Counseling Points - September 2007 - (Page 10)

(tachycardia, hypertension, fever), restlessness, irritability, insomnia, cravings, papillary dilation, lacrimation, rhinorrhea, muscle and joint pain, marked anxiety and dysphoria, and hyperactivity of the gastrointestinal tract (nausea, vomiting, diarrhea). In addition to decreased opioid receptor stimulation, there is evidence for the role of noradrenergic hyperactivity in opioid withdrawal, with elevated norepinephrine metabolite levels. Thus, rational pharmacologic therapies include the use of alpha-2 adrenergic agonists (e.g., clonidine) along with opioid agonists (e.g., methadone) and partial agonists (e.g., buprenorphine) to minimize withdrawal symptoms. Buprenorphine Buprenorphine is a partial mu agonist that exerts its effects by binding to the opioid receptor (Figure 1). It has been reported that up to 95% of receptors are occupied when 16 mg of the drug is administered daily. Due to its high affinity, other drugs, including naloxone, have more difficulty removing buprenorphine from the receptor: indeed, when naloxone is administered to a person who has been taking buprenorphine, there is minimal reversal of its effects. In addition, because buprenorphine has a slow dissociation rate from the receptor, it has a long duration of action. Because of its high affinity and slow dissociation from the mu receptor, if the dose of buprenorphine is sufficient, other opioid drugs (e.g., heroin) waiting to stimulate the receptor will break down before they can attach. Chronic opioid users will often report depressive symptoms. As a partial agonist, buprenorphine has a more limited effect than a full agonist and a putative ability to act as an antagonist, blocking the dysphoric effects produced when the kappa receptor is stimulated. This is a benefit over many other opioids, including methadone, which, in increasing doses over long periods of time, will stimulate the kappa receptor. When buprenorphine is used, chronic opioid users will report a decrease in their depressive symptoms. When the buprenorphine dose is decreased or the drug is stopped, withdrawal is milder than with full agonist opioids. Because it is a partial agonist, autonomic signs of physical dependence are reduced, as is the potential for the development of tolerance. Adverse effects are similar to those seen with other opioids. These factors, along with its ceiling effect on respiratory depression, provide safety in an overdose situation compared with a full opioid agonist. Buprenorphine has poor oral bioavailability, and if swallowed, becomes inactivated by first-pass metabolism in the liver. Thus, sublingual administration is the The Pharmacology of Opioids The effect of opioids on the body is determined by three major properties: affinity for the receptor, the rate of dissociation from the receptor, and the degree to which the drug stimulates the receptor, known as “intrinsic activity.” The drug affinity determines how strong the attraction is to the receptor and how tightly it binds to it. A high affinity makes it difficult for other drugs or neurotransmitters to detach it in order to restimulate the receptor. Dissociation refers to how fast the drug leaves the receptor after it stimulates it. Intrinsic activity determines whether a drug is a full agonist or a partial agonist. A full agonist drug will produce a biologic effect that increases directly in relation to the amount of the drug administered. A partial agonist will have an effect on receptor activation that increases only over a limited dose range (i.e., a “ceiling effect”). Methadone Methadone is a full mu-opioid agonist that produces mu-opioid effects similar to morphine. It is 90% bioavailable, and is highly effective in replacing heroin and other opioids at the receptor, but at a cost— indeed, long-term methadone use produces dependence. In addition, because methadone is a full opioid agonist, a fatal overdose from respiratory depression can occur if the medication is not properly administered. 10 COUNSELING POINTS™

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Welcome Office-Based Medication-Assisted Treatment of Opioid Dependence Summary Continuing Education Posttest Postest Answer and Program Evaluation Form

Counseling Points - September 2007

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