A
cough medicine is a medicinal
drugA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used to treat
coughA cough , in medicine, is a sudden and often repetitively occurring defense reflex which helps to clear the large breathing passages from excess secretions, irritants, foreign particles and microbes...
ing 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
phlegmPhlegm is a sticky fluid secreted by the mucous membranes of humans and other animals. Its definition is limited to the mucus produced by the respiratory system, excluding that from the nasal passages, and particularly that which is expelled by coughing...
) are treated with expectorants that loosen
mucusIn vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. It is a viscous colloid containing antiseptic enzymes and immunoglobulins that serves to protect epithelial cells in the respiratory,...
from the
respiratory tractIn humans the respiratory tract is the part of the anatomy that has to do with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
. These medicines are widely available in the form of cough syrup, also known as linctus.
Examples
CodeineCodeine or methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties.-History:Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent...
is one of the strongest cough suppressants known, along with a number of derivatives such as the
dihydrocodeineDihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin,...
-
hydrocodoneHydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates codeine and thebaine. Hydrocodone is an orally active narcotic analgesic and antitussive. It is commonly available in tablet, capsule, and syrup form, and is often compounded with other...
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
codeineCodeine or methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties.-History:Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent...
,
ethylmorphineEthylmorphine is a drug in the class of both opiates and opioids . Its effects in humans mainly stem from its metabolic conversion to morphine...
(also known as dionine or codethyline),
dihydrocodeineDihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin,...
,
benzylmorphineBenzylmorphine is a semi-synthetic opiate narcotic introduced to the international market in 1896 and that of the United States very shortly thereafter...
,
laudanumLaudanum , also known as opium tincture or thebaic tincture is an alcoholic herbal preparation containing approximately 10% opium and 1% morphine . It is made by combining ethanol with opium latex or powder...
, dihydroisocodeine,
nicocodeineNicocodeine is an opiate derivative, closely related to dihydrocodeine and the codeine analogue of nicomorphine developed as a cough suppressant and analgesic. It is not commonly used in most countries, but has activity similar to other opiates. Nicocodeine and nicomorphine were introduced in the...
,
nicodicodeineNicodicodeine is an opiate derivative developed as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates. Nicodicodeine is metabolised in the liver by demethylation to produce 6-nicotinoyldihydromorphine, and subsequently further metabolised to...
,
hydrocodoneHydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates codeine and thebaine. Hydrocodone is an orally active narcotic analgesic and antitussive. It is commonly available in tablet, capsule, and syrup form, and is often compounded with other...
,
hydromorphoneHydromorphone, a more common synonym for dihydromorphinone and dimorphone, commonly a hydrochloride is a potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, specifically a hydrogenated ketone thereof and therefore a semi-synthetic drug...
,
acetyldihydrocodeineAcetyldihydrocodeine is an opiate derivative developed in Germany around 1900 as a cough suppressant and analgesic. It is not commonly used, but has activity similar to other opiates...
,diamorphine (
heroinHeroin, or diacetylmorphine , also known as diamorphine , is a semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy. It is the 3,6-diacetyl ester of morphine...
),
acetylmorphoneAcetylmorphone is an opiate analogue that is an acetylated derivative of hydromorphone which was developed in the early 1900s as a potential cough suppressant and analgesic...
,
noscapineNoscapine is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive effects. It has also been shown to have anticancer activity...
and
pholcodinePholcodine is a drug which is an opioid cough suppressant . It helps suppress unproductive coughs and also acts as an antifungal agent. It also has a mild sedative effect, but has little or no analgesic effects. It is also known as morpholinylethylmorphine.Pholcodine is found in certain cough...
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
morphineMorphine is a highly potent opiate analgesic psychoactive drug, is the principal active ingredient in Papaver somniferum , is considered to be the prototypical opioid. Like other opioids, e.g...
. Laudanum is still manufactured and used throughout the world at present although it is more common to use
paregoricParegoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties. It was a household remedy in the 18th and 19th centuries, when it was widely used to calm fretful children. In the 20th century...
(several times more dilute than laudanum), solid forms of
opiumOpium is a narcotic formed from the latex released by lacerating the immature seed pods of opium poppies . It contains up to 12% morphine, an opiate alkaloid, which is most frequently processed chemically to produce heroin for the illegal drug trade...
, or alkaloid mixtures such as
pantoponPantopon is a preparation of opiates made up of all of the alkaloids present in opium in their natural proportions as hydrochloride salts. It can sometimes be tolerated by persons who are allergic to morphine....
. Morphine by itself has marginal antitussive properties.
NoscapineNoscapine is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive effects. It has also been shown to have anticancer activity...
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
myrophineMyrophine is an opiate analogue that was developed in 1952. It is a derivative of morphine.Myrophine is substituted with a 3-benzyl group and a 6-myristyl chain. It is metabolised to form benzylmorphine and then further to morphine, and so is a long-acting prodrug for morphine, but with a slow...
.
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
dihydromorphineDihydromorphine is a semi-synthetic opioid invented in Germany in 1900. Structurally, it is very similar to morphine—the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
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,
hydromorphoneHydromorphone, a more common synonym for dihydromorphinone and dimorphone, commonly a hydrochloride is a potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, specifically a hydrogenated ketone thereof and therefore a semi-synthetic drug...
(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
nicomorphineNicomorphine is the 3,6-dinicotinate ester of morphine. It is a strong opioid agonist analgesic two to three times as potent as morphine with a side effect profile similar to that of dihydromorphine, morphine, and diamorphine. Nicomorphine was patented as Vilan by Lannacher Heilmittel Ges. m.b.H...
(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),
diacetyldihydromorphineDiacetyldihydromorphine is a potent opiate derivative developed in Germany in 1929 which is rarely used in some countries for the treatment of severe pain such as that caused by terminal cancer, as a more potent form of diamorphine...
(related to
dihydromorphineDihydromorphine is a semi-synthetic opioid invented in Germany in 1900. Structurally, it is very similar to morphine—the only difference being the reduction of the double bond between positions 7 and 8 in morphine to a single bond...
).
The very popular antitussive
dextromethorphanDextromethorphan is an antitussive drug. It is one of the active ingredients used to prevent coughs in many over-the-counter cold and cough medicines. Dextromethorphan has also found other uses in medicine, ranging from pain relief to psychological applications...
is related to the dextrorotary form of dromoran and is not an opioid but a NMDA antagonist. It is changed to
dextrorphanDextrorphan , or more appropriately dextrorphanol, is a psychoactive drug of the morphinan chemical class which acts as a dissociative psychedelic and putative cough suppressant or antitussive. It is the dextro- stereoisomer of morphanol, the levo- halve being levorphanol...
in the liver.
The antitussive
tipepidineTipepidine is a centrally-acting cough suppressant of the opioid type. It is a member of the thiambutene series of open-chain synthetic opioids, which include Ohton , a strong narcotic analgesic used particularly in veterinary medicine in Japan and other East Asian countries...
is an opioid drug of the
thiambuteneThe Thiambutenes are a family of opioid analgesic drugs. The parent compound thiambutene has no analgesic effects, but several compounds from this group are analgesics with around the same potency as morphine....
group. The protoypes of this family of opioids,
thiambuteneThe Thiambutenes are a family of opioid analgesic drugs. The parent compound thiambutene has no analgesic effects, but several compounds from this group are analgesics with around the same potency as morphine....
, methylthiambutene, and
ethylmethylthiambuteneEthylmethylthiambutene is an opioid analgesic drug from the thiambutene family, around 1.3x the potency of morphine. It is under international control under Schedule I of the UN Single Convention On Narcotic Drugs 1961, presumably due to high abuse potential....
, 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 receptorThe sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP, SA 4503, Ditolylguanidine, Dimethyltryptamine and siramesine.-Classification:...
s and
kappaThe κ-Opioid receptor is a type of opioid receptor which binds the peptide opioid dynorphin as the primary endogenous ligand. κ receptors are widely distributed in the brain, spinal cord, and in pain neurons.-Receptor subtypes:...
and perhaps
deltaThe δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as their endogenous ligands.-Function:...
opioid receptorOpioid receptors are a group of G-protein coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin...
s, the
NMDANMDA is an amino acid derivative acting as a specific agonist at the NMDA receptor, and therefore mimics the action of the neurotransmitter glutamate on that receptor...
system, and
anticholinergicAn anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicyclomine....
effects.
Drugs of the open-chain (methadone) type with antitussive efficacy include
methadoneMethadone is a synthetic opioid, used medically as an analgesic, antitussive and a maintenance anti-addictive for use in patients on opioids. It was developed in Germany in 1937...
, levomethadone,
normethadoneNormethadone is a cough suppressant. It is a desmethyl derivative of methadone....
, and
levopropoxypheneLevopropoxyphene is an antitussive. It is an optical isomer of dextropropoxyphene. The racemic mixture is called propoxyphene. Only the dextro-isomer has an analgesic effect; the levo-isomer appears to exert only an antitussive effect....
, and the more distant relative
isoaminileIsoaminile is an antitussive structurally related to methadone. Psychedelic effects have been noted from doses approximately 300 mg and above. The normal therapeutic dose is 40-80 mg of the cyclamate salt not to exceed five doses in a 24-hour period...
. 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.
DiphenhydramineDiphenhydramine hydrochloride is a chemical mainly used as an antihistamine, antiemetic, sedative, and hypnotic. It is produced and marketed under the trade name Benadryl by McNeil-PPC in the U.S. and Canada, and Dimedrol in other countries...
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 JournalBMJ is a partially open access medical journal. It is among the most influential and widely read peer-reviewed general academic journals in the field of medicine in the world....
indicating that some cough medicines may be no more effective than
placeboA placebo is a sham medical intervention. In one common placebo procedure, a patient is given an inert sugar pill, told that it may improve his/her condition, but not told that it is in fact inert...
s for acute coughs in adults, including coughs related to upper respiratory tract infections. In 2006, the
American College of Chest PhysiciansThe American College of Chest Physicians is a medical organization consisting of physicians and non-physician specialists in the field of chest medicine, which includes pulmonology, thoracic surgery, and critical care medicine....
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
pertussisPertussis, also known as the whooping cough, is a highly contagious disease caused by the bacterium Bordetella pertussis. It derived its name from the "whoop" sound made from the inspiration of air after a cough. A similar, milder disease is caused by B. parapertussis...
(whooping cough) in the elderly.
Recent studies have found that
theobromineTheobromine, also known as xantheose, is a bitter alkaloid of the cacao plant, found in chocolate, as well as in a number of chocolate-free foods made from theobromine sources including the leaves of the tea plant, the kola or cola nut, and acai berries. It is in the methylxanthine class of...
, a compound found in
cacaoCacao , or the cocoa plant, is a small evergreen tree in the family Sterculiaceae , native to the deep tropical region of the Americas. Its seeds are used to make cocoa and chocolate...
, is more effective as a cough suppressant than prescription
codeineCodeine or methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties.-History:Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent...
. 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 effectsIn medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect, and may result from an unsuitable or incorrect dosage or...
in the blind tests.
Mass poisonings due to diethylene glycol
According to the New York Times, at least eight mass poisonings have occurred as a result of counterfeit cough syrup, substituting inexpensive
diethylene glycolDiethylene glycol is an organic compound described by the structural formula HO-CH2-CH2-O-CH2-CH2-OH. It is a clear, hygroscopic, odorless liquid...
in place of glycerin. In May 2007, 365 deaths were reported in
PanamaPanama, officially the Republic of Panama , is the southernmost country of both Central America and, in turn, North America. Situated on the isthmus connecting North and South America, it is bordered by Costa Rica to the northwest, Colombia to the southeast, the Caribbean Sea to the north and the...
, which were associated with cough syrup containing diethylene glycol.
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