Diphenoxylate
Encyclopedia
Diphenoxylate is an opioid
agonist used for the treatment of diarrhea
that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate and therefore stop the formation of loose and liquid stools. It is the main active ingredient in the anti-peristaltic
medication Lomotil
, which also contains atropine
as noted below.
Diphenoxylate is the prototype of a small subfamily of opioids including difenoxin
and diphenoxylic acid (both are
also active metabolites of diphenoxylate produced in the human body) and loperamide
(which unlike the other three work exclusively in the intestines because it does not cross the blood-brain barrier
). It was discovered at Janssen Pharmaceutica
in 1956. It is a congener
to the narcotic
pethidine
of which the common brand names are Dolantin and Demerol amongst others. Other somewhat more distant relatives include alphaprodine (Nisentil) and piritramide
(Dipidolor).
Similar to loperamide and difenoxin preparations, the usual protocol is to take a loading dose (usually two tablets or the quantity of liquid containing 5 mg of diphenoxylate) and then the standard dose of one tablet every 3 to 4 hours prn over a time period not to exceed 48 hours unless so ordered by the physician. Long-term intermittent prn users should contact their physician if the need for it arises more than was usual at the outset of therapy as tolerance to diphenoxylate can occur. Those taking it in large quantities or continuously over an extended period should taper down the dose on a schedule devised by the physician and/or pharmacist.
. Difenoxin is another centrally-acting antidiarrhoeal that is 250 to 400 per cent the strength of diphenoxylate via the oral route and is also able to be manufactured and is distributed as Motofen
, (1 mg difenoxin/25 µg atropine), which was introduced in the United States in the late 1990s after being discovered in 1970 at Janssen.
The Diphenoxylate-Loperamide subfamily of gastrointestinal drugs works directly on opioid receptors, which can be found in the intestine, brain, and spinal cord. Diphenoxylate itself crosses the blood-brain barrier
. This being the case, this medication is potentially habit-forming and can generate significant tolerance if taken continuously for a protracted period. Physical dependence is most common particularly with high doses and/or long-term use. The CNS penetration of diphenoxylate makes it an agent that can cause euphoria
and other psychoactive effects, which could over time lead to habituation and dependency on the drug in the user. As with other medicinal opioids, iatrogenic addiction is uncommon although physical dependence secondary to treatment of a functional bowel disorder with diphenoxylate for more than 45–90 days may very well occur; it typically requires the use of high doses to impart a morbid seek orientation for the drug in the user. Because of this, diphenoxylate is manufactured and marketed as a combination drug with atropine
(Lomotil
, Pfizer
) as an abuse deterrent. Lomotil was used during the Apollo program, as was pethidine.
effect of atropine will produce severe weakness and nausea if standard dosage is exceeded, and at the time diphenoxylate was introduced in the United States a number of manufacturers used this strategy with oral forms of morphine
, methadone
(also using scopolamine
), oxycodone
and others. Currently, the only other narcotic produced in the United States to use this strategy is Motofen (difenoxin
1 mg with 25 µg atropine sulphate).
The 25 µg of atropine present in each 2½ mg Lomotil tablet is 1/40 of the standard therapeutic dose of atropine via the oral route for normal anticholinergic uses.
and/or laudanum
are not currently in general use.
Diarrhoea accompanied by significant cramping or intestinal cramping alone may benefit from either adding another smooth-muscle agent to the protocol such as dicycloverine, papaverine
, or orphenadrine
(which accomplishes several things at once since it is an antihistamine as noted above). Such cases may also benefit from a switch to paregoric
, laudanum
, powdered or granulated opium
, or B&O (i.e. Belladonna & Opium) Suppositories as all of the above include many drugs which work together and have non-narcotic alkaloids like papaverine and other components like oils, waxes, resins &c. which work elsewhere in the body. Pantopon
(Opium Alkaloids Hydrochlorides) and similar preparations have much of the advantages of whole opium in injectable form
of 1961 and also in similarly numbered schedules of laws passed to implement the Convention such as the Canadian Controlled Substances Act and the Betäubungsmittelgesetz in Germany and the Suchtgiftverordnung of Austria. This level of regulation is also implemented in the Misuse of Drugs Act of 1971 (UK), the French opium law of 31 December 1970, and royal decrees and laws passed by practically all other countries in Europe, the Pacific Rim, South Asia and the Middle East.
In many cases, Lomotil type preparations with extra active ingredients are over the counter and/or subject to provincial and/or municipal control or minimal national oversight; the schedule numbers vary by country.
This medication is classified as a Schedule V
under the United States' Comprehensive Drug Abuse Control & Prevention Act of 1970 aka Controlled Substances Act
(CSA) (21 U.S.C. § 801 et. seq.) by the Food and Drug Administration
(FDA) and the Drug Enforcement Administration
(DEA) in the United States when used in preparations. When diphenoxylate is used alone, it is classified as a Schedule II; having one or more other active ingredients makes it Schedule V. As such, diphenoxylate/atropine tablets are under state and local control and where allowed by state law, can be obtained by signing a log book and the customer can receive up to 48 units (tablets or capsules) in any 48-hour period, much like the 4 fl. oz. limit on codeine
, dihydrocodeine
, dionine (ethylmorphine
), and opium
cough syrups and gastrointestinal drugs.
The other Schedule V narcotics, all of which may be obtained in some states without prescription as noted in this article, are cough syrups containing low amounts of codeine
, ethylmorphine
, and dihydrocodeine
and dilute formulations of opium such as Parepectolin. Very dilute syrups of hydrocodone
containing three or more other active ingredients were also Schedule V and often available without prescription until rescheduling to Schedule III circa 1990.
As for the rest of the family, in the United States difenoxin & atropine tablets are Schedule IV and therefore federally controlled and require a prescription, loperamide is unscheduled and not on prescription, and diphenoxylic acid is classified as a form of diphenoxylate. Other Schedule IV narcotics also include butorphanol
nasal spray, pentazocine
, propoxyphene-based mixtures and others of the same type. Unscheduled narcotics and opioid agonists include loperamide
(OTC), nalbuphine
(Rx), and tramadol
(Rx).
As an example of the degree of regulation at the federal level, the most commonly-known Schedule IV drug of any type is Valium as well as nearly all other benzodiazepines, whereas Schedule III contains Vicodin
(hydrocodone
bitartrate), and Schedule II contains cocaine
, secobarbital
, methamphetamine
, methylphenidate
, all forms of morphine
and derivatives like Dilaudid (hydromorphone
hydrochloride), oxymorphone
, and oxycodone
. Examples of a legitimate medical drug which are generally illegal (Schedule I) would include the morphine derivatives Vilan (nicomorphine
HCl), Paramorfan (dihydromorphine
HCl) and the synthetics Ketodur (ketobemidone
), Dipidolor (piritramide
), and Palfium (dextromoramide
).
A Schedule V purchase involves the customer having to sign a dispensary log after presenting proper identification to the pharmacist; the Schedule V ledger lists transactions going back two years and must have pages that are difficult to remove and usually pre-numbered. This schedule devolves control over the drugs therein to state and local governments, so in states where it cannot be bought over the counter it may or may not require the duplicate, triplicate, or quintuplicate narcotic prescription order form defined by state law.
Narcotic preparations for gastrointestinal problems tend to be the more available of the narcotics; other narcotics for pain like the Tylenol With Codeine series, (even No. 1 and other combination products with the same quantity and therefore narcotic content number (7½ or 8 mg, i.e. 1/8 of a grain of codeine
phosphate per tablet) are more restricted and therefore all Schedule III.
Whilst Lomotil is Schedule V
, in some states it may not be available without prescription as it is classified as requiring a prescription order under the general prescription law for other reasons including the atropine content and the dangers of improper use not unlike antibiotics, insulin
, corticosteroids and the like. This is the same as the regulation of Donnagel PG: in some states, when it was available, it was a prescription drug because of the belladonna content. The stimulant pyrovalerone
is another Schedule V but prescription-only drug.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
agonist used for the treatment of diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate and therefore stop the formation of loose and liquid stools. It is the main active ingredient in the anti-peristaltic
Peristalsis
Peristalsis is a radially symmetrical contraction and relaxation of muscles which propagates in a wave down the muscular tube, in an anterograde fashion. In humans, peristalsis is found in the contraction of smooth muscles to propel contents through the digestive tract. Earthworms use a similar...
medication Lomotil
Lomotil
The drug combination diphenoxylate/atropine is a popular oral anti-diarrheal in the United States, manufactured by Pfizer. Its UK BAN generic name is co-phenotrope....
, which also contains atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
as noted below.
Diphenoxylate is the prototype of a small subfamily of opioids including difenoxin
Difenoxin
Difenoxin is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine and more distantly related to alphaprodine and piritramide, and it is an active metabolite of the anti-diarrhoea drug diphenoxylate. Difenoxin et al...
and diphenoxylic acid (both are
also active metabolites of diphenoxylate produced in the human body) and loperamide
Loperamide
Loperamide , a synthetic piperidine derivative, is an opioid drug used against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor, Fortasec, and Pepto Diarrhea Control...
(which unlike the other three work exclusively in the intestines because it does not cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
). It was discovered at Janssen Pharmaceutica
Janssen Pharmaceutica
Janssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...
in 1956. It is a congener
Congener
Congener has several different meanings depending on the field in which it is used. Colloquially, it is used to mean a person or thing like another, in character or action.-Biology:In biology, congeners are organisms within the same genus...
to the narcotic
Narcotic
The term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
pethidine
Pethidine
Pethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
of which the common brand names are Dolantin and Demerol amongst others. Other somewhat more distant relatives include alphaprodine (Nisentil) and piritramide
Piritramide
Piritramide is a synthetic opioid analgesic with a potency 0.65 to 0.75 times that of morphine. A common starting dose is 15 mg IV, equivalent to 10 mg of morphine hydrochloride. Piritramide is commonly used for the treatment of postoperative pain...
(Dipidolor).
Actions and Use
Diphenoxylate works by decreasing the speed and amplitude of wave-like movements of the intestines (peristalsis) therefore allowing the body time to remove moisture from the intestinal contents and consolidate waste product into a dense solid form rather than loose and watery as is diarrhea.Similar to loperamide and difenoxin preparations, the usual protocol is to take a loading dose (usually two tablets or the quantity of liquid containing 5 mg of diphenoxylate) and then the standard dose of one tablet every 3 to 4 hours prn over a time period not to exceed 48 hours unless so ordered by the physician. Long-term intermittent prn users should contact their physician if the need for it arises more than was usual at the outset of therapy as tolerance to diphenoxylate can occur. Those taking it in large quantities or continuously over an extended period should taper down the dose on a schedule devised by the physician and/or pharmacist.
Related Drugs
Diphenoxylate is metabolised in the body to yield difenoxinDifenoxin
Difenoxin is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine and more distantly related to alphaprodine and piritramide, and it is an active metabolite of the anti-diarrhoea drug diphenoxylate. Difenoxin et al...
. Difenoxin is another centrally-acting antidiarrhoeal that is 250 to 400 per cent the strength of diphenoxylate via the oral route and is also able to be manufactured and is distributed as Motofen
Motofen
A comprehensive article about the subgroup of anti-diarrhoeal drugs including Motofen can be found as the article Diphenoxylate.Motofen is the brand name for an antiperistaltic anti-diarrheal medication, containing 1.0 mg difenoxin HCl and 0.025 mg atropine...
, (1 mg difenoxin/25 µg atropine), which was introduced in the United States in the late 1990s after being discovered in 1970 at Janssen.
The Diphenoxylate-Loperamide subfamily of gastrointestinal drugs works directly on opioid receptors, which can be found in the intestine, brain, and spinal cord. Diphenoxylate itself crosses the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. This being the case, this medication is potentially habit-forming and can generate significant tolerance if taken continuously for a protracted period. Physical dependence is most common particularly with high doses and/or long-term use. The CNS penetration of diphenoxylate makes it an agent that can cause euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
and other psychoactive effects, which could over time lead to habituation and dependency on the drug in the user. As with other medicinal opioids, iatrogenic addiction is uncommon although physical dependence secondary to treatment of a functional bowel disorder with diphenoxylate for more than 45–90 days may very well occur; it typically requires the use of high doses to impart a morbid seek orientation for the drug in the user. Because of this, diphenoxylate is manufactured and marketed as a combination drug with atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
(Lomotil
Lomotil
The drug combination diphenoxylate/atropine is a popular oral anti-diarrheal in the United States, manufactured by Pfizer. Its UK BAN generic name is co-phenotrope....
, Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
) as an abuse deterrent. Lomotil was used during the Apollo program, as was pethidine.
Inclusion of Atropine
The atropine additive strategy is designed to discourage use of the drug in a manner inconsistent with its labelling and physician and manufacturer instructions; in theory, the anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
effect of atropine will produce severe weakness and nausea if standard dosage is exceeded, and at the time diphenoxylate was introduced in the United States a number of manufacturers used this strategy with oral forms of morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
(also using scopolamine
Scopolamine
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
), oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
and others. Currently, the only other narcotic produced in the United States to use this strategy is Motofen (difenoxin
Difenoxin
Difenoxin is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine and more distantly related to alphaprodine and piritramide, and it is an active metabolite of the anti-diarrhoea drug diphenoxylate. Difenoxin et al...
1 mg with 25 µg atropine sulphate).
The 25 µg of atropine present in each 2½ mg Lomotil tablet is 1/40 of the standard therapeutic dose of atropine via the oral route for normal anticholinergic uses.
Use In Irritable Bowel Syndrome
Diarrhoea resulting from cyclic or diarrhoea-predominant IBS may not be optimally treated with diphenoxylate or difenoxin, and may not respond to a meaningful degree to loperamide; thus, diarrhoea and cramping which does not respond to belladonna derivatives and non-centrally-acting soothing and/or stool-desiccating agents are often treated with conservative doses of codeine, especially where paregoricParegoric
Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...
and/or laudanum
Laudanum
Laudanum , also known as Tincture of Opium, is an alcoholic herbal preparation containing approximately 10% powdered opium by weight ....
are not currently in general use.
Diarrhoea accompanied by significant cramping or intestinal cramping alone may benefit from either adding another smooth-muscle agent to the protocol such as dicycloverine, papaverine
Papaverine
Papaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm , and occasionally in the treatment of erectile dysfunction...
, or orphenadrine
Orphenadrine
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class with prominent CNS and peripheral actions used to treat painful muscle spasms, other similar conditions, as well as the treatment...
(which accomplishes several things at once since it is an antihistamine as noted above). Such cases may also benefit from a switch to paregoric
Paregoric
Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties.-History:...
, laudanum
Laudanum
Laudanum , also known as Tincture of Opium, is an alcoholic herbal preparation containing approximately 10% powdered opium by weight ....
, powdered or granulated opium
Opium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
, or B&O (i.e. Belladonna & Opium) Suppositories as all of the above include many drugs which work together and have non-narcotic alkaloids like papaverine and other components like oils, waxes, resins &c. which work elsewhere in the body. Pantopon
Pantopon
Pantopon 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....
(Opium Alkaloids Hydrochlorides) and similar preparations have much of the advantages of whole opium in injectable form
Regulation
As noted below, diphenoxylate is listed in national controlled-substances and drugs laws such as pure diphenoxylate being in Annex/Schedule/List II of the Single Convention on Narcotic DrugsSingle Convention on Narcotic Drugs
The Single Convention on Narcotic Drugs of 1961 is an international treaty to prohibit production and supply of specific drugs and of drugs with similar effects except under licence for specific purposes, such as medical treatment and research...
of 1961 and also in similarly numbered schedules of laws passed to implement the Convention such as the Canadian Controlled Substances Act and the Betäubungsmittelgesetz in Germany and the Suchtgiftverordnung of Austria. This level of regulation is also implemented in the Misuse of Drugs Act of 1971 (UK), the French opium law of 31 December 1970, and royal decrees and laws passed by practically all other countries in Europe, the Pacific Rim, South Asia and the Middle East.
In many cases, Lomotil type preparations with extra active ingredients are over the counter and/or subject to provincial and/or municipal control or minimal national oversight; the schedule numbers vary by country.
This medication is classified as a Schedule V
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
under the United States' Comprehensive Drug Abuse Control & Prevention Act of 1970 aka Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
(CSA) (21 U.S.C. § 801 et. seq.) by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) and the Drug Enforcement Administration
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...
(DEA) in the United States when used in preparations. When diphenoxylate is used alone, it is classified as a Schedule II; having one or more other active ingredients makes it Schedule V. As such, diphenoxylate/atropine tablets are under state and local control and where allowed by state law, can be obtained by signing a log book and the customer can receive up to 48 units (tablets or capsules) in any 48-hour period, much like the 4 fl. oz. limit on codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, dihydrocodeine
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
, dionine (ethylmorphine
Ethylmorphine
Ethylmorphine is an opiate narcotic analgesic .Ethylmorphine was invented in Germany at Merck in 1884 and was used as a weaker alternative to heroin for all indications. Chemically, ethylmorphine is a morphine molecule with a -25 group substituted for the aromatic 3- group...
), and opium
Opium
Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...
cough syrups and gastrointestinal drugs.
The other Schedule V narcotics, all of which may be obtained in some states without prescription as noted in this article, are cough syrups containing low amounts of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, ethylmorphine
Ethylmorphine
Ethylmorphine is an opiate narcotic analgesic .Ethylmorphine was invented in Germany at Merck in 1884 and was used as a weaker alternative to heroin for all indications. Chemically, ethylmorphine is a morphine molecule with a -25 group substituted for the aromatic 3- group...
, and dihydrocodeine
Dihydrocodeine
Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, New Bron Solution-ACE, Huscode, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine,...
and dilute formulations of opium such as Parepectolin. Very dilute syrups of hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
containing three or more other active ingredients were also Schedule V and often available without prescription until rescheduling to Schedule III circa 1990.
As for the rest of the family, in the United States difenoxin & atropine tablets are Schedule IV and therefore federally controlled and require a prescription, loperamide is unscheduled and not on prescription, and diphenoxylic acid is classified as a form of diphenoxylate. Other Schedule IV narcotics also include butorphanol
Butorphanol
Butorphanol is a morphinan-type synthetic opioid analgesic developed by Bristol-Myers. Brand name Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations, manufactured by Novex, Mylan, Apotex and Ben Venue Laboratories. Butorphanol is most...
nasal spray, pentazocine
Pentazocine
Pentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
, propoxyphene-based mixtures and others of the same type. Unscheduled narcotics and opioid agonists include loperamide
Loperamide
Loperamide , a synthetic piperidine derivative, is an opioid drug used against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor, Fortasec, and Pepto Diarrhea Control...
(OTC), nalbuphine
Nalbuphine
Nalbuphine is a semi-synthetic opioid used commercially as an analgesic under a variety of trade names, including Nubain. It is noteworthy in part for the fact that at low dosages, it is found much more effective by women than by men, and may even increase pain in men, leading to its...
(Rx), and tramadol
Tramadol
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...
(Rx).
As an example of the degree of regulation at the federal level, the most commonly-known Schedule IV drug of any type is Valium as well as nearly all other benzodiazepines, whereas Schedule III contains Vicodin
Vicodin
Hydrocodone/paracetamol is a combination of two analgesic products hydrocodone and paracetamol used to relieve moderate to severe pain...
(hydrocodone
Hydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
bitartrate), and Schedule II contains cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, secobarbital
Secobarbital
Secobarbital sodium is a barbiturate derivative drug that was first synthesized in 1928 in Germany. It possesses anaesthetic, anticonvulsant, sedative and hypnotic properties...
, methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
, methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
, all forms of morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
and derivatives like Dilaudid (hydromorphone
Hydromorphone
Hydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
hydrochloride), oxymorphone
Oxymorphone
Oxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
, and oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
. Examples of a legitimate medical drug which are generally illegal (Schedule I) would include the morphine derivatives Vilan (nicomorphine
Nicomorphine
Nicomorphine 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...
HCl), Paramorfan (dihydromorphine
Dihydromorphine
Dihydromorphine is a semi-synthetic opioid invented in Germany in 1900. In structure, 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...
HCl) and the synthetics Ketodur (ketobemidone
Ketobemidone
Ketobemidone is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted by it's metabolite norketobemidone. This makes it useful for some types of pain that don't respond well to other opioids...
), Dipidolor (piritramide
Piritramide
Piritramide is a synthetic opioid analgesic with a potency 0.65 to 0.75 times that of morphine. A common starting dose is 15 mg IV, equivalent to 10 mg of morphine hydrochloride. Piritramide is commonly used for the treatment of postoperative pain...
), and Palfium (dextromoramide
Dextromoramide
Dextromoramide is a powerful opioid analgesic approximately three times more potent than morphine but shorter acting. It is subject to drug prohibition regimes, both internationally through UN treaties, and by the criminal law of individual states...
).
A Schedule V purchase involves the customer having to sign a dispensary log after presenting proper identification to the pharmacist; the Schedule V ledger lists transactions going back two years and must have pages that are difficult to remove and usually pre-numbered. This schedule devolves control over the drugs therein to state and local governments, so in states where it cannot be bought over the counter it may or may not require the duplicate, triplicate, or quintuplicate narcotic prescription order form defined by state law.
Narcotic preparations for gastrointestinal problems tend to be the more available of the narcotics; other narcotics for pain like the Tylenol With Codeine series, (even No. 1 and other combination products with the same quantity and therefore narcotic content number (7½ or 8 mg, i.e. 1/8 of a grain of codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
phosphate per tablet) are more restricted and therefore all Schedule III.
Whilst Lomotil is Schedule V
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
, in some states it may not be available without prescription as it is classified as requiring a prescription order under the general prescription law for other reasons including the atropine content and the dangers of improper use not unlike antibiotics, insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, corticosteroids and the like. This is the same as the regulation of Donnagel PG: in some states, when it was available, it was a prescription drug because of the belladonna content. The stimulant pyrovalerone
Pyrovalerone
Pyrovalerone is a psychoactive drug with stimulant effects via acting as a norepinephrine-dopamine reuptake inhibitor , and is used for the clinical treatment of chronic fatigue or lethargy and as an anorectic or appetite suppressant for weight loss purposes...
is another Schedule V but prescription-only drug.