Working Group on PDE5 Inhibitors Chair,
3/13/2014
Working Group on PDE5 Inhibitors Chair, Katerina Mastovska
Outline ? Technical background ? Analytical challenges ? Current analytical methods and techniques ? Fitness for purpose statement ? Questions for SPDS discussion
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3/13/2014
Phosphodiesterase Type 5 (PDE5) Inhibitors
? Used in the treatment of erectile dysfunction (ED) and also explored for the treatment of pulmonary hypertension
? Block degradative action of PDE5 on cyclic guanosine monophosphate (cGMP) in smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis (and arterial walls within the lungs)
cGMP
? cGMP ? second messenger which relaxes smooth muscle tissues, leading to the increased blood flow in blood vessels
PDE5 Inhibitors ? Mechanism of Action
cGMP
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3/13/2014
Approved PDE5 Inhibitor Drugs
In the US:
? Sildenafil (Viagra?, Pfizer, 1998) ? Tadalafil (Cialis?, Elli Lilly, 2003) ? Vardenafil (Levitra?, Bayer, 2003) ? Avanafil (Stendra?, Vivus, 2012)
Other countries:
? Udenafil (Zydena?,Dong-A Pharmaceutical Co. Ltd) in South
Korea and Malaysia
? Mirodenafil (Mvix?, SK Chemicals Life Science) in South Korea ? Lodenafil carbonate (Helleva?, Crist?lia Produtos Qu?mi-cos
e Farmac?uticos) in Brazil
Approved PDE5 Inhibitor Drugs
Patel et al. , J. Pharm. Biomed. Anal. 87 (2014) 176? 190
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Adverse PDE5 Inhibitor Drug Side-Effects
? Nausea ? Headache ? Abdominal pain ? Back pain ? Photosensitivity ? Abnormal vision ? Eye pain ? Sudden hearing loss ? Hypotension ? Face edema ? Joint and muscle pain
? Nasal congestion ? Palpitation ? Tachycardia ? Rash ? Itch ? Priapism ? Heart attack ? Life-threatening drug
interactions (e.g. with nitrates and cardiac antiarrhythmic drugs)
Natural PDE5 Inhibitors
Icariin
? Active component of Epimedium extracts (horny goat weed, yin yang huo, barrenwort, bishop's hat, fairy wings, rowdy lamb herb, randy beef grass)
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3/13/2014
Natural PDE5 Inhibitors
Icariin ? Weak PDE5 inhibitor (studied synthetic derivatives showed
similar PDE5 activity as sildenafil but better specificity) ? Demonstrated to increase production of bioactive nitric
oxide and mimic effects of testosterone ? Used as an aphrodisiac and ED treatment in traditional
Chinese medicine ? Potential to treat osteoporosis
Examples of other herbal drugs and dietary supplements used for sexual enhancement
? Tribulus terrestris
? claimed to increase natural testosterone levels
? Turnera diffusa (damiana)
? aphrodisiac
Plant photos: Wikipedia
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