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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Monday, October 25, 2010

Morphine Ketones Vault

Vintage Dilaudid Advertisement
Hydromorphone

Basic:

Known by the popular name Dilaudid. Hydromorphone is commonly used semisynthetic opiate with 4-5X the potency of morphine. Hydromorphone is one of an entire group of ketone based derivatives of morphine. The drug was one of many semi-synthetic opiates created in Germany in the first part of the 20th century - hydromorphone being created in 1924 and first marketed a few years later. The name "Dilaudid" was given, as to indicate its relation to morphine, similar to the names "Laudanum": the opium tincture product, and "Dicodid": a popular reference to the codeine derivative hydrocodone.

Hydromorphone was first introduced to the US market by Knoll, the original manufacturer of Dilaudid, up until recent years. Name brand Dilaudid is widely used to this day, and is presently marketed by Purdue Pharma, who also manufactures the popular products OxyContin and MS Contin.

Hydromorphone is available in the US (and elsewhere) in the form of fast acting oral tablets, once daily sustained release tablets, oral liquid, rectal suppositories for placement in the butthole, liquid solution for injection by all routes, and a brand name fine powder for use in the preparation of compound products or large volume parenteral preparations (IV drips, anaesthesia, etc).

Use:

Dilaudid tablets - 8mg
Hydromorphone has long gained a respected place in medicine as a first or second line analgesic for treating moderate to severe pain where an opioid is indicated. Hydromorphone is additionally used for the treatment of severe or painful dry cough, stemming from an illness/infection or bronchial irritation due to inhalation of chemical irritants.

Hydromorphone is common in the hospital setting, where it is often preferred over morphine in certain settings: i.e. its higher potency - allowing for a lesser volume of liquid when injection routes are used, in cases where patients respond inadequately to morphine or suffer intolerable nausea, pruritis, etc. Its superior lipid solubility, allowing a rapid onset of effects, or higher selectivity of tissue distribution in cases of epidural or intrathecal administration (spinal routes), and its short half life allowing rapid recovery from the effects in cases of short-term hospitalization such as ER visits.

Hospitalists often take more confidence in using hydromorphone over morphine due to its greater potency, as a typical dose of hydromorphone gives the illusion of seeming a smaller dose than the equivalent amount of morphine. for example: many physicians would feel more comfortable giving 1 to 2 mg of Dilaudid as opposed to a 5 to 10 mg dose of morphine, despite the fact that 1-2mg Dilaudid is equianalgesic to 5-10mg morphine - it simply feels less excessive

Hydromorphone is used in the management of both acute and chronic pain on an outpatient basis, typically in oral form. Hydromorphone brand name tablets (Dilaudid) or generic tablets in traditional standard release form have long been available and are used in treating acute or intermittent moderate to severe pain, such as postoperative pain, post trauma or injury pain, severe headache, dental pain, or breakthrough pain incidents in patients taking a long acting opioid such as MS Contin or transdermal fentanyl. When treating incidents of breakthrough pain in the aforementioned patient population, hydromorphone is particularly useful - its high potency allows the drug to adequately meet the demands of those with a significant pharmacological tolerance for opioids, such as those treated with long acting fentanyl, oxymorphone, or methadone. The fast acting nature of hydromorphone in general suits it well to the nature of sudden onset or breakthrough pain incidents.

With the more recent introduction of a brand name long acting hydromorphone tablet (Exalgo), hydromorphone is now more effectively used for around the clock maintenance of chronic pain conditions both malignant and non malignant. Prior to the reintroduction of long acting hydromorphone tablets, there was no practical option for hydromorphone in around the clock pain control; immediate release preparations such as dilaudid were poorly suited for this purpose due to the short half life of hydromorphone. The drug would require dosing as frequently as every 2 to 3 hours to effectively keep pain at bay, which required amounts of up to 12 (sometimes more) tablets daily, and often several hundred tablets on a monthly basis. With the US introduction of Exalgo, once or twice daily dosing is now possible.

Hydromorphone like other opioids, is used non medically by experimental users, casual users, and "narcotic addicts", many of whom self medicate with the drug for various purposes. When used by either informed or habitual opioid users it is primarily taken by non-oral routes. As many users are aware of the low bioavailability of the drug when taken orally. Hydromorphone tablets are crushed into powder form and snorted, for a slight improvement of bioavailability. The drug may also be taken rectally, which is most effective with crushed tablets which have been dissolved in water and squirted deep into the rectum. Most regular or heavy narcotic users prepare hydromorphone tablets to a solution for intravenous injection, offering complete bioavailability of the drug.

Properties:

Hydromorphone is a semi-synthetic opiate of the morphine family. It is one of a group of ketone based derivatives of morphine - the parent structure known as morphinone, differing from morphine only with the substitution of a 6-ketone group, in the place of morphine's 6-hydroxyl group. Going one step further, hydromorphone lacks a 7,8 double bond in favor of the 7,8 diHydro feature, hence "HYDROmorphone".

Hydromorphone is an opioid agonist with a pharmacodynamic profile similar to morphine. It binds to mu, kappa, and delta receptors in the brain, spinal cord, and gut. Hydromorphone produces its effects mainly by its interaction with micro (mu) opioid receptors, to which it shows a higher affinity than morphine.

Hydromorphone is far more lipophilic than morphine - thus rapidly absorbed and distributed throughout the CNS & smooth muscle organs. Peak levels in the blood are reached within 30 to 60 minutes when taken orally, with a half life of 2 to 3 hours; this is much quicker than with morphine. Peak levels are reached within 5 to 10 minutes when injected intravenously, with a half life of roughly 2 hours. Oral hydromorphone undergoes extensive first pass metabolism, it's bioavailability by this route is about 25%. Hydromorphone is metabolized by the same route as morphine, the majority metabolized by uridine diphosphate enzymes to form the inactive hydromorphone-3-glucuronide. Minor amounts are broken down via 6-ketone reduction to form dihydromorphine. The effects of hydromorphone are due to the parent drug itself and not its metabolites. Excretion of the drug is via the kidneys and out through urine.

Effects & Side Effects:

Hydromorphone produces the typical morphine side effects, but is believed to produce little effect on histamine levels. Effects may include emesis, constipation, miosis, pruritis, peripheral vasodilation, physical warmth, a marked release of physical tension (aches and stiffness melt away), and respiratory depression. Compared with morphine, hydromorphone typically produces less nausea, vomiting, and itching, making it an excellent alternative in patients sensitive to morphine, or a first-choice narcotic itself.

Subjective effects with hydromorphone tend to be extremely variable in intensity depending on the route of administration. Taken by the oral or intranasal route, hydromorphone produces a glow similar to morphine but 'cleaner' - many report effects by this route are quite subtle, however this is often explained by an insufficient dose. When taken by the oral route, one may require 4 to 5 fold higher doses than their typical IV dose to produce similar subjective effects. For one who can handle 100mg of IV morphine or 20mg IV Dilaudid, oral doses in excess of 80mg will likely be needed, in the absence of high dose supply, this a subpar route for euphorigenic purposes. Subjective effects include significant relief of pain, a short-lived sense of well being or euphoria, followed by positive mood with positive thought process, a period of enhanced motivation and productivity, increased sociability with a sense of empathy toward others, a vivid dreamlike state, and a relief of anxiety and depression.

When injected by the venous route, the drug produces an intensely pleasant rush which is similar to that of heroin, with many users including myself having a preference for hydromorphone. Hydromorphone's rush is widely regarded within drug-use circles and is often highly sought for this reason alone. It can be best described as a rapid and warm sudden tension of every muscle throughout the body, followed instantly by a release - with every fiber of the body loosening up to a state of complete relaxation, as if the entire body were dying of a thirst which is instantly quenched. An intense almost tingling sense of warmth is felt in the gut (just as pronounced as a kick or a punch; but over a much wider area, and minus the pain of course) as well as the back of the neck and down the spine, radiating throughout the head, and throughout each limb.

As the initial rush of all encompassing opiate intensity gives way to a steady warmth throughout the body (i.e. body buzz), in its wake lies the emotional sense of resolve and state of well being. All stress and psychic discomfort has become contentment. And gradually to surface is a general sense of love, and an almost laughing passion for life. The euphoric or 'happy' sensations surface with such subtlety that it's hard to identify exactly at which point they appeared. One moment they're not present, and suddenly they are.

These effects are quite intense, however will taper off almost as quickly as they appeared. The noticeable effects of oral or intranasally administered hydromorphone last from 2 to 4 hours; when injected intravenously, effects last roughly 1 to 2 hours.

(Like with morphine however, with large doses comes longer duration - effects may last for up to 6 hours with larger doses done consecutively.)

Oxymorphone

Basic:

Oxymorphone is a semisynthetic opiate with a potency 2-7x that of morphine, depending on the route administered. It was discovered in Germany in the early years of the 20th century and introduced to the US market decades later in 1955. Oxymorphone is one among several opiates of the morphinone (ketones of morphine) class, and is closely related to both morphine and hydromorphone. Oxymorphone like its sister hydromorphone is a derivative of morphine however, is manufactured from thebaine, a naturally occurring alkaloid in opium.

Opana ER 20mg Tablets
Oxymorphone is used in american medicine as a potent analgesic, to treat moderate to severe pain where use of an opioid is appropriate. Oxymorphone is perhaps better known by the trade names Opana or Numorphan, the latter of which is used as a generic term for various oxymorphone products elsewhere in the world. It is available as the water soluble hydrochloride based salt; as tablets for oral use either in traditional or sustained release formulation, or as a liquid preparation for parenteral use by the intravenous, intramuscular, subcutaneous or intraspinal route.

This drug has seen an increase in use with the release of the newly formulated OxyContin tablet, serving as a replacement in therapy for the new oxycodone product which is reportedly ineffective for many patients and has received alarming negative feedback. The choice of oxymorphone comes naturally, as first and foremost; many patients treated with OxyContin had been previously switched from MS Contin products due to side effects, preference, or lack of efficacy. In addition, both drugs (oxycodone/oxymorphone) share specifically similar key properties in addition to the fact that with morphine out of the question, Opana ER is the next closest option. The recent spike in the use and popularity of oxymorphone products (primarily Opana & Opana ER) has led to the increasing availability of oxymorphone on the underground market for non medical use. This carries with it the benefit that for many opiate enthusiasts who had previously only heard or read about this previously rare drug, oxymorphone is now likely to be available for purchase. On the other hand however, with increasing availability of an especially potent opioid will come the increasing likelihood that the drug will be introduced to novice users, inevitably leading to overdose deaths.

Mid 1900's - Advertisement for Numorphan
 (Oxymorphone Hcl)
 Use:

Oxymorphone is indicated for the treatment of moderate to severe pain where the use of an opioid is appropriate.

Oxymorphone may be used in the clinical setting for the following indications: acute pain in the emergency room or trauma unit, sedation and analgesia during difficult procedures such as endotrachial intubation or catheterization, premedication prior to induction of general anaesthesia, perioperative analgesia & sedation during procedures in which the physician opts to use regional anaesthesia such as a nerve block rather than put the patient fully under. It may additionally be used for post operative pain control, or as an analgesic in end of life care (hospice). Oxymorphone in the clinical setting is available as a liquid for parenteral use, and is typically given by the intramuscular or venous route.

Oral oxymorphone is dispensed by prescription for outpatient use, and is indicated for the treatment of moderate to severe pain both chronic and acute. Immediate release tablets are typically used for acute pain such as post-injury or post-operative pain, or or as a fast acting analgesic for incidents of breakthrough pain in patients taking long acting opioids such as Opana ER or transdermal fentanyl. Long acting oxymorphone tablets are available as the brand name Opana ER - a twice daily tablet which releases oxymorphone over a 12 hour period - available in doses ranging from 10 mg to 40 mg. Long acting oxymorphone is prescribed for cases of chronic malignant or non malignant pain conditions, in cases where a consistent level of pain control is needed throughout the day/night. For those who experience breakthrough pain with Opana ER, the first choice in many cases is to add the IR equivalent (Opana) to be taken alongside, as needed.

Oxymorphone can be given as a solution
by injection. Image depicts an Opana
injection package.
Oxymorphone like other opioids is sold illicitly for non-medical use, and is used recreationally by casual narcotic users, and habitually by opiate dependents with the intention of self medicating depression, anxiety, etc. Oxymorphone like hydromorphone is a common second choice for heroin users when heroin is unavailable, owing to its high potency and intense rush upon IV injection. One appealing aspect to IV use of the oral preparations is that so little of the tablet is needed for effect; because of its poor oral bioavailability, the tablets must contain 10x the amount necessarry for a systemic (IV) dose, therefore users may take only 1/10th of their typical oral dose for the same effect.

Due to this poor bioavailability when taken orally, most non-medical oxymorphone use is done by the intranasal or parenteral routes, both of which provide far greater systemic availability of the drug. Opana ER or immediate release tablets can be crushed to a powder for insufflation, or prepared into a solution for IV or IM injection.

Properties:

Oxymorphone is a semi-synthetic morphine analogue, typically derived from thebaine. Molecularly, the drug is a hydrogenated ketone of morphine, with a 14-hydroxy substitution; hence the 'Oxy' in the name; with the "morphONE" at the end indicating it as a keTONE. Oxymorphone is molecularly almost identical to hydromorphone, the only difference being the 14-hydroxy opposed to a 14-hydrogen; both drugs share the dihydromorphinone structure. OM is also structurally similar to oxycodone, the only difference being its 3-HO opposed to oxycodone's 3-methoxy - Oxymorphone is produced in the body as a minor metabolite of oxycodone after the demethylation of the drug, however it has shown to play little role in the efficacy of the parent drug. .

Oxymorphone is a highly lipophilic opioid, and is rapidly distributed throughout the brain, spinal cord, and smooth muscle tissue. Peak plasma levels after oral administration are reached at 30 to 60 minutes. Peak plasma levels after IV administration are reached rapidly within 5 to 10 minutes. As most morphine derivatives, oxymorphone undergoes extensive first pass metabolism when taken orally. Oxymorphone's average oral bioavailability is among lowest of the morphine derived narcotics, being roughly 10%, with significant variations depending on several factors - for instance, oxymorphone peak plasma levels have been shown to increase up to 40% when the drug is taken shortly after a light high-fat meal.

Oxymorphone's extensive metabolism includes conjugation in the liver via uridine diphosphate to form oxymorphone-3-glucuronide, and P450 mediated ketone reduction to form 14-hydroxydihydromorphine (Oxymorphol). Analgesic activity is believed to be produced by the parent drug. Its half life after oral administration ranges 7 to 10 hours which is significantly longer than similar opiates; this results in an extended duration of effects and allows less frequent dosing, generally every 4 to 6 hours and in some cases longer. Elimination half life after IV administration is rapid; averaging 1 to 2 hours, with a duration of effects to hydromorphone. The drug is excreted renally and is present in the urine generally no longer than 5 days.

Oxymorphone has pharmacodynamic properties similar to other typical opiates. It is a potent agonist with high affinity at the mu receptor and low affinity at delta and kappa sites. Agonism at the mu receptor accounts for its effects of clinical importance.

Effects & Side Effects:

As a potent mu-opioid agonist, effects are similar to morphine, but several times more potent. Oxymorphone produces narcotic and analgetic effects with a generally kinder side effect profile than morphine. The drug causes little histamine release and therefore less pruritis and itching. Oxymorphone generally produces less nausea and vomiting than morphine. At any rate, side effects may include pupil constriction (miosis), suppression of cough reflex, constipation, somnolence, sedation, muscle relaxation, respiratory depression, and less likely, peripheral vasodilation or itching in some individuals. Clinical tolerance to most of these side effects (including respiratory depression) develops rapidly with repeated use, with the exception of miosis and constipation - these effects do not disappear with tolerance.

Opana 10mg (Pink) &
Opana ER 20mg (Seagreen)
Patients taking Opana ER or short acting oral forms of the drug for pain generally experience good to excellent analgesia with very few side effects compared to morphine. A downside to recreational use by the oral route with a tolerant or experienced user is the need for 10-fold higher doses than would be required with the parenteral route. Many users who try the drug orally do not dose nearly this high, and often conclude the drug is ineffective by this route. The stark differences in oral and parenteral potency will likely present a danger for those unaware of these  specific properties. All this aside, subjective effects of oxymorphone include; a positive mood, increased sociability or empathy, a sense of motivation and productivity, excitement alternating with sedation, a state of dreamlike contentment and vivid thoughts or dreams, inhibition of anxiety or depressive tendencies, and an overall sense of well being. These subjective effects may be quite subtle when the drug is taken orally, however this depends on the dose; whether a modest therapeutic dose, or a higher recreational dose. The potency of oral oxymorphone is approx. twice that of morphine on a milligram basis - This applies only to analgesia.

Intranasal insufflation of oxymorphone offers a fair bioavailability and potent euphorigenic properties. It is typically with this route of administration that one begins to discover oxymorphone's truly potent nature. Users who crush the tablets and snort the powder intranasally generally report a potent, pronounced high which lasts up to several hours depending on dose. Some claim that oxymorphone produces effects like those of oxycodone, typically with a greater degree of sedation, less irritability and less itching; this makes sense given their close structural resemblance.

Preparation of oxymorphone tablets for intravenous injection has been common among heavier opiate users, such as habitual narcotic users who are physically dependent on strong opioids such as heroin, morphine, hydromorphone and fentanyl. Only by the intravenous route does oxymorphone demonstrate its full potential - the drug by this route is approximately 6.6 times stronger than morphine (in vivo), requiring an IV dose of only 1.5 mg of oxymorphone to produce effects similar to 10 mg of injected morphine.
 
 
 

3 comments:

  1. Hydromorphone is considered 6.6x morphine in potency, oxymorphone 10x (in terms of analgesia)

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  2. I love Hydromorphone! Even taken by mouth I can feel the beast that is Dilaudid...BUT Oxymorphone really is the king...I remember before Opana the idea of Oxymorphone in a pill was insanely rare and costly....Hydromorphone really is great stuff and then they go and make Oxymorphone available...that injectable solution of Opana made my pupils constrict at the thought...er maybe its the OxyContin's I just ate XD. Anyways be safe guys! All of these substances can be like petting a burning dog!

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    Replies
    1. I discovered, unintentionally, that the bioavailability of Opana ER greatly increases with alcohol. I have drank wine or a marguerita with oxy and other opiates, but I found out how strong Opana really is when I drank alcohol with it, or smoked pharmaceutical pot with it.

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