Intended for healthcare professionals

Rapid Response:

Could GPs reduce hospital admissions by prescribing PDE-5 inhibitors to those in community isolation?

Dear Editor

The response to the COVID-19 pandemic has largely been epidemiological with clinical efforts apparently focussed on ventilatory support that is leading to significant pressure on in-patient resources worldwide.

We know that the virus targets ACE2 receptors (1) and that ACE2 ‘deactivates’ Angiotensin II thereby preventing peripheral pulmonary vasoconstriction (PPV) , thereby maintaining peripheral pulmonary flow while permitting circulating Angiotensin II to maintain systemic blood pressure. It follows that, in the presence of PPV both blood-borne immune response and gas transfer will be reduced at the alveoli. This concept is consistent with the clinical findings observed in COVID-19 and with data that shows that ‘at risk’ patients have upregulated ACE2 systems with those on ACE inhibitors (which target ACE1 and do not affect ACE2) being at a putative higher risk (2).

In addition to the reduced flow, it seems inevitable that, without the pulmonary Arterio-Venous shunt, there would be an increase in Pulmonary Arterial Pressure. Increasing the A-V shunt causes deoxygenated blood to dilute the oxygenated blood in the pulmonary vein and, thereby, the peripheral circulation. Thus peripheral pa02 may be a measure of the severity of COVID-19 infection.

In a similar case (3) an oral PDE-5 inhibitor (Tadafil) was used on the basis that reduction of Pulmonary Arterial Pressure would reduce the A-V shunt and thus improve systemic oxygenation. PDE-5 inhibitors are safe oral medications that are widely available. It seems reasonable to consider that oral PDE-5 inhibitors might be considered for COVID-19 cases isolating in the community to delay and avoid hospital admission with prescription perhaps based on serial pa02 measures.

GPs are ideally placed to consider and prescribe drugs considered safe enough to be bought over the pharmacist’s counter and may delay or avoid hospital admission on the basis of current evidence but, unfortunately, basing treatment on known evidence has been eclipsed by a movement requiring any treatment to have evidenced outcomes, ideally meta-analysed randomised controlled trials which takes years of academic activity. The evidence for GP intervention is already there but it requires intelligent reading rather than blind obedience to protocols that recommend that we should ‘fiddle while Rome burns’.

1. Hoffmann M, Kleine-Weber H, Krüger N, Müller M, Drosten C, Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv 2020:2020.01.31.929042.

2. Lei Fang, George Karakiulakis, *Michael Roth Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020 https://doi.org/10.1016/PII

3. Ashworth AJ Enhanced recovery from respiratory infection following treatment with a PDE-5inhibitor: a single case study Prim Care Respir J 2012; 21(1): 17-18 http://dx.doi.org/10.4104/pcrj.2012.00016

Competing interests: No competing interests

14 March 2020
Andrew J Ashworth
GP & Occupational Physician
Bo'ness. West Lothian