Topical Anti-Inflammatory Treatments

The extent of topical corticosteroid absorption through the skin and the subsequent therapeutic effect is determined by many factors, including the chemical vehicle (i.e., the chemical consistency of the ointment 

Vitamin K, which is important to blood clotting (blood coagulation), was discovered in tlie 1930s afrer an outbreak of fatal bleeding among 

In 1936, a growth-promoting factor termed vitamin B was isolated from bovine (cow) milk. There are now several different types of vitamin B known and chemically characterized, and they are collectively described as B complex vitamins because of relative similarities in their properties, physiological functions, and distribution in natural resources. Mostly recognized as coenzymes, the eight B complex vitamins currently include Bj (thiamine), B2 (riboflavin), niacin (nicotinamide), B (pyridoxine), pantothenic acid, biotin, B22 (cyanocobalamin), and folacin (folic acid). 

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Searching journal information continues to be the primary use of SciFinder for the medicinal chemist. One finds it especially useful for searching various topics, for instance, anti-inflammatory treatments. When performing structure/reaction-based searches, many chemists also use Beilstein CrossFire in conjunction with SciFinder. The reaction information from these systems is often complementary, and it is quite useful to have both SciFinder and CrossFire in a medicinal chemistry group. However, companies with restricted budget may have to choose one or the other. 

Treatments available for mouth ulcers are topical anti-inflammatories and preparations containing combinations of anaesthetic, analgesic, antimicrobial and astringent ingredients. 

Kikwai L, Babu ly, Kanikkannan N, and Singh M. Preformulation Stability of Spantide 11, a Promising Topical Anti-inflammatory Agent for the Treatment of Psoriasis and Contact Dermatitis. J Pharm Pharmacol 2004 56 19-25. 

The synthesis of a topical anti-inflammatory, anti-allergic agent that is inactivated in the bloodstream starts with the scission of the dihydroxyacetone side chain of the corticosteroid fluoroprednisolone (34-1) (see Chapter 7, Scheme 7.17) with sodium bismuthate (Scheme 5.34). Reaction of the product, 34-2, with methanethiol affords the thioacetal 34-3. The acetal extrudes one of the thiomethyl groups under acidic conditions to form the enol thioether 34-4. Treatment of that product with ethanethiol restores the thioacetal (34-5). The stereochemistry at Cu is defined by addition of ethanethiol from the more open backside of the thioenol 34-4. 

Newer synthetic glucocorticoids have incorporated chlorine atoms onto the steroid molecule as fluorine substitutes. Beclomethasone, a 9a-chloro analogue of betamethasone, is a potent glucocorticoid with approximately half the potency of its fluoro analogue. It is used topically as its dipropionate derivative in inhalation aerosol therapy for asthma and rhinitis (see Inhaled and Intranasal Glucocorticoids) but not for treatment of steroid-responsive dermatoses (77). The topical anti-inflammatory potency for beclomethasone... 

Observational studies The short-term and long-term safety of topical bevacizumab 5 mg/ml for progressive corneal neovascularization secondary to a variety of corneal diseases and not responding to conventional anti-inflammatory treatment have been evaluated in 30 eyes of 27 patients Five patients (five eyes) developed new corneal epithelial defects. The authors warned against using bevacizumab in patients with epithelial defects and neurotrophic keratopathy. There were no allergic reactions, ocular drug-related complaints, or systemic adverse reactions. 

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

Retinoids, which are highly effective in the treatment of acne, stimulate epithelial cell turnover and aid in unclogging blocked pores. Retinoids also exhibit anti-inflammatory properties through the inhibition of neutrophil and monocyte chemotaxis.8 Because of these comedolytic and antiinflammatory effects, topical retinoids are recommended as first-line treatment for mild to moderate comedonal and inflammatory acne.3 While success is seen with monotherapy, using a retinoid in combination with benzoyl peroxide or topical antibacterials is also an appropriate and effective therapeutic treatment option.3 Tretinoin, adapalene, and tazarotene are topical retinoids available for use in the treatment of acne. Table 62-2 describes the strengths and formulations of these agents. 

With antibacterial and anti-inflammatory properties, and the ability to stabilize keratinization, azelaic acid is an effective alternative in the treatment of mild to moderate acne in patients who cannot tolerate benzoyl peroxide or topical retinoids.3,21 It also has a hypopigmentation effect that may prove effective in patients who are prone to post-inflammatory hyperpigmentation resulting from acne.22... 

About 120 chemical constituents have been identified in chamomile as secondary metabolites, including 28 terpenoids, 36 flavonoids and 52 additional compounds [4]. A substantial part of drag effects are determined by the essential oil content. Oil is collected from flower heads, either by steam distillation or solvent extraction, for yields of 0.24-1.90% of fresh or dry plant tissue. Among the essential oil constituents the most active are /-/-a-bisabolol and chamazulene. /-/-a-bisabolol has demonstrated anti-inflammatory, antispasmodic, antimicrobial, antiulcer, sedative and CNS activity. Chamazulene is also anti-inflammatory. Topical applications of chamomile preparation have shown benefit in the treatment of eczema, dermatitis and ulceration [5]. 

Rovensky J et al Treatment of knee osteoarthritis with a topical non-steroidal anti-inflammatory drug. Results of a randomized, double-blind, placebo-controlled study on the efficacy and safety of a 5% ibuprofen cream. Drugs Exp Clin Res 2001 27 209. [PMID 11951579]... 

Topical metronidazole is effective in the treatment of rosacea. The mechanism of action is unknown, but it may relate to the inhibitory effects of metronidazole on Demodex brevis alternately, the drug may act as an anti-inflammatory agent by direct effect on neutrophil cellular function. Oral metronidazole has been shown to be a carcinogen in susceptible rodent species, and topical use during pregnancy and by nursing mothers and children is therefore not recommended. 

A topical 3% gel formulation of the nonsteroidal anti-inflammatory drug diclofenac (Solaraze) has shown moderate effectiveness in the treatment of actinic keratoses. The mechanism of action is unknown. As with other NSAIDs, anaphylactoid reactions may occur with diclofenac, and it should be given with caution to patients with known aspirin hypersensitivity (see Chapter 36). 

Clinical use Etofenamate (Coletta et al., 1988) is a nonsteroidal anti-inflammatory drug which is used for the treatment of joint, musculoskeletal and soft tissue disorders. Etofenamate is used mainly as a topical formulation (500-1300 mg/day) and is also available for intramuscular injection (1 g/day). 

Clinical use Ketoprofen (Hommeril et al., 1994) is a nonsteroidal anti-inflammatory drug used for the treatment of a variety of acute and chronic pain and inflammatory conditions including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, postoperative pain and dysmenorrhoea. It is given by oral, rectal, topical or intramuscular application (100-200 mg/day, maximal dose 300 mg/day) as the sodium or lysine salt. 

Clinical use Niflumic acid (Auclair et al., 1989) is a nonsteroidal anti-inflammatory drug used for the treatment of inflammation and pain in musculoskeletal and joint disorders such as rheumatoid arthritis as well as traumatic and postoperative pain. Niflumic acid is used in oral, rectal or topical preparations (up to 750 mg/day). 

Comfrey (Symphytum officinale) Uses Topical treatment of wounds, bruises, sprains, inflammation Action Multiple chemical components, allantoin promotes cell division, rosmarinic acid has anti-inflammatory effects, tannin possesses astringent effects, mucilage is a demulcent w/ anti-inflammatory properties, pyrrolizidine alkaloids cause hepatotox Available forms Topical application w/ 5—20% of herb applied on intact skin for up to 10 d Contra Do not take orally d/t hepatotox, do not use if PRG or w/ lactation Notes/SE N/V, exfoliative dermatitis w/ topical use Interactions T Risk of hepatotox W/ ingestion of borage, golden ragwort, hemp, Petasites EMS None... 

In case of an obstruction of the nasal airways, the swelling should first be reduced and then the patient should apply the anti-inflammatory medication to ensure its necessary distribution over the complete mucosa. Antihistamines in addition to oral therapy may also be applied locally, intranasally or conjunctivally. The combination of all three substance groups (H, antihistamines, topic glucocorticoids and antileukotrienes) as a pretreatment as well as a symptomatic treatment during immunotherapy increases the chances of success of hyposensitization in our experience [unpubl. data]. 

Ancient uses of daffodil components included systemic administration for hysterical affections, emesis, dysentery, chronic bronchial congestion, ague, and spasms. In addition, a plaster made of the roots was applied topically to dissolve hard swellings. An extract of the bulbs was also applied to open wounds, presumably as a crude anti-inflammatory agent, although wound treatment with Narcissus bulb extract could produce staggering, numbness of the whole nervous system, and paralysis of the heart. ... 

Oral ibuprofen is often prescribed in lower doses (< 2400 mg/d), at which it has analgesic but not anti-inflammatory efficacy. It is available over the counter in low-dose forms under several trade names. A topical cream preparation appears to be absorbed into fascia and muscle an (S)( ) formulation has been tested. Ibuprofen cream was more effective than placebo cream for the treatment of primary knee osteoarthritis. A liquid gel preparation of ibuprofen 400 mg provided faster relief and superior overall efficacy in postsurgical dental pain. In comparison with indomethacin, ibuprofen decreases urine output less and also causes less fluid retention than indomethacin. Ibuprofen has been shown to be effective in closing patent ductus arteriosus in preterm infants, with much the same efficacy and safety as indomethacin. Oral ibuprofen is as effective as intravenous administration in this condition. 

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