The opioid epidemic is an ever-growing struggle: 72,000 Americans died from a drug overdose last year, the most on record, according to data released in August by the U.S. Centers for Disease Control and Prevention. Increasing use of opioids drove up use, but it is not just increasing use of heroin and illicit use of prescription painkillers that are fueling the rise in opioid deaths. One of the biggest factors in the opioid epidemic is the increasing use of highly dangerous drugs, in particular synthetic opioids like fentanyl.

Drug overdoses are now the leading cause of accidental death in the United States. More Americans die of drug overdoses than in car accidents, which are also frequently the result of substance abuse — nearly half of fatal car accidents involve alcohol or other substances.

To better understand the likelihood of Americans dying from using a specific substance, it is important to also get a better understanding of the substance itself — its properties, interactions with other drugs and alcohol, and how often it is used.

The vast majority of people who drink in the United States — more than half of Americans — do so responsibly. Millions of people also use pain medication every day and do not stray from their prescribed dosage regimens. And while overdoses from prescription opioids are a major factor in the opioid epidemic, they are essential to many Americans who rely on them to function.

The double-edged sword of risk and reward in prescribing opiates is common to many other drugs as well. Approximately half of all people in the United States use at least one prescription drug on a regular basis.

Issues related to substance use — substances that may as easily be fatal as they are vital — tend to be over-simplified. According to Sidney Schnoll, vice president of pharmaceutical risk management at the public health consulting firm Penney Associates, “It’s a little complicated.”

In an interview with 24/7 Wall St., Schnoll explained that the harm from both illicit and prescribed substances is rooted in “the interaction between the person and the chemical.” Both beneficial and deadly outcomes can occur whether the substance is an opioid, an antihypertensive medication, a laxative, or any other drug. “There are people who have adverse reactions to all these things,” he said.

The reactions, behaviors, and adverse health outcomes associated with drug can become substance abuse disorders — acknowledged diseases in the health community that are often treated as criminal problems.

The likelihood of adverse reactions and death increases considerably when substances are mixed with other drugs. “The safety of a drug [also] depends on its interactions with other substances,” Schnoll added.

24/7 Wall St. reviewed 25 of the most dangerous drugs and drug mixtures based on side effect and death rates tracked by the federal government, as well as potential risk of drug combinations measured by medical information organizations and web sources such as MedScape, WebMD, and the American Medical Association. These substances span well-known controlled substances, infamous street drugs produced in unsafe conditions, and lethal combinations of otherwise safe medications. Many of these drugs when taken on their own and under the correct conditions are considered to be widely safe and are only seriously deadly when combined inappropriately with other drugs.

However, no drug is perfectly safe, and some widely-prescribed and popular over-the-counter medications are more likely to pose a risk to more Americans than rare drugs with a higher rate of dangerous side effects. Some of the drugs on this list are a broad category of medication with similar effects and risks, while others are a single formula

Click here to see the 25 most dangerous drugs.
Click here to see our detailed findings and methodology.