Viagra

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Viagra on Prescriptsy

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Viagra is the brand name for sildenafil citrate, developed and manufactured by Pfizer.

It was the first oral phosphodiesterase type 5 (PDE5) inhibitor approved for the treatment of erectile dysfunction (ED) and has been available in the United Kingdom since 1998.

Sildenafil works by enhancing the natural erectile response to sexual stimulation, increasing blood flow to the penis by inhibiting the enzyme that breaks down cyclic guanosine monophosphate (cGMP) in penile smooth muscle.

Viagra is available in 25 mg, 50 mg, and 100 mg film-coated tablets.

The 25 mg and 100 mg doses are prescription-only medicines (POM), while sildenafil 50 mg is available as a pharmacy (P) medicine under the brand name Viagra Connect.

Erectile dysfunction is defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance.

It is a common condition, estimated to affect approximately 4.3 million men in the United Kingdom.

Prevalence increases with age: approximately 40% of men aged 40 have some degree of erectile difficulty, rising to approximately 70% by age 70.

ED can have a significant impact on quality of life, self-esteem, intimate relationships, and mental health.

It is also recognised as an independent marker of cardiovascular risk, as the same vascular pathology (endothelial dysfunction, atherosclerosis) that affects penile arteries can affect coronary and cerebral arteries.

This page provides a comprehensive clinical guide to Viagra, covering its mechanism of action, dosage, side effects, safety warnings, and how to obtain it in the United Kingdom.

Important safety information about Viagra

Before reading further, note these essential safety points.

• NEVER take Viagra with nitrates (GTN spray, isosorbide mononitrate, isosorbide dinitrate, amyl nitrite). The combination can cause a life-threatening drop in blood pressure.
• If you experience chest pain during or after sexual activity, do not use GTN spray. Call 999 and tell the paramedics you have taken sildenafil.
• If an erection lasts more than 4 hours, seek emergency medical treatment immediately.
• If you experience sudden loss of vision or hearing, stop taking Viagra and seek urgent medical advice.

Understanding erectile dysfunction

An erection is a neurovascular event that requires coordinated input from the nervous system, vascular system, and hormonal system.

The process begins with sexual stimulation (visual, tactile, or psychological), which triggers parasympathetic nerve impulses from the sacral spinal cord (S2 to S4) via the pelvic nerve to the cavernous nerves.

These non-adrenergic, non-cholinergic (NANC) nerve terminals release nitric oxide (NO). Endothelial cells lining the penile arteries and sinusoidal spaces also release NO.

Nitric oxide activates soluble guanylate cyclase in smooth muscle cells of the corpus cavernosum, increasing intracellular cGMP.

Elevated cGMP triggers a cascade that reduces intracellular calcium, causing relaxation of arterial and trabecular smooth muscle.

Blood flows into the expanding sinusoidal spaces of the corpora cavernosa, and the expanding corpora compress the subtunical venules against the tunica albuginea, restricting venous outflow (the veno-occlusive mechanism).

This combination of increased arterial inflow and reduced venous outflow produces a rigid erection.

Erectile dysfunction can result from disruption at any point in this process.

Vasculogenic ED (the most common cause) involves impaired arterial blood flow or venous leak due to endothelial dysfunction, atherosclerosis, or structural changes in the corpora cavernosa.

Risk factors include hypertension, hyperlipidaemia, diabetes mellitus, smoking, obesity, and sedentary lifestyle.

Neurogenic ED results from damage to the nerves controlling erection, such as after radical prostatectomy, spinal cord injury, or diabetic neuropathy.

Hormonal ED is less common and includes hypogonadism (low testosterone). Psychogenic ED involves anxiety, depression, relationship difficulties, or performance anxiety, and often has an organic component as well.

Drug-induced ED is common, with antihypertensives (particularly thiazides and beta-blockers), antidepressants (SSRIs, SNRIs), antiandrogens, and opioids among the recognised culprits.

How Viagra works

Sildenafil is a selective, reversible inhibitor of PDE5. By blocking PDE5 in the corpus cavernosum, sildenafil prevents the degradation of cGMP, allowing it to accumulate.

This amplifies the natural erectile response to sexual stimulation by enhancing and prolonging smooth muscle relaxation and blood flow into the penis.

It is critical to understand that sildenafil does not cause erection independently of sexual stimulation; it requires the initial release of nitric oxide triggered by arousal.

Sildenafil is selective for PDE5 over other phosphodiesterase isoenzymes, but it has some activity against PDE6 (found in retinal photoreceptors), PDE1 (found in vascular, cardiac, and brain smooth muscle), and PDE11 (found in skeletal muscle, prostate, and testes).

The weak inhibition of PDE6 explains the visual side effects (blue tinge, light sensitivity) that some users experience.

PDE3 (found in cardiac muscle) is not significantly affected by sildenafil at therapeutic doses, which distinguishes sildenafil from milrinone and other PDE3 inhibitors used in cardiac failure.

Sildenafil is rapidly absorbed after oral administration, reaching peak plasma concentrations in approximately 30 to 120 minutes (median 60 minutes). The absolute bioavailability is approximately 40%.

A high-fat meal reduces the rate but not the overall extent of absorption.

Sildenafil is metabolised primarily by CYP3A4 and to a lesser extent by CYP2C9 in the liver.

The major active metabolite (N-desmethyl sildenafil) has approximately 50% of the potency of the parent compound. The elimination half-life of sildenafil is approximately 3 to 5 hours.

Clinical evidence for Viagra

Sildenafil has been studied in more than 150 clinical trials involving over 8,000 patients since its original approval.

The pivotal Phase III trials demonstrated that sildenafil significantly improved the ability to achieve and maintain erections compared with placebo across a range of ED aetiologies including psychogenic, vasculogenic, diabetic, and post-prostatectomy ED.

In the original pivotal trial, 69% of attempts at intercourse were successful with sildenafil 50 mg versus 22% with placebo.

The International Index of Erectile Function (IIEF) scores improved by 60% to 100% from baseline with sildenafil compared with 10% to 20% with placebo.

Long-term extension studies have demonstrated sustained efficacy and safety over periods of up to 5 years. Sildenafil remains effective in the vast majority of patients who respond initially, with no evidence of tachyphylaxis (loss of effect over time).

NICE clinical guideline CG52 (since superseded by more recent guidance) recommended PDE5 inhibitors as first-line pharmacological treatment for ED. Current NHS policy allows prescribing of sildenafil for all men with ED without the previous restrictions based on underlying cause.

Dosage and administration

The recommended starting dose is 50 mg, taken approximately 1 hour before sexual activity.

The dose may be adjusted to 25 mg or 100 mg based on individual efficacy and tolerability.

The maximum dose is 100 mg, and the maximum frequency is once per day. Viagra can be taken with or without food, but high-fat meals may delay onset.

Alcohol should be consumed in moderation, as excessive alcohol impairs erectile function and may increase side effects.

For patients aged 65 and over, those with hepatic impairment, severe renal impairment, or those taking CYP3A4 inhibitors, a starting dose of 25 mg is recommended.

If also taking an alpha-blocker for BPH, start sildenafil at 25 mg and separate the doses by at least 4 hours.

Side effects of Viagra

Very common side effects (affecting more than 1 in 10)

Headache is the most frequently reported side effect. It results from vasodilation of cerebral blood vessels and is usually mild and self-limiting. Over-the-counter paracetamol can be taken for headache relief.

Common side effects (affecting 1 in 10 to 1 in 100)

Flushing (redness and warmth of the face and chest), dyspepsia (indigestion), nasal congestion, dizziness, and visual disturbances (blue-green colour tinge, increased light sensitivity) are common. These are usually mild and resolve within a few hours.

Uncommon and rare side effects

Back pain, myalgia, nausea, vomiting, rash, epistaxis (nosebleed), palpitations, tachycardia, and hypotension have been reported uncommonly.

Priapism (erection lasting more than 4 hours) is rare but is a medical emergency requiring immediate treatment. Call 999 or go to Accident and Emergency.

Sudden sensorineural hearing loss and non-arteritic anterior ischaemic optic neuropathy (NAION) are very rare but serious.

Stop taking Viagra and seek immediate medical attention if you experience sudden loss of vision or hearing.

Report suspected adverse reactions to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk.

Warnings and precautions

Absolute contraindication with nitrates

Sildenafil must NEVER be taken with organic nitrates in any form. This includes glyceryl trinitrate (GTN) spray or tablets, isosorbide mononitrate, isosorbide dinitrate, and recreational amyl nitrite (poppers).

Both sildenafil and nitrates increase cGMP levels, and the combination can cause severe, potentially fatal systemic hypotension.

If you experience chest pain during sexual activity after taking Viagra, call 999. Do NOT use your GTN spray. Inform the paramedics that you have taken sildenafil.

Cardiovascular assessment

Sexual activity carries cardiovascular demands roughly equivalent to walking 1 mile briskly on the flat or climbing 2 flights of stairs.

Men with significant cardiovascular disease should be assessed for fitness for sexual activity before prescribing Viagra.

Specific contraindications include recent myocardial infarction (within 6 months), recent stroke (within 6 months), unstable angina, uncontrolled hypertension, significant hypotension, life-threatening arrhythmia, and NYHA Class II or greater heart failure.

Eye conditions

Patients with hereditary retinal degenerative conditions such as retinitis pigmentosa (involving PDE6 dysfunction) should not take sildenafil. If you experience sudden painless loss of vision in one or both eyes, stop sildenafil and seek urgent ophthalmological assessment.

Drug interactions

Strong CYP3A4 inhibitors (ritonavir, ketoconazole, itraconazole) increase sildenafil plasma levels significantly. Reduce the starting dose to 25 mg. Alpha-blockers require careful co-administration with dose separation.

Amlodipine causes an additional average 20% reduction in systolic blood pressure. Grapefruit juice may modestly increase sildenafil levels.

How to get Viagra in the UK

Sildenafil 50 mg is available without prescription as Viagra Connect from any registered pharmacy in the UK. The pharmacist will conduct a short health assessment to ensure suitability.

Prescription-strength sildenafil (25 mg, 50 mg, or 100 mg) and branded Viagra are available on NHS prescription from your GP or an authorised online prescriber registered with the GPhC.

Generic sildenafil is typically prescribed for cost-effectiveness. The standard NHS prescription charge in England is 9.90 pounds per item; prescriptions are free in Scotland, Wales, and Northern Ireland.

Sources

• Viagra 25 mg, 50 mg, 100 mg film-coated tablets, Summary of Product Characteristics (EMC)
• Sildenafil, British National Formulary (BNF)
• Erectile dysfunction, NICE CKS
• Erectile dysfunction (impotence), NHS
• MHRA Yellow Card Scheme