One of the medicines that used to treat this condition is from PDE5 inhibitors class. Besides apomorphine, alprostadil, papaverine, phentolamine, and phenylephrine; this is the mostly used medicines to treat erectile dysfunction. PDE-5 inhibitors have some advantages rather than other medicines: it can be taken orally, and it only enhance erectile dysfunction as the response against sexual stimulation. But it also has a warning: it cannot be used altogether with nitrates, due to resultant vasodilatation effect that is potentially fatal when these medicines are taken simultaneously.
Mechanism of action
PDE5 inhibitors inhibits the phosphodiesterase-5 enzyme. This is the enzyme that is the isoform that inactivates cyclic-GMP, meanwhile c-GMP is necessary to enhance vasodilatation/vasorelaxation of penile arteries. So the inhibition of PDE5 enzyme can result on increased level of active c-GMP, thus enhanced vasodilatation.
There are three PDE5 inhibitors currently available in market: sildenafil, tadalafil, and vardenafil.
Sildenafil
Sildenafil once developed for pulmonary hypertension, with the dose of 20 mg. Later, this medicine was known to affect penile vasculature besides the hypertension itself. This lead to development of sildenafil as a new ED medicine.
Its peak plasma concentration is reached within 30-120 minutes after an oral dose. This period is delayed by eating, so sildenafil is advised to be given as a single dose about one hour or more before sexual activity. The dose should be only given as single dose as needed. Sildenafil is metabolized by CYP3A4, which is also induced by several other medicines (such as carbamazepine, barbiturate, rifampicin, macrolide antibiotics, and ritonavir).
It is advised that the dose should be started at 25 mg. Titration only if needed.
Sildenafil is only effective in ED due to psychological factor or due to vascular problem. If ED was caused by spinal cord injury, other damage of innervation, or lacking of libido only; sildenafil (theoritically) is ineffective.
Tadalafil
Longer acting version of sildenafil, means that tadalafil can be given about two hour before sexual activity.
Initial recommended dose is 10 mg, can be titrated up to 20 mg if necessary. Its mean half-life is about 17.5 hours.
Just on October 06, 2011; US Food and Drug Administration (FDA) approved tadalafil is approved to also treat the signs and symptoms of benign prostatic hyperplasia (BPH) as well as a combination of BPH and erectile dysfunction (ED) when the conditions coincide; with the dose of 5 mg daily.
Vardenafil
Vardenafil has a stronger tendency to cause priapism due to its longer duration of action, heart attack, hearing loss, compared to other PDE5 inhibitor.
Recommended dose is initially 2.5 mg, can be titrated up to 20 mg.
Adverse Effects
Sometimes other vascular beds also dilates due to this group of medicines. Several noted adverse effects are: visual disturbances (blue-green discrimination), hypotension, flushing, and headache. Precaution must be addressed when an ED patient is also taking nitrates or every other medicines containing nitrate branches in its structure; because nitrate can potentiate cGMP too. Concomitant use of PDE5 inhibitor and nitrates will result on extensive vasodilatation, which can be fatal in some cases. If the administration cannot be replaced, these medicines should be "separated" by 6 hours or more.
References:
Katzung BG, Masters SB, Trevor AJ. Katzung's Basic and Clinical Pharmacology 11th edition: 2009; 12: 197.
Lowes R. Tadalafil Approved for Benign Prostatic Hyperplasia (available from http://www.medscape.com/viewarticle/751150; October 06, 2011)
Rang HP, Dale MM, Ritter JM et al. Rang & Dale's Pharmacology 7th edition: 2011; 34: 429-430.
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