What is the difference between opioids, opiates, and opium?
In modern parlance, “opioid” is a comprehensive term. It includes every single substance that stimulates opioid receptors in the brain. This includes both natural substances. (eg, derived directly from the opium poppy. That includes morphine) and synthetic substances (eg, created in a lab, such as hydrocodone).
“Opiate” is often used interchangeably with opioids. Though many use the word opiate specifically to refer to natural substances derived from opium—as I do in this chapter. “Opium” is the specific sticky residue that can be extracted from the opium poppy. Opium has been in use since as early as 4000 BC.
Morphine and codeine are natural components of the opium poppy. In the early 1800s, it got discovered. During US Civil war, Morphine was widely used. Most subsequent opioids (including heroin, hydrocodone, oxycodone, and buprenorphine) are termed “semi synthetics.” It means they were all originally derived from one of the opium’s components.
Finally, there are more modern opioids synthesized from basic chemicals in labs. Such as methadone, fentanyl, and tramadol. Generally, synthetic opioids have been developed with higher potency or longer duration of action. Regardless of the origin, opioids are full mu-opioid receptor agonists with very similar effects. (analgesia, euphoria, sedation) And side effects (nausea, constipation, itching).
Differences between these substances are due to lipid solubility. And due to metabolism (which affects a substance’s duration of action).
The only illegal opioid is heroin (DEA Schedule I). Other opioids are found in schedules II, III, or IV. It depends on how widespread an opioid is, its potential for abuse, and other factors.
For example, hydrocodone was reclassified from Schedule III to Schedule II. It is based on epidemiologic data. That indicates that it was more likely to be abused when less restricted. And tramadol was initially unscheduled. But after long-term post-marketing surveillance, it was placed on Schedule IV in 2015.
The popularity of heroin as a drug of abuse peaked in the 1960s. But declined somewhat during the 1970s and 1980s. Due to greater awareness of the risks of overdose. And the increased popularity of cocaine. Throughout the 1990s and 2000s. Liberal prescription of opioid analgesics for acute and chronic pain led to diversion for illicit use. Heroin use has again become a growing epidemic. Because authorities have taken measures to clamp down on prescription opioid abuse. And heroin is cheaper and readily available on the streets.
Over 2 million people in the U.S. have abused prescription opioids. And the trend had been increasing throughout the 2000s. Although the rate of use is starting to plateau. Around half a million people currently use heroin. But these numbers are increasing. Along with the numbers presenting for treatment of opioid use disorder.
Psychological effects: euphoria, tranquility, and mild sleepiness. Opioid-induced drowsiness is referred to as “the nod.” Because users easily nod off to sleep with their chin lowering to their chest, then startle awake.—like drowsy students listening to a boring lecture.
The digestive system-There is an opioid receptor in smooth muscle. Especially in the digestive system in muscle groups. They are responsible for peristalsis in the esophagus and intestines. Nausea is a common—nearly universal—side effect. Though tolerance can develop. Quieting of the large intestine leads to constipation. Which is also nearly universal among opioid users. And tolerance rarely develops for constipation.
The Skin-Opioids increase histamine release, which causes itching over all skin surfaces.
And, Eyes-Opioids have a parasympathetic effect on the eyes. It causes pupillary constriction (pinpoint pupils).
Or breathing-Respiratory depression by opioids is due to a central effect on the respiratory drive. This results in a slower breathing rate. Also even at low doses. And can lead to hypoxia in overdose.
Reproductive system-Frequent use of opioids results in irregular menstrual cycles in women. Also lowered libido in both sexes. And it causes erectile dysfunction in men due to a reduction in testosterone levels.
• Constipation is a long-term effect. The chronic users will typically have only a couple of bowel movements a week instead of every day. They will put up with it.
• Reproductive system. Opioids lower testosterone levels. It results in decreased libido and erectile dysfunction in men. This is often treatable with sildenafil (Viagra). Women who use opioids regularly will develop irregular menstrual cycles.
This results in reduced fertility, but not complete contraception. A woman may still conceive, and it may take longer for her to realize she is pregnant. Because she is used to missing menstrual cycles.
• Route of administration effects. IV use over time results in track marks. Which are thin lines of callus-like skin that follow the course of a vein.
This is due to repeated injections in the same vein. But moving down the course of the vein for fresh injection sites as the previous sites become scarred. IV injection of drugs carries high risk for local infections like abscesses. Or more dangerous infections such as endocarditis.
Withdrawal It takes only 2 weeks of regular use (2 or 3 times a day) to establish tolerance. Withdrawal from opioids is very much like a case of the flu.
The process is very unpleasant even if its not life threatingAlthough not life-threatening. Especially without a medically supervised detox protocol. The early symptoms are : anxiety, craving, nausea, aches in the lower back areas and legs, muscle cramps. And possibly diarrhea. And symptoms get worse and progress to runny nose, watery eyes, intestinal cramps, vomiting, muscle twitches, and the famous “cold turkey” gooseflesh.
Symptoms peak in 12 hours or so, last for 3 to 4 days. Then resolve over the next few days, giving a maximum of 7 days for the withdrawal to run its course. Although it’s possible to withdraw without a detox regimen, relapse rates are high.
Several clinical scales have been developed to measure the severity of opioid withdrawal symptoms. These include the Short Opioid Withdrawal Scale (SOWS). The Clinical Opioid Withdrawal Scale (COWS), and others.
If a person has been using heroin or has been abusing prescription opioids by snorting or injecting.
- Hepatitis A, B, and C
- Complete blood count
- Liver function tests
For patients who are negative for hepatitis A and B, it is recommended that they get vaccinated for both. Because they are at high risk for getting exposed to viruses in the future.
There are many treatment strategies, and different patients are receptive to different approaches. The three main treatment options are:
1. Outpatient tapering
2. Detox (outpatient or inpatient)
3. Maintenance treatment
Some patients can gradually taper down their use of oral opioids without a specific detox protocol. For the most part, these are patients who have been able to obtain the medications legitimately. For example, patients may have started taking opioids because of some dental work. But later found that they became psychologically, then physically dependent. They have been obtaining their drugs by going to multiple providers. Or perhaps one provider has continued to provide refills.
It would be reasonable in this context to try a therapeutic taper. In my experience, the taper will go more successfully if you taper more slowly at the beginning and at the end.
We therefore come up with a fairly simple tapering schedule: Reduce by half a tablet every 3 to 4 days. I reassure F that she is in control of the tapering process; she can slow down the rate if she becomes too uncomfortable from withdrawal symptoms, or taper a little faster if she wishes. I find that giving patients “permission” in this way helps them invest in the process more.
Tapering down opioids can be difficult. Here are some tips:
– Slow down the taper
– Switch to a different opioid for the taper
– Reassure patients that they are in control of the tapering process
Tapering by switching to a different opioid
Another option is to switch your patient to a different, usually long-acting. Opioid before doing the taper, often either buprenorphine or methadone (see sections below for details on these agents). One reason to do this is to interrupt the positive associations a patient might have made with a particular drug. In addition, switching to a longer-acting drug makes for less frequent dosing. The fewer points during the day that people have to choose between taking or not taking something. The more successful they’ll be in following a tapering schedule.
Outpatient detox Detox (detoxification), at its core, is a more medically supervised version of tapering. It’s usually reserved for those with more severe problems. My approach to outpatient detox is similar to the outpatient tapering protocol I’ve outlined with F. Except that I’ll ask the patient to return for more frequent appointments, and I will make referrals to more resources, such as an intensive outpatient program.
I will almost always switch the patient to a longer-acting opioid, either methadone or buprenorphine— this is less common in outpatient tapering. In addition, I may offer extra “comfort” medications to address the common detox symptoms of opioid withdrawal (see Table 11-2).
For inpatient detox
For inpatient detox, the same medication strategy applies, except that everything occurs in an inpatient environment with intensive monitoring for withdrawal symptoms. Patients will also get individual and group Chapter 11: OPIOIDS 169 psychotherapy, as well as 12-step meetings, when the detox occurs at an addiction treatment program facility; they are usually better able to participate after the initial few days of detox.
This extra support is not usually available right away in a hospital’s medical or psychiatric inpatient unit. Relapse rates are high even with a detox regimen. But patients who quit cold turkey often don’t make it through withdrawal before relapsing. Contrary to popular belief, people can die from unsupervised opioid withdrawal. Particularly if they have underlying conditions like diabetes or cardiac arrhythmia.
Buprenorphine is a semisynthetic opioid that has been available as an analgesic since 1981. That includes injectable, sublingual, and transdermal patch. How did buprenorphine end up playing such a central role in treating opioid abuse? Unlike other opioid products such as codeine, hydrocodone, oxycodone, methadone, and even heroin, buprenorphine is a partial agonist—in other words, a combined opioid agonist/antagonist.
This means it occupies the opioid receptors, but doesn’t cause quite the same intensity of receptor activation (or “high”) as full opioid agonists. This is an advantage for people who are in treatment. Because it gives them enough of an effect to ward off withdrawal. But doesn’t make them so high that they are reminded of—and tempted by—the high from other opioids. The bottom line is that buprenorphine, with its push/pull agonist/antagonist properties, it is less likely to be abused than its opioid cousins.
This in itself makes it a good choice for maintenance treatment. But buprenorphine is also much less likely to produce respiratory arrest in overdose. The buprenorphine mono-product (brand name Subutex) has been generic for a few years and is relatively cheap; some insurance companies have it on their preferred formulary list.
For many addiction specialists, plain old buprenorphine is the treatment of choice for both detox and opioid maintenance.
Patients can get a 1-month prescription from a buprenorphine provider with up to 5 refills— although monthly visits at minimum are generally recommended. One of the reasons buprenorphine is less restricted is its safety profile—as an opioid agonist/antagonist. It’s more difficult to overdose on buprenorphine than it is on methadone.
But there’s a catch:
To prescribe buprenorphine (with or without naloxone; see below). You need a waiver from the Department of Health and Human Services. —a system that was established as part of the Drug Addiction Treatment Act of 2000.
You must complete an 8-hour training to obtain this waiver. It will then enable you to prescribe buprenorphine to as many as 100 patients. The Comprehensive Addiction Recovery Act of 2016 raised the patient limit to 275 for addiction treatment providers with advanced training.
Given that buprenorphine alone is an effective treatment for opioid addiction. Why did drug makers create a combination pill of buprenorphine and naloxone? Wouldn’t naloxone—an opioid blocker used to reverse opioid overdoses—neutralize buprenorphine’s effectiveness, rendering it useless?
How to start patients on buprenorphine: Induction
Induction refers to the somewhat complicated process of starting an opioid-dependent patient on buprenorphine (by “buprenorphine” I am referring to any of the preparations, whether mono or combined with naloxone).
It can be done in an outpatient setting and depending on the ultimate dose (based on a patient’s tolerance), the process can take 1–2 days. I start by emphasizing to patients that they should not use opioids for about 24 hours before presenting for induction—otherwise the first dose will cause an unpleasant withdrawal experience.
Buprenorphine treatment should be started in the early stage of withdrawal. It generally means that patients will have noticed some nausea and muscle achiness, rated at 2 or 3 points on the COWS. Your starting dose of buprenorphine will be 2 mg–4 mg, repeated every hour or two until patients are comfortable.
Most forms of buprenorphine are administered sublingually. Buprenorphine has poor oral bioavailability, so a swallowed tablet is a waste of money for the patient. I tell patients to rinse their mouth out thoroughly, and then to get it nice and moist. I then have patients place 1 or 2 tablets (or films) under the tongue and allow several minutes for the dose to dissolve completely.
Patients should not talk or swallow while the medication is dissolving; I try to only ask yes-or-no questions until the medication is gone. It is fine to drink something immediately after the dose has dissolved, which can help with the medicinal taste. I check on patients every hour or so throughout the induction, which usually lasts 4–8 hours. Our clinic has a comfortable waiting room with Wi-Fi, a DVD player, and magazines; I tell patients, “You’re going to be hanging out for a while. There’s a bathroom very close by.”
Medical personnel, myself or my nurse, check on them regularly, and they can get someone’s attention right away. After the second dose, most people feel much better physically. So then it’s just a matter of titrating up to where they feel comfortable without being too sedated. Depending on their tolerance, typical maintenance doses range from about 10 mg to 20 mg a day. At the end of the first day of induction, I make sure patients have someone who can drive them home. I will usually give them a prescription to pick up a small amount of buprenorphine at the pharmacy.
The next morning, they come back, and we pick up where we left off the day before. I give them the whole first day’s dose all at once to start with and make sure they can tolerate it, and then if necessary go up from there. It usually takes us two days to find the right dose; in cases where it takes longer, I’ll have the patient come into the office for a few more days.
After the induction
I will generally see patients weekly, which allows me to make dosage adjustments as needed. I will increase the dose if there are still cravings and withdrawal symptoms, or reduce it if there are opioid side effects, such as constipation or oversedation. While it’s not always easy to determine the right amount of buprenorphine for a given patient, it’s important to do your best. Some patients may exaggerate their withdrawal symptoms to obtain higher doses of buprenorphine, and then divert the extra pills to the black market, either for profit or in exchange for other drugs that the patient likes better.
This is a good reason to do regular random urine drug testing (see Chapter 2) not only for illicit drugs. But also for the presence of buprenorphine (or its metabolite, norbuprenorphine). Another way to detect diversion is with random short-notice medication counts (have patients bring in all their leftover medication between visits on short notice—less than 24 hours—to establish whether they are using it at the expected rate), but this takes time, so I only do it for patients I’m especially concerned about.
Buprenorphine maintenance vs. tapering
Once we have arrived at a stable dose of buprenorphine. I talk with patients about how long they will need to stay on it. Some people need more time on the medication. Because of the severity of their addiction and the harsh consequences of relapse. Having such patients on a maintenance dose for many months allows them time to work on the behavioral components that they are learning in therapy or in 12-step programs. Other patients may start from a better place. A less severe usage problem and a good support system.
These patients might be ready for a taper fairly soon after starting on buprenorphine. We talk about decreasing the dose. The taper is fairly straightforward. The smallest dosage strength is 2 mg. And patients can cut pills or strips in half and taper down in 1 mg increments.
I’ll have patients decrease the dose anywhere from every few days to every few weeks. It depends on the time available and the patient’s physical and psychological comfort level. A typical outpatient taper will take around 2 months.
Typical causes of buprenorphine treatment failure
• Lack of support. A home environment that doesn’t provide the needed support is a major cause of problems with remaining abstinent. Patients need to have family or close nonusing friends for encouragement. And to help them deal with the emotional and physical ups and downs of early recovery.
• Using other drugs. Some people don’t want to give up their marijuana or alcohol. That is another reason for relapse. I do random drug testing. I let people know that their goal is going to be abstinence from all problem substances.
How to choose among the different formulations of buprenorphine
The first buprenorphine/naloxone product to be approved was suboxone (in 2002). And in 2010 its period of marketing exclusivity expired. And at the time of this writing there are six versions to choose from.
The main factor influencing the choice of formulation tends to be the patient’s insurance policy. Some insurance simply covers the cheapest formulation: the generic mono product, buprenorphine without naloxone. However, there are other more meaningful factors distinguishing the products.
Bioavailability refers to the fraction of the drug that makes its way into the bloodstream and to the brain. small intestine absorbs typical drug molecules when taken orally. And then delivered by portal blood vessels to the liver. Which metabolize some fraction of the drug, removing it from circulation. And the degree to which it occurs varies from drug to drug. The only way to completely avoid the first-pass effect is to administer drugs intravenously. Which gets 100% of the drug into systemic circulation (100% bioavailability). Another way to bypass the liver is with sublingual drugs.
These capillaries go directly to systemic circulation.
Most buprenorphine/naloxone preparations exploit the oral mucosa route in some way or another. But they vary in ineffectiveness. The greater the bioavailability, the lower the dose required. This is why, for example, Bunavail (the citrus-flavored buccal film approved in June 2014) 4.2 mg is equivalent to sublingual bup/nal 8 mg.
A faster absorption means that a withdrawal patient in your office will get somewhat faster relief from those symptoms. But we’re only talking about 10 or 15 minutes’ difference at most.
The more bioavailable formulations require a lower number of milligrams to achieve the same effect. A possible disadvantage is a psychological one. This “nocebo” effect (the opposite of the placebo effect) can be significant when it comes to subjective perceptions of opioid effects. With all this in mind, let’s go through the various formulations of buprenorphine (see Table 11-3). In general, I favor the combination product (buprenorphine/naloxone) over the mono product. Because it tends to be more available in pharmacies.
Some patients and their families request the combination because of naloxone’s potential to help prevent abuse. There is one clear role for the mono product over the combination product. For pregnant women to reduce fetal exposure to medications, including naloxone. Recent research has shown that buprenorphine is safe and effective in pregnancy. With similar effectiveness to methadone ( Jones et al, 2010; Jones et al, 2005). Among the combination formulations, Suboxone has been around the longest and patients are most familiar with it.