Re-analyses of samples which had been kept in storage for several years showed that most samples had not changed after being stored in the dark for a couple of years at room temperature. However, storage for more than 5 years often resulted in decomposition, particularly in samples consisting of the SW Asian type of heroin. Abstract Changes in the content of impurities, adulterants and diluents are described for samples of illicit heroin seized in the western part of Denmark during the year period through Analgesic efficacy of intra-articular morphine in experimentally induced radiocarpal synovitis in horses.
Effects of intraarticular ropivacaine and morphine on lipopolysaccharide-induced synovitis in horses. Intra-articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model. Equine Vet J. Intra-articular morphine and saline injections induce release of large molecular weight proteoglycans into equine synovial fluid. Zentralbl Veterinarmed A. Anesth Analg , 5 —, table of contents. In vitro assessment of human chondrocyte viability after treatment with local anaesthetic, magnesium sulphate or normal saline.
Intra-articular magnesium sulfate MgSO4 reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate NMDA receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes. Osteoarthritis Cartilage. Acquisition, culture, and phenotyping of synovial fibroblasts. Methods Mol Med. Volume of the synovia in certain joint cavities in the horse. Acta Vet Scand. Pharmacokinetics of intra-articular morphine in horses with lipopolysaccharide-induced synovitis.
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Lidocaine exhibits dose- and time-dependent cytotoxic effects on bovine articular chondrocytes in vitro. J Int Med Res. Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. A review of translational animal models for knee osteoarthritis.
Download references. We wish to thank Ian Richards for his contribution in the acquisition of data. None of the authors have conflicts of interests. Funding bodies did not take part in the study design or conclusion of the study. Lidocaine hydrochloride is a white powder freely soluble in water where injection of sterile, nonpyrogenic solution of it is indicated for production of local or regional anesthesia by infiltration techniques percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques brachial plexus and intercostal and by central neural techniques lumbar and caudal epidural blocks.
Further, it has been administered by continuous intra-articular infusion to control postoperative pain. Lidocaine binds to neuronal membrane to stabilize and inhibit voltage-gated sodium channels for the initiation and conduction of impulses. Lidocaine has a very rapid onset of action that typically begins working within 4 min and an anesthetic half-life of about 1. Therefore, lidocaine is suitable for infiltration, block, and surface anesthesia where its actions are more intense and its effects are more prolonged when compared to procaine.
Subdural and epidural anesthesias bupivacaine or prilocaine are preferred as longer-acting substances [ 37 , 57 , 58 , 76 ]. The rapid metabolism by the liver enzymes leads to biotransformation of lidocaine in some pathways including oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation.
The pharmacologically active metabolites monoethylglycinexylidide and inactive glycinexylidide are produced as a result of N-dealkylation biotransformation that is a primary metabolism. Monoethylglycinexylidide has a longer half-life but also less potent than lidocaine.
The rate of biotransformation of an amide local anesthetic significantly influences the anesthetic blood levels where increased blood levels can potentially increase toxicity. The concentration of AAG and the concentration of free lidocaine affect the predictability of lidocaine toxicity where higher doses of lidocaine can be tolerated before encountering toxicity based on surgery type and certain disease states.
Albumin is considered as the principal binding protein for acidic compounds, and AAG is the principal binding protein for basic drugs [ 37 , 57 , 58 , 76 , 78 , 79 ]. Procaine, the first synthetic derivative of cocaine, was created in with the trade name of Novocaine, from the Latin nov- new and -caine, a common ending for alkaloids used as anesthetics.
Procaine, an amino ester, is a short-acting local anesthetic that is used as an injection for local infiltration and peripheral nerve block during surgery and other medical and dental procedures. Low potency, slow onset, and short duration of action are the characteristics of procaine. Procaine has a pKa of 8. Due to rapid hydrolysis by plasma cholinesterase, it has very short plasma half-life that is thought to be approximately 20 seconds. It has a very short duration of action based upon extremely poor protein binding.
While toxicity associated with the use of procaine is quite a little, the use of procaine produces metabolite para-aminobenzoic acid which is associated with an increased rate of allergy [ 57 , 80 ]. Benzocaine is an amino ester that is a derivative of procaine with a pKa of 8. Benzocaine binds to sodium channels and reversibly depolarizes the neuronal membrane, consequently blocking the initiation and conduction of nerve impulses. It has a slow onset, short duration, and moderate toxicity.
Benzocaine is considered an oral anesthetic because it numbs the mouth by dulling the nerve endings in painful areas [ 81 ]. Chloroprocaine is a short-acting amino ester which is a chlorinated derivative of procaine.
Because it is the most rapidly metabolized local anesthetic by cholinesterase , it has an extremely short plasma half-life. Chloroprocaine has a pKa of 8. Chloroprocaine has clinical usage mostly in epidural anesthesia and also in peripheral blocks with short duration, whereas combined usage with other long-acting, slow-onset local anesthetics such as bupivacaine and tetracaine to achieve rapid onset with prolonged duration is common.
Owing to the short duration of spinal chloroprocaine, it is a strong alternative to lidocaine for surgical blocks and short or ultrashort surgical procedures for outpatient anesthesia. Tetracaine is a long-acting amino ester with a pKa of 8.
It has been used in spinal anesthesia if long duration of action is needed and also in various topical anesthetic preparations. When compared to the other commonly used ester local anesthetics, tetracaine is more slowly metabolized and considerably more toxic. It is significantly more potent and has a longer duration of action than procaine or chloroprocaine.
Tetracaine is not recommended for peripheral nerve blocks owing to its slow onset and potential for systemic toxicity may be greater if used with epinephrine. It has clinical use in spinal anesthesia with and without the use of epinephrine leading in a considerably reliable and long-onset spinal anesthetic [ 80 ]. Mepivacaine is an intermediate-duration amino amide local anesthetic with a pKa of 7.
In terms of pharmacologic properties, mepivacaine is often compared to lidocaine where mepivacaine has similar onset of action with a slightly longer duration for infiltration anesthesia.
When an intermediate-duration blockade is desired for peripheral nerve block techniques, 1. Low toxicity, rapid onset, dense motor block, and excellent diffusion properties through tissue can be listed as characteristic of mepivacaine. Mepivacaine is clinically used as a local anesthetic for an epidural or spinal block and also used as an anesthetic for dental procedures. Some addictive people try to obtain this drug and inject it themselves because large doses of mepivacaine cause sedation, immobility, confusion, dissociation, and amnesia [ 83 ].
Bupivacaine is introduced in since then it has been one of the most commonly used long-acting local anesthetics in regional and infiltration anesthesia. The structural difference of bupivacaine from lidocaine is the amine-containing group that is a butylpiperidine. Bupivacaine is capable of producing prolonged anesthesia and analgesia, thus reducing the need for repeated administration and rarely required the addition of epinephrine.
Epinephrine can be prolonged even further duration of blockade. Bupivacaine produces more sensory than motor block where anesthesia duration is from 4 to 16 h depending upon the site of injection and the concentration used.
Bupivacaine stabilizes the neuronal membrane and is widely used both in neuraxial and peripheral nerve blockade. Bupivacaine hydrochloride has higher lipid solubility logDpH 7.
This characteristic makes bupivacaine more cardiotoxic than lidocaine. Because of its greater tendency to produce cardiotoxicity, large doses of bupivacaine should be avoided and is not recommended for intravenous regional analgesia. Bupivacaine is widely used both in neuraxial and peripheral nerve blockade, infiltration anesthesia, spinal anesthesia, and epidural and caudal anesthesia. It is not recommended for intravenous regional analgesia because of cardiotoxicity which is much more than other local anesthetics.
When bupivacaine is used, the smallest effective dose is aimed to administer [ 84 — 86 ]. The studies on reducing the cardiotoxicity of bupivacaine resulted to development of ropivacaine with similar physicochemical properties of onset, potency, and duration to those of bupivacaine.
Ropivacaine is used in concentrations of 0. The onset of blockade is almost as fast as 1. Having less cardiotoxicity and central nerve system toxicity, reduced motor block, and an absolute difference in potency are mentioned in the literature as the advantages of ropivacaine over bupivacaine.
However, it can be suggested that there may be no more than slight differences in onset, but no difference between ropivacaine and bupivacaine in duration of block. For these reasons, both drugs have been used as an effective long-acting local anesthetic in peripheral nerve blockade [ 84 , 87 , 88 ]. As a result levobupivacaine is being associated with a lower risk of toxicity alternative to bupivacaine. The route of administration and concentration effects the onset and duration of sensory and motor block where levobupivacaine, dexbupivacaine, or bupivacaine has similar potency as an anesthetic.
However, levobupivacaine is consistently less toxic than bupivacaine. The clinical use of levobupivacaine includes surgical anesthesia or pain management during labor, postoperative analgesia, lumbar epidural or intrathecal anesthesia, thoracic epidural anesthesia, peripheral nerve block, and infiltration anesthesia that have mostly investigated and compared with bupivacaine [ 84 , 88 ]. Opiate describes any of the narcotic opioid alkaloids found in opium plant Papaver somniferum that are morphine, codeine, thebaine, and papaverine or synthetic opioids that are derived from morphine and thebaine oxycodone and hydrocodone.
Opiates and its synthesized derivatives are prescribed in medications used for pain relief with even stronger analgesic properties than their predecessors do. Opium itself contains over 25 different alkaloids, whereas only morphine and codeine are used as opiate analgesics from the point of view of clinical significance. The majority of drugs appearing on a synthetic opioid list are derivatives of these medications. The list of opiate drugs includes natural opiate drugs from natural opium alkaloids and synthetic synthetic and semisynthetic opiate drugs, also called as opioids, made by chemical synthesis in the laboratory according to the chemical structures found in natural alkaloids.
Natural opiate drugs can be listed as morphine, codeine, thebaine, and oripavine. Semisynthetic medications are derived from the naturally occurring alkaloids where small concentrations of natural opium alkaloids go into the making of semisynthetic opiates, thus, a part of synthetic opiates.
Semisynthetic opiate drugs include:. The studies in the laboratory were focused on eliminating the risk for addiction of natural opioid alkaloids and make even more effective than opium itself for relatively safe alternatives for treatment.
However, opiates in any form always carry a risk for addiction. Fully synthetic alkaloids are synthesized from other chemicals and molecules that do not come from alkaloids found in plants [ 61 , 89 ].
Both of these natural and synthetic types of drugs bound to the active site on the receptors called opioid receptors from certain nerve cells in the brain, spinal cord, and gastrointestinal tract.
Once the opioids injected into the epidural or subarachnoid space to manage acute or chronic pain, bound to the specific nerve cells in the brain, block a specific receptor site and sent inaccurate measures of the severity of the pain so that the person who has taken the drug will experiences less pain.
Thus, opiate is used in combinations with a local anesthetic to both enhance the blockade and prolong analgesia in neuraxial blockade. Nevertheless, opioid receptors do not exist in peripheral nerve so opiates do not have an effective clinical role in peripheral nerve blockade.
Taking drugs in these classes also affect how the brain feels pleasure, in other words addictive [ 21 , 90 — 94 ]. Completely synthetic alkaloid molecules called opioids are originally synthesized by pharmaceutical companies because of their potency as an analgesic for the treatment of severe pain.
As opposed to an opiate natural opium alkaloid , they are very similar in structure to morphine, whereas the exact geometry of the molecule largely effects on determining the painkilling activity. For example, the drugs Levorphan and Dextrorphan are both mirror images of one another with quite similar structure to morphine.
Levorphan, the left-handed molecule like naturally left-handed morphine, is several times more potent than morphine and is strongly addictive, while Dextrorphan, the right-handed molecule, has no analgesic ability and is also nonaddictive [ 21 , 90 — 94 ]. The main alkaloid morphine in opium poppy is a naturally occurring analgesic opioid and one of the most potent pain relievers.
Morphine helps to ease the pain particularly before, during, and after major surgeries and acts as an anesthetic without decreasing consciousness. Morphine is a weak base with the pKa of about 8. Morphine exists mostly in ionized form that does not favor passage through the lipid membrane; thus, onset of action is relatively slow 15—30 min.
The basic mechanism depends on the shape of the morphine molecule and its binding to the active site on the receptor protein.
Similarly, phencyclidine derivatives in which the characteristic acetylcholine-like molecular arrangement is modified by various substitutions are shown to loose both anticholinergic and psychotropic behavior.
This close correlation is supported by the identification of molecular regions which will generate the proper molecular arrangement in local anesthetics and morphine, compounds which are known to be involved in cholinergic mechanisms.
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