The BZD-1 selective agonists include zolpidem (Ambien, Edluar), zaleplon (Sonata), and eszopiclone (Lunesta). They are marketed as “safer” alternatives to classic BZDs as treatments for insomnia. However, time has shown that these drugs are no less addictive than their earlier counterparts. Addiction to zolpidem (Ambien, Edluar) can occur accidentally among people taking it as a sleep aid. It acts rapidly and provides relief for anxiety and insomnia, but it also has a seductive euphoric effect that is enhanced when people resist going to sleep after taking it. Opioids The term opiate refers to analgesics with a chemical structure analogous to morphine (i.e., drugs with a phenanthrene chemical nucleus). Opiates include morphine, codeine, oxycodone, hydrocodone, oxymorphone, and even the antagonist naloxone. Opioid is a broader term that encompasses centrally acting analgesics of any chemical structure. Opioids include the opiates (phenanthrenes), methadone (and other phenylheptylamines), and fentanyl (and other phenylpiperidines). The opioid drugs have the potential to produce profound analgesia, mood changes, physical dependence, tolerance, and hedonic (rewarding) effects that may lead to compulsive drug use. They produce their effects by binding to opiate (opiopeptin) receptors that are found in both the CNS and the periphery. The most well-characterized receptors have been cloned and are designated mu, delta, and kappa. They all belong to a large family of receptors that possess seven transmembrane-spanning domains of amino acids (coupled to intracellular mechanisms via G-proteins). The specific pharmacological profile of an opioid depends on which receptor type the drug binds to and whether it acts as an agonist, a partial agonist, or an antagonist. Opioids produce analgesia by mimicking the natural opiopeptins, such as the enkephalins, beta-endorphin, dynorphin, and others. The opioids and the natural compounds produce analgesia by binding to presynaptic sites in pain pathways to inhibit release of excitatory neurotransmitters such as substance P (via effects on calcium channels), or by direct postsynaptic inhibitory mechanisms (via effects on potassium channels). Most opioids act at the mu and delta receptors to produce analgesia, euphoria, respiratory depression, and physiological dependence. Kappa receptors are more likely involved in producing spinal analgesia. The principal therapeutic use for the opioids is treatment of moderate to severe pain. Activation of certain central receptors is the basis for their use as antitussives, whereas activation of receptors in the gastrointestinal tract is the basis for their use in treating diarrhea. Virtually all the clinically used opioids can be classified as full agonists capable of producing equal maximal reactions. The primary difference among the opioids is in the potency of each agent. Although a number of algorithms exist to convert doses of drugs into “morphine equivalents,” care must always be taken when switching from one opioid to another. Such switching, or rotating, of opioids may be beneficial in certain instances due to differences in the receptor profile of individual opioids or due to genetic variability in opioid receptors across the population. Tolerance and dependence are induced by chronic opioid exposure more than is the case for any other group of drugs (Kosten & George, 2002). Tolerance simply means that higher doses of the drug are gradually needed to produce a given effect (Mayo Clinic, 2018a; Volkow, 2014). When tolerance is fully developed, the maximum response attainable with the opioid is also reduced. Evidence suggests that tolerance may result from a gradual separating of opioid receptors from their G-proteins, thus uncoupling receptors from their effector system. Tolerance does not develop for certain opioid effects such as miosis (pupil constriction) and constipation. Accordingly, “pinpoint” pupils are diagnostic for opioid use (abuse) regardless of tolerance
Another drug that deserves mention as a CNS depressant is the drug meprobamate (Miltown, Equanil). In the 1950s and early 1960s, meprobamate was marketed as a safer alternative to existing anti-anxiety drugs and remained quite popular until the introduction of chlordiazepoxide (Librium, Libritabs) and diazepam (Valium, Diastat). It has sedative and muscle relaxant effects with a poorly defined mechanism of action. Although now essentially obsolete, meprobamate is a metabolite of carisoprodol (Soma, Vanadom), which is a widely used muscle relaxant, and is a popular co-drug used in drug combinations. to other effects, and constipation is an issue in individuals using or abusing opioids chronically. The one exception is meperidine (Demerol), which in high doses does not cause miosis because of its anticholinergic activity and ability to block opioid effects on the oculomotor nerve. Although dependence usually accompanies tolerance, they are distinct phenomena. Dependence is not revealed until the drug is removed from its receptors, either by stopping administration or administering an opioid antagonist such as naloxone. This sets in motion a complex brain response characterized by the classic physical symptoms of withdrawal. Dependence generally occurs much more rapidly than tolerance. A number of specific opioids are available for pain treatment, as well as a number of dosage forms for delivering these drugs (see Table 2). The most commonly prescribed products for chronic pain treatment are oxycodone and hydrocodone. Typical oxycodone regimens include a sustained-release baseline product (e.g., OxyContin, Percolone) and various immediate- release products to be taken as needed for breakthrough pain. Oxycodone products are available as single-component products or fixed combinations, usually with acetaminophen; all are classified as Schedule II drugs. Hydrocodone combinations (e.g., hydrocodone with acetaminophen [Vicodin, Lorcet]), which had been classified as Schedule III, are now classified as Schedule II (DEA, 2014). A more recent trend in sustained delivery involves use of skin patches. Fentanyl (Duragesic, Actiq) and buprenorphine (Butrans, Norspan) are examples of such products. A number of pharmacological approaches are available to treat opioid addiction and overdose. Substitution or chemical detoxification through methadone maintenance programs have been a mainstay for decades. More recently, buprenorphine substitution, in an outpatient physician’s office environment, has gained popularity. The principal product used in these programs is buprenorphine/naloxone (Suboxone and generics) sublingual film. Naloxone, an opioid antagonist, is not substantially absorbed by the sublingual route, but is present to prevent abuse by dissolving the films for intravenous injection. Injection of naloxone neutralizes the effects of the buprenorphine and may actually precipitate withdrawal in an opioid-tolerant patient. Opioid antagonists also have other roles in opioid abuse and overdose. Intranasal preparations of naloxone have been successfully shown to reverse respiratory depression in cases of opioid overdose (NIDA, 2018f). Significant public interest currently exists to examine methods for more widely distributing this life-saving therapy. Depending on the state, friends, family members, and others in the community may give the auto- injector and nasal spray formulation of naloxone to someone who has overdosed. Some states require a physician to prescribe naloxone; in other states, pharmacies may distribute naloxone in an outpatient setting without bringing in a prescription from a physician (NIDA, 2018b). In addition, depot injections (deep intramuscular injections of a dosage form that slowly releases active drug) of naltrexone (Vivitrol, ReVia) are available for detoxified patients to block opioid effects in the case of a drug relapse.
Page 8
EliteLearning.com/Dental
Powered by FlippingBook