Cold medicine

Cough medicine often contains cough suppressants and expectorants.

A cough medicine is a medicinal drug used to treat coughing and related conditions. Dry coughs are treated with cough suppressants (antitussives) that suppress the body's urge to cough, while productive coughs (coughs that produce phlegm) are treated with expectorants that loosen mucus from the respiratory tract. These medicines are widely available in the form of cough syrup, also known as linctus.

Examples

Codeine is one of the strongest cough suppressants known, along with a number of derivatives such as the dihydrocodeine-hydrocodone subgroup of opioids, and the semi-synthetics and synthetics mentioned below. Codeine is the standard by which all antitussives are measured. It suppresses coughing by direct action on the cough centre in the brain, and also decreases the rate and/or tidal volume of respiration. The below-mentioned semi-synthetics differ from codeine in such ways as lipid solubility and CNS penetration, overall side-effect profile, and duration of action.

Natural and semi-synthetic opiates with antitussive effects include codeine, ethylmorphine (also known as dionine or codethyline), dihydrocodeine, benzylmorphine, laudanum, dihydroisocodeine, nicocodeine, nicodicodeine, hydrocodone, hydromorphone, acetyldihydrocodeine, thebacon, diamorphine (heroin), acetylmorphone, noscapine and pholcodine and others.

Laudanum, also known as Deodourised Tincture of Opium and Denarcotised Opium Tincture due to the removal of narcotine, an opium alkaloid which causes nausea, is a whole-opium preparation which has both morphine and codeine in it in addition to other alkaloids which relax smooth and striated muscles. It is of value in cases where the disease is causing other problems for the patient which could benefit from the actions of morphine. Laudanum is still manufactured and used throughout the world at present although it is more common to use paregoric (several times more dilute than laudanum), solid forms of opium, or alkaloid mixtures such as pantopon. Morphine by itself has marginal antitussive properties.

Noscapine and pholcodeine are natural opium alkaloids which have some antitussive effect and tend not to have a full spectrum of narcotic effects and low or non-existent physical dependence or addiction liability; preparations thereof are often available over the counter in many countries. Noscapine is used less often these days and has been removed from the standard recipe for pantopon, omnopon and similar opium alkaloids salts preparations in many pharmacopeias because of concerns about carcinogenicity a number of years ago and clinical experience that noscapine is not a necessary or effective component of pantopon-type drugs.

Ethylmorphine is almost identical to codeine in effects and chemistry and is in structure the closest relative of codeine (codeine is also known as methylmorphine). Both ethylmorphine and codeine are partially changed to morphine in the liver.

Benzylmorphine (Peronine), is also closely related to codeine and the strong opioid analgesic myrophine.

Dihydrocodeine, a close chemical relative of codeine which is usually the number-two prescription narcotic antitussive in countries in which hydrocodone is not available, is related to the strong opioid dihydromorphine in the same way codeine is to morphine and a percentage of it is changed to dihydromorphine in the liver. Dihydrocodeine is base of a number of other semi-synthetic opioids, many of which are also effective antitussives.

Hydrocodone (Codiclear, Dicodid, and many others, also Vicodin and other analgesic preparations) is a semi-synthetic ketone about three times stronger than codeine which is related to another powerful analgesic and antitussive, hydromorphone (Dilaudid) in the same way codeine is to morphine; the liver changes a percentage of hydrocodone into hydromorphone.

Hydromorphone itself is marketed as cough syrups and elixirs for dry, violent, painful coughing as Dilaudid Cough Syrup and under other brand names and the generic hydromorphone hcl syrup. Both hydromorphone and hydrocodone are demonstrably stronger antitussives than codeine in most patients and will have some activity in those who cannot metabolise codeine at all because of other medications taken at the same time or unusual absolute and relative levels of the various Cytochrome P-450 liver enzymes.

Nicocodeine is related to the strong analgesic nicomorphine (Vilan) in the same way.

Dihydroisocodeine is chemically similar to isocodeine.

Acetylated semi-synthetics, which differ from the drugs from which they are derived chiefly by entering the central nervous system more rapidly and being stronger on a millgramme basis include thebacon (related to hydrocodone), diamorphine, aka diacetylmorphine and heroin, (related to morphine), acetylmorphone (related to hydromorphone), acetyldihydrocodeine (related to dihydrocodeine), diacetyldihydromorphine (related to dihydromorphine]]

The very popular antitussive dextromethorphan is related to the dextrorotary form of dromoran and is not an opioid but a NMDA antagonist. It is changed to dextrorphan in the liver.

The antitussive tipepidine is an opioid drug of the of the thiambutene group. The protoypes of this family of opioids, thiambutene, methylthiambutene, and ethylmethylthiambutene, are, like tipepidine, most commonly used in Pacific Rim and East Asian countries as both human and veterinary analgesics. Tipepidine is available in some locations OTC although in South Korea and elsewhere it is watched more carefully as it has become a drug of abuse because of the purported psychedelic effects of high doses due to its apparent action on sigma receptors and kappa and perhaps delta opioid receptors, the NMDA system, and anticholinergic effects.

Drugs of the open-chain (methadone) type with antitussive efficacy include methadone, levomethadone, normethadone, and levopropoxyphene, and the more distant relative isoaminile. Methadone Linctus is a liquid preparation of methadone hydrochloride (or less frequently methadone tartrate) used for cough suppression and analgesia which is about one-third the concentration of methadone used for maintenance treatment. Cough syrups containing levopropoxyphene are widely-used in many countries and in many of them have an OTC status similar to that of dextromethorphan.

It is possible that other classes of opioids may have cough suppressants amongst them as well since the effect is the result of the action of the drug on a specific receptor in the central and peripheral nervous systems.

Diphenhydramine and its derivatives are often useful as non-narcotic cough suppressants by themselves and they dry out bronchial secretions, boost the effects of opioids and combat cold/allergy symptoms caused by immune responses which release histamine into the system. Like many of the classical first generation antihistamines, it also boosts the effects of most opioids, with the result that the dose of codeine and other centrally-acting antitussives can be reduced. Because of the drying effect, diphenhydramine may not be ideal for dry coughs and antihistamines of the cyclizine group (Marezine (cyclizine), Dramamine II (meclizine), Atarax and Vistaril (hydroxyzine) and buclizine and others) would be good substitutes for diphenhydramine for use as an opioid potentiator as are cyproheptadine (Periactin) and phenindamine (Nolahist and Thephorin).

Effectiveness

In 2001, researchers at the University of Bristol (Schroeder & Fahey) published the results of their meta analysis in the British Medical Journal indicating that some cough medicines may be no more effective than placebos for acute coughs in adults, including coughs related to upper respiratory tract infections. In 2006, the American College of Chest Physicians published a guideline that had the dual message that many over-the-counter cough medicines are not effective and that those that are effective in treating the symptom do not treat the underlying cause; the underlying disorder emphasized by the guideline was pertussis (whooping cough) in the elderly.

Recent studies have found that theobromine, a compound found in cacao, is more effective as a cough suppressant than prescription codeine. This compound suppresses the "itch" signal from the nerve in the back of the throat that causes the cough reflex. It is possible to get an effective dose (1 g, though 0.5 g may be sufficient) from 50g of dark chocolate, which contains 2 to 10 times more cacao than milk chocolate. Cocoa powder contains roughly 0.1 g per tablespoon (5g). Theobromine was also free from side effects in the blind tests.

Mass poisonings due to diethylene glycol

Main article: Toxic cough syrup

According to the New York Times, at least eight mass poisonings have occurred as a result of counterfeit cough syrup, substituting inexpensive diethylene glycol in place of glycerin. In May 2007, 365 deaths were reported in Panama, which were associated with cough syrup laced with diethylene glycol.

Botanical sources

• Sunflower (expectorant)

See also

• Cough drop

External links

• Cough medicines not helpful - from CNN.com