In this essay we will discuss about the drugs used for the treatment of skin and eye diseases.
Essay # 1. Drugs for the Treatment of Skin Diseases:
The vehicle affects the degree of hydration of the skin, has a mild anti-inflammatory effect, and aids the penetration of an active drug into the skin. The most commonly used bases or vehicles are soft paraffin, hard paraffin, macrogels, lanolin and oils.
i. Calamine:
Calamine is native zinc carbonate tinted pink with ferric oxide and is used as a cream or lotion for pruritus.
ii. Barrier creams:
These contain water repellent substances such as dimeticone or other silicones. They are used to protect the skin in areas around stomas, pressure areas in the elderly, bedsores, nappy and urinary rash, minor burns and abrasions, leg ulcers, moist eczema, fissures and a number of related disorders.
iii. Sunscreen preparations:
Solar ultraviolet irradiation can be harmful to the skin. Depending on the wavelengths of ultraviolet radiation, many skin disorders such as eruptions, urticaria, cutaneous porphyria, aggregation of the preexisting skin disorders, photosensitivity reactions to certain drugs, sunburn and even skin cancer may occur. Sunscreen preparations are lotions or creams which contain aminobenzoates and titanium dioxide which provide protection against both medium length (UVB) and long wave length (UVA) ultraviolet irradiation.
iv. Topical corticosteroids:
Topical corticosteroids are commonly used for acute and sub-acute disorders such as the eczemas, itching (pruritus), refractory dermatoses, and selected cases of psoriasis such as flexural and facial psoriasis. They are of no value in urticaria and are contraindicated in rosacea and in presence of microbial infections unless combined with an appropriate antimicrobial agent. They are generally incorporated in water miscible creams, ointments or lotions. Addition of urea or salicylic acid increases the penetration of the corticosteroids.
Topical corticosteroids are classified according to their potency:
Hydrocortisone ointment is the most commonly used. The only valid use of stronger preparations is in refractory dermatoses and their use is contraindicated in paediatric disorders and for application to the face. Side effects of topical corticosteroids include spread of infection, contact dermatitis, acne and mild reversible depigmentation. Intraregional corticosteroid injections are more effective than the very potent topical preparations and are reserved for localized lesions which do not respond to topical treatment.
Antibacterial agents:
Antibacterial agents are best avoided because of the development of resistant strains and the risk of sensitization leading to contact dermatitis. Penicillin and sulphonamides should never be used on the skin owing to high risk of sensitization. Framycetin, neomycin and polymyxins are the antibiotics only used topically. If large areas of skin are treated, ototoxicity may be a hazard particularly in children, in the elderly and in those with renal impairment. Chlortetracycline and fusidic acid can be used both topically as well as systemically.
i. Mupirocin:
Mupirocin is not related to any antibiotic in use. It is highly effective against Gram positive skin infections. To avoid development of resistant strains, its use should be restricted and best avoided in hospital.
ii. Silver sulphadiazine:
Silver sulphadiazine is used in the treatment of burn infections. It is contraindicated in pregnancy and breast feeding, hypersensitivity to sulphonamides and in neonates.
iii. Antifungal agents:
It is always advisable to confirm the fungal infection before commencement of the treatment. Topical treatment is usually adequate for most localised ringworm infections, including tinea pedis. Whitfield’s ointment (salicylic acid and benzoic acid ointment) is quite effective. Other commonly used preparations are the azoles (clotrimazole, econazole, miconazole and sulconazole) in forms of cream and lotion. The undecenoates and tolnaftate are less effective in ringworm infections.
Amorolfine is a newly introduced antifungal and is available as cream for fungal skin infections and as a lacquer for fungal nail infections. Candidal skin infections are common in diabetic patients and those who have been treated with broad-spectrum antibiotics and immunosuppressive drugs. Nystatin cream or ointment is very effective in candidiasis but not against ringworm skin infections.
Antiviral agents:
Aciclovir or penciclovir cream is the treatment of choice for herpes simplex infection of the skin; treatment should begin as early as possible. Contact with the eyes and mucous membranes should be avoided.
Antiparasitic agents:
i. Scabies:
Benzyl benzoate emulsion is effective for scabies, but is not a drug of first choice. It is an irritant and should not be used in children, in infected skin and mucous membranes. Malathion and permethrin are the drugs of choice for scabies. Aqueous preparations are preferred, because they are less irritating and are applied to whole body only once as against benzyl benzoate which requires 3 applications on consecutive days.
Ivermectin in a single oral dose is used in combination with topical drugs for treatment of hyper-keratotic scabies, which do not respond to topical treatment alone. Head lice and body lice. Carbaryl, malathion and phenothrin are the drugs used as liquid (aqueous) or lotion (alcoholic) preparations for the treatment of lice infection. A contact time of 12 hours or overnight treatment, repeated after 7 days, is required to kill lice emerging from surviving eggs.
ii. Topical circulatory preparations:
Heparinoid cream (Hirudoid) or ointment (Lasonil) are used to improve local circulation in conditions such as bruising, superficial thrombophlebitis, chilbains and varicose veins. Their therapeutic value is questionable.
iii. Topical disinfectants:
There are a large number of agents used to destroy the vegetative bacteria on skin and mucous membranes. They are used during surgical procedures for skin and hand disinfection, mouth wash, bladder irrigation, wound cleansing and many other conditions which require antisepsis.
These are:
a. Iodine is an effective disinfectant and is largely used for skin disinfection. It rarely causes skin sensitization. Its regular use is contraindicated in patients with thyroid disorders or under lithium therapy. The only preparation of iodine used is providone-iodine in alcoholic or aqueous solution, as it is non-staining and less irritant. It is used as a 10% solution for pre and postoperative skin disinfection and as a 7.5% solution for surgical scrub and scalp and skin cleanser.
b. Chlorhexidine is a useful skin disinfectant. It may cause occasional sensitivity. It is used in varying dilutions ranging from 0.02% to 4% solution for disinfection of skin, surgical scrub, cleansing and disinfecting wounds and burns, mouth wash, bladder irrigation and as an obstetric antiseptic and lubricant cream.
c. Hexachlorophene is used as 3% cream for preoperative scrub of hands. It should not be used on badly burned or excoriated skin, in pregnancy and children under 2 years.
d. Cationic surface acting disinfectants emulsify fats and possess bactericidal action. Cetrimide is the most widely used skin disinfectant. Combined with chlorhexidine (Savlon), it is one of the most popular hospital disinfectants for surgical procedures, instruments and utensils. It may cause skin irritation and sensitization.
e. Oxidising agents- Hydrogen peroxide and potassium permanganate liberate oxygen which oxidises bacterial protoplasm. They are mainly used for cleansing and deodorising wounds and ulcers.
There are a large number of other disinfectant like alcohol, saline, chlorinated solutions, weak acids, metallic salts and dyes which are of limited value.
Acne:
Acne vulgaris occurs in at least 90% of adolescents. Acne depends on the action of androgens on sebaceous glands. Excess production of sebum, its retention and hyperkeratosis may result in the formation of comedones (blackheads).
The choice of treatment depends on whether the acne is predominantly inflammatory or comedonal and its severity. Mild to moderate acne is treated by topical preparations. Oral therapy is required for moderate to severe acne, or when topical preparations are not tolerated or ineffective.
1. Topical preparations:
a. Benzoyl peroxide is effective in both inflammatory lesions and comedones. It possesses antimicrobial and anticomedonal properties. Adverse effects include local skin irritation which tends to subside with continued treatment.
b. Retinoids:
These are synthetic vitamin A derivatives and include isotretinoin, acitretin and adapalene. Retinoids have a dramatic effect on the production of sebum, reducing the size of sebaceous glands by 90% in the first month of treatment. Inhibition of sebaceous gland activity is the main reason for their efficacy in acne.
Retinoids also cause desquamation of the skin which accounts for their use in hyperkeratotic hyper-proliferative skin disorders such as psoriasis. Adapalene and isotretinoin are applied locally in mild to moderate acne.
Topical retinoids give rise to local reactions including erythema with resultant sore, pain or marked dermatitis or desquamation.
c. Azelaic acid is as effective as benzoyl peroxide and retinoids without causing their irritant side effects.
d. Antibiotics:
Topical antibiotics are generally less effective than their oral counterparts and do not appear to be more effective than topical azelaic acid or retinoids. Erythromycin, clindamycin and tetracycline lotion or gel may produce mild irritation, rarely sensitization and antibiotic resistance and are not the drugs of choice for local application. Topical corticosteroids should not be used.
2. Oral preparations:
a. Antibiotics- Oral broad spectrum antibiotics are standard treatments for moderate or severe acne. Adequate doses for 3 months combined with a topical peeling agent such as benzoyl peroxide or retinoic acid achieves good control of acne. Oxy-tetracycline, doxycycline and minocycline are most commonly used.
b. Hormonal treatment is no more effective than oral antibiotics. Hormonal manipulation is often successful in women who fail to respond to antibiotics and require oral contraceptives. Cyproterone acetate, an anti-androgen combined with ethinylestradiol is indicated in women refractory to oral antibiotics.
Acne rosacea is not comedonal. The pustules and papules respond effectively to topical metronidazole. Oral broad-spectrum antibiotics for prolonged periods are also effective, but their use is associated with usual antibiotic disadvantages.
Psoriasis:
Psoriasis is characterized by epidermal thickening and scaling. It affects about 2% of population and has no curative treatment.
1. Topical treatment:
Standard topical treatment for psoriasis includes coal tar and dithranol alone or in combination with salicylic acid.
a. Coal tar is more potent keratolytic than salicylic acid and has anti-inflammatory and anti-scaling properties. It is used as an ointment or paste in combination with an emollient (calamine) or salicylic acid. It should not be used in sore, acute or pustular psoriasis or in presence of infection.
b. Dithranol is highly effective in psoriasis. The most useful advancement in the topical treatment has been “short contact dithranol treatment”. High concentration dithranol (2-4%) is applied to lesion for one hour and then washed off. Its use is contraindicated in hypersensitivity and in acute and pustular psoriasis.
c. Photo-chemotherapy (PUVA). It consists of administration of psoralen (usually methoxsalen) either by mouth or topically combined with ultraviolet A irradiation (UVA) for the treatment of plaque psoriasis. Adverse effects include short-term hazard of severe burning and long-term hazards of development of skin cancer and cataract formation, unless protected.
d. Calcipotriol and tacalcitol are the topical analogue of calcitriol, a biologically active form of vitamin D. Calcitriol inhibits the proliferation of keratinocytes. They are widely used for plaque psoriasis and may cause local irritation, dermatitis and also aggravation of psoriasis. They are contraindicated in disorders of calcium metabolism.
e. Retinoids- Tazarotene is available for topical use in mild to moderate plaque psoriasis.
f. Corticosteroids- Topical corticosteroids also provide relief in mild to moderate psoriasis; weaker corticosteroids (hydrocortisone 1%) for flexural and facial psoriasis and more potent (betamethasone 0.1%) for scalp psoriasis.
2. Oral treatment:
a. Retinoids:
Acitretin, a third generation retinoid, is a metabolite of etretinate (tigason). It has a marked effect on keratinising epithelium. Its mode of action is unknown. In psoriatic skin mitosis is reduced and acanthosis is diminished.
Acitretin is effective in generalised pustular psoriasis, and in chronic disabling form of pustular psoriasis, palmoplantar psoriasis, severe chronic plaque psoriasis and erythrodermic psoriasis. Rates of relapses are high on stopping the treatment.
Acitretin is teratogenic and is contraindicated in pregnancy. Hyperlipidemia and hepatotoxicity may occur and acitretin is not used in hepatic and renal impairment.
b. Immunosuppressants:
Methotrexate is effective in severe psoriasis that is resistant to or intolerant to other forms of topical or oral treatment. It is a cytotoxic drug and is contraindicated in renal and hepatic impairment and in pregnancy.
Cyclosporin, isolated from soil fungi, is a potent immunosuppressant and is particularly used in the field of organ and tissue transplantation to prevent the rejection of allografts. Low dose cyclosporin also seems to be effective in resistant psoriasis and severe atopic dermatitis. Potentially toxic effects include nephrotoxicity and hypertension.
c. Interferons:
Interferons possess a broad spectrum antiproliferative action that includes an effect on human keratinocytes. Interferon gamma administered systemically appears to resolve psoriatic lesions, though its role in psoriasis remains to be established.
Miscellaneous skin preparations:
A large number of drugs are available for application to the skin.
Some of the common skin disorders and drugs used are:
a. Topical antihistamines and local anesthetics are not very effective in pruritus and may occasionally cause sensitization. Topical corticosteroids are useful in treating insect stings. Calamine lotion is not useful.
b. Irritants and counterirritants were used for relief of local muscle and joint pain, but have been largely replaced by topical NSAIDs. The ingredients of counterirritants include volatile oils, menthol, camphor, methylsalicylates, capsicum and cantharidin.
Warts and calluses- Warts are caused by a human papiloma virus and results in horny projection on the skin. Salicylic acid is a useful keratolytic and may be used to soften callosities, such as corns in the feet.
Formaldehyde, glutaraldehyde or silver nitrate is other keratolytic agents which may be applied to wart bearing regions. Podophyllum paint is used for external and perianal warts.
Melanising agents increase sensitivity to solar radiation and promote repigmentation of vitiliginous areas of skin. Psoralens (methoxsalen) or photoactivation (sunlight or UV radiation) stimulates melanocytes and their proliferation.
Minoxidil, a potent vasodilator antihypertensive drug, topically may stimulate limited hair growth in male pattern baldness (men and women) but only as long as it is used. It may cause irritant dermatitis and allergic contact dermatitis.
Contact dermatitis (eczema) is produced by external agents such as topical medicaments, preservatives in creams and cosmetics, clothing and due to photosensitivity reactions. The skin gets inflamed which is associated with itching.
Atopic eczema is the most common and is treated with regular application of emollient with short courses of mild topical corticosteroids. Coal tar and gamolenic acid are used occasionally in chronic atopic eczema.
Tacrolimus and ascomycin derivative are topical immunosuppressive drugs that are a recent development in the treatment of atopic eczema. Gamolenic acid, an extract from evening primerose may be taken orally for symptomatic relief of atopic eczema. It decreases the sensitivity of the breast to hormones and is also used in mastalgia. Adverse effects are mainly GIT disorders and rarely hypersensitivity reactions.
Ichthammol is indicated for chronic lichenified forms of eczema to control pruritus. It is used alone or in combination with zinc as an ointment or cream. It may cause irritation of the skin.
Drugs Used for the Treatment of Eye Diseases:
Eye drops and eye ointments are frequently used in the treatment of eye disorders.
i. Antibiotics:
Chloramphenicol and ofloxacin are active against a broad spectrum of bacteria and are the drugs of choice for superficial eye infections. They are well tolerated and have fewer local side effects than gentamycin. The risk of aplastic anemia following chloramphenicol eye drops is not well founded.
Tetracycline, a wide spectrum antibiotic, is used in the treatment of chlamydial infections particularly those causing trachoma. It is available as a 1% ointment and its use together with systemic administration has brought trachoma under control — a wide spread and blinding condition.
Two ocular disorders which respond well to prolonged administration of systemic tetracycline in low doses are chronic staphylococcal blepharitis (inflammation of the eyelid margins) and ocular involvement in cutaneous acne rosacea.
Penicillin and sulphonamides eye drops have practically become obsolete, because they have a marked tendency to cause allergic reactions. Sodium fusidate is particularly active against penicillin-resistant staphylococci. It has the property of being concentrated in bone and other connective tissues including the sclera of the eye and the vitreous and is useful in treating intra-ocular infections.
Other antibacterial drugs with a broad spectrum activity include quinolones (ciprofloxacin, lomefloxacin, moxifloxacin) and aminoglycosides (gentamycin and neomycin), framycetin, and polymyxin. Gentamycin, ciprofloxacin and oxfloxacin are effective for infections caused by P. aeruginosa.
ii. Antivirals:
Aciclovir (3% ointment) is highly effective for ocular herpes simplex infections and has minimal, if any, toxic effects. Its action is usually supplemented by oral administration which is especially useful in cases of herpes simplex keratitis. Trifluorothymidine (F3T) has antiviral activity against herpes simplex. A freshly prepared solution is used mainly against adenovirus which causes acute conjunctivitis with corneal involvement.
iii. Anti-Inflammatory drugs:
Corticosteroids are commonly used for treating anterior segment inflammation, including that which occurs from surgery. Betamethasone (Betnesol) drops or ointment (0.1%) is most commonly used steroid. Dexamethasone eye drops have good penetration into eye and is useful in iritis.
Topical corticosteroids should not be used indiscriminately as their improper use is associated with serious complication such as:
a. Rapid spread of infection, leading to aggravation of the symptoms, corneal ulceration with possible damage to vision and even loss of the eye. For this reason they are rarely used for virus infections of the eye and never in presence of dendritic ulcer.
b. Steroids glaucoma should always be borne in mind in elderly and susceptible individuals.
c. Steroid cataract may follow prolonged use.
d. Thinning of the cornea and sclera.
Other anti-inflammatory drugs:
A large number of drugs are available for topical use in inflammatory conditions and allergic conjunctivitis. These are:
a. Topical antihistamines:
Antazoline, azelastine and levocabastine are used for allergic conjunctivitis. They may cause mild transient irritation.
b. Sodium cromoglicate and nedocromil sodium:
These are two chemically different compounds which possess similar antiallergic and anti-inflammatory properties. They prevent the release of inflammatory mediators from mast cells. As 2% eye drops they are effective in allergic conjunctivitis and vernal keratoconjunctivitis.
c. NSAIDs:
Diclofenac sodium 0.1% solution is used post operatively in cataract surgery to counter the inflammation and miosis caused due to liberation of prostaglandins. It also lowers the incidence of macular edema following cataract removal.
d. Miscellaneous drugs:
These used for seasonal allergic conjunctivitis include lodoxamide and emedastine eye drops.
Autonomic drugs:
1. Mydriatics and cycloplegics:
These are parasympatholytics and their synthetic substitutes. They are used for the examination of fundus of the eye (Table 21.1).
2. Miotics and other drugs for glaucoma:
Glaucoma is due to an abnormally high intraocular pressure.
Miotics include parasympathomimetics: pilocarpine and carbachol. They are used prior to surgery for acute angle closure glaucoma. They act by facilitating the drainage of aqueous humor by opening up the ineffective drainage canal of Schlemm in the trabecular meshwork resulting from contraction or spasm of the ciliary muscles.
The drugs used for chronic simple glaucoma are:
a. β blockers:
These reduce intraocular pressure by reducing the rate of production of aqueous humor. Timolol is the most commonly used P-blocker. It has the advantage of not possessing any irritative effects on the eye.
However, systemic absorption may follow topical application and timolol is contraindicated in cardiac disorders such as bradycardia, heart block or heart failure and in asthmatic patients. Betaxolol is similar, but is less potent and less liable to cause systemic effects. It is claimed to increase the optic nerve blood supply.
b. Sympathomimetics:
Adrenaline probably acts both by reducing the rate of production of aqueous humor and by increasing the outflow through trabecular network. It is contraindicated in angle closure glaucoma because it is a mydriatic. It is used topically as such or as a prodrug dipivefrine or in combination with guanethidine.
c. α2 adrenoreceptor stimulants:
Brimonidine can be used when beta-blockers are contraindicated, as in patients with cardiac disorders or asthma.
d. Prostaglandin analogue:
Latanoprost increases the uveoscleral outflow of aqueous humor. It is used in patients whose glaucoma is resistant to other drugs or who are allergic to them and in ocular hypertension.
e. Carbonic anhydrase inhibitors:
Acetazolamide (diamox) inhibts the enzyme carbonic anhydrase, that is necessary for the secretion of aqueous humor. It is given orally.
Dorzolamide, a topical carbonic anhydrase inhibitor has the advantage of the reduction in side effects of oral therapy. It is used as alternative to tropical P-blockers or as an adjunct to them.
f. Osmotic diuretics:
In emergency or before surgery, mannitol intravenous or glycerol by mouth is given which produces a vigorous diuresis with resultant dehydration of body tissues including the eye and also inhibits the secretion of aqueous and are useful short-term ocular hypotensive drugs, and for the emergency management of raised intraocular pressure.
Local anaesthetics:
a. Surface anaesthesia:
Amethocaine and oxybuprocaine are the most widely used local anesthetics for the cornea and the conjunctival sac. Amethocaine is a longer acting but causes stinging when first instilled and for this reason oxybuprocaine, though short acting, are preferred especially in children.
b. Retro-bulbar anesthesia:
Lidocaine or a mixture of lidocaine and bupivacaine is injected behind the eyeball and within the cone of muscles that surround the optic nerve for surgery of the globe itself. Combination with adrenaline is generally avoided because of the danger of injecting directly in the orbital vein.
c. Peribulbar anesthesia:
The local anesthetic is directly injected into the tissue space surrounding the globe and the extra-ocular muscles of the eye instead of directly into the muscle cone. It is preferred because of safety over retro-bulbar anesthesia.
Stains:
Fluorescein and rose Bengal topically stain ulcers and abrasions of the cornea due to injury or disease and are used for the diagnosis of corneal lesions and foreign bodies.
Miscellaneous ophthalmic preparations:
There are a number of preparations which are used to moist the eye in chronic soreness associated with deficient or abnormal tear secretion such as in Sjogren’s syndrome. These all contain water binding substance or a mucolytic substance and are useful to treat the ‘dry eye’.
1. Hypromellose contains a high molecular weight organic sugar, which retains the water in the eyes. It is widely used and is the preparation of choice for tear deficiency.
2. Acetylcystine is mucolytic and is used in impaired or abnormal mucous production resulting in tear deficiency. It is generally used in combination with hypromellose.
3. Polyacrylic acid clings to the eye surface and is highly effective in the treatment of the dry eye including keratoconjunctivitis sicca and unstable tear film. It is available as an ophthalmic gel (gel tears).
Other substances used as ocular lubricants include polyvinyl alcohol eye drops and liquid paraffin ointment.