Reflex cough

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Oxolamine [959-14-8] (57) is sold in Europe. It is an oxadiazole, and its general pharmacological profile is described (81). The compound possesses analgesic, antiinflammatory, local anesthetic, and antispasmodic properties, in addition to its antitussive activity. Although a central mechanism may account for some of the activity, peripheral inhibition of the cough reflex may be the dominant effect. The compound has been shown to be clinically effective, although it is less active than codeine (82,83). The synthesis of oxolamine is described (84). 

Ethyl dibunate [5560-69-0] (59), which is sold ia Canada, is the ethyl ester of 3,6-(/ f2 -butyl)-l-naphthalenesulfonic acid. It is stmcturaHy unrelated to most of the classical antitussives and is a selective central inhibitor of the cough reflex. Also significant is its low toxicity. The oral LD q is greater than 5000 mg/kg in the rat. The clinical and pharmacological profile of this compound has been reviewed (89). 

Antitussive. A drug that blocks the cough reflex,... 

Gough-suppression of the cough reflex (antitussive effective) by exerting a direct effect on the cough center in the medulla. Gbdeine has the most noticeable effect on the cough reflex. 

Opiates activate the chemoreceptor trigger zone in the medulla (by disinhibition) to cause nausea and vomiting, and cough suppression also occurs because of the inhibitory effects of opiates on the brainstem nuclei in the cough reflex pathway. Dextromethorphan is the non-opiate isomer of the opiate levorphanol and is an effective cough suppressant. 

TRPVl is involved in the cough reflex [155] and 5-iodo-RTX was shown to function as a potent antitussive drug in guinea pigs [156]. 

Morphine and related opiates are known to suppress the cough reflex these compounds have thus been used extensively in antitussive preparations. Since this activity is not directly related to the analgesic potency, the ideal agent is one that has much reduced analgesic activity and thus, presumably, lower addiction potential. The weak analgesic codeine (4) is... 

Respiratory depression increases progressively as doses are increased. It often manifests as a decrease in respiratory rate, and the cough reflex is also depressed. Patients with underlying pulmonary dysfunction are at risk for increased respiratory compromise. Respiratory depression can be reversed by naloxone. 

The cough-suppressant (antitussive) effect produced by inhibition of the cough reflex is independent of the effects on nociception or respiration (antitussives codeine, noscapine). 

It suppresses the cough reflex in the congh center of the mednlla, and it is used for severe and chronic reflex coughing. 

Use cautiously in people with acute or chronic respiratory impairment, particularly children, because phenothiazines may suppress the cough reflex. If hypotension occurs, epinephrine is not recommended because phenothiazines may reverse its usual pressor effect and cause a paradoxical further lowering of blood pressure. Because these drugs have an antiemetic action, they may obscure signs of intestinal obstruction, brain tumor, or overdosage of toxic drugs. 

Pharmacology Benzonatate anesthetizes stretch receptors in respiratory passages, lungs, and pleura, dampening their activity, and reducing the cough reflex. It has no inhibitory effect on the respiratory center in recommended dosage. Onset of action is... 

Cough reflex Exercise caution when using narcotic analgesics postoperatively and in patients with pulmonary disease because cough reflex is suppressed. Intraoperative awareness Intraoperative awareness has been reported in patients younger than 55 years of age when remifentanil has been administered with propofol infusion rates of 75 mcg/kg/min or less. 

Antiemetic effects Drugs with antiemetic effect can obscure signs of toxicity of other drugs, or mask symptoms of disease (eg, brain tumor, intestinal obstruction, Reye syndrome). They can suppress the cough reflex aspiration is possible. 

Opiate mu receptor OPRMl Agonism Analgesia, Sedation. Physical dependence. Bowel dysfunction. Respiratory depression. Modulation of cough reflex. 

CNS effects include decreased pain perception, altered reaction to pain, euphoria and hypnosis, nausea and vomiting, respiratory depression and suppression of cough reflexes. Increased tone of the gastrointestinal tract is primarily mediated by fx receptors in the bowel. 

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. 

Meperidine differs from morphine in that it has far less antitussive effect and little constipative effect. The drug is particularly useful in cancer patients and in pulmonary patients, in whom the cough reflex must remain intact. However, it does have more seizure-inducing activity than morphine. Although meperidine produces spasms of the biliary tract and colon, such spasms are of shorter duration than those produced by morphine. 

Other reported reactions have included increases in cholesterol level, dry mouth, nasal congestion, constipation, urine retention, mydriasis, weight gain, fever, and suppression of the cough reflex [5,9,20,25]. 

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. 

---