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News From MEDTOX Scientific Inc

Buprenorphine and HIV TreatmentIn communities where intravenous use of drugs is rampant, sois HIV. When people with HIV are also addicted to opiates,treating both simultaneously helps improve outcomes andreduces the spread of HIV or other infections that aretransmitted through needle sharing and/or risky sexualbehaviors. Combining and coordinating care for the HIV-opiateaddicted patient has been spotty. Treatment systems typicallyfail to integrate the care of one condition in coordination of theother. Patients with HIV and opiate dependencies havetraditionally been unable to get coordinated treatment for theirconditions in one clinical setting.With expansion of buprenorphine treatment into clinics staffedby HIV clinicians, patients now have the option of receivingtreatment of both opioid addiction and HIV infectioncontemporaneously. With this development, a growing body ofevidence suggests that patients and the state of public healthwill benefit. Since 2002, buprenorphine has been available inthe U.S. as an office-based treatment for opioid dependency.This development represented a substantial realignment ofdrug treatment resources from the inpatient clinicenvironment to smaller outpatient offices where individual orsmall groups of physicians organize and manage drugtreatment. Physicians who want to prescribe buprenorphinemust undergo a training program and become certified by theSubstance Abuse and Mental Health Services Administration(SAMHSA). Buprenorphine has been a game-changing drugbecause of its ability to expand access to treatment for opiateaddicts. Nearly 19,000 physicians are currently certified toprescribe buprenorphine; most are medical doctors andosteopathic physicians working general practices and familymedicine.Studies suggest that patients with HIV infection and untreatedopiate addictions often experience delayed treatment until thelater phases of the disease. Delays in treatment of HIV resultin extended period of risky behavior and I.V. drug use thatputs them and their partners at risk for new infections.Treating affected patients for both HIV and opiate dependencycan improve their outcomes on both counts. New researchsuggests that buprenorphine has several advantages overtraditional methadone maintenance programs. A recentrandomized trial found that office-based care can improveaddiction related outcomes for patients with HIV and opioiddependency and may lead to more effective interventions. [1]The results of the trial indicated that patients randomized to


clinic-based buprenorphine therapy entered addictiontreatment much more quickly than those who were assignedto specialty addiction treatment centers elsewhere. Retentionin the clinic-based treatment programs was much better thanit was in the more distant treatment centers. Patientsreceiving buprenorphine in the clinic environment also hadfewer urine test results that were positives for other opiates orcocaine. These patients also visited their primary HIVphysicians more frequently. These are all positive outcomeseffecting treatment success rates.It may also be the case that buprenorphine has fewerinteractions with antiretroviral drugs than methadone.Methadone is the more traditional opiate agonist used innarcotic replacement therapy regimens. Studies suggest thatan antiretroviral can trigger withdrawals in some patientstaking methadone; this does not seem to happen whenbuprenorphine is used. Trying to get HIV patients to abide bytheir treatment plans and take antiretroviral drugs is difficultwhen they're experiencing the gnawing pangs and pains ofopiate withdrawal. Buprenorphine may well enhancecompliance with HIV treatment regimens. As a mixed propertynarcotic analgesic, buprenorphine is less sedating thanmethadone and poses fewer side effects and interactions withHIV treatment.Buprenorphine is a drug that can be used in a variety ofdifferent settings to treat stubborn opioid addiction. Withgreater expansion of buprenorphine-trained physicians intocommunity clinical settings, HIV patients and others withcomplicated medical histories may experience betterhealthcare outcomes and a more satisfying quality of life.[1] Lucas GM et al. Annals of Internal Medicine 2010, Clinic-Based Treatmentof Opioid-Dependent HIV-Infected Patients Versus Referral to an OpioidTreatment Program. 2010; 152:704-711.


Name That DrugThe subject of this month's "name that drug" is a substance ofsignificant complexity and great potential. A relativenewcomer to the mean streets of drug abuse, this substancehas established itself as one of the most after prescriptiondrugs in the world for reasons that youmight not expect. This month's drugcame into the pharmaceutical world as(2S)-2-[(-)-(5R,6R,7R,14S)-9α-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol. Embedded in theInternational Union of Pure and AppliedChemistry (IUPAC) nomenclature is a hardclue as to this drug's biochemical makeup.The drug is an opiate, a distillate of theminor opium constituent called Thebaine.This month's drug is one of a half-dozennotable Thebaine derivatives that includes oxymorphone(Opana), oxycodone (Oxycontin) and naloxone (Narcan). Thedrug is a semi-synthetic opioid controlled in the United Statesunder terms of DEA Schedule III. This drug resembles thechemical actions and mixed characteristics of pentazocine(Talwin), the subject of July's newsletter "name that drug"column.The drug is available by prescription in several different formsand iterations. In addition to a transdermal patch application,the drug can be found in sublingual and tablet forms. There isa formulation for intramuscular injection and an even newerapplication that involves an implantable depot format designedfor slow, even absorption into the bloodstream. Like Talwin,the drug has been compounded with naloxone to reduce thepotential of intravenous injection and parenteral addiction. Asa Schedule III medication, the potential for abuse of this drugis rather modest, viewed similarly to drugs like hydrocodoneand the opiate cough syrups. In its early years as aprescription medication, the drug was assigned to the muchless confining spaces of federal Schedule V. Recent reportsand studies of this drug suggest that abuse of it is becomingwidespread. This drug is a game changer however. Initiallyconjured as an opiate analgesic, the drug has since morphedinto a powerful means for treating opiate dependency. It hastransformed the way opiate addicted patients are now treatedand managed. It is foreseeable that this drug may ultimatelydispatch more traditional methods of treatment (methadonemaintenance).


The drug is one of the most powerful opiates in the modernpharmaceutical armamentarium. It possesses affinity foropiate receptors that bests all other modern narcotics, a broadclass of medications that includes other powerful drugs suchas morphine, fentanyl, methadone and heroin. But what setsthis drug apart from other drugs of the opiate class is thebinding strength that it demonstrates at opiate receptor sitesin the brain. The drug is classified as a mixed propertynarcotic, and although it possesses unparalleled affinity foropiate receptor sites, it performs as an agonist at some and anantagonist at others. These characteristics make the drugcomplicated to deal with. Physicians who prescribe the drugmust undergo specialized training and certification before theycan begin treating patients. This is the only drug of its typewhere specialized medical instruction is required beforeutilization. Because of the drug's mixed properties at opiatereceptors, someone under the influence of the drug will notexperience a traditional opiate euphoria. In fact, some users ofthe drug describe the effects of this drug as more of an edgydysphoria. Because of its exclusive action at opiate receptors,the drug can effectively reverse the effects of other opiatesthat may be present in the bloodstream; this drugcompetitively preempts other narcotics from opiate receptorsin the brain. This effect can be dramatic. For instance,someone who is abusing and is physically dependent on heroinwould be put into instant opiate withdrawal if this month'sdrug were taken. The drug would act similarly and interruptthe action of any other opiate were it to be inadvertentlymixed in to a patient or addict's narcotic regimen.Because of this drug's unique chemistry, it acts in blockade atopiate receptor sites, making it important in the practice ofdrug treatment and rehabilitation. For nearly two generations,methadone has been the go-to therapy in the treatment andmanagement of opiate dependency. Addicted patients whofailed in therapy or those who experienced multiple relapses,methadone (dolophine) represented a fairly safe and reliablemeans of managing the problem. "Methadone maintenance"has been the standard of care therapy in treatment of patientswith chronic opiate abuse histories. Methadone substitutiontherapy crafted a pharmacological solution whereby opiateaddicts could pull back from their lives on the street, pull theneedles from their arms and transition to a medicallysupervised therapy that provided them with the necessarynarcotics to stave off withdrawals. But in the end, methadoneis one of a slew of very potent narcotic analgesics itself, not allthat different than the abused opiates it replaces. Methadoneis frequently abused too, sometimes fatally. Heroin addicts"chip" and add bits and pieces of other narcotics on top of


their methadone therapy to get high. Some methadonepatients take to the abuse of drugs like Xanax to create asuper methadone cocktail that is uniquely stupefying. Thismonth's mystery drug may dislodge methadone from itsprimacy in narcotic replacement therapy and become thestandard of care for the treatment of narcotic addicts.When utilized in the roll of narcotic replacement therapy, thismonth's drug can be tricky to use. Physicians have to follow astrict set of protocols to bridge heroin and methadone addictsover to short acting narcotics, such as morphine, before thesubstitution therapy with this drug can begin. In fact, anaddicted patient must actually descend into a mildly acutewithdrawal before therapy can begin. Once those withdrawalsare evident, the drug is administered. Withdrawals stopshortly afterwards. The dose is adjusted over the course ofseveral days of trial and error. Once sufficient concentrationsof the drug are present to suppress withdrawals and a patienthas become stable, he/she can then be titrated down off thedrug. Becoming more vogue however is the utilization of thedrug in the roll of substitution therapy. As is the case withmethadone maintenance, affected patients are weaned downto as small a dose as possible and then maintained on a lowdose of it over and extended period of time.As an analgesic, this month's drug does not hold a great dealof promise. Its mixed property status makes it a poorcandidate to treat most types of moderate and serious pain.But there are some patients where the drug may be anappropriate fit. To that end, physicians have options thatinclude the transdermal patch, a product not to be confusedwith a fentanyl transdermal patch. As a drug of abuse, therehave been sporadic reports of "outbreaks" in communitieswhere the drug is commonly used in treating narcoticdependency. In the club scene, the drug has been found in thepossession of those who tend to use ecstasy, GHB andhallucinogens. Many people who use the drug to get high areoften disappointed with their purchase. The mixed agonistantagonistproperties of this drug often cause it to be a dud onthe party scene. And although this drug may come off a littleflat for those looking to get high, its real value is in thestabilization, detoxification and maintenance of the addictedopiate patient. For the narcotic dependent and the addicted,this month's drug may be nothing short of a miracle.August 2010 Mystery Drug: Buprenorphine (Suboxone,Subutex, Buprenex)

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