This document discusses drugs used to treat disorders of the eye, ear, nose, and throat (ENT), and skin. It focuses on eye disorders like glaucoma, keratitis, and conjunctivitis. It describes classes of drugs used for the eye, including antimicrobials, anti-inflammatories, glaucoma drugs. For glaucoma, it discusses drug classes that lower intraocular pressure by increasing outflow or decreasing aqueous humor production. The document also briefly discusses ENT disorders like allergic rhinitis and vertigo, as well as various skin disorders and their treatments.

1. Drugs used in the disorders of Eyes,
ENT and Skin
Miss. Naziya A. Tamboli.
M. Pharm. Pharmacology (Associate Professor)
Sahyadri College of Pharmacy Methwade, Sangola

2. Drugs used in the disorders of eye, ENT and skin:
• Eye - Glaucoma, keratitis, conjunctivitis
• ENT- Allergic rhinitis, vertigo.
• Skin- Acne, candidiasis, eczema, contact dermatitis, pediculosis, psorasis, scabies, urticaria,
pruritis.

3. Eye - Glaucoma, keratitis, conjunctivitis
Eye complaints are common in general practice and some of them, if neglected, can lead to blindness. The eye is
readily accessible to observation, and the diagnosis of several eye diseases can be made easily. The drug treatment of
eye problems is largely concerned with alleviation of inflammation, control of infection and reduction in intraocular
pressure
Classification of drugs used in the eye:
I Antimicrobials: Anti-bacterials; Anti-virals; Anti-fungals; Anti-protozoals.
II Anti-inflammatory agents such as NSAIDs.
III Glucocorticoids.
IV Anti-histaminics and mast cell stabilisers.
V Mydriatics and Miotics.
VI Drugs for glaucoma.
VII Immunomodulatory drugs such as Immunosuppressives, VEGF antibodies and
Antimitotic agents.
VIII Local anaesthetics.
IX Diagnostic agents such as Fluorescin and Rose bengal.; and
X Miscellaneous drugs such as tear substitutes and Zinc preparations.

4. Drug Therapy of Glaucoma
Glaucoma, the second most frequent cause of blindness in the world, is a disease of unknown origin. It is
characterised by
(1) Progressive degeneration of retinal ganglion cells and optic nerve fibers, and
(2) Is usually accompanied by, but not always, increased intraocular pressure (IOP).
If untreated, it leads to optic neuropathy with loss of optic nerve tissue and excavation or ‘cupping’ of the
ophthalmoscopically visible optic nerve head. This may be accompanied by loss of vision. Most forms of glaucoma
are painless initially and the loss of vision is insidious. If diagnosed and treated early, most patients retain good
vision. Reduction in IOP may protect against damage to the optic nerve head.
Glaucoma is classified into: (a) open angle, (b) closed angle, (c) congenital, and (d) drug induced. The condition
may be either primary or secondary. The etiology of primary glaucoma is not known. The common causes of
secondary glaucoma include inflammation, neovascularisation, pigment dispersion syndrome and drugs.

5. Table 72.5
Drugs used in glaucoma
* Pilocarpine drops 0.25–4.0% Pilocarpine ocusert
• Cholinesterase inhibitors (Miotics)**
** Physostigmine 0.25% ointment
Demecarium 0.125 – 0.25% drops.
Echothiophate 0.03–0.25% drops
• Prostaglandin analogues
Latanoprost 0.005% drops
Bimatoprost 0.01%
Unoprostone 0.15 %
Travoprost 0.004%
Tafluprost 0.0015%
II Those which decrease the production of aqueous humor by the ciliary body
• Non selective beta adrenergic blockers: Timolol 0.25–0.5 % drops
• Selective beta1 adrenergic blocking agents Betaxolol 0.5% drops,Carteolol 1%, Levobunolol 0.5%,Metipranolol 0.3%
• Non selective adrenergic agonists Adrenaline hydrochloride 0.1 – 2.0 % drops
• Selective alpha2 adrenergic agonists Apraclonidine 0.5–1% drops, Brimonidine 0.2% drops
• Carbonic anhydrase inhibitors
(a) Topical: Brinzolamide 1% suspension Dorzolamide 2%
(b) Systemic: Acetazolamide (Diamox) 250 mg qid; Methazolamide 25 mg bid.
• Combinations of above agents
Brinzolamide + Brimonidine
Timolol + Brimonidine
Timolol +Dorzolamide

6. Elevated IOP may be reduced by:
• Increasing the outflow of aqueous humor through:
(1) The trabecular meshwork (cholinergic agonists and cholinesterase inhibitors),
(2) The uveoscleral pathway (PG analogues) or
(3) a surgically created pathway; and/or
• Decreasing the production of aqueous humor by the ciliary body .
In acute (narrow angle) congestive glaucoma, the iris probably blocks the entrance to the trabecular space at the canal of
Schlemm. This blockade causes a precipitous increase in IOP and severe pain, headache, nausea and often loss of vision due
to optic atrophy. The reversible anti-cholinesterases are invaluable for reducing the increased IOP. The contraction of
sphincter of iris induced by the anticholinesterases removes the iris blockade and facilitates the drainage of the intraocular
fluid. Acute congestive glaucoma is a medical emergency and a combination of pilocarpine nitrate (4%), timolol and
apraclonidine is the preferred treatment. Adjuvants such as acetazolamide (a carbonic anhydrase inhibitor) are also
employed. In an emergency, 20% mannitol (maximum 500 ml) may be infused IV to lower the IOP. Once the acute attack is
controlled, definitive surgery is advised. Even after surgery, continuation of drug therapy may be required.
Chronic open angle glaucoma has an insidious onset and needs lifelong drug therapy.
The cause of raised IOP is not known. Because the decline in vision is gradual, the diagnosis is often delayed. The mechanism
of reduction of tension in this condition by drugs is not definitely understood; there is no physical obstruction.
The major goals of therapy are:
(1) To maintain an IOP below which further optic nerve damage is unlikely to occur (target IOP);
(2) To reset the IOP to a lower level if deterioration occurs;
(3) To minimise the local and systemic side effects of the drugs, and to improve the quality of life;
(4) To educate the patient about his/ her disease and emphasise the importance of compliance.

7. In general, the initial aim is to achieve a 20-50% reduction in the IOP at diagnosis, with the least amount of
medication. The PG analogues eg. latanoprost are usually the drugs of choice to start with because of their once-a-
day dosage, fewer systemic effects and good therapeutic efficacy. However, they are very expensive. Alternatively, a
beta adrenergic blocker timolol may be used. The α2 adrenergic agonists appear to be less effective than the above
two. Brimonidine should be avoided in children for fear of respiratory arrest.
Topical carbonic anhydrase inhibitor preparations, dorzolamide and brinzolamide, cause less systemic toxicity and
are preferred to oral acetazolamide. The latter is used in resistant cases in the dose of 0.25-1.0 g daily, in 3-4 divided
doses.
Reversible anticholinesterases give fairly satisfactory results in glaucoma following cataract surgery. They are
avoided in patients with cataract because they may impair vision further; the long acting miotics may exacerbate
cataract and increase the risk of complications (retinal detachment) during and after cataract surgery.
Sufficient transconjunctival absorption of anti-ChE drugs can occur following their repeated instillation and can
cause systemic adverse effects. Absorption can be minimised by digital compression of the inner canthus of the eye
during and after instillation.
Pilocarpine is now less often used because of its short duration of action and ADR.
Beta adrenergic blockers may cause cardiovascular and respiratory adverse effects. PG agonists may cause increase
in growth of eyelashes, irreversible darkening of the iris and rarely macular edema. Finally, it is important to
remember that lowering of IOP may not necessarily halt the progression of the disease and damage to the optic nerve
in all cases of glaucoma.

8. Table 72.2
Anti-infective drugs used in the eye
Chloramphenicol 0.5% S, 1% O, Ciprofloxacin 0.3% S, Norfloxacin/Ofloxacin
Besifloxacin 0.6% S, Gatifloxacin 0.3% S,O, Erythromycin 0.5% O
Gentamicin/Tobramycin 0.3% S,O, Sulfacetamide 10 % S, Tetracycline 1% S
Combinations:
Bacitracin + Polymyxin B
Trimethoprim + Polymyxin B
Antiviral:
Acyclovir 3% O; 400–800 mg tab oral
Ganciclovir, Foscarnet IV, intra-vitreal, Idoxuridine 0.1% S,
Vidarabine 3% O, Trifluridine 1% S
Antifungal:
Amphoterecin B 0.1–0.5% S; 0.8–1.0 mg subconjunctival; 5 mcg intra-vitreal
Natamycin 5% S,
Fluconazole oral,
Ketoconazole oral
Miconazole 5–10 mg subconjuntival

9. Acute conjunctivitis and bacterial corneal ulcers can be treated with one of the preparations shown in Table 72.2. The bacteria commonly
encountered are staphylococci, streptococci, pneumococci and Hemophilus species. Ophthalmia neonatorum, caused by chlamydia,
gonococci or other organisms, needs more aggressive treatment. Gonococcal illness needs systemic as well as local therapy. Chlamydial
infection (trachoma) is best treated with topical tetracycline plus oral azithromycin Tetracycline ointment may be applied to the conjunctivae
prophylactically in neonates at risk.
Antiviral agents: The common viral infections of the eye are conjunctivitis, keratitis, iridocyclitis and retinitis. They are due to herpes simplex
virus, herpes zoster virus and cytomegalovirus.
Viral keratitis is either (a) epithelial which responds to topical treatment with antiviral dugs; or (b) stromal and requires administration of the
same drugs orally.
Herpes zoster ophthalmicus is more serious and needs systemic acyclovir in addition to local antiviral therapy.
Viral retinitis requires prolonged treatment with antiviral drugs, by either intra-vitreal or IV route.
Antifungal agents: Fungal infections of the eye are rare. The important ones are keratitis, scleritis, endophthalmitis and canaliculitis. They are
best left to the specialists.
Antiprotozoal agents: The protozoa causing eye infections are Toxoplasma gondii and Acanthamoeba. Ocular toxoplasmosis is the ocular
manifestation of a systemic infection. Acanthamoeba causes deep eye infections which occur more commonly in contact lens users. They
require a combination of topical and systemic multi-drug therapy.
Onchocerciasis caused by Onchocerca volvulus is one of the major causes of blindness.
Anti-inflammatory Drugs
The drugs belonging to this group are the NSAIDs such as diclofenac (0.1% eye drops), flurbiprofen (0.03% eye drops) and ketorolac (0.5%
eye drops). They are commonly used topically during and following ocular surgery such as cataract extraction, for prevention of intraoperative
miosis and postoperative inflammation.
Anti-histaminics and Mast Cell Stabilisers
Allergic conjunctivitis can be treated with topical antihistaminics such as antazoline 0.05%, emedastine 0.05% and levocabastine 0.05%.
Mast cell stabilisers such as cromolyn sodium 4%, ketotifen 0.025%, nedocromil 2% and epinastin 0.05% can also be used to treat allergic and
vernal conjunctivitis.

10. Mydriatics and Miotics
Mydriatics: These drugs produce pupillary dilatation. They are of two types:
• Muscarinic receptor antagonists, atropine and atropine substitutes, which also cause paralysis of the iris and ciliary body
and lead to cycloplegia (paralysis of accommodation) by blocking the muscarinic receptors. The main drawback of atropine is
its long duration of action so that the cycloplegia lasts for 7-10 days. Atropine substitutes which have a shorter duration of
action and produce minimal cycloplegia are preferred.
• α-Adrenergic receptor agonists (sympathomimetic agents) which directly stimulate the adrenergic receptors in the radial
muscle fibres of the iris, and do not lead to cycloplegia.
Mydriasis is required for:
(1) Determination of refractive error.
(2) Fundoscopic examination of the eyes.
(3) Treatment of iridocyclitis, an inflammation of the iris and the ciliary body in which there is severe pain due to spasm of
these muscles; atropine paralyses these muscles and relieves the pain; and
(4) Breaking the adhesions between the lens and the ciliary body, by alternating mydriatics with miotics.
Miotics: These drugs produce constriction of the pupils by acting as:
• Muscarinic receptor agonists (pilocarpine), or
• Anticholinesterases (physostigmine)
They act on the circular fibres of the iris. They also constrict the ciliary muscle, thus improving trabecular pathway. They are
used in the treatment of glaucoma. Their ADR include headache, browache, vascular congestion, conjunctival congestion,
burning and blurred vision. Prolonged use may cause myopia and vitreous hemorrhage.
Miotics are contraindicated in acute iritis and acute uveitis. They should be avoided in acute inflammatory diseases of the
anterior segment.

11. Table 72.4 Mydriatics and miotics
Anti-muscarinic
Atropine 0.5–2% drops
Homatropine 2–5% drops
Eucatropine 2–5% drops
Cyclopentolate 0.5–2% drops
Tropicamide 0.5–2% drops
Sympathomimetic
Phenylephrine 0.12–10% drops
Miotics
Cholinomimetic
Pilocarpine 0.5% drops; ocusert
Cholinesterase inhibitors
Physostigmine 1% drops

12. ENT- Allergic rhinitis and vertigo.
Drug Therapy of Rhinitis
Rhinitis, an inflammation of the nasal mucosa can be:
• Non-infectious e.g., allergic and non-allergic rhinitis, which is frequently caused by seasonal allergy (e.g., hay fever, pollinosis) and leads to sneezing, nasal
stuffiness, ocular pruritus, lacrimation and a postnasal drip.
• Infectious e.g., viral common cold and bacterial infection.
Chronic or non-seasonal rhinitis, often referred to as perennial rhinitis, results in daily episodes of rhinorrhoea, nasal congestion and sneezing that are present for
several weeks during most months of the year. It is caused by various allergic and non-allergic nasal disorders. It includes:
(1) Vasomotor Rhinitis (VMR), a no allergic, non-infectious rhinitis in which eosinophils are generally absent on nasal smear; and
(2) Non-allergic, Non-infectious Rhinitis with eosinophilia (NARES).
Chronic rhinitis can also be induced by drugs such as adrenergic blockers, cholinesterase inhibitors, estrogen preparations (including oral contraceptives), and by
the presence of a foreign body, nasal polyps, tumours and nasociliary disorders.
Non-Drug therapy for all types of rhinitis is similar. Exposure to cigarette smoke, pollutants, allergens and other irritants should be avoided. In patients with
pharyngitis, saline gargles, steam inhalation and warm mist therapy is helpful. Local instillation of hyperheated, humidified air directly into the nasal passages
significantly relieves symptoms of allergic rhinitis. When nasal congestion is severe, nasal irrigation with warm saline solution, prepared by dissolving one
tablespoonful each of table salt and baking soda in a pint of warm (37°C) tap water, may relieve the congestion. The patient should drink plenty of fluids.
Drug Therapy: No drug is likely to abolish the symptoms completely.
In general, (i) drugs are more effective in allergic rhinitis than in non-allergic forms and (ii) Acute rhinitis responds more favourably than the chronic form.
The treatment is directed at preventing the release of inflammatory mediators such as histamine and leucotrienes, or blocking their effects. The drugs used are:
• Anti-histaminics
• Nasal decongestants
• Anti-allergic drugs
• Anticholinergic drugs; and
• Local corticosteroids
The selection of drugs in individual patients requires that the non-infectious, allergic forms be distinguished from the infectious forms (common cold). The agents
useful in the former, anti-histaminics, cromolyn sodium and intranasal corticosteroids, have little value in the latter. Nasal decongestants are beneficial in both.
However, antibiotics should be reserved only for patients with bacterial infections.

13. Anti-histaminics and anti-allergic drugs: In allergic rhinitis, H1 anti-histaminics help to relieve rhinorrhoea, sneezing, nasal pruritus and conjunctivitis but do not
affect nasal congestion. They are usually effective in seasonal allergic rhinitis when sneezing and rhinorrhoea predominate and edema and congestion are minimal.
They can be used prophylactically in smaller doses by susceptible patients during the allergen exposure period even when symptoms are absent. A single daily dose
of an antihistaminic with a long t½ taken at bedtime, may relieve symptoms the following day. The non-sedating anti-histaminics such as cetirizine and loratadine,
are preferred when sedation needs to be avoided.
Anti-allergic drugs like glucocorticoids and cromolyn sodium prevent the release of inflammatory mediators. The nasal spray of cromolyn sodium is as effective as
an oral antihistaminic in preventing the symptoms of allergic rhinitis. They are reasonably safe.
Nasal decongestants: These drugs are synthetic alpha-adrenergic agonists. When used locally by spray or as drops, they constrict the dilated blood vessels in the
mucosa of swollen turbinates and help to reduce edema. The drugs commonly used are:
• Ephedrine 0.5%.
• Phenylephrine 0.25%.
• Naphazoline 0.05%
• Oxymetazoline 0.05% and
• Xylometazoline 0.05%.
They provide temporary symptomatic relief in allergic rhinitis, common cold, and acute rhinitis associated with other respiratory infections. NARES, sinusitis, and
in acute otitis media with eustachian tube blockage.
Oral decongestants such as pseudophedrine may be preferred when sinuses are involved. They are not useful in VMR. The most common adverse effects of the
orally administered nasal decongestants ( phenylephrine, pseudoephedrine) are insomnia and irritability. Topical decongestants sometimes cause local discomfort,
stinging, burning, dryness of the mucosa, rebound congestion and rhinitis medica mentosa.
Nasal decongestants are only palliative. Only a few drugs in very dilute solution are safe. Ephedrine hydrochloride in isotonic saline, used as nasal drops, is as
effective as any other drug, and cost effective. In infants and children, imidazole drugs such as naphazoline and tetrahydrozoline are known to cause disturbance of
body temperature, CNS depression and even coma. Hence, decongestants should be stored beyond the reach of children.
Anticholinergic drugs: Rhinorrhoea is primarily the result of glandular hypersecretion , mediated by the cholinergic innervation of the nasal mucosa. Some patients
with severe rhinorrhoea and congestion obtain more relief from topical anti-muscarinic, ipratropium bromide, than from nasal decongestants.

14. Topical glucocorticoids exert a marked anti-inflammatory effect on the nasal mucosa by inhibiting the release of inflammatory mediators from the mast cells and
basophils, and by blocking the inflammatory effect of leucocytes in the nose. Intranasal glucocorticoids are safe, and are the most effective agents available for the
prophylaxis and treatment of seasonal and non-seasonal allergic rhinitis and for weaning the patients with rhinitis medicamentosa from topical decongestants.
NARES also responds to local glucocorticoids, but their effectiveness in VMR is limited. Topical glucocorticoids occasionally shrink nasal polyps and reduce nasal
obstruction significantly. Small polyps may even disappear. The efficacy of nasal spray preparation of beclomethasone dipropionate, flunisolide, budesonide,
fluocortil butyl and fluticasone is similar. However, local use of dexamethasone formulations is contraindicated as the drug is rapidly absorbed and can cause
systemic adverse effects. Sneezing, headache, drying and nasal bleeding can occur after the use of these drugs. In patients with infection, topical steroids, if
required, should be used along with appropriate systemic antibiotics. They should be used with caution in patients with ocular herpes zoster.
Injudicious use of commercially promoted combinations of decongestants with anti-histaminics, glucocorticoids and antibiotics may be hazardous and not
recommended.
Hyposensitisation: This comprises carrying out skin tests with several antigens individually, followed by serial injections of desensitising vaccines prepared from
the ‘offending’allergens.
The use of such vaccines may benefit
(i) patients with allergy to pollens (causing seasonal hay fever); and
(ii) those with allergy to wasp and bee venom. It is currently felt that:
(a) Most atopic (allergic) patients are allergic to multiple allergens and are not likely to benefit from vaccines prepared from single allergen.
(b) Diagnostic tests are unreliable, if used by themselves.
(c) The allergen extract desensitising vaccines can precipitate either severe asthma or anaphylaxis and
(d) Vaccines prepared from house dust, house dust mite, animal danders and foods have not been shown to be effective.
All such vaccines should be avoided in asthmatics, pregnant women, children under 5 years and those taking beta-blockers.

15. Therapy of Vertigo
Vertigo is a hallucination of movement, generally spinning, caused by a disturbance of the orientation-detecting system of a person.
It can be precipitated when there is a inter-sensory mismatch among the stabilizing systems. It can occur in normal subjects following a spin or even unfamiliar
head movement. Commonly it is due to disturbances of vestibular, visual or somatosensory systems. It can also occur in the brain stem or cerebellar lesions and
with migraine. Finally, phobic postural vertigo is observed in patients with panic attacks. In all cases of vertigo, complete neurological examination is a must. If a
cause for vertigo can be established, it may be amenable to specific treatment. Orientation in space is achieved by integrating information mainly from:
• Vestibular system.
• Vision; and
• The proprioceptors in the muscles and joints. (Somatosensory)
The collected information is processed in the sensory integrating areas of the reticular formation. Such processing occurs at the subconscious level in normal
persons. When the information contains a new or an unusual element, vertigo can occur. Dizziness is less specific than vertigo and comprises all symptoms of
disequilibration including light headedness, giddiness, swimminess, floating etc; its pathogenesis is similar to that of vertigo. Individual patients may not be able
to differentiate between vertigo and dizziness. Both are caused by different pathological processes in CNS, CVS and metabolic disease.
Cawthorne-Cooksey exercises help to induce a compensation mainly in vertigo due to peripheral vestibular disorders. The principle is to retrain the eye, neck
and body musculature to generate visual and proprioceptive input to compensate for the lost vestibular information. The movements that cause vertigo must be
especially practised, since the more often vertigo is induced, the more quickly compensation occurs. They should be started as soon as possible after an acute
attack due to a peripheral vestibular disorder.

16. Skin- Acne, candidiasis, eczema, contact dermatitis, pediculosis, psorasis, scabies, urticaria,
pruritis.
Drug Therapy of Acne Vulgaris
Acne vulgaris (pimples) is a common, chronic skin disorder, particularly in teenagers, and it generally regresses with time. However, it can persist for a
long time and in some individuals, can cause disfigurement and permanent scarring. It usually affects the face but can also spread to the trunk. Acne is
known to develop frequently in patients with androgen excess. Most patients with acne probably have sebaceous glands that are hyperresponsive to
androgens, rather than have over production of androgens.
Pathophysiology: The important features are:
• Increased sebum production by the sebaceous glands.
• Hyperkeratinisation and excessive desquamation of epithelial cells from the walls of the hair follicle, leading to blockade of the follicular openings.
• Formation of comedone, a fleshy, hyperkeratotic plug blocking the opening of the pilosebaceous follicle (’Black’ and ‘White’ heads).
• Proliferation of locally present Propionibacterium acnes and a few Staphylococci. These bacteria split the sebaceous fat to form irritant fatty acids
leading to.
• Local inflammation
The therapy of acne is, therefore, directed to:
• Counteract the excessive production of sebum.
• Prevent the abnormal desquamation of epithelial cells in sebaceous follicles; and
• Treat and control the growth of P. acnes.
Drugs used in the treatment of acne are given in Table 71.5. Dietary modifications have not been shown to modify the course of acne vulgaris and undue
diet restrictions are unnecessary. However, the application of cosmetic oils and greases to the affected area should be avoided. Prolonged and vigorous
washing will not resolve the lesions. On the contrary, scrubbing may damage the delicate openings of the hair follicles, and block the flow of sebum, thus
worsening the acne.
Table 71.5
Drugs used in the treatment of acne
Local: Erythromycin, Clindamycin, Azelaic acid, Benzoyl peroxide
Systemic: Tetracyclines, Erythromycin, Minocycline, Cotrimoxazole

17. Comedolytics and exfoliants:
TRETINOIN (Trans-retinoic acid, Retin-A) used topically is an effective local comedolytic. It enhances the penetration of other anti-acne agents into the
epidermis. Frequent application of this agent, however, produces redness and peeling of the skin. Improved appearance may take as long as two months to
develop. It is applied as 0.01 to 0.025% gel, 0.025% lotion or as 0.025% cream. Gels are preferred in hot and humid climate and cream in cold and dry
climate. People using retinoic acid should avoid exposure to sun because of increased susceptibility to sunburns. Its long term use should be avoided for
fear of possible photo-carcinogenesis. It should be avoided in pregnancy. Tretinoin is also useful in treating acanthosis nigricans and skin striae such as
those of Cushing’s syndrome.
ADAPALENE: This 3rd generation retinoid selectively binds to retinoid receptors. Used as 0.1% cream, it acts like tretinoin but is claimed to be less
irritant. It is stable in sunlight.
Salicylic acid has a keratolytic property and is used as 0.5 to 2% hydroalcoholic formulation. All these drugs can be combined with local or systemic
antimicrobial agents.
Sebostatics: Sebaceous glands are androgen dependent and therefore, estrogens and anti-androgenic drugs are useful in therapy of acne. Estrogens are
usually prescribed as COC pill containing ethinyl estradiol 50 mcg and a non androgenic progestin such as desogestrel or cyproterone acetate 2 mg. The
COC pill must be given for 3-4 months before substantial improvement is observed. More prolonged therapy is needed to avoid relapse.
Cyproterone acetate, a potent anti-androgen, can be used in place of OC pill but is more expensive.
Spironolactone in the dose of 50-200 mg/day reduces sebum production, but again several months of therapy is required to get maximal benefit.
Combination OC pills containing cyproterone acetate 2 mg (Diane, Ginette) are also effective. For obvious reasons only women should receive the anti-
androgen therapy.
ISOTRETINOIN (13-cis-retinoic acid): This vitamin A metabolite, given orally, as well as applied topically, can cause prolonged remission, permanent in
40%, In fact, oral isotretinoin would be a drug of choice for most patients with acne but for its serious toxic effects and cost.
It: (a) causes marked atrophy of sebaceous glands, and inhibits sebaceous secretion (Sebostatic action),
(b) normalises keratinisation of the hair follicle, thus reducing the formation of comedones; and
(c) suppresses inflammation by inhibiting growth of P. acne.
A dramatic reduction in the oiliness of the skin is apparent within a month of starting treatment. It is usually prescribed at a dose of 0.5-1 mg/kg body
weight daily for 3-4 months. Its bioavailability is increased if it is taken during or after meals. The improvement persists even after its stoppage.
Adverse reactions: Common effects include dryness of the skin and itching. Less commonly, it can cause hyperlipidaemia, hypercalcaemia,
photosensitivity, hair loss, arthralgia, intracranial hypertension, premature fusion of epiphyses, depression and psychosis.
The drug is highly teratogenic and if it is used in women of child-bearing age, pregnancy should be ruled out and two methods of contraception should be
continued for one month after stopping the treatment. There is no risk to male patients treated with this drug. Anyone taking this drug should not donate
blood for one month after stopping it. Due to its toxicity and high cost, the drug should be reserved for severe pustular acne not responding to other
medications. This drug is not useful in the treatment of psoriasis.

18. Antimicrobial drugs for P. acnes: Antibiotics used against P. acnes are listed in Table 71.5.
Applied locally once or twice daily, they exert a beneficial effect both by killing P. acnes and indirectly, by inhibiting the production of pro-inflammatory mediators
by the organisms.
Combination of erythromycin 3% with benzoyl peroxide 5% appears to be highly effective. Clindamycin is also effective.
Benzoyl peroxide (2.5-10%) as gel or lotion is lipophilic and suppresses effectively the growth of P. acnes. It is also keratolytic. Drug resistance does not develop.
It has no anti-inflammatory property. It can cause local irritation and allergy.
Antibiotics used for the systemic therapy of acne include doxycycline (100-200 mg daily), minocycline, erythromycin (500-1000 mg daily) and co-
trimoxazole. Generally, doxycycline is preferred. These drugs need to be given for 4-6 weeks and then tapered off gradually by 10 to 12 weeks. This is followed by
topical treatment with tretinoin and benzyl peroxide for 6 months.
The suggested therapeutic approach for treating acne is outlined in the Table 71.6.
Table 71.6
• Mild cases without inflammation Topical: Tretinoin cream/gel;adapalene0.1% gel; salicyclic acid, benzoyl peroxide
• Mild cases with inflammation Topical antibiotics, Benzoyl peroxide or combination of erythromycin and Benzoyl peroxide for 4 to 6 weeks
• Severe cases with inflammation : Topical Tretinoin plus systemic antibiotic therapy. If response is unsatisfactory, particularly in multinodular cystic
lesions, add oral isotretinoin in women of reproductive age, use OC pill or cyprotenone acetate
Drug therapy of acne vulgaris
To prevent recurrence, topical treatment must be continued for 6 months. Rarely, severe acne may be associated with fulminating systemic symptomatology such
as fever, arthralgia, glomerulonephritis and bone pain. In such case, addition of oral short term glucocorticoids to antibiotics may be useful.
Agents that predispose to the formation of comedones include topical agents such as lanolin, butyl stearate, lauryl alcohol and paraffin in commercial cosmetic and
hair preparation. Industrial compounds that contain impure paraffin oil, halogenated hydrocarbons, coal tar and its derivatives can also precipitate or worsen the
condition. Local or systemic glucocorticoids used for long periods can also cause acne.

19. • Candida species which cause mucocutaneous candidiasis; and
• Pityrosporon orbiculare, also known as Malassezia furfur, which causes tinea versicolor.
Majority of superficial fungal infections can be treated by local antifungal agents, and azoles are preferred because of their
wide spectrum and safety. Only chronic, resistant infections may need systemic antifungal therapy. Because tinea infections of
the foot are often complicated by bacterial infections and other factors, an ideal antifungal medication for the foot should have
antifungal and antibacterial properties.
AZOLES: Various azoles used to treat skin fungal infections are listed.
Azoles for dermal skin infections
Clotrimazole, Miconazole, Econazole, Butaconazole, Oxiconazole, Sulconazole, Ticonazole, Sertraconazole, Luliconazole
• For systemic use:
Ketoconazole, Itraconazole, Fluconazole, Voriconazole. (These can also be used locally.)
Imidazoles like clotrimazole and miconazole are preferred for treating mild to moderate, localised Candida or Tinea pedis/
cruris infection. They are used locally as creams, powders, lotions, and as vaginal tablets or suppositories. Generally, they are
safe and do not stain the skin or clothing.
In patients with chronic, extensive infection, infection of the scalp and nails resistant to local therapy and in
immunocompromised patients, systemic therapy with itraconazole or fluconazole is indicated. Ketoconazole is not preferred
because of its toxicity profile. In all fungal infections, therapy has to be carried out for a few weeks to 3-4 months, depending
on the severity,.
BENZOIC ACID AND SALICYLIC ACID: Salicylic acid is a weak antifungal agent but has keratolytic properties. Benzoic
acid compound ointment (Whitfield’s ointment) containing 6 % of benzoic acid and 3 % of salicylic acid. It is effective in
treating dermatophytosis. It is relatively cheap and is in use for ages. Sometimes it may cause local irritation.

20. Drug Therapy of Allergic Skin Disorders
Urticaria:
Urticaria may occur as acute episodes but is considered chronic when it lasts longer than six weeks. It may occur in a person with atopic history but often
such history is absent. In a few cases, an allergen (fish, seafood, nuts, eggs; food additives such as citric acid, preservatives and colouring agents like
tartrazine; drugs such as aspirin and other NSAID; vegetable gums), an offending physical agent (mechanical trauma, cold, heat),
history of insect bites and stings, or underlying disease (infection, connective tissue disorder) may be identified. However, no such factor is found in majority
of cases. A detailed history and thorough physical examination must precede laboratory tests. If a causative agent can be identified, it must be avoided if
possible and treated if it is a systemic disease. But, a witch-hunt for a ‘septic focus’ is unrewarding. The treatment of choice for acute urticaria (and acute
angioedema) is a SC injection of adrenaline (1 : 1000 aqueous solution) in the dose of 0.3 ml, repeated if necessary. If adrenaline is contraindicated, an
antihistaminic (50 mg of diphenhydramine IM or IV) may be used.
Oral anti-histaminics are the drugs of choice in chronic urticarias; they are more effective when given, prophylactically on a regular basis, than after urticarial
lesions start; the non-sedative anti-histaminics may be preferred. Alternatives to the anti-histaminics are cyproheptadine, doxepin (an antidepressant with a
potent antihistaminic action) or a beta adrenergic agonist such as ephedrine. In resistant cases, an H2 blocker such as cimetidine or ranitidine may be added to
the H1 blocker. Very few patients need corticosteroids and then, they should be used for the shortest possible period. Topical application of calamine lotion is
useful for its cooling and soothing effects and can be used alone in mild cases.
Atopic Dermatitis: Atopy is defined as a genetically determined tendency to hyper-react to common environmental allergens with the production of Ig E and
immediate hypersensitivity/ allergic (Type I) reaction. Majority of the patients have a family history of asthma or hay fever. Atopic dermatitis, a chronic
condition, is a cutaneous expression of the atopic state. The clinical presentation differs according to the age of the patient. The infantile form is the most
common and is characterised by weeping and encrusted inflammatory lesions distributed on the face, neck and extensor surfaces. Itching is prominent.
Secondary infection may be present. Atopic dermatitis in infants often resolves spontaneously.
The treatment includes:
• Avoidance of cutaneous irritants like soaps, detergents and hot water.
• Adequate cutaneous hydration; and
• Judicious use of mild topical glucocorticoids to control itching and inflammation.
Infection should be treated with systemic antibiotics. Oral sedative H1-antihistaminics may be useful to control the itching. The role of dietary allergens in
atopic dermatitis is controversial. However, if such an allergen can be identified, particularly in children, it should be avoided. For local application low
potency steroids are to be preferred and used for consecutive two weeks. Severe exacerbations need to be treated with high potency topical steroids and/or
systemic glucocorticoid therapy. Although such treatment will generally clear the skin, the lesions may return after stoppage of therapy.

21. An antidepressant, doxepin, 5% cream exhibits significant anti-pruritic activity in atopic dermatitis. It has some
antihistaminic property. It can get absorbed from the skin and may cause drowsiness and anticholinergic effects.
Immunomodulating agents such as calcineurin inhibitor, tacrolimus have been reported to be useful when given
orally. They are, however, toxic. Tacrolimus ointment is also claimed to be effective
Allergic contact dermatitis: This condition is caused by contact of the skin with some offending agents. The
commonest type is plant dermatitis caused by members of the Rhus family. It is characterised by erythema,
vesiculation, and severe itching at the areas of contact. The other common sensitisers include preservatives in
topical preparations, fragrances, formaldehyde, potassium dichromate, detergent, rubber curing agents, synthetic
paints, plastic/synthetic bed and pillows and drugs. Chronic and excessive exposure to water and detergents can
initiate or aggravate hand dermatitis. The condition is common in housewives and food handlers. However, many
times, the offending agent is difficult to identify. The ideal treatment is to avoid the offending agent. Symptomatic
relief can be achieved by local calamine lotion or with topical glucocorticoids for about two weeks.
Eczema: Eczema is a common form of inflammation of the skin (dermatitis), with variable clinical and
histological features. It may be the common final expression of allergic conditions, such as atopic dermatitis, contact
dermatitis, or may accompany seborrheic dermatitis (see earlier). Initial lesions occur as erythematous macules,
papules, or vesicles which later coalesce to form patches and plaques. Eczema is associated with itching and may be
of two types:
• Weeping (oozing); or
• Dry

22. Pruritus: In the management of pruritus, identification and rectification of the underlying cause are important. When pruritus is a skin manifestation of systemic
diseases such as drug allergy, obstructive jaundice, Hodgkin’s disease, chronic iron deficiency and psychological illness, it responds poorly to antihistaminic drugs.
The exact mechanism of itch/pruritus is not clear but it probably involves both, central and peripheral components. Generally, it is associated with local liberation of
histamine and other autocoids. Histamine causes itch by stimulating ‘C’ nerve fibers different from those that signal pain. The impulse is carried to thalamus, via
spino-thalamic track; it leads to liberation of endogenous opioids. Experimentally, naloxone, an opioid antagonist relieves itch to some extent. Presence of pain has
inhibitory effect on itch; thus when local inflammation subsides and pain is reduced, one feels like scratching the area. Conversely, excessive scratching may relieve
itch but causes pain.
Topical anti-histaminics and local anaesthetics are generally partially effective. Anti-histaminics or anxiolytics such as doxepin or hydroxyzine given systemically,
however, are useful in itching due to inflammatory or allergic skin diseases; In such cases, these can be combined with topical steroid application. Minor local
conditions may respond to calamine lotion and/ or 2% menthol in aqueous cream. Emollients or urea cream may be useful when pruritus is associated with dry skin.
In cases of pruritus ani, presence of piles, local candidiasis or oxyuriasis should be looked for and treated. Pruritus due to neuropathy (diabetes, vitamin deficiency)
may respond to carbamazepine, gabapentin and local anaesthetics.
Drug Therapy of Scabies and Pediculosis
Scabies: Scabies is caused by the itch mite Sarcoptes scabiei var. hominis. The female mite burrows into the superficial layers of the skin to form tortuous channels
in which the eggs are deposited. Transmission of the mites occurs by close body contact. Away from the human body, the itch mite survives in a moist environment
for 1-2 days only. Unhygienic conditions and crowded housing favour the spread of the infection, which is characterised by intense itching, usually worse at night. It
is important to note that scabies can give rise to urticarial rash and eczematous lesions, which can be mistaken and wrongly treated with local and even oral steroid
therapy. The principles of treatment are:
• All members of the household must receive the treatment simultaneously.
• The medicament is applied to the whole body surface below the lower jaw. Contact with the eyes and the urethral meatus should be avoided carefully for fear of
irritation.
• The drug is applied 3-4 times at 12-24 hour intervals, with bathing and scrubbing of the body before and after the complete course.
• Complications are treated either simultaneously or after the basic treatment is over.
• Intimate clothing and bedding used during the previous 48 hours should be disinfected by boiling or by steam, and
• Education regarding personal hygiene.

23. Drugs used in the treatment of scabies are:
SULFUR: The scabicidal effects of sulfur, the oldest remedy, is probably due to its conversion into hydrogen sulfide and parathionic acid. In addition to its
use in scabies, sulfur is also employed in the treatment of other chronic skin conditions like psoriasis and seborrhoea.
Sulfur ointment contains 5% (2.5% in children) of sublimated sulfur in a simple ointment base. Because it is irritant, it should not be applied to the face. It
stains the clothes and has an unpleasant odour. Hence, though cheap, it is now obsolete.
BENZYL BENZOATE: Benzyl benzoate is a highly efficient acaricide and is the drug of choice. It is usually applied in the form of benzyl benzoate 25%
emulsion. Even after cure of infection, the itching may persist for a few weeks but usually responds to calamine liniment. Children are treated with 12.5%
application. Secondary bacterial infection can be successfully treated only after the primary infestation is eradicated. The drug is slightly irritant and has an
unpleasant smell. Although effective in pediculosis, benzyl benzoate is not recommended in its treatment because of its feeble ovicidal activity and short
duration of action.
PERMETHRIN, 5% application, left for 12 hours, is highly effective
GAMMA BENZENE HEXACHLORIDE (GBH): This gamma isomer of hexachlorocyclohexane is an insecticide, larvicide and acaricide. Applied
externally, it is not so toxic; but when ingested, it can cause convulsions. The drug is excreted slowly from the body. The other serious but rare toxic
manifestation is aplastic anaemia.
A vanishing cream containing 1% of the drug, applied to properly dried skin all over the body below the neck in the form of a thin film without preliminary
bathing, results in total eradication of scabies. The film is left over for a period of 12 hours following which the patient is given a bath. An average adult
requires 25 g of the cream per treatment. Unlike benzyl benzoate and sulfur, the agent is odourless and non-irritant and can, therefore, be applied safely to
the face but care should be taken to prevent contact with eyes and mucus membranes. The agent is neurotoxic, if absorbed. The treatment may be repeated
after a week. Not more than two applications should be used during pregnancy. Because of enhanced skin absorption and the risk of CNS toxicity,
gammexane should be avoided in infants and children.
It is also useful in pediculosis.
As an insecticide 0.1 to 0.5% solution in kerosene is lethal to flies and mosquitoes. It may be combined with other insecticides, such as a pyrethroid
(permethrin) to obtain a rapid, lethal effect.
IVERMECTIN: Given orally in a single dose of 200 mcg/kg, ivermectin, an antifilarial drug, is reported to be highly effective in clearing up scabies.
Repetition of the dose after two weeks gives almost 95% cure.
MONOSULPHIRAM: It is an effective acaricide and is used as 25% solution diluted with 2 to 3 parts of water. It is also incorporated in soap,
recommended for the prophylaxis of scabies. The drug may cause mild irritation. Adults using this drug should avoid alcohol because monosulphiram is
related chemically to disulfiram .
CROTAMITON: This is available as 10% lotion and as cream. It is applied thrice at 24 hour intervals, followed by a bath.

24. Pediculosis: Pediculosis, a common condition in tropical countries, is caused by the louse Pediculus humanus and usually affects the scalp (capitis),
the body (corporis) and pubic area (pubis). It is responsible for intense itching and may cause impetigo and eczematous lesions. Further, during famine
and natural calamities, the body louse can act as a vector for typhus, relapsing and trench fevers. Finding of nits or the lice on hair clinches the diagnosis.
Table 71.4
Drugs used in pediculosis
PERMETHRIN: This is a synthetic pyrethroid, available as 1% cream or lotion. Applied to clean damp hair, left on for 10 minutes and then rinsed off the
hair, it is an effective pediculocide with a residual effect for two weeks. The small quantity absorbed is rapidly metabolised to inactive compounds, and
excreted in the urine. It may cause local reactions. It does not have the biological disadvantages of gammexane, and is usually preferred.
MALATHION: This organophosphorus compound applied as 0.5% lotion is rapidly pediculocidal and ovicidal in the treatment of head lice, even in
patients resistant to permethrin. The drug is well tolerated and no systemic adverse effects have been reported. It is usually applied and left in place for 8-
12 hours, and the application is repeated 7-9 days later. It is inflammable because of the alcohol base. Care should be taken to keep the lotion away from
heat and open flame, and to avoid its contact with the eyes.
DICOPHANE (DDT): Used as a 10% dusting powder, it is an effective pediculocide. Its prolonged residual effect makes it lethal to the larvae which
hatch out later.
For pediculosis capitis, permethrin cream/lotion is preferred for initial treatment. For failures, malathion, the fastest-acting and the most ovicidal
pediculocide, is recommended. However, it has an objectionable odour. Because it is inflammable, a hair dryer and a curling iron should not be used
during the treatment. In resistant cases, ivermectin is safe and highly effective when used as two doses of 200- 400 mcg/kg each, a week apart; the second
dose is required as the drug is not ovicidal.
The other drugs used are Gamma BHC, DDT and kerosene. Gamma BHC (lotion, cream 1% or shampoo 2%) and DDT (2% dusting powder) are
generally used as two applications, 7-10 days apart. The application of kerosene, though not very pleasant, is the cheapest and effective treatment for head
lice. It destroys lice and suffocates nits by covering them with an impervious film. Usually, one tablespoonful of kerosene is rubbed into the whole scalp
and the head wrapped in a piece of cloth. Two hours later, it is washed thoroughly with soap and water. Kerosene does not cause irritation and usually, a
single application is all that is necessary. Of course, the individual must keep away from fire.
In patients with pediculosis corporis or pubis, DDT used as 10% dusting powder is highly effective. A single application can give an adequate residual
effect against the larvae which hatch out later. Gamma BHC is also equally effective. However, its persistence in the environment and its degradation to
toxic products makes it undesirable in this condition. Further, lice can develop resistance to all above drugs. Hence, malathion or newer pyrethroids are
preferred. The clothing should be disinfected with heat and all the contacts are treated simultaneously.

25. Drug Therapy of Psoriasis
Psoriasis is a common, chronic, inflammatory dermatosis. It is characterised by erythematous, well demarcated plaques, and rounded scales which look like silvery
mica. Pruritus may be present. Lesions are usually symmetrical and occur on the extensor surfaces such as the elbows and knees, and on the scalp. About 50% of
the patients have involvement of the finger nails and some have psoriatic arthritis. Genetic predisposition to psoriasis is known. Further, drug-induced flares of
psoriasis can occur (Table 71.7). Infections, particularly due to streptococci can trigger an attack.
Table 71.7
Possible risk factors in psoriasis
• Injury to the skin
• Infection, particularly streptococcal
• Some systemic drugs beta blockers, ACEI’s, lithium, indomethacin, chloroquine
• Psychological stress
Pathogenesis: The commonest variety of psoriasis is characterised by plaques, which consist of greatly thickened horny layer of the skin (hyperkeratosis). They
are characterised by hyperproliferation of the epidermal keratinocytes and inflammation of both the epidermis and the dermis, along with angiogenesis. These
changes are due to cytokines released by T-lymphocyte, which initate autoimmune dermal response to unidentified antigenic stimuli (keratinocyte proteins). The
affected dermis shows predominance of CD4 lymphocytes. The activated T cells from the dermis cause the keratocytes to proliferate; the inflammatory changes
include infiltration of the epidermis by leucocytes. It is now known that TNF-a is the primary activator of the T-lymphocytes and it also contributes to the
maintenance of a complex inflammatory reaction. The permissive role of bacterial super antigens in its pathogenesis is now well established.
The current therapy only suppresses the disease and recurrence is common. However, the disease may undergo spontaneous remission.
Treatment of psoriasis: It depends on the type, the location and the extent of the lesions. The patients are advised to avoid known exacerbating factors (Table
71.7).
Mild cases of psoriasis may not warrant any drug therapy, since the drugs used can produce toxicity. Indications for drug treatment are:
• Marked local symptoms such as pain and itching.
• Prominent hand, leg or facial lesions
• Diminished mobility.

26. Drugs used in the treatment of psoriasis are listed in Table 71.8. These drugs either cause keratolysis and/or inhibit cell division. They do not cure the disease.
Table 71.8
Drugs used in psoriasis
• Emollients
• Keratolytic agents: Salicylic acid 2–10%.
• Cytostatic agents: Coal tar, Dithranol
• Glucocorticoids.
• Calcipotriol, Tacalcitol
• Retinoids
Systemic therapy
• Etretinate, Acitretin
• Immunosuppressants: Methotrexate, Cyclosporine,
Mycophenolate mofetil.
• Biological agents
(a) T cell activation inhibitors: Alefacept
(b) TNF-α inhibitors: Etanercept, Infliximab.
(c) IL-12 and IL-23 blocker: Ustekinumab
• Systemic Glucocorticoids.
Phototherapy
• Ultraviolet B irradiation with or without Coal tar application.
• Ultraviolet therapy with Psoralens.
I Topical therapy:
Emollients: These act by hydrating and softening the scales. They are used in mild cases. The commonly used emollients are yellow, soft paraffin and aqueous cream.
Although greasy emollients are sometimes preferred, they are less well accepted by the patients.
Salicylic acid: This is the most widely used keratolytic agent, used either alone or with coal tar. It is an irritant, and care should be taken to avoid contact with the eyes.
Cytostatic agents (dithranol and coal tar) are used, along with UVB phototherapy, in the treatment of psoriasis and other hyperplastic skin disorders. In these
conditions they restore a normal rate of epidermal proliferation. In severe cases, systemic therapy with either etretinate or methotrexate both of which, act as cytostatic
agents in the skin, may be needed.
Crude coal tar (3% ointment) : This has been used to treat chronic, lichenified lesions. Coal tar, even in low concentration, has an unpleasant odour, and can cause
irritation and acneform eruption. Hence it is less acceptable.

27. DITHRANOL (Anthralin): This synthetic substitute for chrysarobin reduces the epidermal cell DNA synthesis and mitotic activity (antimitotic) of the
hyperplastic epidermis. It is an irritant and should not be applied to the face, scalp and to tender skin. The drug is used as an ointment, paste or paint. Since
some patients are allergic to this drug, a preliminary test on a patch of skin should be carried out. It is used in the increasing concentrations of 0.05 to 0.5%, for
½ hour daily along with ultraviolet B light therapy, for 2 to 3 weeks. It stains the skin and fabric brown and is not suitable for treatment of lesions on the face.
A commercial preparation, Derobin, contains dithranol 1.15% with salicylic acid and coal tar.
GLUCOCORTICOIDS: Topical glucocorticoid preparations of the mild and moderately potent varieties are preferred because of their efficacy, high degree of
acceptability to the patients and low cost. Once a day application to the lesions is probably as effective as the twice a day regimen and is less liable to cause
ADR. They act mainly as anti-inflammatory agents. Relapse rate is higher than with other forms of therapy. The use of potent and very potent, topical,
glucocorticoid preparations should be reserved for the specialist.
CALCIPOTRIOL: This vitamin D derivative is applied locally to mild to moderate psoriatic lesions. It has minimal effect on calcium metabolism. The drug is
as effective as topical, medium potency glucocorticoids but is much less toxic. It is applied daily as an ointment containing 50 mcg/g for about 8 weeks. The
ointment is colourless, does not stain clothes and does not have unpleasant smell. It can sometimes cause irritation and hypercalcemia. Tacalcitol is another
vitamin D analogue which is effective. Combination of a topical vitamin D analogue and phototherapy is a well accepted regimen for psoriasis.
II Systemic therapy: Although most patients with psoriasis respond to local therapy, about 20% may require systemic therapy. The latter is expensive, more
toxic and needs supervision. The drugs used are:
ETRETINATE: This second generation retinoid is also known as methoxsalen. It inhibits keratinisation and proliferation, and normalises differentiation of
epithelial tissues. Used alone, it has limited efficacy in psoriasis. It is usually combined with psoralen and UV-A phototherapy in chronic plaque psoriasis. The
drug accumulates in the adipose tissue and the liver. It is administered orally in the dose of 0.5-1.0 mg/kg per day.
The adverse reactions include dryness, scaly erythema and tenderness. It is teratogenic and should not be used in woman of the reproductive age until
pregnancy is excluded. Further, the patient must avoid pregnancy during treatment and for at least 3 years after the treatment is over because of its long half
life (about 120 days). Similarly, anyone taking this drug should not donate blood for 3 years after stopping it. The drug has no sebostatic action and is of no use
in acne.

28. Acitretin, a metabolite of etretinate, is now preferred to etretinate in therapy. Its limitations are similar to those of etretinate. Topical tazarotene, a retinoid applied
once daily, is also effective.
METHOTREXATE: This folic acid antagonist acts by blocking DNA synthesis and inhibiting cell proliferation. Methotrexate may also act as an
immunosuppressant. It is given orally in 3 doses, usually 2.5-5.0 mg. at 12 hourly, intervals, every week. It is preferred in severe case with arthritis, where coal tar-
U V therapy has failed. It should be used only in patients with normal hematological, renal and hepatic status. The drug is usually well tolerated in the doses
recommended. The main long term toxicity is hepatic cirrhosis .
CYCLOSPORINE: This drug is used as an immunosuppressant and acts by inhibiting the production of IL2, a cytokine necessary for proliferation of activated T
cells, and other T cell cytokines. The important adverse effects are hypertension and renal toxicity which may be irreversible. It is reserved for patients with severe
refractory psoriasis.
MYCOPHENOLATE MOFETIL: This immunosuppressant has been reported to be useful in the treatment of psoriasis. Adverse effects reported are mild and
dose dependent. The drug has also been used to treat pyoderma gangrenosum, pemphigus vulgaris and systemic vasculitis.
Biological agents: Recently, biological agents have been introduced in the treatment of psoriasis. Given parenterally, they are effective in about 30-70% of
patients with moderate to severe psoriasis. They are:
(1) Alefacept binds to CD2 on activated T cells and impairs the co-stimulatory signals of leucocyte-function-associated antigen-3 (LFA-3). This decreases the
number of T cells.
(2) Infliximab inihibits TNF-α functionally.
(3) Etanercept is a recombinant human TNF receptor antagonist.
(4) Adalimumab, humanised IgG1mAb, blocks TNF-α. Chances of development of neutralising antibody are less compared to infliximab.
(5) Ustekinumab: This human monoclonal antibody reduces skin inflammation by blocking the activity of IL-12 and IL-23. It is indicated in patients with
moderate to severe plaque psoriasis who cannot take standard therapy.
In addition, TNFα inhibitors, golimumab and certolizumab, are approved for psoriatic arthritis. They are all very expensive.
Selective phosphodiesterase -4(PDE-4) inhibitor, apremilast, is also available for psoriatic arthritis.
Systemic glucocorticoids: Systemic glucocorticoid therapy, though very effective, needs high doses to suppress the disease, and therefore causes ADR. Further,
the relapse rate is high. Hence, it should be reserved for acutely ill patients with erythrodermic psoriasis.