Opioid Drugs, Part 2: Addiction and Overdose

Opioid drugs are a well-known class of drug due to both their ability to kill pain and kill people. Watch part 2 of this two-part series to learn how opioid drugs can cause addiction and overdose, as well as a bit of the history behind the opioid epidemic in North America.

Watch Part 1 here: https://youtu.be/s60KzN4GJdQ

*Two great articles about the opioid crisis:*

The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622774/)

The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction (https://www.annualreviews.org/doi/full/10.1146/annurev-publhealth-031914-122957)

*Mechanism of cAMP*

Two key functions of cAMP have been discovered in neurons. The first is the activation of ion channels to let positive charge into cells, called a “pacemaker current”, which depolarizes the neuron to activate it. Increased cAMP makes it easier for ion channels to open. Without cAMP, it is harder for these channels to open, resulting in less positive charge entering the neuron to depolarize and activate it. The second function of cAMP in neurons is to increase neurotransmitter release. Certain neurotransmitters are released via a protein kinase A dependent pathway, which is initiated by cAMP. Without cAMP, these neurotransmitters are not released. These two functions combined point to cAMP acting as a neuron activator, and thus when opioids decrease cAMP levels, neuron function is also inhibited.

*Methadone and Buprenorphine Mechanisms*

Methadone (Dolophine) is a long-acting opioid receptor activator that does not cause as much euphoria as morphine. Patients with opioid use disorder patients can enroll in a “methadone maintenance” program, in which they receive a dose of methadone every day. This prevents withdrawal symptoms and unsafe activities obtaining and administrating illicit drugs, helping patients get their lives back on track. Its ability to activate NMDA receptors may also be a reason why this drug is effective at eliminating addiction, tolerance, and withdrawal, but the true mechanisms are still being investigated.

Buprenorphine is a partial agonist of the opioid receptor. This means at low doses it can activate the receptor, but at high doses it inhibits the receptor. Thus, the risk of overdose is limited with buprenorphine and thus can also be used to wean patients off of opioids, albeit slower than methadone.

References:

Kosten TR, George TP. 2002. The neurobiology of opioid dependence: implications for treatment. Science and Practice Perspectives, 1(1): 13-20

Kolodny A, Courtwright D, et al. 2015. The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annual Review of Public Health, 36: 559-574

Williams JT, Christie MJ, Manzoni O. 2001. Cellular and synaptic adaptations mediating opioid dependence. Physiological Review, 81(1):299-343

Видео Opioid Drugs, Part 2: Addiction and Overdose канала Medicurio