Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe

Mounteney, Jane; Giraudon, Isabelle; Denissov, Gleb; Griffiths, Paul

doi:10.1016/j.drugpo.2015.04.003

Cited by 147 publications

(138 citation statements)

References 14 publications

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“…273 Fentanyl marketed as heroin has also been associated with lethal overdoses in some countries. 274 Part of the advantage of prescribed and medically administered heroin as treatment for opioid dependence in Switzerland, Germany, and several other countries, for example, is the health authority’s ability to control and know the dosage and purity of the heroin prescribed. Countries that pursue the goal of drug prohibition may object to heroin-assisted therapy as feeding rather than eliminating an addiction.…”

Section: Drug Policy and Death From Overdosementioning

confidence: 99%

Public health and international drug policy

et al. 2016

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Executive summary In September 2015, the member states of the United Nations endorsed sustainable development goals (SDG) for 2030 that aspire to human rights-centered approaches to ensuring the health and well-being of all people. The SDGs embody both the UN Charter values of rights and justice for all and the responsibility of states to rely on the best scientific evidence as they seek to better humankind. In April 2016, these same states will consider control of illicit drugs, an area of social policy that has been fraught with controversy, seen as inconsistent with human rights norms, and for which scientific evidence and public health approaches have arguably played too limited a role. The previous UN General Assembly Special Session (UNGASS) on drugs in 1998 – convened under the theme “a drug-free world, we can do it!” – endorsed drug control policies based on the goal of prohibiting all use, possession, production, and trafficking of illicit drugs. This goal is enshrined in national law in many countries. In pronouncing drugs a “grave threat to the health and well-being of all mankind,” the 1998 UNGASS echoed the foundational 1961 convention of the international drug control regime, which justified eliminating the “evil” of drugs in the name of “the health and welfare of mankind.” But neither of these international agreements refers to the ways in which pursuing drug prohibition itself might affect public health. The “war on drugs” and “zero-tolerance” policies that grew out of the prohibitionist consensus are now being challenged on multiple fronts, including their health, human rights, and development impact. The Johns Hopkins – Lancet Commission on Drug Policy and Health has sought to examine the emerging scientific evidence on public health issues arising from drug control policy and to inform and encourage a central focus on public health evidence and outcomes in drug policy debates, such as the important deliberations of the 2016 UNGASS on drugs. The Johns Hopkins-Lancet Commission is concerned that drug policies are often colored by ideas about drug use and drug dependence that are not scientifically grounded. The 1998 UNGASS declaration, for example, like the UN drug conventions and many national drug laws, does not distinguish between drug use and drug abuse. A 2015 report by the UN High Commissioner for Human Rights, by contrast, found it important to emphasize that “[d]rug use is neither a medical condition nor does it necessarily lead to drug dependence.” The idea that all drug use is dangerous and evil has led to enforcement-heavy policies and has made it difficult to see potentially dangerous drugs in the same light as potentially dangerous foods, tobacco, alcohol for which the goal of social policy is to reduce potential harms. Health impact of drug policy based on enforcement of prohibition The pursuit of drug prohibition has generated a parallel economy run by criminal networks. Both these networks, which resort to violence to protect their markets, and the police and sometimes military ...

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Section: Drug Policy and Death From Overdosementioning

confidence: 99%

Public health and international drug policy

et al. 2016

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“…However, the use of fentanyl in combination with benzodiazepines may cause decreasing cardiac output and stroke volume [7]. Sufentanyl, remifentanil, alfentanil and carfentanil are analogs of fentanyl and are being used as sedatives before surgeries and as analgesics and have the same side effects as fentanyl [82].…”

Section: Fentanylmentioning

confidence: 99%

Opioids and Cardiac Arrhythmia: A Literature Review

2018

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Objective: One of the most important side effects of opioids is their influence on the electrical activity of the heart. This review focusses on the effects of opioids on QT interval prolongation and their arrhythmogenic liability. Methods: By using various keywords, papers published up to 2018 in different databases were searched and identified. The search terms were opioids names, corrected QT interval, human-ether-a-go-go gene, torsades de pointes (TdP), cardiac arrhythmias, opioid dependence and other relevant terms. It emphasized the effects of each opioid agent alone on electrocardiogram (ECG) and some interactions. Results: Available data indicate that some opioids such as methadone are high-risk even at low doses, and have potential for prolongation of the QT interval and development of TdP, a dangerous ventricular tachycardia. A number of opioids such as tramadol and oxycodone are intermediate risk drugs and may develop long QT interval and TdP in high doses. Some other opioids such as morphine and buprenorphine are low-risk drugs and do not produce QT interval prolongation and TdP at least in routine doses. Opium-consumers are at higher risk of supra-ventricular arrhythmias, sinus bradycardia, cardiac block and atrial fibrillation. Conclusion: The cardiac arrhythmogenicity of various opioids is different. Methadone has a higher capability to induce long QT interval and dangerous arrhythmias in conventional doses than others. To reduce of arrhythmogenic risk, high doses of opioids must be used cautiously with periodic monitoring of ECG in high-risk consumers such as patients under opioid maintenance treatment.

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“…[9] In addition to the US, fentanyl abuse is on the rise across Europe; while the most overdose deaths occurred in Estonia, the highest consumption of fentanyl per capita was reported in Germany and Austria. [10]…”

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confidence: 99%

Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs

et al. 2016

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Fentanyl is an addictive prescription opioid that is over 80 times more potent than morphine. The synthetic nature of fentanyl has enabled the creation of dangerous 'designer drug' analogues that escape toxicology screening, yet display comparable potency to the parent drug. Alarmingly, a large number of fatalities have been linked to overdose of fentanyl derivatives. Herein, we report an effective immunotherapy for reducing the psychoactive effects of fentanyl class drugs. A single conjugate vaccine was created that elicited high levels of antibodies with cross-reactivity for a wide panel of fentanyl analogues. Moreover, vaccinated mice gained significant protection from lethal fentanyl doses. Lastly, a surface plasmon resonance (SPR)-based technique was established enabling drug specificity profiling of antibodies derived directly from serum. Our newly developed fentanyl vaccine and analytical methods may assist in the battle against synthetic opioid abuse. Fentanyl is an effective synthetic opioid that is used legally as a schedule II prescription pain reliever. However, fentanyl presents a significant abuse liability due to the euphoric feeling it induces via activation of μ-opioid receptors (MOR) in the brain; the same pharmacological target as the illegal schedule I opioid, heroin.[1] Excessive activation of MOR results in respiratory depression which can be fatal.[2] Fentanyl exceeds the potency of heroin by >10-fold, and morphine by >80-fold posing a significant risk of overdose when it is consumed from unregulated sources.[3] Furthermore, the ease of fentanyl synthesis enables illegal production and the creation of designer drug analogues.[4] The fact that the pharmacology of these analogues has yet to be properly characterized makes them particularly dangerous, especially when certain modifications, even methyl additions, can increase potency, notably at the 3-position (Figure 1 The basis of this strategy involves active vaccination of a protein-drug conjugate to generate an in vivo 'immunoantagonist', which effectively minimizes concentrations of the target drug at the sites of action. As a result, the vaccine reduces the addiction liability and overdose potential of the specific drug. In this work, we report the first instance of an efficacious fentanyl conjugate vaccine. Upon immunization, this vaccine successfully stimulated endogenous generation of IgG antibodies with specificity for fentanyl class drugs. Moreover, mouse antiserum showed nanomolar affinity for a variety of fentanyl analogues by SPRanalytical methods. When mice were dosed with potentially lethal quantities of fentanyl analogues, the vaccine imparted significant protection. No other vaccines to date have demonstrated blockade of the acutely lethal effects of any drugs of abuse. Importantly, our research efforts have yielded significant progress for mitigating the pharmacodynamic effects of fentanyl class drugs. In developing a fentanyl vaccine, hapten design presented the initial and possibly the most crucial challenge. As ...

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Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe

Cited by 147 publications

References 14 publications

Public health and international drug policy

Public health and international drug policy

Opioids and Cardiac Arrhythmia: A Literature Review

Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs

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