Mexican weightlifter Cinthya Vanessa Dominguez Lara and baseball players Nelson Gomez (Puerto Rico) and Javier Jesus Ortiz Angulo (Colombia) were all kicked out of the multi-sport event after testing positive for anabolic steroids.
Another baseball player, Mario Mercedes Castillo from the Dominican Republic, was caught using a banned stimulant.
"The medical commission is, in a certain way, surprised to have so many cases at the beginning of the Games, but the numbers will (ultimately) be more or less the same that we have at every Games," said Eduardo De Rose, chairman of the Pan American Sports Organisation.
"But we are working here under the new regulation of WADA so the controls are much harder than the controls that we had (for the 2011 Pan Ams in) Guadalajara."
On the penultimate day of the swimming competition the United States grabbed three of the eight gold medals that were contested after wins in the men's 100m backstroke, women's 100 backstroke and 50 freestyle.
Coughlin, a 12-times Olympic medallist who had to settle for two silvers earlier this week after squandering leads, missed out on gold again and was held to a bronze in the 50 freestyle.
Finishing a spot ahead of Coughlin was Etiene Medeiros, whose time of 24.55 broke her own South American and Brazilian record of 24.74.
Medeiros, the first Brazilian woman to win an individual medal at a world championships, won the 100 backstroke earlier in the night with a 59.61 that broke the Pan Am, South American, and Brazilian records.
Hosts Canada enjoyed yet another solid day as they captured 12 medals, including gold in the men's 400m freestyle, women's 400 freestyle, team squash and a pair each in women's track cycling and wrestling.
After an incredible start to the Games, Canada have 109 medals overall and padded their lead in the gold medal count with 45, six more than the United States.
In the overall medals race, the United States lead with 113.
Canadian Ryan Cochrane, a gold medal contender at the upcoming world championships in Russia, captured the men's 400 freestyle with a Pan Am record-setting time of 3:48.29.
"It's been a year of many ups and downs. To come here and actually swim a decent time, I think was what our goal was," said Cochrane.
"We're gonna go back to work for the world championships. But man, it feels good to win a medal."
(Editing by Peter Rutherford)
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