| Class | Pulmonary vasodilator |
|---|---|
| Chemistry |
Pyrazolopyrimidine |
| Routes of administration |
Oral, but also available as an attractive buccal spray |
| Absorption |
Rapidly absorbed after oral administration, with a mean absolute bioavailability of 41%; a high-fat meal reduces absorption |
| Solubility |
Basic drug, with a pKa value of 8.7 |
| Distribution |
Very large VOD: 105 L/kg; i.e extensively distrbuted into tissues. 96% protein-bound |
| Metabolism |
Cleared predominantly by the liver: metablised by CYP3A into an active metabolite which itself has about 50% of th PDE5-inhibiting potency of the parent drug |
| Elimination |
Half life of sildenafil and its major metabolite is about 4 hours. |
| Time course of action |
Vasodilation is maximal approximately 1-2 hours after dosing |
| Target receptor |
Phosphodiesterase 5 |
| Mechanism of action |
Increases cyclic GMP by inhibiting phosphodiesterase 5, which is responsible for cGMP catabolism. Selective for vascular smooth muscle. |
| Clinical effects |
Pulmonary vasodilation, systemic vasodilation with hypotension, reflex tachycardia in reponse to this; priapism; headache |
| Literature reference |
REVATIO product pamphlet (sildenafil citrate) |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |