Journal of Medical Pharmaceutical www.jmpas.com And Allied Sciences ISSN NO. 2320 - 7418

REVIEW ARTICLE

A EXTENSIVELY

SECOND-HAND DRUGS:

TOPICAL AGENTS Correspondence Dr. Kiran Jagtap1*, Dr. Ramesh Agarwal2, Dr.Lata.Kale3, Dr.Kiran Jagtap Dr. Nilofar Zaidi4, Dr.Sonia.Sodhi5, Dean, HOD. Prof, Department of Oral Pathology. Dr. Shaikh Tauseeef Ahmed6, Dr. Sayyed Mohammed Qadri7, 8 9 SMBT Institute Of Dental Dr.Pratik.C.Parkarwar , Dr.Kirandevi.C.Puranik , Sciences & Research 10 Dr. Swati Rathod , Dhamgoan, Nashik. Keywords 1- Dean, HOD. Prof. Department of Oral Pathology, SMBT Institute Of Dental Sciences & Research Dhamgoan, Nashik. topical, face, perioral, 2- Reader, Dept Of General Surgery.PDU Dental College, dermatologic, skin, mucosa. Solapur Received 3- HOD. In dept of OMR.CSMMS Dental College and Hospital, 20 January 2017 Aurangabad. Reviewed 4- PG student .In dept of OMR.CSMMS Dental College and 10 February 2017 Hospital, Aurangabad. Accepted 5- Asso. Prof. In dept of OMR.CSMMS Dental College and 15 March 2017 Hospital, Aurangabad. 6- PG Student, Oral & Maxillofacial Surgery. CSMMS Dental College and Hospital ,Aurangabad 7- PG Student, Dept of Orthodontics. PDU Dental College, Solapur 8- Sr. Lecturer. Dept Of OMR .PDU Dental College,Solapur 9- PG Student, Dept of OMR. Albadar Dental College, Kalaburgi. 10- Lecturer In dept of OMR.CSMMS Dental College and Hospital , Aurangabad.

ABSTRACT The skin & mucosa form the largest organ system in the body. There are many dermatologic conditions that affect the skin of the face & perioral areas. Several diseases that are primary to the or systemic diseases with oral manifestation that may require topical agents.

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721 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 greasy & they vanish when rubbed into skin

Introduction: • Ointment- Semisolid emulsions of water Topical agents deliver the medication directly to droplets suspended in oil. They are the target organ that needs treatment and occlusive & form a film on skin or provides high concentration of the desired mucosa that creates a membrane that medication to the specific site with less risk of causes an increase in the local skin provoking systemic side effects.Several vehicles temperature & its water content . This deliver a drug topically, and vehicle is important effect makes it easier for the topically part of effectiveness of the drug. applied substance to melt at body temperature & penetrate the skin’s outer Topical pharmaceuticals are used for the protective layer. following purposes. • Solution -Liquid preparations that  Protecting an injured area from the contain soluble chemicals dissolved in environment so as to permit the rejuvenation either water or alcohol of the skin. • Gels -Semisolid emulsions that liquefy  Providing skin hydration or for an emollient at body temperature when applied to the effect skin or mucous membrane  Providing a method of conveying a • Lotions -Either suspension of insoluble medication to the skin or mucosa for a powder in liquid (Calamine lotion) or specific effect either topical or systemically. pourable emulsions of oil in water. They

are easily applied, their effects are short

acting & they tend to wear off faster than List of common topical vehicles : creams/ ointments • Creams- Semisolid emulsions of oil & water intended for external application that contains medicaments dissolved or The decision to use a cream, ointment, gel, or suspended in water soluble cream base. lotion depends on the degree of skin penetration They are usually soft, white, and non desired, the characteristics of the skin, the characteristics of the area to which the

722 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 medication is applied & the properties of the  Antiviral medication. The amount of drug that penetrates  Antifungal & vigor of rubbing, the surface area covered, the condition of the skin ,& the occlusive effect of Topical steroids the base. It possess anti inflammatory &antimitotic activity& are corner stone of treatment for many Creams are usually applied to areas in which inflammatory skin & mucosal conditions.They they can be rubbed vigorously into the skin or to are absorbed at different rates from different moist, weeping lesions because they produce parts of body , for E.g – from eyelids & genitals drying by having the exudate absorbed into the is 30%, face- 7% forearm – 1% , palm -0.1% .Its aqueous external phase of the cream. available in cream, ointment, gel, & liquid Ointments are generally used on dry scaly vehicle. When comparing different forms of the lesions because they stay on longer & their steroid preparation , ointment are generally emolient properties aid in rehydration stronger than creams because they penetrate Pastes are thick , stiff ointments that do not better & absorbed best. flow at body temperature & serve as protective coatings over the area to which they are applied. Usage: Orabase is one such agent. It is widely used  It needs to be in contact with the mucosa dental paste that is agent for several topical for some minutes for it to have any medications that are used intraorally. It contains significant effect. gelatin, pectin, &carboxymethylcellulose  Patients should not eat or drink for sodium in plastibase (plasticized hydrocarbon 30min after using the steroid, in order to gel, a polyethylene & mineral oil gel base.) prolong contact with the lesion.  The steroid can usefully be applied in a . plastic splint worn overnight for treatment of desquamative . Classification:  Corticosteroid Topical steroids in OLP in increasing order of  Immunomodulators potency.  Analgesics  Triamcinolone acetonide 0.1% (Tess,  Antibacterial Ledocort , Kenocort )tid/day for 1month

723 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733  Fluocinolone acetonide 0.025% (fluzone )tid/day for 2months with tapering dose  Clobetasone propionate 0.05% (clobetol Immunomodulators cream , cosvate gel)bid/day for 2months Topical Calcineurin Inhibitors  It acts by binding to immunophilins  RAS-Topical steroid like flucinonide , (cyclophilin & macrophilin) & these betamethasone, or clobetasol, placed direcly complexes inhibit calcineurin, which on ulcer reduces healing time . under normal circumstances induces the  Oral lesions of lupus erythematosis -0.05% transcription of IL-2 . flucinonide & 0.05%clobetasol gel placed  Tacrolimus : (Tacrotec, Tacrovate ) on lesion bid for 2weeks  Inhibits T – lymphocyte activation &  Bullous -High potency topical prevents the release of inflammatory steroids , clobetasol, betamethasone cytokines & mediators from mast cells invitro after stimulation by antigen Ig Adverse reactions: E complexes.  Local -Skin atrophy, striae, telangiectasia,  Available in 0.03% ointment , twice aceniform eruption & & daily application hypersensitivity reactions

 Cyclosporine - 100mg /ml may be used  Systemic- When large amounts of steroids as mouth rinse or finger rub application are absorbed through the skin , fluid using very low doses of cyclosporine retention , raised blood pressure, & 48mg/day in adhesive base was found to secondary diabetes may develop or it may be effective in suppressing T cell aggravate these conditions in pateints cytokine production. already in therapy .Supression of the

hypothalamic-pituitary-adrenal axis with the Topical agents for neuropathic pain : use of topical steroids is uncommon.  As neuropathic pain frequently is Adrenal supression caused by topical steroid associated with a peripheral ectopic use is seen more frequently in small children generator (for instance, a triggering zone because their body surface area is large near the tissue surface in trigeminal relative to their total body weight.

724 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 neuralgia), it is logical to use a topical nerve endings of mucous membranes & abraded anesthetic to desensitize the painful site. skin. It has fastest onset & short duration  This approach may decrease the Indications – mucosal pain , superficial facial neuronal firing and relieve the pain. pain. Local anesthetics are prepared for Dosage – 10%, 15%, 20% gel qid topical use in several different forms, Side effects –methemoglobinemia such as aqueous or viscous gels, sprays and ointments. With neuropathic Lidocaine conditions, the application of the  It is amide type local anaesthesia . Its anesthetic usually is limited to a small mode of action is similar to that of area, and in those cases, a sticky benzocaine. ointment or viscous gel often is preferred Lidocaine Patch: (Lidoderm patch ) As a topical preparation, the lidocaine patch 5% is well tolerated and has an excellent safety Topical anesthetics: profile..  It delivers the analgesic at the site from  Indications – mucosal pain , superficial which the pain originates & minimizes facial pain. systemic effect of the drugs .  Dosage - maximum of 3 patches per day  The main type of topical anesthetic agents for up to 12 hours total directly to the available for use on mucosa are benzocaine, area of maximum pain and/or . lidocaine, tetracaine & cocaine  The patch should not be used in patients with herpes zoster or those with other Benzocaine (Topicale, Hurricaine , Orajel, types of open skin lesions as the Mucopain) available formulation is not sterile. It reversibly stabilizes the neuronal membrane,  Side effects - erythema, burning , edema which decreases its permeability to sodium ions. Depolarization of neuronal membrane is Eutectic mixture of local anesthesia(EMLA ) inhibited, which blocks the initiation &  It is a mixture of lidocaine 2.5% in 1:1 conduction of nerve impulses .It is effective on ratio.

725 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733  Lidocaine & prilocaine by themselves release, erythema and thereby primary produce a 20% anesthetic concentration and allodynia to penetrate intact skin.  The central release of excitatory  It inhibits the neuronal membrane ion aminoacids and neuropeptides resulting refluxes. from the peripheral stimulation of the C-  Indications – PHN , fiber nociceptors by capsaicin causes  Trade name -AstraZeneca central sensitization that results in the

phenomena of secondary hyperalgesia Capsaicin :(Zostrix) and an expanded skin response area for  Active pungent ingredient in hot the sensitized neurons peppers, is used commonly as a topical

medication for neuropathic pain  It was initially postulated that chronic conditions of the skin or oral mucosa. application of capsaicin depleted the  Capsaicin exerts strong pharmacological peripheral sensory fibers of substance P, effects on the peripheral system and the but now it is suggested that repeated CNS. capsaicin application actually only  Of particular interest is its effect on the inhibits the peripheral terminal function. Cfiber type of primary afferent neurons It should be noted that when the and on a specific membrane recognition capsaicin application has been site identified as an ionotropic vanilloid discontinued, the pain typically returns. receptor.  Indication: Stomatodynia, superficial

neuropathic facial pain Capsaicin stimulates the nociceptors to  Dosage – 0.025% , 0.075% cream release substance P and other peptide should be applied to the affected area 3- neurotransmitters, not only at the peripheral 4 times daily. site of application, but also centrally.  Pain relief from topical capsaicin is

usually seen in 14 to 28 days regular  The peripheral release causes local topical application. Maximal response excitation and sensitization, manifested may require 4 to 8 week as prolonged cutaneous pain, histamine

726 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 Topical NSAIDs. norepinephrine, thereby decreasing the  Topical NSAIDs have shown C-fiber stimulation effectiveness in relieving pain in acute  Clonidine for local extraoral therapy is and chronic conditions, with lower available as a transdermal patch. incidence of adverse gastrointestinal  For intraoral use, it is better to have effects than they have when taken orally. clonidine compounded into a Some of the medications used topically transdermal penetrating cream and for pain include ketoprofen (a propionic dispensed in a calibrated syringe so that acid derivative), diclofenac (a the dose can be better controlled. benzeneacetic acid derivative), aspirin and ibuprofen. Anti bacterial agents: Topical antibacterial agents may be useful in  Topical aspirin also has been specifically preventing infections in studied for dermal neuropathic pain,  clean wounds providing analgesia within 20 to 30  Early treatment of infected dermatoses minutes.. & wounds  Topical application of 5% Ibuprofen tid  In reducing colonization of the nares by /day was effective in TMJ pain staphylococci,  The selection of particular antibiotic Sympathomimetic agents. depends of course upon the diagnosis &  Sympathomimetic agents may be useful when appropriate in vitro culture & in some forms of chronic neuropathic sensitivity studies of clinical samples. pain.  Prepacked topical antibacterial  It has been shown that injured C fibers preparation that contain multiple express α1 receptors on their peripheral antibiotics are available in fixed dosages membranes. Sympathetic activity then well above the therapeutic thersholds. would excite the C fibers, signaling pain.  Clonidine, an α2-adrenergic agonist, has Bacitracin ointment been used as a topical agent for  It is a bacteriostatic against gram- neuropathic pain because it is able to positive and some gram negative interrupt the peripheral release of bacteria and may also possess some

727 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 bactericidal activity at certain pustular acne, pustular psoriasis, infected concentrations. seborrheic dermatitis, infected contact  Bacitracin works by interfering with the dermatitis. mucopeptide transferring process and therefore prevents bacteria cell wall development  Indications :Prevention of skin and skin Neomycin : structure infections after a minor  Neosporin (neomycin+ bacitracin+ compromise in skin integrity such as polymyxin B) minor burns or skin .  Prevention of skin and skin structure infections, including wound Neomycin & gentamicin – management for skin abrasion and minor  Neomycin and gentamicin are burn wound infection aminoglycoside antibiotics with gram- positive and gram-negative bactericidal Metronidazole :(Metrogel) activity.  Metrohex- metronidazole +  It works by establishing irreversible chlorhexidine binding to receptors present on the 30S  It disrupts bacterial &protozoal DNA, ribosomal subunit of bacteria. inhibiting nucleic acid synthesis.  The binding prevents the initiation Produces bactericidal , anti complex between the bacterial inflammatory & immunosuppressive messenger RNA and the ribosomal effects subunit which results in the misreading  Indications: Anerobic bacterial of the bacterial DNA and formation of infections such as dental abscesses, acute nonfunctional proteins. and acute ulcerative gingivitis Gentamicin 0.1% cream (garamycin)  Indicated in treatment of minor bacterial Antifungal agents: skin infection including, folliculitis,  Indications - Candidiasis furunculosis, impetigo, eczema, Cotrimazole: infectious eczematoid dermatitis,

728 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733  It inhibits the growth of pathogenic  Dosage – 2% cream: rub gently into the yeast by binding to phospholipids in affected area 1-2 times daily. fungal cell membrane which alters the  Side effects – irritation, pruritus permeability of the membrane & causes ,stinging a loss of essential intracellular elements. Miconazole  Dosage –  It inhibits the growth of the common  Clotrimazole 1% cream (candid , dermatophytes Epidermophyton canesten) 5times /day for 2 weeks floccosum & the yeast like fungus C.  Clotrimazole 2% gel (candid V) 5 albicans. The drug has no times/day for 2weeks contraindications.  Side effects – nausea , vomiting , local  Inidications: angular , various mild burning , irritation, stinging forms of candidiasis, Antiviral agents : Nystatin (Nystat , Mycostatin)  The viral conditions that the oral &  It binds to sterol in fungal cell maxillofacial surgeon most likely membrane & changes the cell wall encounters is . The agents permeability, which allows for leakage that are used topically for this condition of cellular contents . are penciclovir & zovirax ointment  Dosage – 100,000 U/g cream & ointment, apply to affected area 4-5 Acyclovir:(Acivir , Cyclovir , Herperax , times/day Herpex )  Side effects – nausea , vomiting ,  It interferes with virus diarrhea, stomach pain , contact DNA polymerase &inhibit viral DNA dermatitis. replication. It is also effective against Ketoconazole (Nizoral) other viruses.  It is broad spectrum synthetic antifungal  It seems to shorten the course of the agent functions by altering the herpetic eruptions & produces a slight permeability of the cell membrane of the decrease in pain. organism by way of the drug impairing  Dosage : 5% cream,topical application the synthesis of ergosterol , a vital to lesion 4times daily for 4 days component of fungal cell membrane.  Side effects – pain , burning , stinging

729 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 Penciclovir Cream 1% (Denavir Cream)  Side effects – tingling at application site.  It is active against herpes viruses. It Topical opiates selectively inhibits herpes virus DNA  Are increasingly applied for the relief of synthesis & prevents viral replication. pain . Mu receptor agonists are the most  Indicated in herpes labialis . potent topical opiod analgesics delta &k  Dosage – the cream should be applied to being effective. the lesion every 2 hours during waking  Opiod receptor are present on the hours for a period of 4 days . Treatment peripheral terminals of thinly myelinated should be started as soon as possible & unmyelinated cutaneous sensory during the prodrome or as soon as the fibers . pateint become aware of lesion.  However peripheral opiods actions are  Side effects – mild erythema, not prominent in normal tissue & appear occasionally headache after the induction of due to enhanced opiod receptor expression . Docosanol: (Abreva)  According to a study topical morphine  It is saturated 22-carbon aliphatic was used in pateints of head & neck alcohol that inhibits HSV replication cancer receiving chemotherapy , it intracellular events surrounding viral decreased the severity of pain & duration entry into target cells. Its mechanism of of pain & duration of functional action is still poorly understood . impairment  It is high lipophilic compound & targets (Advanced studies in medicine 2003 ) viruses with lipid containing envelope such as HSV.  It probably inhibits fusion of the HSV Amlexanox:(lexanox ) envelope with the plasma membrane&  Potent anti-allergic , anti inflammatory therefore blocks subsequent viral effect. replicative events.  It inhibits the release of histamine and  Dosage – 10% cream is available , thin leukotrienes from mast cells, basophils film is applied 4 times daily until healed. and neutrophils in in vitro settings, It reduces the healing time by 1.6 to 4.6 possibly through increasing intracellular days cyclic AMP content in inflammatory

730 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733 cells, a membrane-stabilising effect or DESENSITIZING AGENTS inhibition of calcium. Definition.Desensitizing agents are defined as  Indication – aphtous ulcers drugs that alleviate painful sensations that  Dosage – 5% paste, 4 times /day until sometimes occur in exposed and ulcer heals .  Side effect- Transient pain, stinging or  Types of Desensitizing Agents. burning, contact mucositis, nausea and  Fluoride. (in the form of sodium diarrhea. fluoride, stannous fluoride, acidulated- Mouth rinses : phosphate fluoride, and so Chlorhexidine 0.2%( Clohex, Nitrahex, forth)itdecrease the permeability of Rexidine,peridex) dentin in vitro, possibly by precipitation  It is potent , chemoprophylactic agent. It of insoluble calcium fluoride within the has a broad spectrum action & effective tubules. against G+ve than G-ve bacteria. It acts  : In 1981, Greenhill and by binding readily to negatively charged Pashley reported that 30 percent bacterial cell wall thereby disrupting caused a 98 percent membrane integrity &affecting its reduction in dentin permeability in functions. In high concentration it is vitro.. Oxalate products reduce dentin bactericidal. permeability and occlude tubules more  Indicated in gingivitis consistently in laboratory studies  Dosage – 10ml swish & expectorate ,  Calcium phosphates. Calcium bid phosphates may reduce dentin sensitivity  Side effects – teeth staining , taste effectively. Calcium phosphates occlude change , tongue discoloration dentinal tubules in vitro and decrease in vitro dentin permeability Povidone-iodine  Potassium nitrate. Potassium nitrate,  Indications which usually is applied via a  Used as an aid to desensitizing toothpaste, also can reduce  Presentations: As a 1% . dentin sensitivity when applied topically  Dose :10 ml undiluted or diluted to 20 in an aqueous solution or an adhesive ml with water as a rinse 4 times daily. gel.

731 Journal of Medical Pharmaceutical and Allied Sciences (March_2017); 721-733  Potassium nitrate does not reduce dentin  Used in treatment of leucoplakia, permeability in vitro, but potassium ions chronic hyperplastic candidiasis do reduce nerve excitability in animal  Trade name – Retin-A models  Bonding resins and dentin adhesives. References With the newer systems becoming more 1. Burket’s 11th edition pg 15- 18 adherent to dentin, these materials have 2. Crispian scully – oral & maxillofacial become very popular. Resins and medicine adhesives are now designed to flow into 3. Bertam . Katzung – basic & clinical dentin tubules to seal the dentin surface pharmacology when they are set. 4. Sharav – & headache Desensitizing 5. Topical medications for orofacial toothpastes/dentifrices(sensoform , sensidyne neuropathic pain: a review . JADA 2000 ) 6. Topical analgesics : a review of recent  Most desensitizing toothpastes contain a clinical trials & their applications to clinical potassium salt such as potassium nitrate, practice . Advanced studies in medicine or . 2003 7. Drug Index Vitamin A(retinoic acid 0.01% to 0.5%) 8. Antibiotics, Topical Review 2010 Provider  Retinoids have been noted to have Synergies, L.L.C. All rights reserved.Printed antikeratinizing and immuno-modulating in the United States of America. effects, they stimulate macrophage 9. Efficacy of topical retinoic acid compared activation and antibody dependent cell- with topical triamcinolone acetonide in the mediated cytotoxicity . treatment of oral .Acta Medica  Moreover, retinoids may reduce CD4 Iranica, 42(2): 108-113; 2004 lymphocyte infiltration and increase the 1. Managing dentin hypersensitivity. JADA, macrophages in OLP lesions, thus 2006. accelerating the healing process.

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