| IHS | Diagnosis | ICD-10 |
|---|---|---|
| 8.1.1.2 | Delayed NO donor-induced headache [X44] | G44.400 |
Diagnostic criteria:
- Headache, in a person who suffers from primary headache, with the characteristics of that primary headache type1 and fulfilling criteria C and D
- Absorption of a NO donor
- Headache develops after NO is cleared from the blood2
- Headache resolves within 72 hours after single exposure
Notes:
- Normal subjects rarely develop delayed NO donor-induced headache whilst migraineurs develop an attack of migraine without aura, tension-type headache sufferers develop a tension-type headache and cluster headache sufferers develop a cluster headache attack.
- Migraine and tension-type headache develop after a mean of 5-6 hours, cluster headache typically after 1-2 hours.
Comments:
The headache is typically bilateral, pulsating and frontotemporal in location.
All NO donors (eg, amyl nitrate, erythrityl tetranitrate, glyceryl trinitrate [GTN], isosorbide mono- or dinitrate, sodium nitroprusside, mannitol hexanitrate, pentaerythrityl tetranitrate) can cause headache of this subtype particularly in persons with migraine. GTN is the best studied substance. It reliably induces headache in most normal individuals and migraine sufferers develop a more severe immediate headache than non-migraine sufferers. GTN can also cause a delayed headache in migraine sufferers which fulfils the diagnostic criteria for 1.1 Migraine without aura, even in patients whose spontaneous migraine attacks are with aura. In people with chronic tension-type headache, GTN has been shown to induce a delayed headache which has the characteristics of tension-type headache. It is not known if it has the same effect in sufferers of episodic tension-type headache. Cluster headache sufferers do not develop delayed headache outside cluster periods but, during a cluster period, GTN fairly reliably induces a cluster headache attack usually occurring 1-2 hours after intake. The delayed headache in those with migraine or tension-type headache occurs at variable times but on average 5-6 hours after exposure.
Headache is well known as a side effect of therapeutic use of nitroglycerine and other NO donors. With chronic use tolerance develops within a week, and GTN-induced headache disappears in most patients within that time. With intermittent use headache continues, and may be severe enough to compromise the use of NO donors for angina. Most heart patients are, however, male and beyond middle age, which probably explains why the problem is not of greater magnitude.
Other NO donors have been much less studied but available evidence suggests that they too may produce headache. Isosorbide mononitrate has been the subject of one formal double-blind placebo-controlled study and causes a much longer lasting headache than GTN owing to its slow release of NO.
