Pain and coughs are as common as the medication we can prescribe for them, but taking the wrong medicine may induce heart disease. Drugs come with side effects, sometimes toxic, which is why they are advised to be taken under the guidance of a doctor. But some drug usage may come with risks even under the guidance of a doctor: opioids, for instance, are a class of drug prescribed for coughs and pains, and an unexpected culprit of heart disease.
“This, coupled with an increase in opioid abuse, has led to a surge in unintentional deaths, drug-related acute coronary syndromes (ACS) and endocarditis.”
Which Drugs are Opioids?
Opioids are the most commonly used pain relievers in clinical practice, including weak opioids and strong opioids.Weak opioids include tramadol, dihydrocodeine, and codeine, etc. Strong opioids include morphine, oxycodone, hydromorphone, pethidine, fentanyl, buprenorphine, methadone, and tapentadol, etc. For moderate to severe pain (acute myocardial infarction, surgery, cardiac resuscitation, etc.), strong opioid analgesics are generally selected.
Why Do Opioids Cause Heart Disease?
Studies have shown that the effects of narcotic analgesics on the cardiovascular system are largely attributable to opioid receptor-mediated targeting.There are three main opioid receptors in healthy people, and when opioids enter the body, they act by activating opioid receptors in the central nervous system. This might cause symptoms including analgesia, euphoria, ventilatory depression, constipation, and pruritus. This pathway is exploited clinically for a number of FDA approved indications, including prescription analgesics (e.g., oxycodone), over-the-counter antitussives (e.g., dextromethorphan), and over-the-counter remedies for diarrhea (e.g., loperamide).
Despite these established effects, opioid-receptor modulation is increasingly recognized to affect the cardiovascular system because of the presence of substances in the human heart called “endogenous opioid peptides” that are involved in the modulation of pain information.
When opioids bind to opioid receptors, the production of this endogenous opioid peptide is inhibited, which may lead to lower blood pressure and tachycardia. Outside the central nervous system, opioid receptor functions include regulation of heart rate, positive inotropic status (strength of heart contraction), vascular function, and cellular adaptation to ischemic (reduced blood flow) injury.
In general, chronic opioid use, abuse, overdose, and withdrawal are associated with complications of cardiac disease, including vascular, valvular, and arrhythmic sequelae. Acute opioid receptor-induced cardiovascular disease is well known, including hypotension, orthostatic, syncope, and bradycardia. In the United States, opioids such as morphine are commonly used in the treatment of acute coronary syndrome because of its vasodilatory properties, which makes it highly effective.
The researchers pointed out that a variety of factors may have contributed to this result. We cannot rule out that morphine may be a sign of poor medical care. Furthermore, morphine use may only be a marker for more severely ill patients, such as those with persistent chest pain or congestive heart failure, since morphine is a widely used treatment for both conditions. Alternatively, the pain relief effects of intravenous morphine may reduce the severity of the chest pain without actually improving the actual disease or injury causing the chest pain.
The Timing and Dose of Opioids May Also Be a Contributing Factor
Opioids lead to cardiovascular disease mainly by activating opioid receptors. The effects of opioids on the cardiovascular system also include many factors. For example, the timing and dose of opioids taken by patients are closely related to cardiovascular disease.The rise in opioid abuse has led to a surge in unintentional deaths, as well as an increase in drug-related acute coronary syndrome and endocarditis (inflammation of heart’s inner lining). Although opioids play an important role in the treatment of many diseases, their side effects on the heart cannot be ignored. Therefore, it is prudent to delay the use of opioids to suppress pain, at least until a doctor has made the diagnosis and decided on a final treatment plan.
Employ Risk Reduction Strategies
To prevent the side effects of opioids, there’s certain things we can do. For example, the Centers for Drug Abuse Treatment recommends QTc interval screening during methadone treatment and a 12-lead ECG at baseline, within 30 days, and annually thereafter, and if the methadone dose exceeds 100 mg/day.Opioids have a depressive effect on breathing and also carry a risk of cardiac arrhythmias in susceptible individuals. Electrocardiogram (ECG) screening is recommended for this in the American Heart Rhythm Association and American Pain Society collaborative guidelines for people with chronic pain.
Risk reduction strategies need to address respiratory depression, ventricular arrhythmias, and the rising incidence of endocarditis. Cardiovascular specialists should carefully decide the amount of opioids to prescribe to postoperative patients, and long-term prescriptions should be avoided.
Opioid withdrawal also triggers hypertension, tachycardia (heart rate over 100 beats per minute), stress cardiomyopathy (heart muscle disease), and potentially acute coronary syndrome.
What Painkiller Can One Take Instead of Opioids?
In recent years, scientists have been working to find drugs that can replace opioids.Over 100 million Americans are affected by chronic pain, and a quarter of them experience pain on a daily basis, a burden that costs an estimated $600 billion in lost wages and medical expenses each year. For many of these patients—those with cancer, diabetes, or trauma, for example—their pain is neuropathic, meaning it’s caused by damage to pain-sensing nerves.
To treat chronic pain, prescriptions for opioid painkillers have increased exponentially since the late 1990s, leading to a rise in abuse and overdoses. Despite the desperate need for safer pain medications, development of a new prescription drug typically takes over a decade and more than $2 billion according to a study by the Tufts Center for the Study of Drug Development, explains study leader Enas S. Kandil, M.D., associate professor of anesthesiology and pain management at UTSW.
Seeking an alternative to opioids, Kandil and her UT Southwestern colleagues explored the potential of drugs already approved by the FDA.
The team focused on EphB1, a protein found on the surface of nerve cells, which Mark Henkemeyer, a professor of the same university, and his colleagues discovered during his postdoctoral training nearly three decades ago. Research has shown that this protein is key for producing neuropathic pain. Mice genetically altered to remove all EphB1 don’t feel neuropathic pain, he explained. Even mice with half the usual amount of this protein are resistant to neuropathic pain, suggesting EphB1’s promise as a target for pain-relieving drugs. Unfortunately, no known drugs inactivate EphB1.
Exploring this angle further, Mahmoud Ahmed, one of the study authors, used computer modeling to scan a library of FDA-approved drugs, testing if their molecular structures had the right shape and chemistry to bind to EphB1. Their search turned up three tetracyclines, members of a family of antibiotics used since the 1970s. These drugs—demeclocycline, chlortetracycline, and minocycline—have a long history of safe use and minimal side effects, Ahmed says.
To investigate whether these drugs could bind to and inactivate EphB1, the team combined the protein and these drugs in petri dishes and measured EphB1’s activity. Sure enough, each of these drugs inhibited the protein at relatively low doses.
In three different mouse models of neuropathic pain, injections of these three drugs in combination significantly blunted reactions to painful stimuli such as heat or pressure, with the triplet achieving a greater effect at lower doses than each drug individually. When the researchers examined the brains and spinal cords of these animals, they confirmed that EphB1 on the cells of these tissues had been inactivated, the probable cause for their pain resistance. A combination of these drugs might be able to blunt pain in humans too, says Kandil. With research, more alternatives to opioids are expected to be found in the future, which will help alleviate the occurrence of various heart diseases caused by opioids.
In 2021, Dey S. and Vrooman BM from Geisel School of Medicine at Dartmouth College proposed a variety of non-drug pain relief methods including: exercise, physical activity, physical therapy, behavioral therapy, and others.
Not every therapy is suitable for every patient. That said, a patient’s care team should be aware of the large number of non-opioid treatment options available. Existing medical and psychiatric comorbidities and patient preferences should also be considered when making treatment decisions. A bio-psycho-social model is recommended to design an individualized multimodal treatment plan. Pain outpatient consultation should be considered early in the care of patients with chronic pain to aid in optimal treatment options.
