What is Dihydrocodeine?
What is Dihydrocodeine? (DHC, Figure 1) is a semi-synthetic opioid, licensed in most countries to treat moderate to severe pain (1, 2). It is a so-called “weak” opioid that can be used if nonopioid analgesics such as paracetamol and nonsteroidal anti-inflammatory drugs provide insufficient pain control (2, 3). Bioavailability of DHC after oral administration is ∼20%, which indicates that its analgesic efficacy after oral administration is slightly stronger than that of codeine (bioavailability after oral administration approximately equals 30–40%) (4). After DHC oral administration, the maximal serum concentration appears after 1.7 h, plasma half-life is 3.5–5.5 h and analgesia period is 4 h. However, there is little
data available on DHC pharmacokinetics.
DHC and diazepam (IS) were obtained from Sigma (St. Louis, MO, USA). Acetonitrile and methanol were of HPLC grade and purchased from Merck Company (Darmstadt, Germany). HPLC grade water was obtained using a Milli Q system (Millipore, Bedford, USA).
In this study, different sample treatment approaches were investigated to achieve a simple and inexpensive extraction procedure. Protein precipitation extraction was initially tried, but low DHC concentration was not detectable during our method development. Then, a liquid–liquid extraction (LLE) technique was investigated and found to be more sensitive. LLE methods using a mixture of organic solvents have been investigated for the extraction of DHC from biological samples. In this study, different organic solvents including diethyl ether, chloroform and ethyl acetate were investigated. Among them, ethyl acetate was found to be optimal solvent for extraction yielding satisfactory results in terms of both sample cleaning and the analyte extraction recovery. Moreover, the boiling point of ethyl acetate is low, so it was evaporated to dryness more quickly. Hence, ethyl acetate was chosen as the extraction solvent. This one-step extraction with ethyl acetate is cheaper than the reported method, which makes the method suitable for low-cost clinical study (16).
Further optimization in chromatography conditions was performed to test different mobile phases. In our assessment of different mobile phases, acetonitrile–water (containing 0.1% formic acid) was found to be optimal for this study, which provided symmetric peak shapes of the analyte and IS. The total time required for the chromatographic run was 4.0 min. The addition of 0.1% formic acid helped to obtain improved signals
As with other opioids, tolerance and physical and psychological dependence develop with repeated dihydrocodeine use. All opioids can impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving or operating machinery if taken in large doses.
Itching and flushing and other effects of blood vessel dilation are also common side-effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First-generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor-Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine-driven side-effects, but are analgesic-sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms.
As with all drugs, side-effects depend on the person taking the medication. They can range in severity from mild to extreme, from headaches to difficulty breathing.
Constipation is the one side-effect of dihydrocodeine and almost all opioids which is near-universal. It results from the slowing of peristalsis in the gut and is a reason dihydrocodeine, ethylmorphine, codeine, opium preparations, and morphine are used to stop diarrhoea and combat irritable bowel syndrome (IBS) in its diarrhoeal and cyclical forms as well as other conditions causing hypermotility or intestinal cramping. Opium/opioid preparations are used often as a last resort where pain is severe and the bowels are organically loose. It is generally better to treat IBS with a non psycho-tropic opioid such as loperamide hydrochloride which stays contained in the bowel, thereby not causing drowsy effects and allowing many people to work using machines etc. For IBS, hyoscine butylbromide (Buscopan in the UK) and mebeverine hydrochloride (Colofac) can be effective with or without an opium related compound.