Opioid combination analgesics

Opioid combination analgesics, butorphanol nasal spray... 

When prescribing strong opioids as analgesics for severe pain, it is even recommended to combine the treatment with prophylactic use of laxatives to avoid constipation. The effect of opioids on the bowel is to cause almost no movement at all in the bowels and therefore it is unavoidable to use stimulating laxatives sometimes combined with bulk forming preparations. 

Pain - Management of persistent moderate to severe chronic pain in patients requiring continuous opioid analgesia for pain that cannot be managed by lesser means such as opioid combinations, nonsteroidal analgesics, or IR opioids. 

Many analgesic effectiveness studies involving combination drug formulations (an opioid combined with a nonopioid) have been reported. For example, in the treatment of moderate to severe postoperative obstetric or gynecologic pain, 2-tablet dose of hydrocodone 7.5 mg with ibuprofen 200 mg was comparable in efficacy to the 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg. Obviously both of these treatments were superior to the placebo [23]. In contrast, for treatment of chronic pain, the 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg was more effective than either the 1 -tablet dose of this combination or the 2-tablet dose of codeine 30 mg and acetaminophen 300 mg combination [24]. In a double-blind, randomized controlled trial involving 118 patients with chronic cancer pain, the combination formulation of hydrocodone (25 mg/d) and acetaminophen (2500 mg/d) was effective in relieving pain in 56.5% of the patients [25]. 

Combination analgesics represent important alternatives for those patients who cannot or should not take vasoconstricting medications or opioids. The acetaminophen compound of Fioricet is also a major alternative to those patients who cannot use NSAIDs. Nevertheless, Fioricet and Fiorinal contain the shortacting barbitmate butalbital and may be habit-forming and addictive. Serious adverse effects may be associated with acute overdose or prolonged overuse. 265... 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

The combination of opioid analgesics with alcohol or other CNS depressants amplifies CNS depression and is potentially harmful and possibly lethal. 

The combination of an opioid and nonopioid oral analgesic often results in analgesia superior to monotherapy and may allow for lower doses of each agent. An NSAID with a scheduled opioid dose is often effective for painful bone metastases. 

Interactions are seen between cocaine and the opioid system in analgesia. A synergistic effect occurs when cocaine is combined with a ju agonist (morphine) in the hot-plate test and a k agonist (U69,593) in the hot-plate test (Waddell and Holtzman 1999). Cocaine enhances morphine analgesia in several analgesic paradigms (e.g., formalin test, hot-plate test, and thermal tail-flick test)... 

Co-codamol is a combination of paracetamol (nonnapioid analgesic) and codeine (opioid analgesic). One of the side-effects of opioids is constipation. Naprosyn is a proprietary (trade name) preparation of the non-steroidal antiinflammatory drug naproxen Adalat is a proprietary preparation of the calcium-channel blocker nifedipine Amoxil is a proprietary preparation of the beta-lactam amoxicillin and Dulco-lax is the brand name of the stimulant laxative bisacodyl. 

A common strnctnral feature required for centrally acting analgesic activity in the opioids is the combination of an aromatic ring and a piperidine ring that maintains the stereochemistry at the chiral centre, as shown below. 

Pentazocine (Talwin) (see also page 252) Street Names Crackers, poor man s h oin, T s and R s> Ts and Rits (all refer to combinations w/ Ritalin) (brands Talwin, Talwin Nx [CIV]) Use Medically used as opioid analgesic euphoria similar to heroin when mixed w/antihistamines combined w/ methylphenidate (Ritalin) is new abuse combination Actions Agonist-antagonist narcotic naloxone, a narcotic antagonist added to Talwin (Talwin NX) has reduced incidence of abuse Effects Euphoria, hallucinations, skin necrosis w/ illicit injection route... 

Ketorolac (Toradol) is an NS AID with very mild antiinflammatory and antipyretic activity. It is a potent analgesic for postoperative pain. Its efficacy is equivalent to that of low doses of morphine in the control of pain. For this reason it is often combined with opioids to reduce opioid dose and related side effects while providing adequate pain relief. It is also used to replace the opioids in some patients with opioid sensitivity. The mechanism of action of ketorolac involves the inhibition of COX and decreased formation of prostaglandins. However, some evidence exists that ketorolac may stimulate the release of endogenous opioids as a part of its analgesic activity. 

Like morphine, codeine is a naturally occurring opioid found in the poppy plant. Codeine is indicated for the treatment of mild to moderate pain and for its antitussive effects. It is widely used as an opioid antitussive because at antitussive doses it has few side effects and has excellent oral bioavailability. Codeine is metabolized in part to morphine, which is believed to account for its analgesic effect It is one of the most commonly used opioids in combination with nonopioids for the relief of pain. The administration of 30 mg of codeine in combination with aspirin is equivalent in analgesic effect to the administration of 65 mg of codeine. The combination of the drugs has the advantage of reducing the... 

Levorphanol (Levo-Dromoran) is an L-isomer morphi-nan derivative of morphine that is five to seven times more potent than morphine. It produces all of the side effects associated with morphine but less nausea. It is indicated for moderate to severe pain as a preoperative anxiolytic. It is often used in combination with thiopental to reduce the latter drug s anesthetic dose and to decrease postoperative recovery time. The o-isomer of levorphanol, dextrorphan, does not possess opioid analgesic activity but is a useful antitussive. 

Diphenoxylate (marketed in combination with atropine as Lomotil in the United States) is chemically related to both analgesic and anticholinergic compounds. It is as effective in the treatment of diarrhea as the opium derivatives, and at the doses usually employed, it has a low incidence of central opioid actions. Diphenoxylate is rapidly metabolized by ester hydrolysis to the biologically active metabolite difenoxylic acid. Lomotil is recommended as adjunctive therapy in the management of diarrhea. It is contraindicated in children under 2 years old and in patients with obstructive jaundice. Adverse reactions often caused by the atropine in the preparation include anorexia, nausea, pruritus, dizziness, and numbness of the extremities. 

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