FDA opiod drugs   Drugs of Abuse

Most over-the-counter pain medications fall into two categories; nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. NSAIs releive pain, reduce fever and treat some cold symtpoms. Their ability to reduce inflammation often make them more effeective than acetaminophen, which is used to treat mild to moderate pain and to bring down fevers.

Many plant derived compounds have anti-inflammatory activities. Most of their actions are related to their ability to inhibit cytokine, chemokine or adhesion molecule synthesis and/or action. Many inflammatory disorders including sepsis, rheumatoid arthritis and asthma are intimately associated with an imbalance of the cytokine network.

A substantial body of evidence obtained from both in vivo and in vitro studies supports the concept that various plant-derived compounds with anti-inflammatory properties exert their effects through the modulation of the cytokine system. Plant-derived medicines such as flavonoids, tannins, and anthraquinones have been shown to exhibit anti-inflammatory activities, although their exact anti-inflammatory mechanisms are not well established.

Receptors that transmit impulses perceived as pain in animals are called nociceptors. Some of these receptors are free nerve endings found in the skin and other tissues and are stimulated by actual or potential tissue damage. Vertebrate nociceptors communicate with other pain pathway sensory neurons using two main neurotransmiters, substance P and glutamate. These carry the messages through the spinal cord and to the brain respectively. When tissue is damaged, prostaglandins are released, increasing the sensitivity of nociceptors and subsequently the intensity of pain. The analgesic effects of ibuprofen and aspirin are a function of their ability to inhibit the production of prostaglandins.

Mammals produce natural painkillers called endorphins and enkephalins. These neurotransmitters inhibit the release of substance P by binding to opiate receptors in the spinal cord. This same mechanism is responsible for the powerful analgesic effects of narcotics such as morphine and heroin.

Types of Pain:

Arthritis:

–Capsaicin: Capsaicin cream warms the skin when applied over the joint and temporarily blocks “sutance P” which delivers paid messages to the brain. It has shown some effectiveness in treials for osteorthritis and rheumatoid arthritis and is useful adjunctive therapy for some people. Use gloves and avoid getting the eyers in your eyes, nose or mouth when applying.

–Curcumin: is the active ingredient of the spice turmeric, which is known to have anti-inlflammatory proeprties.

–EGCG: is an antioxidant forund in green teach. EGCG may protect cartilage and bond and lower the rsik of both osteoarthritis and rheumatoic arthritis.

–Vitamin D: is important for helping the body adsorb calcium, which keeps bones strong. It can also help fight inflammation. People with RA consistently had lower levels of vitamin D in their blood than those without arthritis wen studied. If you are low in vitamin D, your smptoms of RA could also get worse.

–Glucosamine: is one of the most popular supplements for arthritis. Glucasamine supplements may hep lubricate joints and help cartilage retain water and prevent its breakdown. Blucasmine supplements are generally safe but can interact with blood thinners like wararin (Coumadin). They may also affect blood surage levels. There are no majr foood sources of glucosame. Most supplements are made from chitosame, a natural substance found in the outer shells of shrimpt, lobsters and croabs. Other types of glucosame are made in the lab if you are allegeric to shellfish.

Supplements containing both glucosame and chondroitin are also very popular. Healthy cartilage naturally has glucosamine and chondroitin. Glucosamine and chondroitin seem to have anti-inflammatory properties which may help with pain, swelling and some of the symptoms of arthritis.

–Omega-3 Fatty Aids: are found in ish oils and can help control inflammation.

–Salicylates: Certain arhtritis creams which contain salicylates (compounds related to saspirin) work by decreasing pain and inflammation. Some brand names include Aspercrem, Benay, Flexall and Sportscreme. Their effectivenss is unclear.

–Topcial NSIDS:  penetrate the skin and give short temr relief. It is likely that the topical route is safer than taking NSAIDs by mouth. Several available products by precription include Pennsaid and Voltaren gel.

–Lidocain Patches: 

Knee Pain:

–MACI (autologous cultured chondrocytes on porcine collagen membrane) (Vericel): is an autologous cellularized scaffold product which is approved for repair of symptomatic, single, or multiple full-thickness cartilage defects of the knew with or withon bone invovement in adults.

Common Pain Medications:

Common OTC nonsteroidals include aspirin (Bayer, Anacin, Bufferin), naproxen (Aleve) and ibuprofen (Advil, Motrin). Prescription NSAIDs are commonly used to treat pain from arthritis, gout, menstrual cramps and headaches.

Ibuprofen and naproxen are NSAIDs that keep your body from making prostagladins, which are linked to both inflammation and pain. The are prescribed for things like headaches, back pain, arthritis and lupus. NSAIDs such as asprin and ibuprofen exert their effects through inhibition of COX.

Acetaminophen includes brands such as Tylenol and Actamin.

Traditional non-steroidal anti-inflammatory drugs (“NSAIDS”) such as aspirin, ibuprofen, ketoprofen, and naproxen are believed to function by inhibiitng the activity of enzymes called cyclooxygenases. Cyclooxygenases catalyze the production of a molecule called prostaglandin H2, which is a precursor for other prostaglandins that perform various functions in the human body. In the early 1990s, scientists discovered the existence and separate functions of two distinct cyclooxygenaseses, referred to as “COX-1” and “COX-2”. COX-1 is epressed (i.e., produced biologically) in the gastrointestinal tract, where it is involved in the production of prostaglandins that serve a beneficial role by, for example, providing protection for the stomach lining. COX-2 is expressed in response to inflammatory stimuli, and is thought to be responsible for the inflammation associated with diseases such as arthritis. It is now known that the traditional NSAIDs inhibit both COX-1 and COX-2, and as a result they not only reduce inflammation, but also can cause undesirable side effects such as stomach upset, irritation, ulcers, and bleeding. After the separate functions of COX-1 and COX-2 were discovered, it was hypthesized that it would be possible to reduce inflammation without gastrointestinal side effects if a method could be found for selectively inhibiting the activity of COX-2. To that end, University of Rochester scientists developed a screening assay determing whether a particular drug displayed such selectivity, and filed US Patent Application 5,837,479 which was issued in 1998. The patent contained a claim to a method for selectively inhibiting PGHS-2 activity in a human host, comprising administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene produced in a human host in need of such treatment. Unfortunately for Rochester, the patent was latter held invalid for lack of written description when it went to sue Pfizer for its sale of its COX-2 inhibitors Celebrex®. The Court held the patent invalid because it did not disclose any compounds that could be used in its claimed methods. This case could be distinguished from a different case named In re Herschler, 591 F.2d 693 (CCPA 1979) where the written description was satisfied by a specificaiton that described a claimed compound by the process by which it was made, rather than by its structure, because the application taken as a whole, reasonable leads persons skilled in the art to the recited reactions and, concomitantly, to the calimed compound. In Hershler, the court found adequate written description support for broad claims to processes for topically adminsitering a physiologically active steroidal agent to a human or animal by concurrently adminsitering the steroidal agent and dimethyl sulfoxied even though the specification disclosed only one example of a physiologically active steoridal agent because unlike non-steoridal compounds that selectively inhibit activity of the PGH@-2 gene product, numerous physiologically active steoridal agents were known to those of ordinary skill in the art. University of Rochester v. Searle Co Inc., USCA, Federal Circuit, 2004).

–Newer NSAIDS: selectivity of COX-2 is the main feature of celecoxib, etoricoxib. Because COX-2 is usually specific to inflamed tissue, there is much less grastric irritation associated with COX-2 inhibitors, with a decreased risk of peptic ulceration. However, the selectivity of COX-2 does not seem to negate other side-effects of NSAIDs, such as the risk of kidney failure, and there is evidence that indicates an increase in the risk of heart attack thrombosis and stroke through an increase of thromboxane unblanced by prostacylin (which is reduced by COX-2 inhibition). Rofecoxib (brand name Vioxx) was withdrawn in the 2004 because of such concerns. Some other COX-2 selective NSAIDS, such as celecoxib and etoricoxib are still on the market.

Side Effects and Contraindications: NSAIds are normally safe for occasional use. If taken too long, however, they can damage the kidney by reducing blood flow to the kindeys. If taken when one is dehydroated or when blood prossure is low, they can cause acute kidney injury. Ibuprofen dose should not exceed 400 mg (two of the 200 mg pills) eveyr 6 hours. The naproxen OTC dose should not exceed 220 mg every 8 hours.

Muscle Relaxants:

—Cyclobenzaprine is a muscle relaxant. It works by blocking nerve impulses (or pain sensations) that are sent to your brain. Cyclobenzaprine is used together with rest and physical therapy to treat skeletal muscle conditions such as pain or injury. See Drugs.com

Natural COX inhibition: 

Flavonoids: have been found to inhibit COX-2.

Fish oils: such as cod liver oil provide alternative fatty acids to arachidonic acid. These acids can be turned into some anti-inflammatory prostocyclins by COX instead of pro-inflammatory prostaglandins. Fish oils have been proposed as a reasonable altnerative for the treatment of rheumatoid arthritis and provide less cardiovascular sik than other treatments including.  NSAIDs.

Hyperforin: has been shown to inhibit COX-1 around 3-18 times as mucha s asprin.

Calcitriol (vitamin D) significantly inhibits the expression of the COX-2 gene.

Herbal Medicines for Anziety

Ashwagandha (Withania somnifera): Withania somnifera (WS), widely known as ashwagandha, is an Ayurvedic herb that has recently gained recognition as a treatment for anxiety and stress in the United States. Although used as a broad-spectrum remedy in India for centuries, WS has only recently been under investigation in laboratory settings. WS is categorized as an anti-inflammatory and antioxidant herbal supplement. ( Morely, “An Alternative Treatment for Anxiety: A Systematic Review of Human TrialResults Reported for the Ayurvedic Herb Ashwagandha (Withania somnifera)” J Alternative Medicine 2014)

Herbal Medicines for Pain

Artemisia: has been traditionally used in Korean herbal medicine to treat uteritis and jaundice. Flavonoids, such as 5,6,3′,5′-tetramethoxy 7,4′-hydroxyflavone (p7F), isolated from Artemisia are also known to possess anti-inflammatory activityies. For example, p7F reportedly inhibited the epxression or production of proinflammatory mediators such as COX-2/PGE2 and iNOS/NO in LPS stimulated RAW 264.7 cells. p7F also suppressed the sesrium level of TNF-alpha in mice treated with collagen and inhibited NF-0kB as well as NF-kB promoter activity in RAW 264.7 cells stimulated with LPS.

Aspirin: Sodium salicylate (S) is the active component of aspirin and is one of the most widely used over the counter drugs for the treatment of pian, fever, inflammation in addition to heart attacks, chest pain and other health conditions. It is not recommended for children, however, because it may cause Reye’s syndrome. High doses of salicylate also induce temporary hearing loss and tinnitus.

Coumarins (known as 1,2-benzopyrone or o-hydroxy-cinnamic acid-8-lactone) compirse a very large class of phenolic derivative found in plants and consist of fused benzene and alpha-pyrone rings. Over 1300 have been identified, chiefly as seocndary metablolites in green plants in fugi and bacteria.

Curcumin: is a non-nutritive, non-toxic compound in turmeric, a spice that has been used for centuries in India and elsewhere as an herbal medicinal treatment of wounds, jaundice and rhematoid arthritis. In addition, it inhibits the proliferation of a variety of tumor cells and exhibits potent anti-oxidant activity, which depends upon dthe presence of phenolic groups in the aryl rings. a compound obtained from the rhizome of Curcuma longa L (Zingiberaceae) is a polyphenol with antiflammatory activity and was reported to significantly block IL-12 mediated T cell proliferation and Th1 differentiation, an action that possibly implies its ability to reduce the production of pro-inflammatory cytokines.

Baicaline, Baicalein and wogonin are flalvonoids present in Scutellaria baicalensis (Georgi (Lamiaceae), a plant used in the treatment of a variety of inflammatory dieases such as bronchitis, nephritis, hepatitis, astham, and atopic dermatitis. The anti-inflammatory activites of these falvonoids have been attributed to their antioxidant properties and to their ability to inhibit LPS pinduced NO production and iNOS gene expression, as well as the increase in TNFalpha levels by RAW264.7 cells.

Dietary Polyunsaturated fatty acids (PUFAs): especially the n-3 series that are found in marine fish oils have significant benefits such as decreased morning stiffness and numbers of tender joints.

Ginkgo biloba: Clinical trails with AD pateints have demonstrated potential benefits in cognitive function and memory impairments from treatment with the extract of Ginkgo biloba, known to be enriched with flavonoids. Ginkgo biloba extract has been shown to proten hippocampal neurons from nitric oxide or beta-amyloid derived peptides-induced neutrotoxicity.

Flavavonoids:

–Quercetin: belongs to the flavonoids group and like vitamin C has antioxidant properties. It is a polyphenol dervied from plants such as onions, apples, green tea, berries and St John’s wort. In fact it has been used to remove “zombie” cells which are agining or deteriotating cells thought to cause many problems associated with aging such as arthritis.

–Green tea: appears to act like true antioxidants such as vitamin C, being protective at low concentrations, while at high concentrations becoming pro-oxidant.

Fish Oil: OmegaXL is sold commercially and reported to be very effective against inflammation and pain.

–-Krill Oil:

Krill oil is a good source of omega-3s. SeperBalKrill

Terpenes

Extract of T. wilfordii could be useful as a source and template for novel antiarthritic and cartilage-protective drugs. It has been reported to markedly inhibt mRNA synthesis and protein expression of MMP-3 and MMP-13, incuded by the pro-inflammatory cytokines IL-1?, IL-17 and TNF? as assessed in primary osteoarthritic human or normal bovine chondrocytes.

Celastrol has been reproted to inhibt rat adjuvant-induced arthritis. Celastrol has been rpoposed as possibly useful for improving performance in memory, learning and psychomotor activites, and common features of the nuerodegenerative diseases accompanied by inflammation, such as Alzheimer’s disease.

Ginsenosides Rb1 and Rb2, the major constituents of Panax ginseng C.A. Meyer are reported to inhbit RNF-alpha production in RAW 264.7 and U937 cells stimulated with LPS. The inhibtory activity of Rb1 and Rb2 was significantly increased by inhibitors of protein kinase C and A, protein tyrosine kinase or by drugs used for the treatment of arthritis (chloroquine and steroid drugs), but not by AMP phosphodiesterase inhibitors. It has been susggested that ginenosides could be of clinical interest for the management of TNF-alpha mediated diseases, such as arthritis.

1,25(OH)2D3: is the activated form of Vitamin D. It is a secosteroid hormone that has, in addition to its central function in calcium and bone metabolism, important effects on the grwoth and differentiation of many cell types and pronounced immunoregulatory properties. Its biological effects are mediated by the Vitamin D receptor (VDR), a member of the superfamily of nuclear hormone receptors functioning as a ligand activated transcription factor that fbinds to specific DNA sequence elements, Vitamin D responsive elements, in Vitamin D responsive genes and ultimately influences theri rate of RNA polymerase II-mediated transcription. APCs, and notably DCs, express teh VDR and are key targets of VDR ligands.

inhibits pro-inflammatory and Th-1 cytokine production, reducing the expression of co-stimulatory and MHC class II molecules on antigen presenting cells. Out of many drugs targeting DCs, only 1,25(OH)2D3 and its analogues were able to enhance the secretion by DCs of IL-10, a potent anti-inflammatory cytokine.

Macrolid antibiotics: have been shown to affect a number of processes involved in inflammation, including migration of neutrophils, the oxidative burst in pahgocytes, and the production of various cytokines by bronchial epithelial cells, lympocytes, and monocytes. Although it is presumed that NF-kB and AP-1 which are crucial regulators of proinflammatory gene expression, are potentially the most important targets for at least some anti-inflammatory effects of macrolides, the precise mechaisms remain to be clarified.

Parthenolide is a sesuiterpene lactone in Tanacetum parthenium which is one of Mexican-Indian medicinal plants used as anti-infalmmatory agents. It has reported antinocicptive action and anti-inflammatory effect in vitro. Parthenolide exerts anti-inflammatory activity by inhibiting the expression of inducible cycolooxygenase, proinflammatory cytokines and inducible nitirc oxide synthase. In addition, sesquiterpene lactones specifically inhibit activaiton of NF-kB by preventing the degradation of IkB-alpha and IkB-beta.

Triptolide: has been used extensively as an anti-inflammatory and immunosuppressive agent for the treatment of various autoimmune diseases and prolongation of allograft survival in organ transplantation. 

Barbituates:

Barbituates are sedatives like phenobarbital, pentobarbital (Nembutal) and secobarbital (Seconal). They help with anziety, sleep problems and some seizures. They can be addictive, however, particularly in higher doses.

Benzodiazepines:

Benzodiazepines include alprazolam (Xanax), clonazempan (Klonopin), and diazepam (Valium). They can help with anziety, panic attachs and sleep problems. They work well and are safer than barbituates. But overuse can also lead to addiction.

Opiods: 

Fentanyl is a powerful synthetic opioid up to 100 times more potent than morphine. As little as two milligrams, about the size of 5 grains of salt, can be fatal. Recent overdoses and deaths have occurred following use of illicit drugs, including marijuana, cocaine, and counterfeit prescriptions, as a result of these illicit substances containing fentanyl or similar extremely potent compounds. Individuals may not be aware that these illicit substances contain fentanyl and can be fatal. Recent overdoses and deaths have occurred following use of illicit drugs, including marijuana, cocaine, and counterfeit prescriptions, as a result of these illicit substances containing fentanyl or similar extremely potent compounds. Individuals may not be aware that these illicit substances contain fentanyl and can be fatal.

In 2013, illegally manufactured fentanyl and fentanyl analogs (IMFs) entered the U.S. illegal drug supply as adulterants of or replacements for white powder heroin in the Northeast and have now replaced heroin as the dominant opioid in the United States.

–Carfentanil: a fentanyl analog 100 times more potent than fentanyl, has reemerged in the U.S. drug supply. Introduction of illegally manufactured fentanyls has led to a sharp rise in overdose deaths, likely because of their high potency and rapid onset of effects.

Oxycodone: is another type of painkiller. Its in drugs like OxyCotin, Percocet, Percodan, and Roxicodon.

Availability of counterfeit prescription pills (counterfeit pills) containing illegally made fentanyl, including counterfeit M-30 oxycodone (counterfeit M-30) pills, has risen sharply in the United States and has been increasingly linked to overdose deaths.

–Oxycodone hydrochloride: is the active pharmaceutical ingredient in OxyContin®, an opioid analgesic used to treat moderate to severe pain. Constipation is a common side effect of taking opiods so you may need a stool laxative. Other possible side effects include naseua, drowsiness and having a hard time getting an erection.

Hydrocodone: is an opioid that is widely used to treat pain and has been FDA approved since 1943. It is marketed in both extended release (Zo-hydro ER) and immediate release formulations and is often combined with other active ingredients. Like many opiods, hydrocodone is primarily metabolized in the human liver. If liver function is impaired, metabolism of opiods is slowed. Thus, the same does of hydrocodone may pose a higher isk of overdose in a patient with hepatic impairment than in a healthy patient due to potential build-up of the drug int eh pateint’s bloodstream.

Drugs like Vicodin, Lortab, and Lorcet cotain hydrocodone + acetaminophen.

Morphine: Brands of morphine include Avinza, Kaian, and MS contin. Doctors usually prescribe morphine for extreme pain and codeine for milder pain. These drugs dull pain but in higher doses also cause a euphoric high.

Vicodin and Percocet: are short acting opiods. Withdrawl symptoms are more likely with these opiods. Various devices have also been used to deliver the naloxone. For example, a device called the Mucosal Atomoization Device allows a liquid form

Opiod Overdose Treatment:

–-Naloxone: Numerous naloxone products have been used to treat opiod overdose. Naloxone is an opioid receptor antagonist that blocks opids form reaching the opioid receptors, thus helphing reverse the effects of opiod overdose. It is known to administer naloxone intranasally.

Sleep Medicines:

Drugs like Zolpidem (Ambien), eszopiclone (Lunesta), zaleplon (Sonata) can help one sleep better.

Local Anesthetics

Benzyl alchohol: can be used as a local anesthetic, especially with epinephrine.