1. SILDENAFIL CITRATE HISTORY

How was Sildenafil Citrate discovered?
Sildenafil Citrate was initially developed to treat heart disease (angina). In trial studies, the penile erection enhancing effects were noticed. Sildenafil Citrate was patented in 1996, approved by the FDA on March 27, 1998 (becoming the first pill approved to treat erectile dysfunction in the United States) and offered for sale in the United States later that year. It soon became a great success.

2. SILDENAFIL CITRATE FACTS

It has been suggested that Sildenafil Citrate would lead to a marked drop in the demand for certain traditional remedies, such as tiger penises and rhinoceros horns and that Sildenafil Citrate may therefore help to preserve these endangered species. However, this is unlikely in that these parts of endangered species are not only used to treat impotence. Rhinoceros horns, for example, are used as a treatment for high fever. Further, since Sildenafil Citrate has not been shown to possess aphrodisiac properties, it is unclear that the natural remedies would compete with Sildenafil Citrate.

3. ABOUT SILDENAFIL CITRATE MEDICATION

Sildenafil Citrate is used to treat erectile dysfunction (impotence).

Sildenafil Citrate relaxes muscles within the penis. This allows increased blood flow into the penis, necessary to achieve and maintain an erection.

Erectile Dysfunction

What is erectile dysfunction?
When a man can't get an erection to have sex or can't keep an erection long enough to finish having sex, it's called erectile dysfunction. Erectile dysfunction is also called impotence.

Is erectile dysfunction just a part of old age?
Erectile dysfunction doesn't have to be a part of getting older. It's true that as you get older, you may need more stimulation (such as stroking and touching) to get an erection. You might also need more time between erections. But older men should still be able to get an erection and enjoy sex.

What causes erectile dysfunction?
Medical problems that can cause erectile dysfunction:
Diabetes (high blood sugar)
Hypertension (high blood pressure)
Atherosclerosis (hardening of the arteries)
If you can't keep your blood sugar or your blood pressure under control, you can get erectile dysfunction. It's important that you take your medicines for these problems just the way your doctor tells you.

Sometimes your hormones get out of balance and this causes erectile dysfunction. Your doctor will decide if you need blood tests to check your hormones.

Some medicines can cause this problem. If this is true for you, your doctor may take you off that medicine or give you a different one.

Drinking too much alcohol, smoking too much and abusing drugs can also cause erectile dysfunction.

Problems in your relationship with your sexual partner also can cause erectile dysfunction. You might try therapy to see if improving your relationship helps your sex life. Therapy will probably be most effective if your sex partner is included. Couples can learn new ways to please one another and to show affection. This can reduce any of your anxiety about having erections.

 

Physical causes of erectile dysfunction Alcoholism Fatigue Atherosclerosis (hardening of the arteries) Diabetes Brain or spinal-cord injuries Hypogonadism (which leads to lower testosterone levels) Liver or kidney failure Multiple sclerosis Parkinson's disease Radiation therapy to the testicles Stroke Some types of prostate or bladder surgery

 

Data source: The Impotence Resource Center, Boston University.

How is erectile dysfunction diagnosed?
Your doctor will probably start by asking you some questions and doing a physical exam. Samples of your blood and urine may be tested for diseases and disorders. Other tests may also be needed. Your doctor will determine which tests are right for you.

Feelings that can lead to erectile dysfunction Feeling nervous about sex, perhaps because of a bad experience or because of a previous episode of impotence Feeling stressed, including stress from work or family situations Being troubled by problems in your relationship with your sex partner Feeling depressed Feeling so self-conscious that you can't enjoy sex Thinking that your partner is reacting negatively to you

How is erectile dysfunction treated?
How erectile dysfunction is treated depends on what things are causing it. After your doctor checks you for medical problems and medicines that might cause erectile dysfunction, he or she may have you try a medicine like Sildenafil Citrate to help with erectile dysfunction. Sildenafil Citrate is taken by mouth.

Sildenafil Citrate blocks an enzyme that causes an erection to go flaccid. Although Sildenafil Citrate is similar to Levitra and Tadalafil, its dose, onset of action, and duration of action is unique.

However not everyone can use Sildenafil Citrate. Your doctor will help you decide if you can try Sildenafil Citrate .

What other options do you have?
If the medicines aren't right for you, you could also try using vacuum pump devices, or you could have surgery. Your doctor may send you to an urologist to talk about these options.

4. SILDENAFIL CITRATE EFFECTIVENESS

When is Sildenafil Citrate best taken?
Absorption: Sildenafil Citrate is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes of oral dosing in the fastest state. When Sildenafil Citrate is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in T max of 60 minutes and a mean reduction in C max of 29%. The mean steady state volume of distribution for Sildenafil Citrate is 105 L, indicating distribution into the tissues. Sildenafil Citrate and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations.

Based upon measurements of Sildenafil Citrate in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients.

Metabolism and Excretion: Sildenafil Citrate is cleared predominantly by the hepatic microsomal isoenzymes. The major circulating metabolite results from N-desmethylation of Sildenafil Citrate, and is itself further metabolized. Plasma concentrations of this metabolite are approximately 40% of those seen for Sildenafil Citrate, so that the metabolite accounts for about 20% of Sildenafil Citrate's pharmacologic effects.

Sildenafil Citrate is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach.

5. SILDENAFIL CITRATE EFFECTS ON SPECIAL POPULATION
How do different people react to Sildenafil Citrate?

Geriatrics : Healthy elderly volunteers (65 years or over) had a reduced clearance of Sildenafil Citrate, with free plasma concentrations approximately 40% greater than those seen in healthy younger volunteers (18-45 years).

Renal Insufficiency: In volunteers with mild and moderate renal impairment, the pharmacokinetics of a single oral dose of Sildenafil Citrate was not altered. In volunteers with severe renal impairment, Sildenafil Citrate clearance was reduced, resulting in approximately doubling concentration compared to age-matched volunteers with no renal impairment.

Hepatic Insufficiency : In volunteers with hepatic cirrhosis, Sildenafil Citrate clearance was reduced, resulting in increases in concentration compared to age-matched volunteers with no hepatic impairment.

Therefore, age >65, hepatic impairment and severe renal impairment are associated with increased plasma levels of Sildenafil Citrate. A starting oral dose of 25 mg should be considered in those patients.

6. SILDENAFIL CITRATE EFFECTS ON MEDICAL CONDITIONS

How does Sildenafil Citrate affect your existing condition/ailment?
Effects of Sildenafil Citrate on Patients with Blood Pressure :
Single oral doses of Sildenafil Citrate (100 mg) administered to healthy volunteers produced decreases in supine blood pressure. The decrease in blood pressure was most notable approximately 1-2 hours after dosing, and was not different than placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of Sildenafil Citrate, therefore the effects are not related to dose or plasma levels within this dosage range. Larger effects were recorded among patients receiving concomitant nitrates.

Effects of Sildenafil Citrate on Vision :
At single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. An evaluation of visual function at doses up to twice the maximum recommended dose revealed no effects of Sildenafil Citrate on visual acuity, intraocular pressure, or pupillometry.

7. OTHER/ALTERNATE USES OF SILDENAFIL CITRATE

What else does Sildenafil Citrate treat?
Studies have shown that apart from in erectile dysfunction; Sildenafil Citrate is also effective in the rare disease pulmonary arterial hypertension (PAH).

Sildenafil Citrate appears to relax the arterial wall, decreasing the pressure on the lung vasculature and improving symptoms of right-sided heart failure.

8. ADVERSE/SIDE EFFECTS of SILDENAFIL CITRATE

What are the side effects of Sildenafil Citrate?
Sildenafil Citrate was administered to over 3700 patients (aged 19-87 years) during clinical trials worldwide. Over 550 patients were treated for longer than one year.

In placebo-controlled clinical studies, the discontinuation rate due to adverse events for Sildenafil Citrate (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature.

In trials of all designs, adverse events reported by patients receiving Sildenafil Citrate were generally similar. In fixed-dose studies, the incidence of some adverse events increased with dose. The nature of the adverse events in flexible-dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed-dose studies.

When Sildenafil Citrate was taken as recommended in flexible-dose, placebo-controlled clinical trials, the following adverse events were reported:

Other adverse reactions occurred at a rate of >2%, but equally common on placebo: respiratory tract infection, back pain, flu syndrome, and arthralgia.

In fixed-dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses. At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently.

The following events occurred in <2% of patients in controlled clinical trials; a causal relationship to Sildenafil Citrate is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful:

Body as a whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, and accidental injury.

Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy.

Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis.

Hemic and Lymphatic: anemia and leukopenia.

Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.

Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.

Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia.

Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased.

Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.

Special Senses: mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, deafness, ear pain, eye hemorrhage, cataract, dry eyes.

Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.

9. USEFUL SITES

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

http://familydoctor.org

Newer Pharmacologic Alternatives for Erectile Dysfunction

http://www.aafp.org/afp/990915ap/1159.