of chronic, once-daily use of the drug. In June 2007, the European Commission approved low-dose (2.5 mg and 5 mg) Cialis to be used as single-daily ED therapy.

BRAND NAMES OF PAROXETINE
In India Paxidep (Sun Pharmaceuticals) and Pexep (Intas) markets Paroxetine Tablets in power of 10, 20, and 40mg. CR is controlled release preparation (Paxidep CR), which is not better than plain paroxetine (Pexep).
In the US and Europe the popular brand of Paroxetine is PAXIL (Pfizer).

DOSE OF PAROXETINE
Paroxetine dose per day is 10 mg or 20 mg. This dose is good enough to delay ejaculation in most men. I prefer to give this daily. Talking medicine few hours before sex may be tried in select cases.
Duration of treatment is 3 months or best decided by doctor who has examined the person.

Note that the dose of Paroxetine for delaying discharge is much less than the dose required for treatment of Depressive disorder, which requires upto 80 mg/day for at least 6 weeks.

COMMON SIDE EFFECTS OF PAROXETINE
In my clinical practice yawning and excessive sedation are two side effects that have been reported more often than any other side effect. One has to keep watch for other side effects as well.

Note that everybody taking Paroxetine does not get side effects.

SIDE EFFECTS OF PAROXETINE
Paroxetine has side effects, which are common to other (SSRIs) SELECTIVE SEROTONIN REUPTAKE INHIBITORS. They are as follows.
Nausea
Diarrhea
Headache
Insomnia
Agitation
Sexual Dysfunction like impotence, decreased libido, anejaculation
Difficulty in passing urine
Sweating
Tremor
Blurred vision
Dry mouth
Dizziness
On withdrawl or discontinuation of medicine often Premature ejaculation returns. Hence, along with medicine counseling is required whereby you learn other methods of delaying ejaculation.
Other Withdrawl reactions aren’t seen as the dose required for the treatment of PE is much less compared to the dose given for treatment of Depressive disorders.
GOOD NEWS is for this very same reason side effects are often not seen when Paroxetine is given for treatment of PE.

Which are the other medicines of SSRI group?
Fluoxetine
Sertraline
Escitalopram
Citalopram

The above information is threadbare. For starting Paroxetine one has to not only know more details, but also have experience giving this medicine.
It is essential to choose right medicine and right dose after detail examination and consultation by accredited, qualified medical doctor.

Viagra ® (and its cousins Cialis ® and Levitra ® all belonging to class of medicines called PDE 5 inhibitors) act at the level of penis whereas Apomorphine acts at the level of brain producing erections.
Keywords
Apokyn® , Ixense® , Spontane® , Uprima®
VR004 Apomorphine for inhalation
Viagra ® Sildenafil citrate
Cialis ® Tadalafil (Adcirca ® for the treatment of pulmonary arterial hypertension)
Levitra ® Vardenafil citrate

Cons
It was found to be of poor efficacy in a large-scale study by Researchers at the UK’s Drug Safety Research Unit and University of Portsmouth and discontinued in the UK in January 2006. Around 65-70% of doctors felt it was ineffective, with 60% of over 11,000 patients (avg age 61) discontinuing in month 1 and a further 23% in month 2. UK studies concentrated on males with generalized erectile dysfunction.
However, in clinical practice, older patients with multiple vascular risk factors and systematic vascular damage show poor overall response to apomorphine SL for the treatment of ED.
http://en.wikipedia.org/wiki/Apomorphine
# ^ a b c Pharmaceutical Business Review, “Study shows Abbott’s Uprima ineffective for most UK patients”
# ^ MedicineNet study review

# ^ http://www.ncbi.nlm.nih.gov/pubmed/16732690

Gene therapy is highly innovative and poses some unique and potentially unknown risks. However, it also presents unique possibilities and the hope to cure and treat diseases in a manner differently, and in some cases potentially better or more safely, than some currently available treatments.

Q: How do these products work?
A: Genetic material can be used to replace defective genes in a person’s body that are responsible for a disease or medical problem. It can also be used to treat disease through the expression of a protein that the gene codes for. Currently, all gene therapy is investigational.

Q: What is the potential impact of these products for consumers?
A: Research in this area has the potential to revolutionize the treatment of diseases that currently are incurable or have inadequate treatments. Gene therapy is being studied to meet unmet medical needs in diverse areas such as genetic diseases, heart disease, cancer, diabetes and stopping the replication of HIV in AIDS patients.

Q: What is FDA’s role in regulating these products?
A: Since the first human gene transfer in the late 1980s, CBER has provided proactive scientific and regulatory guidance in this area of novel product development.

CBER works closely with product sponsors of potential investigational new drug (IND) applications, and encourages early and frequent dialogue to help define the best scientific approaches and clarify FDA regulatory requirements. These meetings between CBER review staff and product sponsors help reduce product development time and risk.

Q: Have any gene therapy products been approved yet?
A: No. FDA has not yet approved for sale any human gene therapy products.

Q: What are the challenges that scientists and government agencies face in making these products widely available?
A: The development of gene therapy products is a relatively new field compared to other biologics and to traditional drugs. It takes time and careful evaluation for medical interventions based on the administration of genetic material to modify or manipulate the expression of a gene or to alter the biological properties of living cells to develop and potentially result in licensed products.

We continue to see broad interest in the development of a number of different gene therapy vectors used to treat a wide variety of diseases and medical conditions.

Source
This article appears on FDA’s Consumer Update page, which features the latest on all FDA-regulated products.

Article Title
Human Gene Therapies: Novel Product Development
Q&A with
Celia M. Witten, Ph.D, M.D.

Date Posted: October 15, 2007
Date accessed: June 22, 2009
URL http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm103331.htm
About Author
Celia M. Witten, Ph.D., M.D.,
is Director of the Office of Cellular, Tissue and Gene Therapy at FDA’s Center for Biologics Evaluation and Research (CBER). She worked for more than 10 years as a practicing physician at the National Rehabilitation Hospital in Washington, D.C., before joining FDA as Division Director of General, Restorative, and Neurological Devices in the Center for Devices and Radiological Health. Before attending medical school at the University of Miami, she received a Ph.D. in Mathematics from Stanford University.

NEW MEDICINE FOR TREATMENT OF ERECTILE DYSFUNCTION

Name of the medicine
© ZYDENA TAB.
Erectile dysfunction (PDE5 inhibitor) | In-house
zydena ©
For PICTURE click here.
Active Ingredients
In 1 tab, udenafil 100mg, 200mg

Indications & Usage
Treatment of erectile dysfunction of adult males.

Dosage & Administration
About 1 hour and 30 minutes to 2 hours before the sexual intercourse of adult males. QD.

Package
2 tabs/PTP, 2 PTP/Box

Udenafil is a NEW PGE5 inhibitor.
How does Udenafil work
Udenafil works as medicine for treatment of erectile dysfunction. It is the newest cousin of drugs such as sildenafil, tadalafil, and vardenafil.
zydena © is developed by Dong-A Pharmaceutical, and is awaiting US FDA approval.

IS VIAGRA SILDENAFIL SAFE?

Safety is important. So it’s nice to know that VIAGRA® has an established safety profile of over 10 years.

For men with other health issues
VIAGRA® has been shown to work safely in men who have ED and other health issues. These include:

* High blood pressure
* High cholesterol
* Heart disease
* Diabetes
* Prostate problems
* Depression

For men taking other medicines
VIAGRA can be taken safely with many other medicines, like those for high blood pressure and depression.

If you have prostate problems or high blood pressure for which you take medicines called alpha blockers, your doctor may start you on a lower dose of VIAGRA.

Who should not take VIAGRA
VIAGRA has been shown to work safely in most men. But if you take any medicines that have nitrates in them (like nitroglycerin for chest pain)—every day or even once in a while—you should NOT take VIAGRA.

Important safety information
Discuss your general health status with your doctor to ensure that you are healthy enough to engage in sexual activity. If you experience chest pain, nausea, or any other discomforts during sex, seek immediate medical help.

Don’t take VIAGRA if you take nitrates, often prescribed for chest pain, as this may cause a sudden, unsafe drop in blood pressure.

As with any ED tablet, in the rare event of an erection lasting more than 4 hours, seek immediate medical help to avoid long-term injury.

If you are older than age 65, or have serious liver or kidney problems, your doctor may start you at the lowest dose (25 mg) of VIAGRA. If you are taking protease inhibitors, such as for the treatment of HIV, your doctor may recommend a 25-mg dose and may limit you to a maximum single dose of 25 mg of VIAGRA in a 48-hour period.

In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicines, including VIAGRA) reported a sudden decrease or loss of vision. It is not possible to determine whether these events are related directly to these medicines or to other factors. If you experience sudden decrease or loss of vision, stop taking PDE5 inhibitors, including VIAGRA, and call a doctor right away.

Sudden decrease or loss of hearing has been rarely reported in people taking PDE5 inhibitors, including VIAGRA. It is not possible to determine whether these events are related directly to the PDE5 inhibitors or to other factors. If you experience sudden decrease or loss of hearing, stop taking VIAGRA and contact a doctor right away.

If you have prostate problems or high blood pressure for which you take medicines called alpha blockers, your doctor may start you on a lower dose of VIAGRA.

VIAGRA® does not protect against sexually transmitted diseases, including HIV.

The most common side effects of VIAGRA® are headache, facial flushing, and upset stomach. Less commonly, bluish vision, blurred vision, or sensitivity to light may briefly occur.

source:
viagra.com official web site of pfizer

http://www.viagra.com/viagra-safety.aspx

HEALTH CLAIMS

ALCAR supplementation may be useful in treating peripheral nerve injury.^[3] It may have some neuroprotective benefit in the treatment of Parkinson’s disease, but further research is required.^[4]
ALCAR supplementation has been shown to be neuroprotective in instances of cerebral ischemia in rats^[2] and
Note:
Further research into the compound’s safety and efficacy is required.

References

For Further Study on This Promising Neuro Protective Nutritional Supplement, ALCAR
1
http://en.wikipedia.org/wiki/Acetylcarnitine
/j.1440-1681.2006.04425.x. PMID 16895547. 
3
Wilson AD, Hart A, Brännström T, Wiberg M, Terenghi G (2007). “Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury”. J Plast Reconstr Aesthet Surg 60 (2): 114–8. doi:10.1016/j.bjps.2006.04.017. PMID 17223507. 
4
Beal MF (2003). “Bioenergetic approaches for neuroprotection in Parkinson’s disease”. Ann. Neurol. 53 Suppl 3: S39–47; discussion S47–8. doi:10.1002/ana.10479. PMID 12666097.

How to Prevent Sexual Dysfunctions due to Diabetes?

Review Author

Dr. Ashok Koparday

How does Diabetes affect Sexual Function?

Diabetes, a widely prevalent metabolic disorder, amongst other organ systems of the human body also affects male and the female sexual organs. Diabetic neuropathy (= damage to the nerves) and angiopathy (=damage to the blood vessels) cause sexual dysfunctions in men and women.
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How common is Diabetic Neuropathy?

6 to 7 people out of 10 people with Diabetes have Diabetic Neuropathy in the United States ^[1].

Review of Epalrestat

Epalrestat, new medicine to prevent Diabetic Neuropathy, brings hope in the prevention and treatment of Erectile Dysfunctions in people with Diabetes Mellitus. (Diabetes Type II).
At present treatment options for Diabetic Neuropathy include

• antidepressants,
• anticonvulsants,
• tramadol, and
• capsaicin.

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Research study Epalrestat

Data from six clinical trials were evaluated, and it was determined that epalrestat may improve motor and sensory nerve conduction velocity and subjective neuropathy symptoms as compared with baseline and placebo. ^[3]

What is the dose of Epalrestat?

50 mg 3 times/day

Side effects of Epalrestat:

Most frequent

• elevations in liver enzyme levels
• nausea and vomiting.

“Long-term treatment with epalrestat is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in subjects with good glycemic control and limited microangiopathy,”^[2]

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How does Epalrestat act?

An enhanced polyol pathway within the central nervous system is part of the etiology of neuropathy among diabetic patients,
Epalrestat is an aldose reductase inhibitor
Data from experimental studies indicate that epalrestat reduces sorbitol accumulation in the sciatic nerve, erythrocytes, and ocular tissues in animals, and in erythrocytes in humans.
Epalrestat improves motor and sensory nerve conduction velocity and subjective neuropathy symptoms.
“As aldose reductase is a key enzyme of the polyol pathway, aldose reductase inhibitors (ARIs) have received much attention worldwide…. Epalrestat is easily absorbed into neural tissue and potently inhibits aldose reductase with minimum adverse effects.”[4]
Epalrestat may serve as a new therapeutic option to prevent or slow the progression of diabetic neuropathy. Long-term, comparative studies in diverse patient populations are needed for clinical application.
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CONLCUSION

Take home message

Long term treatment with Epalrestat may delay symptoms caused by diabetic neuropathy in people who have well controlled blood glucose level (tight glycemic control) ^[6]

[1]1: Pharmacotherapy. 2008 May;28(5):646-55.
Ramirez MA, Borja NL.
Department of Pharmacy Practice, Nova Southeastern University College of Pharmacy, Fort Lauderdale, Florida, USA.
[2] Diabetes Care. 2006;29:1538-1544

[3]http://www.ncbi.nlm.nih.gov/pubmed/18447661
[4] Nigishi Hotta, MD, PhD, from Chubu Rosai Hospital in Nagoya, Japan, and colleagues from the Aldose Reductase Inhibitor-Diabetes Complications Trial (ADCT) Study Group.
[5]
[6] http://www.diabetes.org/diabetes-research/summaries/Hotta-Epalrestat-Delays-Nerve-Damage.jsp

Legal Disclaimer

The material presented here does not necessarily reflect the views of Samadhan India: Center for Therapy, Education, Research in Sex, Marrriage and Relationships or its educational websites

http://mydoctortells.com

http://mysexdoctor.blogspot.com

http://milansamadhan.blogspot.com

that support free online Sex Education for Sexual Wellbeing.
These materials may discuss therapeutic products that have not been approved by the Food and Drug Administration authorities of various countries.
A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational website.
©2009 MY DOCTOR TELLS
Further Reading
http://www.akademiai.com/content/v1m67g2122636k68/