Chicago filed a federal lawsuit Tuesday accusing the top three distributors of opioids of “placing profits over public health” and fueling a public health crisis blamed on “rampant over-prescribing and abuse” of pharmaceutical opioids.

Four years ago, Chicago blazed a legal trial with a lawsuit accusing leading opioid manufacturers of knowingly misrepresenting the benefits of opioids, concealing serious addiction risks and targeting the elderly and veterans by making bogus medical claims.

Two years later, Mayor Rahm Emanuel announced an agreement that called for Pfizer, Inc. to adhere to strict standards for the marketing and promotion of prescription opioids.

On Tuesday, the mayor escalated the city’s ongoing legal battle in response to the burgeoning drug epidemic.

The city filed a lawsuit in U.S. District Court, targeting AmerisourceBergen Drug Corporation, Cardinal Health Inc. and McKesson Corporation for what City Hall claimed was their “unfettered and unlawful distribution of opioids” in Chicago. The three companies could not be reached for comment.

According to City Hall, those “Big Three” companies account for roughly 90 percent of all revenues from prescription drug distribution nationwide. They also dominate the wholesale drug distribution market in Chicago and took full advantage of that position.

“Defendants flooded many communities with opioids without conducting the due diligence required by law to prevent the diversion of opioids to an illicit market in these drugs that predictably developed and the defendants helped create, expand and maintain,” the lawsuit states.

The three pharmaceutical giants are in a position of “special trust and responsibility” as registered distributors of controlled substances, the suit contends. They are also “paid to securely deliver opioids” and are the “closest link to pharmacies” across the country.

Because of their direct relationship with pharmacies in the supply chain, the “Big Three” companies are “uniquely capable of determining whether a pharmacy is facilitating the diversion of prescription opioids.” And they are legally obligated to “report and reject suspicious orders” that “exceed reasonable volume” or have an “unusual frequency” or “raise other red flags,” the suit states.

“Yet defendants shipped orders they knew or should have known were being diverted or used other than for legitimate medical purposes….deepening the crisis of opioid abuse addiction and death in the city,” the suit alleges.

“Defendants had financial incentives to continue to supply opioids to pill mills, doctors clinics or pharmacies that prescribe or dispense opioids inappropriately or for non- medical reasons because they may entitle them to volume-based rebates and discounts they may then leverage to further increase their sales volumes and profits.”

As a result of that negligence, Chicago and the nation are “swept up” in what the Centers for Disease Control has called a public health epidemic and the U.S. surgeon general has branded an “urgent health crisis,” the suit contends. From 1999 to 20015 more than 183,000 Americans died of drug overdoses. That’s higher than the death toll for the Vietnam War.

“Chicago suffered 741 opioid related overdose deaths in 2016, a roughly 75 percent increase from the year before. The cost of this human tragedy cannot be calculated or ever adequately compensated. But the financial burden to the city is staggering,” the lawsuit states.

The Healthcare Distribution Alliance, a national trade association representing wholesale distributors, said the “misuse and abuse” of prescription opioids is a “complex public health challenge that requires a collaborative and systemic response that engages all stakeholders.”

“Given our role, the idea that distributors are responsible for the number of opioid prescriptions written defies common sense and lacks understanding of how the pharmaceutical supply chain actually works and is regulated,” the group’s senior vice-president Joh Parker was quoted as saying in an emailed statement.

“Those bringing lawsuits would be better served addressing the root causes, rather than trying to redirect blame through litigation.”

Tuesday’s lawsuit is the latest in a string of steps the city has taken in response to the opioid epidemic.

Two years ago, Emanuel dramatically increased spending to combat opioid and heroin abuse and licensed pharmaceutical representatives to prevent the over-prescription of opioids.

A $700,000 investment in drug-treatment programs – a 50 percent increase over prior funding – was directed first to “opioid treatment deserts,” that had a disproportionate level of addiction and were largely concentrated on the West Side.

That’s where gang members had been pushing the deadly combination of fentanyl and heroin that’s been blamed for a spike in deaths this year.

More recently, the city announced that Chicago Police officers in four South and West Side districts with the greatest number of opioid overdoses would soon be carrying the antidote naloxone, and get two hours of training in how to administer it.