My Health Book: July 2014

Sildenafil (viagra) in infants

Sildenafil in the treatment of pulmonary arterial hypertension in infants ...

Definition

Pulmonary arterial hypertension(PAH) is a progressive, and often fatal, debilitating disorder.

The increased pulmonary artery pressure found in PAH is due to disturbances in key vascular mediator pathways including relative deficiencies of vasodilators such as nitric oxide (NO) and prostacyclin, as well as exaggerated production of vasoconstrictors such as endothelin and thromboxanes.

Symptoms

Progressive breathlessness, exertion limitation, frequent decline and failure of the right ventricle.

Mechanism of action of sildenafil

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5). Present throughout the body, PDE5 is found in high concentrations in the lungs. Inhibition of PDE5 enhances the vasodilatory effects of nitric oxide in pulmonary hypertension by preventing the degradation of cyclic guanosine monophosphate (cGMP), which promotes relaxation of vascular smooth muscle and increases blood flow. In animal models and human trials, sildenafil has been found to produce a relatively selective reduction in pulmonary artery pressure without adverse systemic hemodynamic effects after 3 months of oral therapy. Inhibition of PDE5 by sildenafil may also enhance the platelet antiaggregatory activity of nitric oxide and inhibit thrombus formation.

Infant’s dose

The protocol for dosing was

(1) first dose of 1 mg/kg/dose within 30 minutes admission or within 12 hours of delivery (whichever earlier),

(2) Dosing every six hours for a maximum of 8 doses,

(3) Dose was doubled if the oxygenation index (OI) or SpO2 did not improve (If OI continued to be <10% of previous value and SpO2 was not increasing >5 of previous value) and blood pressure remained stable.

how can i prepare the infant's dose from viagra tablet???

newborns received oral Sildenafil solution through feeding tube which was prepared by crushing a 50 mg tablet of sildenafil in distilled water or simple syrup to make a concentration of 5 mg/ml.

notes

At 2012The U.S.Food and DrugAdministration (FDA) is recommending that sildenafil not be prescribed to children (ages 1 through 17) for pulmonary arterial hypertension. This recommendation against use is based on a recent long-term clinical pediatric trial showing that: (1) children taking a high dose of sildenafil had a higher risk of death than children taking a low dose and (2) the low doses of sildenafil are not effective in improving exercise ability.

References

1) Clavecilla SQ. New insights into the treatment of pulmonary arterial hypertension. Formulary, 2003 Mar; 38(3): 150-4, 157-8, 160.

2) Mehta S. Sildenafil for pulmonary arterial hypertension: exciting, but protection required. Chest. 2003 Apr; 123(4): 989-92.

3) Pfizer Inc. FDA Approves Pfizer’s Revatio as Treatment for Pulmonary Arterial Hypertension.http://www.pfizer.com/pfizer/are/news_releases/2005pr/mn_2005_0606.jsp#additional. Accessed June 23, 2005.

4) Kataoka M, Satoh T, Manabe T, Anzai T, Yoshikawa T, Mitamura H, Ogawa S. Oral sildenafil improves primary pulmonary hypertension refractory to epoprostenol. Circ J. 2005 Apr;69(4):461-5.

5) Kanthapillai P, Lasserson T, Walters E. Sildenafil for pulmonary hypertension. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD003562.

6) Karatza AA, Bush A, Magee AG. Safety and efficacy of Sildenafil therapy in children with pulmonary hypertension. Int J Cardiol. 2005 Apr 20;100(2):267-73.

7) Leuchte HH, et al. Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension. Chest. 2004 Feb; 125(2): 580-6.

8) Chockalingam A, Gnanavelu G, Venkatesan S, Elangovan S, Jagannathan V, Subramaniam T, Alagesan R, Dorairajan S. Efficacy and optimal dose of sildenafil in primary pulmonary hypertension. Int J Cardiol. 2005 Mar 10;99(1):91-5.

9) Lee AJ, Chiao TB, Tsang MP. Sildenafil for pulmonary hypertension. Ann Pharmacother. 2005 May;39(5):869-84.

10) Sastry BK. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossoverstudyImage. J Am Coll Cardiol, 2004 Apr;43 (7), pp. 1149-53.

11) Ng J, Finney SJ, Shulman R, Bellingan GJ, Singer M, Glynne PA. Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil? Br J Anaesth. 2005 Jun;94(6):774-7.

12) American Heart Association rapid access journal report. Impotence drug may help children with fatal lung disorder. 06/23/2005.http://www.americanheart.org/presenter.jhtml?identifier=3031499. Accessed: June 23, 2005.

National Heart, Lung, and Blood Institute: "What Is Pulmonary Arterial Hypertension?" National Heart, Lung, and Blood Institute: "Living with Pulmonary Arterial Hypertension." WebMD Medical News:"Viagra Label May Note Rare Vision Problems. “ViagraThe Associated Press.

Links

http://www.sciencedaily.com/releases/2006/11/061101151450.htm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1772024/

http://thoracic.org/career-development/residents/ats-reading-list/pulmonary-hypertension.php

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994020/

http://www.medscape.com/viewarticle/471168

http://www.globalrph.com/sildenafil.htm

http://www.fda.gov/drugs/drugsafety/ucm317123.htm

http://www.sciencedirect.com/science/article/pii/S0735109704004759

http://www.webmd.com/lung/news/20050608/viagra-ingredient-okd-for-lung-problem

http://eurheartj.oxfordjournals.org/content/25/5/431.ful l

http://www.nhs.uk/medicine-guides/pages/medicineoverview.aspx?condition=Pulmonary+hypertension&medicine=sildenafil+citrate