1. Drugs dermatological conditions Dr Sura Al Zoubi
MMS
Pharmacology
Lecture 4
Drugs dermatological conditions Dr Sura Al Zoubi

2. The Skin The skin is the largest organ system of the body.
It has many essential functions including:
serving as a protective barrier,
helping to regulate temperature,
offering defense against infections and toxic chemicals,
serving as a source of vitamin D, and
providing sensation to touch, temperature, sexual pleasure, and pain

3. Drugs for Dermatologic Disorders
Skin disorders, such as acne and dermatitis, are among the top reasons that patients seek medical attention.
Pharmacological approaches to correct skin abnormalities, including infections, can be administered topically or systemically, depending on the nature and extent of the disorder.

4. The skin

5. The skin
The skin is composed of two main layers, the epidermis and the dermis.
The epidermis itself is composed of many layers and serves as a defense against pathogens.
The outermost layer of the epidermis, the stratum corneum, consists of a lipophilic keratinous layer of skin.
The dermis is located between the epidermis and the subcutaneous tissue, and it is composed of connective tissue. It also contains specialized structures such as sweat glands, sebaceous glands, hair follicles, and blood vessels

6. TOPICAL PREPARATIONS
Use of topical agents for treatment of dermatologic disorders is not only convenient but also minimizes systemic adverse effects.
Topical agents may be formulated as:
sprays,
powders,
lotions,
creams,
pastes,
packed dressings,
ointments, and
aerated foams.

7. The bioavailability of these agents and the ability to retain therapeutic effect on the skin involve factors such as the vehicle (water or oil based) and the physical methods used to localize them, such as the use of a patch formulation.
The therapeutic efficacy of topical agents is dependent on the thickness of the stratum corneum, the drug concentration and permeability, frequency of dosing, and other factors such as age and health of the skin.
Lipophilic agents are more readily absorbed than those that are hydrophilic

8. This lecture Acne Bacterial skin infection Ectoparacitic infection
Pigmentation disorders
Psoriasis

9. Acne

10. Acne
Acne vulgaris (common acne) is a common skin disorder that is characterized by pimples, comedones, pustules, and sometimes nodules and scarring.
Comedones are clogged hair follicles (pores) in the skin, which can be open (blackhead) or closed (whitehead).

11. Acne occurs due to alterations in pilosebaceous units (skin structures that contain a hair follicle and a sebaceous (oil) gland).
Androgens stimulate sebaceous
glands, thereby producing sebum
that leads to follicular keratinization
and obstruction.
Propionibacterium acnes, part of the normal skin flora, can enter the clogged pore and multiply, causing redness and inflammation and leading to papillary, pustulary, and cystic acne.

12. Treatments for acne Reduce sebum production or Control P. acnes.
(Use of oral contraceptives may help decrease circulating levels of free androgen and reduce symptoms of acne)

13. AGENTS FOR ACNE

14. Benzoyl peroxide
Benzoyl peroxide is considered the first-line agent for mild to moderate acne with no inflammation.
MOA: antiseptic effects against P. acnes as well as opening of the pores.
Administration: it is a topical agent that is available in many over-the-counter acne treatment products, as well as some prescription products.
Adverse effects: Dry skin, peeling, and irritation are local

15. Salicylic acid
Salicylic acid is used as a treatment for mild acne and is available in many over-the-counter facial washes and medicated treatment pads
MOA: it penetrates the pilosebaceous unit and works as an exfoliant to clear comedones (Its comedolytic effects are not as pronounced as those of the retinoids), the drug has mild anti-inflammatory activity and is keratolytic at higher concentrations.
Administration: Topically.
Adverse effects: Mild skin peeling, dryness, and local irritation.

16. Azelaic acid
Azelaic acid is used for the treatment of mild to moderate inflammatory acne.
MOA: Azelaic acid, a dicarboxylic acid, has antibacterial activity against P. acnes as well as anti-inflammatory actions. Azelaic acid normalizes keratinization and is anticomedogenic.
Administration: It is available as a topical preparation.
Adverse effect: It is generally well tolerated, with mild skin irritation as the most common adverse effect.

17. Antibiotics
P. acnes is a gram-positive rod that is associated with inflammatory lesions in acne.
For moderate to severe acne with inflammatory lesions, use of topical or oral antibiotics is useful for inhibition of P. acnes.
Topical formulations of erythromycin and clindamycin (preferred) are available.
These agents may be combined with benzoyl peroxide or the retinoids for better effectiveness.

18. Oral antibiotics
Commonly used for the management of moderate to severe acne include
minocycline,
doxycycline, and
erythromycin.
Erythromycin is used infrequently due to gastrointestinal adverse effects.

19. Dapsone
It is a synthetic sulfone, is available as a topical gel that treats acne.
Its mechanism of action in the treatment of acne is unknown.

20. Metronidazole
as a topical agent is useful in adult acne, also known as rosacea.

21. Retinoids
Retinoids are derivatives of vitamin A that are highly effective in the treatment of:
acne,
psoriasis and
photoaging.
Tretinoin and isotretinoin are first-generation retinoids that are used for the management of acne.

22. Third-generation retinoids include adapalene and tazarotene.
Third generation agents are less irritating and more effective than first generation retinoids and are considered first-line therapy for comedonal and inflammatory acne.
These agents are applied topically, with the exception of isotretinoin, which is an oral drug.
Due to the adverse effect profile, use of isotretinoin should be reserved for severe cystic acne.

23. Mechanism of action
Retinoids influence a wide variety of biological activities, including cellular proliferation and differentiation, immune function, inflammation, and sebum production.
Unlike the first-generation agents, the third-generation agents do not influence sebum production.
They are comedolytic and anti-inflammatory.
The molecular actions of retinoids are mediated through nucleic retinoic acid receptors.
Once bound to the receptors, retinoids function as transcription factors that enhance initiation of transcription

24. Adverse effects
Irritation, dryness, and skin peeling are all complications with the use of retinoids.
Photosensitivity is also an adverse effect, and patients should be cautioned to wear sunscreen.
Other adverse effects include dry mucous membranes and dry eyes.
Suicide or suicide attempts have been associated with the use of oral isotretinoin.
There is a very high risk of birth defects if pregnancy occurs while taking isotretinoin, and this drug as well as other retinoids are contraindicated in pregnancy

25. Bacterial skin infection

26. TOPICAL ANTIBACTERIAL AGENTS
Organisms such as staphylococci and streptococci can cause folliculitis, abscesses, fasciitis, cellulitis, impetigo, and many pus-forming infections.
Several gram-positive and gram-negative bacteria cause infections that are not limited to the skin and may cause serious diseases, since they can spread and become systemic infections

27. Gram-positive infections
Bacitracin
Bacitracin is a peptide antibiotic active against many gram-positive organisms.
It is used mainly in topical formulations; if used systemically, it is toxic.
Bacitracin is mostly used for the prevention of skin infections after burns or minor scrapes.
It is frequently found in combination products with neomycin and/or polymyxin.

28. Mupirocin
Mupirocin is a protein synthesis inhibitor that is useful in treating impetigo (a contagious skin infection caused by streptococci or staphylococci) and other serious gram positive skin infections, including infections caused by methicillin resistant Staphylococcus aureus.
Retapamulin, is a newer protein synthesis inhibitor that treats impetigo.
Adverse effects are minimal
with these agents and usually
consist of mild local skin reactions.

29. Gram-negative infections
Polymyxin B
Polymyxin B is a cyclic hydrophobic peptide that disrupts the bacterial cell membrane of gram-negative organisms.
It is commonly combined with neomycin and bacitracin (“triple antibiotic”) in topical products used for the prevention of skin infections after minor skin trauma.

30. Neomycin
Neomycin in combination with other agents and also gentamicin can be used to treat skin infections caused by gram-negative organisms such as Pseudomonas, E. coli, and Klebsiella sp.
Topical use of these agents rarely causes systemic side effects.
Rare adverse reactions such as allergic dermatitis and other sensitivities occur with neomycin.

31. AGENTS USED IN ECTOPARASITIC INFECTIONS
Ectoparasites are parasites that live on the skin of animals from which they derive nutrition.
Pediculosis (infestation with lice) and scabies (caused by Sarcoptes scabiei, human mite) are common ectoparasitic infections.
Lice infestations may be caused by Pediculus capitis (head louse), Pediculus corporis (body louse), or Pthirus pubis
(pubic or crab louse).

32. Lindane
it is a cyclohexane derivative that is available as a cream or shampoo.
Lindane is toxic when absorbed by the parasite and is an effective pediculicide (kills lice) and scabicide.

33. Permethrin
It is a synthetic pyrethroid that is neurotoxic to lice (1% nonprescription) and is effective in 5% concentration by prescription to treat scabies.
Permethrin is preferred over lindane for the treatment of lice and scabies, since lindane can cause neurotoxicity.

34. Synergized pyrethrins
Synergized pyrethrins with piperonyl butoxide is a nonprescription product approved to treat head and pubic lice.
Pyrethrins are pesticides and piperonyl butoxide prevents the lice from metabolizing the pyrethrins, thereby enhancing their effect.
Due to a low risk of toxicity, this agent is considered a first-line treatment for pediculosis.

35. Crotamiton Crotamiton is a scabicide and has antipruritic functions.
Its mechanism of action is unknown.

36. AGENTS FOR PIGMENTATION DISORDERS
Treatment of hyperpigmented skin conditions
and vitiligo

37. Hydroquinone
Hydroquinone is a topical skin whitening agent that reduces hyperpigmentation associated with freckles and melasma.
It is often used in combination with topical retinoids to treat the signs of photoaging.
MOA: inhibition of the
tyrosinase enzyme required
for melanin synthesis.

38. Hydroquinone lightens the skin temporarily and is commonly used as a 4% preparation.
Adverse effects: Local skin irritation, it should not be used in higher concentrations, or in excessive quantities for an extended duration, as it is associated with possible carcinogenicity.
Monobenzone , the benzyl ether of hydroquinone, is sometimes used to even out the skin discoloration associated with vitiligo (depigmentation disorder of the skin).
The drug may cause permanent depigmentation and is no longer available in many markets.

39. Methoxsalen
MOA: Methoxsalen is a photoactive substance (psoralen) that stimulates melanocytes and is used as a repigmentation agent for patients with vitiligo.
It must be photoactivated by UV radiation to form a DNA adduct inhibiting DNA replication by a method called PUVA (psoralen plus UVA radiation).
Methoxsalen inhibits cell proliferation and promotes cell differentiation of epithelial cells.

40. Administration: Topical methoxsalen may be used for small patches of vitiligo, and oral therapy is used for more widespread disease.
Adverse effects: Because of the possibilities for aging of the skin and possible carcinogenicity, it is used with caution.

41. DRUGS FOR PSORIASIS
Psoriasis is a skin disease that presents with erythematous scaling plaques.
It manifests with increased epidermal cell proliferation.
Psoriasis appears to have both genetic factors and T-cell–mediated immune components.

42. The majority of patients have mild to moderate psoriasis, and this can be managed with topical treatments including retinoids, vitamin D analogues, keratolytic agents, and corticosteroids.
More severe cases require systemic therapy with phototherapy (methoxsalen followed by UVA or UVB alone), methotrexate, cyclosporine, or biologic response modifiers (for example, etanercept, adalimumab)

43. Retinoids
Tazarotene is a topical retinoid used for the treatment of plaque psoriasis.
Adverse effects are similar to other retinoids.
Acitretin is a second-generation retinoid used orally in the treatment of pustular forms of psoriasis.
It is a metabolite of etretinate (no longer available), which has a half-life of 120 days.

44. Since ingestion of ethanol can increase transesterification of acitretin to etretinate, ethanol is contraindicated with this agent.
Like other retinoids, acitretin is teratogenic and women must avoid pregnancy for at least 3 years after the use of this drug (due to the long duration of teratogenic potential).
Adverse effect: Cheilitis, pruritus, peeling skin, and hyperlipidemia are common adverse effects.

45. Vitamin D analogues
Calcipotriene and calcitriol are synthetic vitamin D3 derivatives used topically to treat plaque psoriasis.
MOA: They inhibit keratinocyte proliferation and increase keratinocyte differentiation.
Their therapeutic effectiveness does not appear to decrease upon continued use.
Transient elevations in calcium levels have been reported in some patients.
Adverse effects: itching, dryness, burning irritation, and erythema.

46. Keratolytic agents
Keratolytic agents such as coal tar and salicylic acid are effective in localized psoriasis, especially on the scalp. They improve corticosteroid penetration.
Coal tar inhibits excessive skin cell proliferation and may also have anti-inflammatory effects.
Because it is cosmetically unappealing, coal tar may have a low acceptance rate among patients and, consequently, its use has been largely supplanted by the newer topical agents.

47. Thank you