Opioids cough

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. 

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. 

Nociceptin and orphanin are synonyms for the peptide that acts at an opioid-like receptor. Nociceptin may act by inhibiting tachykinin release from sensory C-fibres, and a clinical trial has started to test its effects on cough. 

The large numbers of opioid receptors in areas of the brainstem such as the solitary tract and adjacent areas are probably related to respiratory effects of opiates, cough suppression and nausea and vomiting. Opiates acting in the brainstem reduce the sensitivity of the respiratory centres to pC02 and this is the most common cause of death from overdose with street use of opiates. 

Cough medicines, etc. with small amounts of opioids which are non-prescribed, and can be bought over the counter... 

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. 

Modest abuse potential with possible medical value in U.S. Mild opioid analgesics, some cough syrups, etc. 

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. 

Alkaloids such as boldine, codeine, narceine and morphine are active factors in their receptors. Boldine has morphine-like properties and is active on opioid receptors. It may be used to treat stomach disorders and as metabolic stimulant. As it is similar to morphine, boldine can also be considered in the possible development of treatments for narcotic dependence. Codeine also binds to opiate receptors, and specifically functions to reduce bronchial secretions. Codeine can also be used as a cough suppressant when acting on the centre of the medulla oblongata and as a sedative agent. 

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. 

Mechanism of Action-. An opioid agonist that binds to opioid receptors at many sites in the CNS, particularly in the medulla. This action inhibits the ascending pain pathways. Therapeutic Effect Alters the perception of and emotional response to pain, suppresses cough reflex. 

Mechanism of Action An opioid agonist, similar to morphine, that binds at opiate receptor sites in the central nervous system (CNS). Therapeutic Effect Reduces intensity of pain stimuli incoming from sensory nerve endings, altering pain perception and emotional response to pain suppresses cough reflex. 

Propoxyphene is a synthetic opioid that is similar to methadone but much less potent. Propoxyphene is the active ingredient in the pharmaceutical products Darvon-N and Darvocet-N. It is used by some physicians to treat severe pain and coughs but is hotly debated as a useful medication. Many doctors refuse to prescribe the drug because of its highly addictive nature. 

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. 

Schedule V Substances with limited potential for abuse for example, some codeine preparations for cough, and Lomotil (which contains the opioid diphenoxylate) for diarrhea. 

Action on cough centre Morphine suppresses cough reflexes, but cough suppression by opioids may allow accumulation of respiratory secretions and may produce airway obstruction. 

One of the more benign ancillary activities of morphine lies in its activity in suppressing the cough reflex. Catalytic reduction of codeine (1-2) leads to the dihydro derivative (4-1). Oppenauer oxidation of the hydroxyl group leads to hydrocodone (4-2) [3], a compound used extensively in cough remedies it is of note, however, that this drug retains considerable opioid activity. 

Desflurane does not have a marked bronchodilator effect and in cigarette smokers it is associated with significant bronchoconstriction. In clinical practice, both humidification of inspired gases and opioids are thought to reduce airway irritability but even at moderate concentrations (2 MAC), desflurane is more likely to cause coughing than sevoflurane. In common with other volatile agents, desflurane causes dose-related respiratory depression. Tidal volume is reduced and respiratory rate increases, initially. As inspired concentrations of desflurane increase, the trend is to hypoventilation and hypercardia and apnoea is to be expected at concentrations of 1.5 MAC or greater. 

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... 

Suppression of the cough reflex is a well-recognized action of opioids. Codeine in particular has been used to advantage in persons suffering from pathologic cough and in patients in whom it is necessary to maintain ventilation via an endotracheal tube. However, cough suppression by opioids may allow accumulation of secretions and thus lead to airway obstruction and atelectasis. 

Suppression of cough can be obtained at doses lower than those needed for analgesia. However, in recent years the use of opioid analgesics to allay cough has diminished largely because a number of effective synthetic compounds have been developed that are neither analgesic nor addictive. These agents are discussed below. 

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. 

The most commonly abused prescription drugs are opioids and opiates such as oxycodone and morphine, central nervous system depressants such as barbiturates and benzodiazepines, and stimulants such as dextroamphetamine and methylphenidate. Brand-name painkillers such as Vicodin and OxyContin, depressants such as Valium and Xanax, and stimulants such as Ritalin and Dexedrine are commonly abused (as are some OTC cough remedies). Although helpful and safe when used appropriately, these drugs can cause serious harm when taken in unapproved ways. 

Among the compounds that fall within this class are hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin—an oral, controlled-release form of the drug), morphine, fentanyl, codeine, and related medications. Morphine and fentanyl are often used to alleviate severe pain, while codeine is used for milder pain. Other examples of opioids prescribed to relieve pain include propoxyphene (Darvon) hydromorphone (Dilaudid) and meperidine (Demerol), which is used less often because of its side effects. In addition to their effective pain-relieving properties, some of these medications can be used to relieve severe diarrhea (for example, Lomotil, also known as diphenoxylate) or severe coughs (codeine). 

The narcotic analgesics are also called the opioids because they are related structurally to the natural products of the opium poppy. The medicial properties of opium have been known for thousands of years. It has been used by shamans and medicine men and women for pain, sleep, coughing, and diarrhea. The key chemical compound among the 20 or so isolated from the resin of the... 

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