| Class | Nitrate vasodilator |
|---|---|
| Chemistry |
Organic nitrate |
| Routes of administration |
Oral |
| Absorption |
Oral bioavailability 100%; rapidly absorbed |
| Solubility |
pKa -5.9; amphoteric; excellent solubility in both water and fat |
| Distribution |
Minimally protein bound (<5%). VOD ~ 0.6L/kg |
| Metabolism |
Renal metabolism, where is is converted to a glucuronide metabolite (which is still active) |
| Elimination |
Time to peak effect: 30-60 minutes; elimination half-life 5 hours |
| Time course of action |
Relatively slow offset of effect, which leads to troughs of activity, and therefore protects against tachyphylaxis with regular use |
| Target receptor |
Soluble guanylyl cyclase (which is induced by NO) |
| Mechanism of action |
Acts as a donor of nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in vascular smooth muscle. This hyperpolarises the membrane by increasing potassium channel conductivity and decreases the availability of inracellular calcium, thereby decreasing the resting tone and contractility of vascular smooth muscle |
| Clinical effects |
Systemic vasodilation - preferentially venodilation; reduced preload, reduced afterload. Increased intracranial pressure, headache, reflex tachycardia, methaemoglobinaemia (rare). Tolerance develops over sustained use (tachyphylaxis). |
| Literature reference |
Australian PI from the TGA |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |