Antitussives opioids

Opioids ( opioid systems) are thought to exert their antitussive effects by acting as agonists at p- and K-opioid receptors in the CNS. Activation of these receptors activates various G-proteins and leads to the inhibition of... 

BW443C is a novel opioid used for the treatment of cough, but which does not enter the brain and so exerts its effects only on peripheral nerves. It has not been tested as an antitussive in humans due to its rapid metabolism in the lungs but the concqrt of a peripheral opioid is still possible. 

These dm may produce withdrawal symptoms in those physically dependent on the narcotics. The patient must not have taken any opiate for the last 7 to 10 days. Naloxone may prevent die action of opioid antidiarrheals, antitussives, and analgesics. This drug is used cautiously during lactation. 

Prophylactic, continuous use of antibiotics has no effect on the frequency of exacerbations antibiotics should only be used for treating infectious exacerbations. Antitussives are contraindicated because cough has an important protective role. Opioids may be effective for dyspnea in advanced disease but may have serious adverse effects they may be used to manage symptoms in terminal patients. 

Although opioids have been used for thousands of years for their analgesic, euphoric, antitussive, and gastrointestinal effects, only relatively recently has their impact on... 

Codeine, dextromethorphan and pholcodine are opioid cough suppressants indicated for dry cough. Sedating antihistamines, such as diphenhydramine, tend to have an antitussive action as well. Vitamin C is not used in the management of cough but may be used as a prophylaxis against colds. 

Dextromethorphan is an opioid antitussive similar in action to codeine and pholcodine. Codeine and pholcodine are considered to be more potent than dextromethorphan. Dextromethorphan tends to cause less constipation and dependence than codeine. Cough suppressants are not usually recommended in children under 2 years. 

Dextromethorphan (Mediquell, Benylin DM, PediaCare 1, Delsym, Others) [OTC] [Antitussive] Uses Control nonproductive cough Action Suppresses medullary cough center Dose Adults. 10-30 mg PO q4h PRN (max 120 mg/24 h) Peds. 2-6 y 2.5-7.5 mg q4-8h (max 30 mg/24 h) 7-12 y 5-10 mg q4-8h (max 60 mg/24/h) Caution [C, /-] Not for persistent or chronic cough Contra < 2 y. Disp Caps, lozenges, syrup, Liq SE GI disturbances Interactions T Effects W/ amiodarone, fluoxetine, quinidine, terbinafme T risk of serotonin synd Wf sibutramine, MAOIs T CNS depression Wf antihistamines, antidepressants, sedative, opioids, EtOH EMS Will not affect cough caused by asthma,... 

The opioids block cough by a mechanism that is not yet understood. No stereoselectivity of the opioids for blockade of the cough reflex has been shown. Thus, the isomers of opioids, such as dextrorphan, are as efficacious as the L-isomers as antitussives. This lack of stereoselectivity prompted the development of the D-isomers of opioids as antitussives since they are devoid of the dependence liability of h-isomers. Drugs with predominantly antitussive effects are described later in this chapter. Certain of the opioids, such as propoxyphene and meperidine, are relatively devoid of antitussive effects. 

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. 

Certain opioids are used mainly for their antitussive effects. Such drugs generally are those with substituents on the phenolic hydroxyl group of the morphine structure. The larger the substituent, the greater the antitussive versus analgesic selectively of the drugs. 

Mecfianism of Action An opiate and antitussive that binds with opioid receptors in the CNS. Therapeutic Effect Alters the perception of and emotional response to pain suppresses cough reflex. 

An antitussive agent, then, is a drug that suppresses or prevents cough. Codeine and dextromethorphan are the most commoniy used antitussives. Other opioids are also effective antitussive agents, but are not used as medicines to suppress cough. 

The opioids contain natural and synthetic compounds that are medicinally used as analgesic, antidiarrheal, and antitussive agents. Opioids are CNS depressants and decrease blood pres-... 

Central nervous system depression is the usual effect of morphine, and sedation and drowsiness are frequently observed with therapeutic doses. When given in the absence of pain morphine may sometimes produce dysphora—an unpleasant sensation of fear and anxiety. The most important stimulatory effects of morphine in man are emesis and miosis. Miosis, due to stimulation of the Edinger-Westphal nucleus of the third nerve, occurs with all opioids. The combination of pinpoint pupils, coma, and respiratory depression are classical signs of morphine overdosage. Stimulation of the solitary nuclei may also be responsible for depression of the cough reflex (antitussive effect). Pharmacokinetics and metabolism... 

Codeine, one of the principal alkaloids of opium, has an analgesic efficacy much lower than other opioids, due to an extremely low affinity for opioid receptors. It is approximately one-sixth as potent as morphine. It has a low abuse potential. In contrast to other opioids, with the exception of oxycodone, codeine is relatively more effective when administered orally than parenterally. This is due to methylation at the C3 site on the phenyl ring (Figure 7.3), which may protect it from conjugating enzymes. It is used in the management of mild-to-moderate pain, often in combination with non-opioid analgesics, such as aspirin or paracetamol. It is valuable as an antitussive and for the treatment of diarrhoea. Side effects are uncommon and respiratory depression, even with large doses, is seldom a problem. 

The opioid analgesics are among the most effective drugs available for the suppression of cough. This effect is often achieved at doses below those necessary to produce analgesia. The receptors involved in the antitussive effect appear to differ from those associated with the other actions of opioids. For example, the antitussive effect is also produced by stereoisomers of opioid molecules that are devoid of analgesic effects and addiction liability (see below). 

The physiologic mechanism of cough is complex, and little is known about the specific mechanism of action of the opioid antitussive drugs. It appears likely that both central and peripheral effects play a role. 

The opioid derivatives most commonly used as antitussives are dextromethorphan, codeine, levopropoxyphene, and noscapine (levopropoxyphene and noscapine are not available in the USA). They should be used with caution in patients taking monoamine oxidase inhibitors (see Table 31-5). Antitussive preparations usually also contain expectorants to thin and liquefy respiratory secretions. Importantly, due to increasing reports of death in young children taking dextromethorphan in formulations of over-the-counter "cold/cough" medications, its use in children less than 6 years of age has been banned by the FDA. Moreover, due to variations in the metabolism of codeine, its use for any purpose in young children is being reconsidered. 

Levopropoxyphene is the stereoisomer of the weak opioid agonist dextropropoxyphene. It is devoid of opioid effects, although sedation has been described as a side effect. The usual antitussive dose is 50-100 mg every 4 hours. 

Analgesic efficacy and clinical use Levomethadone like racemic methadone is a potent and long-acting opioid analgesic and can be used for the treatment of moderate to severe pain (Jamison, 2000 Davis and Walsh, 2001). It has an action profile similar to morphine and has significant antitussive properties, for which it is used in terminal lung cancer. The long duration of action makes the compound suitable for substitution treatment of opioid addiction (Joseph et al., 2000 Pallenbach, 2002). For practical and economic reasons the racemate instead of the levo-enantiomer is used in addicts. 

In addition to their use as pharmacological tools, selective 8 opioid antagonists may have clinical potential in the treatment of a variety of disorders where endogenous opioids play a modulatory role, e.g. disorders of food intake, shock, constipation, mental disorders, CNS injury, alcoholism, drug addiction and immune function (Spetea et al., 2001). It is also worth mentioning that 8 antagonists have been shown to possess an antitussive effects in rodents, thus indicating another possible clinical application for these compounds (Kamei et al., 1994). 

Kamei, J., Iwamaoto, Y., Suzuki, T., et al. Involvement of 8-,-opioid receptor antagonism in the antitussive effect of S-opioid receptor antagonists, Eur. J. Pharmacol. 1994, 257, 291-294. 

Hydrocodone is a semisynthetic opioid derived from codeine.18It is utilized as an analgesic and antitussive available for oral administration, often in combination with acetaminophen or ibuprofen. As a rule, potent analgesics containing a methoxyl group at position 3 (e.g., hydrocodone, K, = 19.8 nM) bind the mu receptor relatively weakly, but their O-demethylated metabolites (such as hydromorphone, Kt = 0.6 nM) bind more strangely. As with oxycodone, the possibility exists that some of their ability to relieve pain may actually derive from their active metabolites 48... 

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