Opioid cough suppressant effects

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. 

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 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). 

While it is true that dextromethorphan is not technically a member of the opiate family, it is distantly related in its chemical composition. Dextromethorphan is created by from levomethorphan, which is classified as an opioid, the synthetic or semi-synthetic relatives of the natural chemical family called the opiates. Levomethorphan has most of the same qualities of all drugs in the opiate and opioid classes. This includes strong suppressive effects on the respiratory system. It is these strong effects on the respiratory system that make dextromethorphan an effective anti-cough agent. Opiate and opioid compounds have anti-cough properties but produce greater overall respiratory depression than dextromethorphan. 

The effects of opioids on the central nervous system are to produce analgesia (particularly effective in chronic or acute pain of a constant nature), elevation of mood (euphoria), respiratory depression (occurs at therapeutic doses), cough suppression, nausea and vomiting and miosis (pin-point pupils). 

Kappa receptor activation does not appear to be responsible for dependence, euphoria, or effects on smooth muscle. Increases in cerebral blood flow and (possibly) increased intracranial pressure result from the respiratory depressant actions of opioid analgesics. The latter effects are due to increased arterial PrOj, which results from mu receptor inhibition of the medullary respiratory center. However, the activation of kappa receptors contributes to analgesia at the spinal level and is probably responsible for sedative actions of the opioids. The answer is (D). Codeine and possibly nalbuphine could decrease gastrointestinal peristalsis but not without marked side effects (and a prescription). Dextromethorphan is a cough suppressant. The other two drugs listed are opioids with antidiarrheal actions. Diphenoxylate is not available over-the-counter since it is a constituent of a proprietary combination that includes atropine sulfate (Lomotil). Loperamide is available over-the-counter. The answer is (D). 

Opioids are a category of narcotic analgesics. All relieve pain and all, except meperidine (Demerol), have an antitussive (cough suppression) and antidiar-rheal effect. 

Currently there are few effective cough suppressants and it has been concluded that patients requiring symptomatic relief in chronic cough derive a very low level of benefit from available drugs (Bolser 2006). Most effective are opioids such as codeine which produce a reduction in the frequency of cough of 19-60% (Bolser 2006 Morice et al. 2007). However, the usefulness of opioids is limited by their sedative properties and dependence liability (Bolser 2006). 

Various other receptors have been associated with cough suppression in animal models, such as non-opioid receptors (NOP-1) (Bolser et al. 2001 McLeod et al. 2001, 2004 Lee et al. 2006), cannabinoid receptors (Gordon et al. 1976 Jia et al. 2002 Morita and Kamei 2003 Patel et al. 2003), and dopaminergic receptors (Kamei et al. 1987a Li et al. 2002). In humans, dopaminergic receptors appear to have no effect on irritant-induced cough in normal subjects (O Connell 2002). 

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,... 

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. 

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 effects of k and 8 opioid receptor activation on the cough reflex have been particularly investigated by Kamei and coworkers. They showed that U-50,488H (Fig. 7), a selective k opioid receptor agonist, suppressed the cough reflex induced by capsaicin inhalation in rats. This antitussive effect was blocked by coadministration of the k receptor antagonist, nor-BNI (Fig. 7). This suggested that the k opioid receptor had mediated the antitussive effects (Table 2) [33],... 

Figure 8 shows the mechanism proposed for the antitussive effect of NTI [36]. When the respiratory tract is stimulated by irritants, e.g., xenobiotics, the cough reflex occurs, and the stress of coughing triggers the secretion of endogenous opioid peptides, which may simultaneously stimulate three types of opioid receptors. In a disease state, the stimulation of the 8 opioid receptor could block the p and k opioid receptor-mediated suppression of the cough reflex, which would result in continual coughing (Fig. 8a). When a selective 8 opioid antagonist, e.g., NTI, is administered,...

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