Drugs for Erectile Dysfunction
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Direct answer
Phosphodiesterase-5 inhibitors are first-line oral therapy for erectile dysfunction: sildenafil 50 mg (range 25-100 mg) taken about an hour before sexual activity, or tadalafil 10-20 mg, which works up to 36 hours and comes in a daily 2.5-5 mg regimen. They potentiate nitric oxide signalling in corporal smooth muscle, so they do nothing without sexual arousal — a counselling point that prevents "drug failure" labels. The absolute contraindication is any nitrate: within 24 hours of sildenafil and 48 hours of tadalafil, the combination can produce irreversible hypotension. Refractory cases move to second-line alprostadil (intracavernosal injection or medicated urethral system), while testosterone is reserved for proven hypogonadism, since it treats a hormone deficiency, not the erection itself.
What you must remember
- Dosing anchors: sildenafil 50 mg one hour before activity (heavy meals delay absorption); tadalafil 10-20 mg on demand or 2.5-5 mg daily — the "weekend drug" with a 36-hour window.
- Nitrate rule: nitrates are absolutely contraindicated within 24 hours of sildenafil and 48 hours of tadalafil; conversely, never give nitrates for PDE-5 inhibitor-induced hypotension — use alpha-agonists and volume.
- Adverse effects: headache, flushing, dyspepsia, nasal congestion; sildenafil at high dose tints vision blue (PDE-6 cross-inhibition); non-arteritic anterior ischaemic optic neuropathy is a rare caution.
- Alpha-blocker caution: co-prescription can cause postural hypotension — start low, separate dosing, or prefer tadalafil.
- Second line: alprostadil intracavernosal (erection in 5-20 minutes) or intraurethral; complications are local pain and priapism — an erection beyond four hours is a urological emergency.
- Testosterone only for hypogonadism: morning total testosterone confirmed low on two occasions; it will not restore erections in eugonadal men.
- Assess the vasculature: erectile dysfunction preceding angina by a few years is a well-known pattern — the penis is a sensitive barometer of endothelial disease.
A clinic case, worked through
A 54-year-old man with type 2 diabetes and known coronary disease on isosorbide mononitrate reports six months of erectile dysfunction. The pharmacological decision is not "which PDE-5 inhibitor" but "can he ever take one while on a nitrate". Two paths open. If his angina is stable and the cardiology assessment concludes the nitrate is optional, it can be withdrawn and, after the appropriate washout, a PDE-5 inhibitor started at 25-50 mg — sildenafil first, watching for the headache and flushing that make some men abandon therapy. If the nitrate is genuinely needed, oral therapy is closed; the conversation moves to alprostadil, with careful teaching of injection technique and an explicit warning about priapism.
The rest of the consultation is where the marks hide. He is asked about depression, sleep, alcohol and his lipid profile; his glycaemic control is optimised; and he is told that the tablet works only with stimulation, taken on an empty stomach when possible, and tried on six to eight occasions before declaring failure — inadequate trials, not pharmacology, account for much apparent non-response. Diabetes produces endothelial and autonomic neuropathy, so dose escalation to 100 mg is expected rather than exceptional.
How the exam frames it
The near-certain question is the nitrate interaction: a man on sublingual nitroglycerin who asks for "the blue pill" — the answer is a firm no, and the vignette may add "he took sildenafil last night and now has chest pain, what do you not give?" to force the same answer from the other direction. The second framing is pharmacokinetic discrimination: tadalafil's long half-life distinguishes it in a matching list, and its daily dosing suits couples who prefer spontaneity. Viva examiners like the mechanism chain — sexual arousal releases nitric oxide, guanylate cyclase raises cGMP, PDE-5 degrades it, the inhibitor sustains it, smooth muscle relaxes — because it explains both the drug and its failure without arousal. An Indian-context line worth adding: unregulated "herbal" and counterfeit phosphodiesterase-5 inhibitors sold online or by quacks frequently contain undeclared sildenafil, which is how nitrate-using patients get harmed without ever having been prescribed the drug.
Frequently asked questions
What is the first-line drug for erectile dysfunction?
An oral PDE-5 inhibitor — sildenafil or tadalafil — in any man without nitrate therapy, dosed on demand before sexual activity.
Why are nitrates absolutely contraindicated with PDE-5 inhibitors?
Both dilate through the nitric oxide-cGMP pathway; together they cause profound, refractory hypotension, so the gap must be 24 hours for sildenafil and 48 for tadalafil.
Do PDE-5 inhibitors cause erections without arousal?
No — they sustain the nitric-oxide-mediated signal that arousal generates; absence of stimulation is a common reason for apparent failure.
What is second-line therapy when PDE-5 inhibitors fail or are contraindicated?
Intracavernosal or intraurethral alprostadil, with counselling about local pain and priapism.
When is testosterone indicated in erectile dysfunction?
Only when biochemical hypogonadism is confirmed on repeat morning testing; it corrects the hormone deficiency rather than the erection per se.