Phosphodiesterase type 5 (PDE5) inhibitors are oral drugs that block the enzyme (PDE5) that normally breaks down cGMP in the penis. More cGMP hanging around means more smooth muscle relaxation, more blood flow in, and an erection — but only with sexual stimulation. One interaction on this page is ABSOLUTE and can kill: nitrates.
🔗 Related page: the nitrate contraindication on this page is the same drug class covered in depth on NG-216 · Nitrates — read that page for the full nitric-oxide/preload mechanism of nitrates themselves.
⛽ Blocks PDE5More cGMP stays around → vessel relaxation → blood flow in → erection, only with stimulation.
⏱️ Timing differs by drugSildenafil/vardenafil ≈ 4 hr window; tadalafil up to 36 hr — "the weekend pill."
🚨 Erection > 4 hoursPriapism — seek medical attention immediately.
💊
WHAT IT DOES
STEP 1 · THE MECHANISM
One enzyme, one pathway — PDE5 inhibitors don't create arousal, they just let the body's own erection signal last longer.
⛽ The NO → cGMP → PDE5 pathway
EXAM TIP Sexual stimulation releases nitric oxide (NO) in the penis, which raises cGMP and relaxes smooth muscle, letting blood flow in. The enzyme PDE5 normally breaks cGMP back down, ending the erection. PDE5 inhibitors block that breakdown — cGMP lasts longer, so the erection lasts longer.
🧠 "No stimulation, no show." Sildenafil has no effect without sexual stimulation — it doesn't create arousal, it just lets an existing erection signal last. That's a key teaching point: the drug is not a substitute for arousal.
🔤 Class & category
Phosphodiesterase type 5 (PDE5) inhibitors
Oral drugs, taken before planned sexual activity
Sildenafil (as Revatio) is also used for pulmonary arterial hypertension
Tadalafil, low daily dose, is also used for BPH
🧠 "5 for 5." PDE-5 inhibitor. If you see -afil at the end of a drug name, think PDE5 inhibitor.
⭐ Indication
Allows blood flow into the penis, resulting in an erection — used for erectile dysfunction. Determine that ED is present before starting therapy.
🧠 The drug enables the physical mechanism; it does not create desire or arousal on its own.
💊 Know your three — dose & timing
Generic
Trade
Use
Typical dose & timing
Sildenafil
Viagra (Revatio for PAH)
Erectile dysfunction
25–100 mg PO, 30–60 min before sexual activity; not more than once/day
Tadalafil
Cialis
ED, BPH
5–20 mg PO; daily low-dose for BPH, or as needed — effective up to 36 hr before activity
Vardenafil
Levitra, Staxyn
Erectile dysfunction
5–20 mg PO, ~60 min before activity; window ≈ 4 hr
⚠️
WATCH FOR
STEP 2 · THE DANGER LIST
One contraindication is absolute, one complication is a urologic emergency, and two symptoms mean stop and call.
🚨 ABSOLUTE contraindication — nitrates
PDE5 inhibitors and nitrates both raise cGMP / nitric oxide-driven vasodilation. Given together, the two vasodilating effects stack — the result can be severe, life-threatening hypotension and cardiovascular collapse. Always ask about ED medication use before giving a nitrate, and never give a PDE5 inhibitor to a patient on nitrate therapy.
🧠 "Blue pill, red flag." Any ED drug question that also mentions chest pain / nitroglycerin use is testing this exact interaction. See NG-216 · Nitrates for the nitrate side of this mechanism.
⚠️ Caution — alpha-adrenergic blockers
Do not take concurrently with alpha-adrenergic blockers (e.g., drugs for BPH) unless the patient is on a stable dose — both classes drop BP, and together they raise the risk of symptomatic hypotension.
🧠 Two vasodilators, two chances to fall — orthostatic teaching applies here too.
🚨 Priapism — erection > 4 hours
🧠 "4 is the floor." Any erection lasting longer than 4 hours is a urologic emergency, not something to "wait out."
👁️ Report immediately — vision & hearing changes
👁️Sudden vision lossone or both eyes
👂Sudden hearing lossor decrease
🔔Ringing in the earstinnitus
💫Dizzinesswith any of the above
Also expect and teach: headache, flushing, GI upset, nausea, nasal congestion/runny nose as common (non-emergency) adverse reactions.
🧠 "Eyes, ears, and erections — all reported." Vision loss, hearing loss/ringing, priapism, and chest pain during sexual activity are the four "call now" symptoms for this drug class.
🗣️
TEACH
STEP 3 · WHAT THE CLIENT NEEDS TO HEAR
Timing, honesty with every provider about ED med use, and what this drug does not protect against.
✅ Teaching checklist
1
⏱️ Take as directed — timing before activity varies by drug
2
❌ Not more than once per day for sildenafil
3
💬 Tell every provider and dentist you take an ED drug — before any nitrate is ever prescribed
4
🚨 Chest pain during sex → seek immediate medical attention, do not take a nitrate first
5
🛡️ No STI protection — this drug offers none; discuss protection separately
🧠 "If chest pain hits, don't reach for nitro." A patient on sildenafil who develops chest pain during intercourse must get emergency care — nitroglycerin at that point could be fatal.
Antihypertensives — increase the antihypertensive's effect → additive hypotension
Nitrates — absolute contraindication, see above
Alpha blockers — caution unless on a stable dose
🧠 Always screen the full med list, OTC drugs, and herbal products before giving these agents — several categories stack with the same vasodilation.
🆚 Not for women, not a cure, not stimulation
Myth
Reality
"It creates arousal"
No — it only sustains an erection once sexual stimulation has already started. No stimulation, no effect.
"Women can take it too"
Not indicated for use in women.
"It's fine with my nitro spray"
Absolute contraindication — risk of severe hypotension.
"It protects against STIs"
It does not — counsel on protection separately.
🧠 "Wingman, not magic." The drug supports a signal that's already there — it doesn't create desire, doesn't replace protection, and doesn't mix with nitrates.
⚡
QUICK RECALL
SAY IT OUT LOUD
⛽ Blocks PDE5cGMP stays up, erection sustained — only with stimulation
🚫 Nitrates = ABSOLUTE nosevere/fatal hypotension risk — see NG-216
⏱️ Sildenafil/vardenafil ≈4hTadalafil up to 36h — "weekend pill"
🚨 >4hr erectionpriapism — emergency
🎯 Cover & check — 4 rapid-fire questions
Q1: How do PDE5 inhibitors work?
They block the enzyme PDE5, which normally breaks down cGMP — cGMP stays elevated, smooth muscle stays relaxed, and blood flow into the penis is sustained. They require sexual stimulation to have any effect.
Q2: What is the one absolute contraindication, and why?
Nitrates — both drug classes vasodilate through the same nitric-oxide/cGMP pathway, and combined they can cause severe, life-threatening hypotension and cardiovascular collapse.
Q3: A client reports an erection lasting 5 hours. What is this, and what should they do?
Priapism — a urologic emergency. Seek medical attention immediately to prevent permanent tissue damage.
Q4: Which two symptoms besides chest pain require the client to notify the provider promptly?
Sudden vision loss/decrease in one or both eyes, and sudden hearing loss or ringing in the ears (tinnitus), often with dizziness.