1 OLD IS GOLD In Topical Therapy SULPHUR

Yellow, non metal insoluble in water. SUBLIMED & PRECIPITATED forms. The latter has small particle size & greater efficacy. Sulphur combines with cytseine in epidermal cells to form cystine and hydrogen sulphide. Cystine promotes normal keratinization, while hydrogen sulphide in higher concentration can break down keratin. Also it gives rise to pentahionic and polythionic acids, which are antifungal and antiscabetic respectively. Sulphur is indicated in the management of Acne vulgaris (as precipitated sulphur and as Vlemincxs solution- suphurated potash), Seborrheic dermatitis, Pityriasis Versicolor, Dermatophytosis, Scabies: Infanitle, in Pregnancy, Perioral Dermatitis, demodicidosis and Verruca. Suphur Stings, stinks and stains. It can rarely cause contact dermatitis and Kligman states that it is comedogenic on the ear of rabbits.

SALICYLIC ACID
It is aO-hydroxyorthobenzoic acid which is derived from the bark of willow tree while methyl salicylate is derived from the wintergreen plant. It is sparingly soluble in water, soluble in castor oil and alcohol. It is keratoplastic at low concentration but keratolytic at higher concentration due to dissolution of intercellular cement. This results in shedding of epidermal cells rather than lysing of keratin. There is no effect on basal cells. It is antimycotic and antimicrobial. It has an anti inflammatory action by inhibiting arachidonic acid prostaglandin cascade and synthesis of PG-2 in skin. It promotes the penetration of other drugs especially corticosteroids. Salicylic acid prevents oxidation of the essential H atoms of dithranol. However, salicylic acid can react with ZnO to form zinc salicylate which is inactive. Its clinical use is in Warts: in combination with lactic acid, in psoriasis especially under occlusion, in hyperkeratotic and ichthyosiform disorders (6% SA, 60% propylene glycol & 20% ethanol), in tinea Infections as Whitfields ointment (12% benzoic acid and 6% salicylic acid in white petroleum jelly), in navulsion: 10% SA + 20% Urea, in acne for keratolysis and comedolysis. Octyl salicylate and homomenthyl salicylate in sunscreens (UVB) and as a peeling agent. Side effects are local : Irritant (Common) Allergic (Rare). Systemic side areeffects more in children and can occur within few days of therapy. Tinnitus is earliest symptom. It is caused by increased labyrinthine pressure and vasoconstriction with damge to cochlea. Later nausea, vomiting, confusion, delirium, stupor, coma. There is stimulation of respiratory center with marked hyperventilation & respiratory alkalosis. Metabolic acidosis ca occur in infants & children while hypoglycemia can occur especially in patients with renal insufficiency.

COAL TAR
Obtained as by product during destructive distillation of coal which may be anthracite (hard), bituminous (soft) or natural gas. It is a complex mixture of 10000 compounds including hydrocarbons: benzene, toulene, xylene, naphthalene, anthracene, Phenolic compounds: phenol, cresol and heterocyclic oxygen, sulfur, nitrogen compounds. Mechanism of action is inhibition of DNA synthesis of basal cells, vasoconstrictive, astringent & antipruritic action and phototoxic effects due to presence of benzpyrene & anthracene. Orthoquinones & preoxides formed after irradiation inactivate epidermal sulphhydryl group. There is decrease in elevated levels of TGF alpha messenger RNA in subcorneal layer. Preparations of coal tar include Crude coal tar: 2-10%, liquor carbonis detergens: CCT 20%, Soap bark 10%, 95% alcohol qs; Coal tar and Zinc ointment: 10% CCT,30% ZnO in paraffin, Coal Tar Paste: 7.5% coal tar solution in compound zinc paste and Coal Tar Paint: 10% coal tar in acetone. Goeckermanns original regimen in psoriasis : 1-5% CCT in zinc oxide and petrolatum is applied to lesions for 12-24 hours. Excess tar washed off with olive oil, leaving a thin film of tar on skin. Then Patient exposed to air cooled quartz lamp in sub erythematogenic dose, followed by soap and water bathing. This is repeated, usually daily or on alternate days. In the University of Miami modification, 1-5% CCT applied to skin for 2 hours and exposure in UVB light cabin to achieve mild erythema. After UVB regimen, cleansing bath is given Head, neck or flexures are not treated with tar but low potency steroids. Remission can be obtained in 1-3 weeks. Shale tars are obtained by consolidation of clay. Ichthammol is a dark brown liquid obtained from destructive distillation of shales rich in oily residue left from fossilized fish. H2SO4 and NH3 also added. It is water soluble, mild acting. It is useful in eczematous disorders.

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Wood Tars are obtained from Destructive distillation of woods likejuniper, pine, birch or leech. It contains acetic acid but not sulfur and is insoluble in water. It can be used as counterirritatnts (contain turpentine and guaicol).Juniper Tar (Oil of cade)is used for scalp Psoriasis. Tars can cause messiness, tar smarts: Irritation, stinging, reddening, increased risk of sunburn. Tars have a doubtful risk for cancers (benzpyrene content). Tar therapy is indicated in psoriasis (as Goeckermann regimen or in combination with UVA-TUVA therapy), atopic dermatitis and other eczemas.

DITHRANOL (ANTHRALIN)
It is a derivative of Goa Powder (Chrysorabin) obtained from araroba tree. Anthralin is synthetically prepared and is chemically 1,8 dihydroxy-9 anthrone. Undergoes spontaneous oxidation to anthralin free radicals,reactive oxygen species, danthron & dianthron. The latter two are responsible for staining. In presence of light it forms free radicals which destroys DNA and inactivates pro inflammatory enzymes. Does NOT form adducts- non mutagenic. It inhibits cell proliferation, mitochondrial respiration and alters function of membrane proteins. Cyokine profiles are altered: TGF alpha m-RNA expression reduced and EGF receptor binding decreased in keratinocytes, IL-8 reduced.It acts on DNA to cause its destruction, on lipids to cause peroxidation and cytotoxicity and on cellular enzymes to cause their inactivation. It is used in Psoriasis, alopecia areata, seborrheic dermatitis, warts and inflammatory linear verrucous epidermal nevus. Ingram Regimen Patient soaks in bath of dilute coal tar, then is exposed to suberythemal UV. Then 0.5-1% anthralin in Lassars paste applied and talcum powder dusted over lesions. Body covered in stockinette sleeve dressing for 24 hours. This is repeated daily. Modifications of anthralin therapy are : Short Contact Therapy, Micanol: Anthralin encased in a special lipid covering which releases anthralin only when it is contact with body temperature, thus reducing risk of staining. Stanford Regimen: Combining anthralin with topical steroids without UV light. There is an additive effect with tar, urea, UVB, tazarotene. There are no systemic side effects, there may be irritation of affected and perilesional skin and reddish brown pigmentation.

DYES IN DERMATOLOGY: GENTIAN VIOLET

GV is antibacterial against Gram +ve, MRSA, pseudomonas. It is given for candida infections of mouth, pharynx, vagina (including HIV patients). It acts by inhibition of protein synthesis and cell wall. Also photodynamic action visible light causes photoreduction of GV to free radicals. Triple dye solution (GV, BG, Proflavin) used in care of umbilical stump in neonate. 0.5-2%: solution, paint, pessaries, creams, ointments can be used. Rarely it can cause staining, irritation, sensitization, ? mutagenic.

DYES IN DERMATOLOGY: FUCHSIN

It is a mixture of pararosaniline and rosaniline. It is dark green powder, water and alcohol soluble. Effective against Gram positive bacteria and in treatment of pyoderma, dermatitis, intertrigo, eczema, and burns as solution 2 to 5%. Castellanis paint in superficial dermatophytes, especially when moist eczematous dermatitis. It is used in acid fast staining, Van Gisson and Mallorys stain. Side effects: staining and ? mutagenic.

UREA
It is water and alcohol soluble, can attract and hold water. Therefore useful as an emollient & humectant . Proteolytic at 40% strength and can macerate dystrophic nails (chemical nail avulsion).

PODOPHYLLINE
It is obtained from roots of the plants Podophyllum peltatum and Podophyllum emodii. Unstandardized podophylline contains podophyllotoxin, 4 demethyl podophyllotoxin and peltatins. It interrupts cellular activity in metaphase by combining with tubulin. It inhibits purine synthesis & incorporation into RNA and also disrupts microcirculation. Podophyllin is responsible for causing an increase markedly in the number of mitotic figures, but it does not result in crowding or pleomorphism of nuclei of keratocytes (Podophyllin cell). Podophyllin versus Podophyllotoxin Non-standardised, unstable Standardised, stable Local toxicity high Local toxicity low Systemic toxicity high (CNS depression) Systemic toxicity negligible Teratogenic and fetotoxic Non-teratogenic

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High mutagenicity Carcinogen effect? Low efficacy Clinic treatment No mutagenicity No carcinogen effect High efficacy Self treatment

BENZOYL PEROXIDE
It is an organic peroxide insoluble in water. It is antimicrobial.antinflammatory, keratolytic and has wound-healing properties. Bactericidal activity through oxidation, with release of highly reactive oxygen intermediates that oxidize proteins in bacterial cell membranes. BPO is highly keratolytic in deeper layers of epidermis and increases TEWL. Besides acne, used in leg ulcers and pressure sores. It can cause sensitization, bleaching of hair and skin.

ANTIPRURITICS
Thymol: Alkyl derivative of phenol; bactericidal, fungicidal, antiseptic; it is anirritant. Camphor: Derived from cinnamon; antipruritic and cooling Mentholis cyclic terpene alcohol derived from peppermint plant ; causes a sensation of cooling (actiivation of TRPM 8 receptors) and relief of pruritus. Also antimicrobial. It activates -opioid receptors. Different opioid receptors have contrasting effects upon pruritus. -opioid receptor agonists, -opioid receptor antagonists increase itch. -opioid receptor antagonists, -opioid receptor agonists decrease itch. Menthol can disrupt the lipid bilayer of the stratum corneum and serve as a penetration enhancer.

ZINC OXIDE
Cooling, covering, protective, astringent. It is a component of most dusting powders, pastes, shake lotions. It enhances the covering power of powders and gives consistency to pastes but can inactivate salicylic acid.

CALAMINE
Calamine (BP): Basic zinc carbonate colored with ferric oxide. Calamine (USP): Zinc oxide made coloured with a small proportion of ferric oxide. It is Bland, soothing and anti pruritic.

RESORCINOL
Prepared from benzene; water, alcohol soluble. It is Antiseptic, disinfectant, mild keratolytic. Mildly antipruritic. Taken orally, may cause giddiness, salivation and convulsions.

EXTEMPORANEOUS COMPOUNDING
It is the art or science of assembling individual chemical components into a usable drug. Typically, this is done by an individual physician seeking a drug that may otherwise be unavailable from commercial pharmaceutical manufacturers. It is a creative process that allows us to inject a little of our own personality, philosophy, and experience into treating patients. Combination products may be convenient & cost effective. Problems in such compounding are : Medical- unpredictable efficacy & bioavailability (release of drug from vehicle and percutaneous absorption). Drug interactions: Mixing tretinoin with BPO can lead to chemical breakdown of the former; calcipotriol can be inactivated by salicylic acid; adding urea can lead to breakdown of triamcinolone and decreased absorption of fluocinolone. Sterility: All water containing products are at a risk for contamination; mixing two products containg different preservatives will reduce the levels of each preservative. Stability: Compounding can change the pH of the drug, may cause oxidation (anthralin to anthraquinone), light degradation (tretinoin). Cosmesis: Vehicles used for compounding are often not cosmetically acceptable Economic Issues: Compounded preparations are often expensive Legal Issues: responsibility of using an unapproved drug.

EXAMPLE OF A PRESCRIPTION
The prescription below indicates a dry paste, stabilized with 4% bentonite, containing 5% sulphur and 5% resorcinol with equal proportions of powder and liquid.

Quantity 100 g

Quantity 30 g

Percentage Proportion 4% 5% 5% 18% 18% 25% 25%

Bentonite Sulphur Resorcinol Zinc oxide Talc Glycerol Water

4 aa 5 aa ad 50 aa ad 100 aa

1.2 aa 1.5 ad 15

aa ad 30

SPECIAL ACNE LOTION

Sulphur precipitated3.0 g, Resorcin-3.0 g, Zinc oxide-3.0 g, Glycerin- 2.5 ml, Methylated spirit10.0 ml, water to 100.0 ml

OIL OF CADE OINTMENT

Oil of Cade-20, Precipitated sulfur-10, Salicylic acid-.5, Hydrophilic Ointment qs ad 100

STANDARD DITHRANOL PASTE

Dithranol-0.1 1g, salicylic acid-2g, zinc oxide- 25g, starch- 25g white soft paraffin qs ad 100g. 5-15% hard paraffin can be used in addition. Dithranol is relatively stable in zinc pastes, on condition that an antioxidant is included in the formula, such as salicylic acid. Zinc oxide increases the oxidation of dithranol, which is suppressed by salicylic acid.

DITHRANOL POMADE
Dithranol- 0.3g, salicylic acid - 0.3g, Yellow soft paraffin- 4.3g Emulsifying ointment to make 100g

EMULSIFYING OINTMENT
Emulsifying wax - 30, Liquid paraffin-20, White soft paraffin qs ad 100

CASTELLANIS PAINT
Basic fuchsin 0.3% (local anesthetic, bactericidal, fungicidal), Ethyl alcohol 95% 10.0 (cooling), Boric acid 1.0 (antiseptic), Phenol liquef. 4.0 (antipruritic), Acetone 5.0 (cooling, cleansing, solvent), Resorcinol 10.0 (antipruritic, keratolytic, antimycotic)Water to 100.0.

CALAMINE LOTION
Prepared calamine-12.0 g, Talcum powder(purified, sterilized) 12.0 g, Glycerinof rose to 100.0 ml 10.0 ml, Water

CALAMINE LINIMENT (W/O)

Calamine- 8, Zinc Oxide- 8, Olive Oil-50, Calcium Hydroxide ad 100

PUSEYS CALAMINE EMULSION (O/W)

Phenol- 0.2, Tragacanth-1.0, Zinc Oxide- 6.0, Calamine- 6.0, Olive Oil-33.0 Distilled water qs ad 100. 0

FLEXIBLE COLLODION
Camphor- 2%, Castor Oil- 3%, Pyroxylin- 4%, Ethyl Alcohol 31%, Diethyl Ether 60%

WART LOTION
Salicylic Acid-16.7%, Lactic Acid-16.7%, Flexible collodion..qs.

PODOPHYLLINE TINCTURE
Podophyllum resin. 20, Tincture benzoin co qs ad..100