Saturday, April 09, 2005

DRUGS USED IN DERMATOLOGY

This article has been published by the International Biopharmaceutical Association www.ibpassociation.org . Please note this article does not give any medical advice.

The project is sponsored by KRC CRO and training services ( www.kriger.com ) and ClinQua CRO (www.clinqua.com )

Start your Clinical Research Career Now


DRUGS USED IN DERMATOLOGY


General principles
1. Thirty grams of topical medication will cover the entire adult human body.
2. Remember, children have more surface area per volume than do adults and so more chance for systemic effects.
3. Skin permeability is highest on the face, in the intertriginous areas and on the perineum.
4. Need to take into account that some dermatological disorders alter the properties of the skin and so its response to topical preparations.
5. Moist skin takes up drug better.
6. Vehicles for drugs have varying ability to hydrate – the least hydrating are soaks, then lotions (powders in water suspensions), solutions (drugs dissolved in solvents) and creams (oil-in-water emulsions), with ointments (water-in-oil emulsions) being the least drying. In general, drying preparations are for use in acute inflammation, hydrating preparations for chronic inflammation.

Glucocorticoids
1. Glucocorticoids have anti-inflammatory and immunosuppressive properties and are widely used in skin disease.
2. They may be for systemic or topical use or injected into the skin lesion. They may be given orally, intramuscularly or intravenously for systemic use.
3. The glucocorticoids available for topical use are divided into seven classes according to their potency, with Class 1 being the most potent and Class 7 the weakest.
4. Effects
5. Uses – inflammatory skin diseases
a. Topical steroids need only be applied twice daily – more often does not increase efficacy and increases risk of systemic effects.
b. Triamcinolone preparations are used for intralesional injection.
c. Oral steroids are used in severe skin disease. Long-term therapy is necessary in the collagen vascular diseases (SLE, dermatomyositis, inflammatory vasculitis), sarcoidosis, capillary hemangiomas, bullous diseases (bullous pemphigoid, pemphigus vulgaris, gestational herpes) and pyoderma gangrenosum. Other conditions – acute contact dermatitis, atopic dermatitis, lichen planus, erythema nodosum and exfoliative dermatitis – can be treated with short-term use of steroids.
d. Best to give oral steroids every other day to reduce side effects. Need to treat with as low a dose as is effective and for as short a time period as possible.
e. Intramuscular injection is not recommended due to poorer absorption and increased toxic effects.
6. Side effects
a. Topical preparations may cause skin atrophy, striae, purpura, teleangiectasias, acne-like skin rash, dermatitis and hypopigmentation. Also common is secondary bacterial and fungal growth. Prolonged use near the eye may cause cataract or glaucoma. The frequent and/or extensive use of high potency preparations can suppress the hypothalamus-pituitary-adrenal axis, especially in children.
b. Intralesional injection can also cause skin atrophy and hypopigmentation.
c. Side effects from oral use are many and are dose-dependent. Among the most important are myopathy, cataracts, avascular necrosis, hypertension and psychiatric disorders.
d. Intravenous use can cause changes in blood pressure, hyperglycemia, changes in potassium balance, psychosis, seizures, anaphylactic shock and even death.
e. Withdrawal from use of systemic steroids should be gradual, with tapering of the dose every other day or less often. Otherwise, a withdrawal syndrome characterized by arthralgia, myalgia and joint effusions may develop and, in some cases, the original disease flares up. Acute withdrawal after long-term use may cause adrenal insufficiency, as the endogenous production of steroids has been suppressed and takes time to become active again.

Retinoids
1. Derivatives of vitamin A that act on the differentiation and proliferation of epithelial cells, sebaceous secretions, inflammation and the immune response
2. There are three generations – the first is the endogenous retinol, tretinoin and isotretinoin. The second generation are synthetic analogs – etretinate and aciretin. The third generation is not yet in clinical use.
3. Uses
a. Etretinate is used in psoriasis, especially the inflammatory types, and also in psoriatic arthropathy. It is usually used together with ultraviolet A or B radiation.
b. Isotretinoin is useful in acne because it normalizes the keratinization, reduces sebum production and reduces the bacteria involved in acne – Propionibacterium acnes. It is given orally for moderate to severe acne and is also used in Gram-negative folliculitis, acne rosacea and hidraenitis suppurativa.
c. Tretinoin reduces hyperkeratinization and so prevents the lesions of acne. It is used topically.
d. Isotretinoin and etretinate are used in ichthyoses, leukoplakia and skin cancer – basal cell carcinoma, squamous cell carcinoma, keratoacanthoma and cutaneous T-cell lymphoma. Actinic keratosis is treated by tretinoin or etretinate.
e. Other conditions that respond to retinoids are sarcoidosis, discoid lupus, Reiter’s syndrome, warts, acanthosis nigricans and lichen planus.
f. Retinoids may also be used in malignant disease of the heads, skin, neck and lung and in premalignant conditions of the skin, mouth and uterine cervix.
4. Side effects
a. Tretinoin – local effects on the skin such as peeling, burning, redness and stinging pain; photosensitivity can be avoided by applying the preparation before bedtime.
b. Isotretinoin mostly affects the skin and the eyes – cheilitis, dry eyes, blepharoconjunctivitis. Staph. aureus may colonize but rarely causes clinical infection. Loss of hair and photosensitivity may be seen. Systemic side effects include hyperlipidemia, muscle and joint pains and headaches. Long-term use may cause hyperostoses and extraskeletal ossification; in children there may be premature closure of the epiphyses.
c. Etretinate – less effect on the eye; alopecia, disturbed liver functions, sticky, easily-bruised skin and exfoliation are common.

Retinoids are contraindicated in pregnancy – even when used topically – because of the risk of fetal malformations. FDA recommendations allow the use of tretinoin only if potential benefits are greater than the risks. The others are absolutely contraindicated. The critical period is the first three weeks, when the woman usually does not even know she is pregnant, so all women of child-bearing age who use retinoids must be careful in using contraception and should take regular pregnancy tests. Many doctors advise using two methods of birth control, beginning a month before and ending a month after therapy with retinoids (for three years after in the case of etretinate due to its long half-life). Malformations include head-face, thymus, heart and CNS anomalies. Miscarriage is also more common.


Antibiotics used in skin disease

For acne
1. Acne is assoicated with the anaerobe Propionibacterium acnes.
2. Topical use of benzoyl peroxide, clindamycin and erythromycin is effective in acne.
3. Acne rosacea responds to topical metronidazole.
4. Systemic therapy may be necessary – tetracycline is the most common, but erythromycin, minocycline, clindamycin and trimethoprim-syulfamethoxazole are also used.

For infections of the skin
1. usual microorganisms involved are S. aureus and S. pyogenes.
2. Topical treatment is by mupirocin, neomycin, polymyxin B or bacitracin – alone or in combined ointments. These may also be used for prophylaxis.
3. Systemic treatment is used for impetigo or cellulitis. Erythromycin or penicillinase-resistant penicillin are drugs of choice.

Cytotoxic drugs used in skin disease

1. Methotrexate – used in psoriasis, pityriasis rubra pilaris, vasculitides; watch for hepatotoxicity
2. Azathioprine – used instead of steroids in pemphigus and pemphigoid
3. Fluorouracil (5-FU) – used in actinic keratoses and basal cell carcinoma; can be injected into the lesions of keratoacanthomas, warts and porokeratoses
4. Cyclophosphamide – used in cutaneous T-cell lymphoma, pemphigus, Behcet’s disease, scleromyxedema and cytophagic histiocytic panniculitis; used only in refractory cases due to increased risk of secondary malignancies, especially bladder and myeloproliferative and lymphoproliferative diseases
5. Cyclosporine – used in severe psoriasis, lichen planus, epidermolysis bullosa acquisita, alopecia, pemphigus, bullous pemphigoid; watch for nephrotoxicity

Other drugs used in skin disease

1. Dapsone – used in dermatitis herpetiformis, leprosy, pemphigoid diseases, pemphigus, vasculitides; watch for G6PD deficiency
2. Sulfasalazine – used in psoriasis and pyoderma gangrenosum
3. Antimalarials (chloroquine, hydroxychloroquine, quinacrine) – used in discoid and systemic lupus erythematosus; watch for retinopathy
4. Antihistamines – H1blockerscan be given topically for pruritus; H2 blockers for pruritus and warts


Other drugs used in psoriasis

Calcipotriene
1. Vitamin D analog
2. Used as topical ointment – not for use on the face or in intertriginous areas
3. Toxic effect – hypercalcemia

Anthralin
1. mechanism of action unknown
2. given topically as paste, often together with salicylic acid
3. best not to use on face and intertriginous areas
4. side effects – stains skin and anything else it touches, local irritation

Phototherapy
1. Ultraviolet light can both damage and heal skin.
2. Psoralen Ultra-Violet A (PUVA)
a. combination of psoralen (given as capsules or topically) and ultraviolet A rays
b. used mostly in vitiligo and psoriasis, but also in cutaneous T-cell lymphomas, atopic dermatitis, alopecia and urticaria pigmentosa
c. side effects – nausea, blisters, painful red skin; chronic therapy may lead to development of actinic keratoses and squamous cell carcinoma
3. UVB and coal tar are used in psoriasis. The only serious side effect is folliculitis
4. Watch for photosensitizing drugs such as phenothiazines, thiazides, sulfonamides, NSAIDs, tetracyclines, benzodiazepines, etc.



DRUGS USED IN OPHTHALMOLOGY

Antibiotics
1. Topical formulations for use in the eye include the following antibiotics – chloramphenicol, ciprofloxacin, erythromycin, gentamicin, tetracycline, tobramycin, polymyxin B, bacitracin, sulfacetamide, and sulfisoxazole. They are used in corneal ulcers, conjunctivitis, keratitis, endophthalmitis, dacryocystitis, blepharitis, hordeolum (stye). They may also be injected into the vitreous humor (in cases of endophthalmitis) or, if necessary, even given parenterally.
2. Antiviral agents are also used in the eye. Most commonly used are acyclovir, ganciclovir, foscarnet, vidarabine, idoxuridine and trifluridine. They are used in viral keratitis, herpes zoster ophthalmicus and viral retinitis. They can be given topically, intravitreally or parenterally.
3. Antifungal agents in use include amphotericin B, nystatin, ketoconazole, flucytosine and others. They may be applied topically, into the conjunctiva or into the vitreous humor.
4. Antiprotozoal agents – used in infections usually caused by Acanthamoeba and Toxoplasma gondii. Most common used is topical combinations of polymyxin B, bacitracin zinc and neomicine (Neosporin), also imidazole and clindamycin.

Drugs used in treatment of glaucoma
a Cholinergic agonists
Acetylcholine (Miochol), Carbachol (Miostat), Pilocarpine – useful for miosis in glaucoma treatment and ocular surgery
Side effects – corneal edema, myopia, decreased vision, retinal detachment, brow ache
b Anticholinesterase agents
Physostigmine (Eserine), Demecarium, Echotiophate, Isoflurophate
Side effects – retinal detachment, miosis, cataract, iris cyst, brow ache, stenosis of nasolacrimal system
c Sympathomimetic agents
Dipivefrin (Propine)
Side effects – photosensitivity, conjuctival hyperemia, hypersensitivity
d Adrenergic antagonists
Betaxolol, Carteolol, Timolol, Metipranolol, Levobunolol
Side effects – conjuctival hyperemia
e Osmotic agents
Glycerin, mannitol, isosorbide – for sort-term treatment of acute rise of intraocular pressure.
Available orally, glycerin also topically (but oral preparations is preferred in acute rise of intraocular pressure)

Other agents for ophthalmic therapy
1 Vitamins –
Vitamin A – for treatment of xerophtalmy, keratomalacia, keratoconjuctivitis – topical and systemic usage.
Vitamins C and E – topically for treatment of cataract as antioxidants.
2 Wetting agents and tear substitutes
In use for management of dry eyes, includes artificial tears and ophthalmic lubricants.
Most common used are cellulose polymers (carboxymethyl cellulose, hydroxyethylcellulose, methylcellulose), polyvinyl alcohol and dextran.


For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group ( www.kriger.com ) at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)