|DB00316||Acetaminophen||Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects.|
|DB00945||Acetylsalicylic acid||The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Acetylsalicylic acid also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)|
|DB00921||Buprenorphine||Buprenorphine is a derivative of the opioid alkaloid thebaine that is a more potent (25 - 40 times) and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use.|
|DB00201||Caffeine||A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling.|
|DB09061||Cannabidiol||Cannabidiol, or CBD, is one of at least 85 active cannabinoids identified within the Cannabis plant. It is a major phytocannabinoid, accounting for up to 40% of the Cannabis plant's extract, that binds to a wide variety of physiological targets of the endocannabinoid system within the body. Although the exact medical implications are currently being investigated, CBD has shown promise as a therapeutic and pharmaceutical drug target. In particular, CBD has shown promise as an analgesic, anticonvulsant, muscle relaxant, anxiolytic, antipsychotic and has shown neuroprotective, anti-inflammatory, and antioxidant activity, among other currently investigated uses [A32477, A32469]. CBD's exact place within medical practice is still currently hotly debated, however as the body of evidence grows and legislation changes to reflect its wide-spread use, public and medical opinion have changed significantly with regards to its usefulness in a number of medical conditions ranging from anxiety to epilepsy.
From a pharmacological perspective, Cannabis' (and CBD's) diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon endogenous cannabinoid receptors of the body [A32584]. Cannabinoid receptors are utilized endogenously by the body through the endocannabinoid system, which includes a group of lipid proteins, enzymes, and receptors that are involved in many physiological processes. Through its modulation of neurotransmitter release, the endocannabinoid system regulates cognition, pain sensation, appetite, memory, sleep, immune function, and mood among many other bodily systems. These effects are largely mediated through two members of the G-protein coupled receptor family, cannabinoid receptors 1 and 2 (CB1 and CB2)[A32585,A32824]. CB1 receptors are found in both the central and peripheral nervous systems, with the majority of receptors localized to the hippocampus and amygdala of the brain. Physiological effects of using cannabis make sense in the context of its receptor activity as the hippocampus and amygdala are primarily involved with regulation of memory, fear, and emotion. In contrast, CB2 receptors are mainly found peripherally in immune cells, lymphoid tissue, and peripheral nerve terminals [A32676].
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two types of cannabinoids found naturally in the resin of the marijuana plant, both of which interact with the cannabinoid receptors that are found throughout the body. Although THC and CBD have been the most studied cannabinoids, there are many others identified to date including cannabinol (CBN), cannabigerol (CBG), [DB14050] (CBDV), and [DB11755] (THCV) that can be found within the medical cannabis [A32830]. While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. If not provided in their activated form (such as through synthetic forms of THC like [DB00470] or [DB00486]), THC and CBD are obtained through conversion from their precursors, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA), through decarboxylation reactions. This can be achieved through heating, smoking, vaporization, or baking of dried unfertilized female cannabis flowers.
The primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body [A32469]. Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site which is clinically significant as direct agonists (such as THC) are limited by their psychomimetic effects such as changes to mood, memory, and anxiety[A32469].
In addition to the well-known activity on CB1 and CB2 receptors, there is further evidence that CBD also activates 5-HT1A/2A/3A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gamma-aminobutyric acid (GABA), and cellular uptake of anandamide, acts on mitochondria Ca2+ stores, blocks low-voltage-activated (T-type) Ca2+ channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) [A31555, A31574].
CBD is currently available in Canada within a 1:1 formulation with tetrahydrocannbinol (THC) (as the formulation known as "nabiximols") as the brand name product Sativex. It is approved for use as adjunctive treatment for symptomatic relief of spasticity in adult patients with multiple sclerosis (MS). Sativex was also given a conditional Notice of Compliance (NOC/c) for use as adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis and as adjunctive analgesic treatment for moderate to severe pain in adult patients with advanced cancer [L886].
In April 2018, a Food and Drug Administration advisory panel unanimously recommended approval of Epidiolex (cannabidiol oral solution) for the treatment of two rare forms of epilepsy - Lennox-Gastaut syndrome and Dravet syndrome, which are among the two most difficult types of epilepsy to treat [L2721, L2719]. Epidiolex was granted Orphan Drug designation as well as Fast Track Approval from the FDA for further study in these hard to treat conditions. Notably, phase 3 clinical trials of Epidiolex have demonstrated clinically significant improvement in Lennox-Gastaut syndrome and Dravet syndrome [L2720]. On June 25th, 2018, Epidiolex was approved by the FDA to be the first CBD-based product available on the US market.|
|DB01401||Choline magnesium trisalicylate||Choline magnesium trisalicylate is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. Trisalicylate significantly reduces methotrexate renal clearance, displacing methotrexate from protein, increasing the fraction unbound by 28% [A19653, A19654].|
|DB00318||Codeine||The relief of pain (analgesia) is a primary goal for enhancing the quality of life of patients and for increasing the ability of patients to engage in day to day activities. Codeine, an opioid analgesic, was originally approved in the US in 1950 and is a drug used to decrease pain by increasing the threshold for pain without impairing consciousness or altering other sensory functions. Opiates such as codeine are derived from the poppy plant, _Papaver somniferum_ (Papaveraceae) [A175096].
Codeine is utilized as a central analgesic, sedative, hypnotic, antinociceptive, and antiperistaltic agent, and is also recommended in certain diseases with incessant coughing [FDA label], [A175096].|
|DB00861||Diflunisal||Diflunisal, a salicylate derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with pharmacologic actions similar to other prototypical NSAIAs. Diflunisal possesses anti-inflammatory, analgesic and antipyretic activity. Though its mechanism of action has not been clearly established, most of its actions appear to be associated with inhibition of prostaglandin synthesis via the arachidonic acid pathway. Diflunisal is used to relieve pain accompanied with inflammation and in the symptomatic treatment of rheumatoid arthritis and osteoarthritis.|
|DB01551||Dihydrocodeine||Dihydrocodeine is an opioid analgesic used as an alternative or adjunct to codeine to treat moderate to severe pain, severe dyspnea, and cough.
It is semi-synthetic, and was developed in Germany in 1908 during an international search to find a more effective antitussive agent to help reduce the spread of airborne infectious diseases such as tuburculosis. It was marketed in 1911.|
|DB00573||Fenoprofen||An anti-inflammatory analgesic and antipyretic highly bound to plasma proteins. It is pharmacologically similar to aspirin, but causes less gastrointestinal bleeding.|
|DB00813||Fentanyl||A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)|
|DB00956||Hydrocodone||Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant.|
|DB01050||Ibuprofen||Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) derived from propionic acid and it is considered the first of the propionics.[A39074] The formula of ibuprofen is 2-(4-isobutylphenyl) propionic acid and its initial development was in 1960 while researching for a safer alternative for aspirin.[A39075] Ibuprofen was finally patented in 1961 and this drug was first launched against rheumatoid arthritis in the UK in 1969 and USA in 1974. It was the first available over-the-counter NSAID.[A39076]
On the available products, ibuprofen is administered as a racemic mixture. Once administered, the R-enantiomer undergoes extensive interconversion to the S-enantiomer _in vivo_ by the activity of the alpha-methylacyl-CoA racemase. The S-enantiomer is believed to be the more pharmacologically active enantiomer.[A39194]|
|DB00854||Levorphanol||A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection.|
|DB00939||Meclofenamic acid||A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.|
|DB00784||Mefenamic acid||A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.|
|DB00454||Meperidine||A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.|
|DB01028||Methoxyflurane||An inhalation anesthetic. Currently, methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with nitrous oxide to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation. (From AMA Drug Evaluations Annual, 1994, p180)|
|DB00844||Nalbuphine||A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors. Nalbuphine is the only opioid analgesic that is not a controlled substance in the United States.|
|DB01183||Naloxone||Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs, particularly within the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide. More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors. When taken in large quantities, opioid medications such as morphine, hydromorphone, methadone, heroin, or fentanyl are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils. If untreated, this can progress to vomiting, absent pulse and breathing, loss of consciousness, and even death. Naloxone is indicated for the rapid reversal of these symptoms of central nervous system depression in opioid overdose. It's important to note that naloxone only works on opioid receptors within the body, and is therefore not capable of reversing the effects of non-opioid medications such as stimulants like methamphetamine or cocaine, or benzodiazepines like lorazepam or diazepam.
Also known as the brand name product Narcan, naloxone is currently available by intramuscular (IM) or subcutaneous (SubQ) injection, nasal spray, or intravenous (IV) infusion. Naloxone IM injections are commonly available in the form of "kits", which is ideal for making overdose treatment accessible and readily available for administration by minimally trained individuals within the community. Kits commonly include the supplies necessary to treat an overdose in a non-medical setting such as alcohol swabs, syringes, a rescue breathing mask, and instructions for use. Frequently also carried by medical and emergency personnel and at events known to be associated with heavy drug use like music festivals, naloxone kits are considered a key component of harm reduction strategies.
When injected intramuscularly (IM), naloxone acts within 3-5 minutes and can last from 30-60 minutes before its effects wear off. Administration of naloxone is associated with very few side effects. Notably, if injected into a person not currently using opioid medications, there would be no noticeable effects at all. However, for individuals using opioid medications or experiencing an overdose, IM injection of naloxone rapidly reverses opioid effects and can cause the injected individual to immediately experience withdrawal symptoms. Common symptoms of opioid withdrawal include nausea, vomiting, sweating, runny nose, aches, and diarrhea. Although certainly physically uncomfortable, opioid withdrawal symptoms are not life-threatening like they are for alcohol withdrawals. Administration of naloxone is therefore appropriate for any person appearing to have any symptoms of an opioid overdose. Due to its short duration of action, person's injected with naloxone should be monitored for responsiveness and potentially injected a second time or taken to the hospital.
Naloxone is also available within the combination product Suboxone with the opioid medication buprenorphine. Suboxone is used for the maintentance treatment of opioid dependence and addiction. When taken orally, naloxone has no pharmacological effect and does not reduce the effectiveness of the opioid effect of buprenorphine. The primary purpose of including naloxone within Suboxone is to act as a deterrent to injection, as injected naloxone would rapidly reverse the effects of buprenorphine.|
|DB01192||Oxymorphone||An opioid analgesic with actions and uses similar to those of morphine, apart from an absence of cough suppressant activity. It is used in the treatment of moderate to severe pain, including pain in obstetrics. It may also be used as an adjunct to anesthesia (From Martindale, The Extra Pharmacopoeia, 30th ed, p1092). On June 8, 2017, FDA requested Endo Pharmaceuticals to remove the medication from the market due to opioid misuse and abuse risks associated with the product's injectable reformulation.|
|DB00652||Pentazocine||The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)|
|DB00193||Tramadol||Tramadol, with the chemical formula cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol hydrochloride, is a 4-phenylpiperidine analog of codeine.[A173983] It is a usual go-to medication as it has less potential for abuse and respiratory depression. Tramadol can be found as 2 enantiomers with active analgesic properties however, the mechanism of action of each of the enantiomers differs greatly.[A173980] In the FDA records, the first approved tramadol product was developed by Actavis Elizabeth and FDA approved in 2002.[L5125]|