Morphine 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). 

Narcotic Antitussives. Since its isolation in 1832, codeine [76-57-3] (27) has been one of the most widely used and effective compounds for the treatment of cough. Though less potent than morphine [57-27-2] (28), it has become the reference against which most antitussives are measured. 

Codeine, like morphine, is isolated from the opium poppy. However, the low yield of 0.7—2.5% does not provide sufficient material to meet commercial demands. The majority of marketed codeine is prepared by methylating the phenolic hydroxyl group of morphine. Morphine yields from opium poppy are 4—21%. When prescribed for cough, the usual oral dose is 10—20 mg, three to four times daily. At these doses, adverse side effects are very few. Although the abuse potential for codeine is relatively low, the compound can substitute for morphine in addicts (47). 

Alkaloids range from the belladonna alkaloids, such as atropine and scopalomine—which are used as poisons, cold remedies, and truth serums —to dextromethorphan, a cough suppressant (anti-tussive). But the most widely known alkaloids are the opiates, such as morphine, heroin, fentanyl, oxycodone, and methadone. These act on... 

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... 

In addition, morphine has served as a point of departure for the discovery of many medically usefnl derivatives. These inclnde codeine, a pain reliever and cough suppressant, levophanol, an orally active analgesic (morphine is not active when given orally and is nsnally given by injection), and many other modem and highly potent opiate analgesics. 

The same type of reasoning allows production of pholcodine, an effective cough suppressant, from morphine. In this semi-synthesis, the electrophile is Ai-(chloroethyl)morpholine, and the leaving group is chloride. 

Hydrocodone is an opium analgesic (pain reliever) and antitussive (cough suppressant). It is related in structure to other alkaloids used as drugs, such as morphine and codeine (see Section 8). It increased 20% in number of prescriptions for one year. Its synthesis from codeine is by simple reactions. 

Codeine occurs naturally in opium but the amount is too small to be useful. It is prepared from morphine by methylating the phenolic hydroxyl group with diazomethane, dimethyl sulfate, or methyl iodide. Codeine does not possess the same degree of analgesic potency as morphine but is used as an antitussive, a cough suppressant. Hydrocodone was discussed in Section 3.4. It is made from codeine. 

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. 

Morphine and narceine are active on / -opiate and K-receptors. They are also known as analgesic agents. These alkaloids may be used as pain relievers. Narceine is also known to be used in the treatment of a cough. 

Oxymorphone is 10 times as potent as morphine, with actions similar to those of hydromorphone. Oxymorphone, however, has httle antitussive activity, and as such is a useful analgesic in patients with pulmonary disease who need to retain the ability to cough. 

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. 

MecHanismofAction A chemical relative of morphine without the narcoticproperties that acts on the cough center in the medulla oblongata by elevating the threshold for coughing. Therapeutic Effect Suppresses cough. 

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. 

These drug products are used in a number of ways to treat various medical conditions, including the common cough, diarrhea, and pain. Surgeons and dentists also use morphine, the most important chemical substance within the opium poppy, as an anesthetic. Unfortunately, most opium is turned into heroin and ends up in the veins of addicts. 

Codeine is a close chemical relative of morphine, differing in only one chemical group. Once administered, codeine is actually metabolized by enzymatic action, and its actions mimic those of morphine. Codeine is used primarily as a cough suppressant, although it certainly also possesses significant analgesic properties (approximately one tenth those of morphine) as in the relief of pain from toothache. 

Codeine is a natural alkaloid found in the opium plant. As a pharmaceutical, codeine is used as an analgesic, antitussive, and antidiar-rheal. Codeine is also commonly combined with other cough suppressants as well as with aspirin and ibuprofen. In the United States, codeine is a Schedule III controlled substance, which means that its distribution is more tightly regulated than unscheduled drugs. Codeine has pain-relieving qualities principally because, once in the body, about 10 percent of codeine turns into morphine. This conversion occurs in the liver, where an enzyme changes codeine s... 

It is a reduction/decrease in the activity of specialized cells. For example barbiturates depress central nervous system, quinidine depresses myocardium. Certain drugs stimulate one type of cells but depress others e.g. morphine stimulates the vagus and chemoreceptor trigger zone but depresses the vomiting and cough centres. Similarly acetylcholine stimulates intestinal smooth muscle but depresses SA node in the heart. 

Effect on CNS The main action of morphine is CNS depression which further results in analgesia, depression of respiratory centre, cough centre and sleep. In addition it causes euphoria or dysphoria and dependence. 

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

Codeine, which is an opium alkaloid is most commonly opiate used as antitussive and more selective for cough centre. Like morphine, it depresses cough centre but is less constipating and abuse liability is low. It is relatively safe drug used in cough along with analgesic property and it s only important adverse effect is constipation. 

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. 

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... 

N.A. Thebaine, oripavine, morphine, codeine.99-100 Mild sedative to induce sleep in babies, ease cough, relieve pain, narcotic analgesic, antitussive. 

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