Clinical Pharmacology in Eye, ENT, and Skin Diseases

Dra.Yuliastuti,M.Kes.,Apt.

Depatment of Pharmacology and TherapyFaculty of Medicine

Universitas Gadjah MadaYogyakarta

Ear, Nose and Throat Diseases

• Infeksi Bakterial pada telinga, hidung dan tenggorokan cari m.o. penyebab (penting u/ pemilihan pengobatan)

• Terapi sistemik:– phenoxymethylpenicillin (penicillin V),

erythromycin atau bila juga ada + infeksi oleh H. influenzae dapat diterapi dengan amoxilin/clavulanic acid, clotrimoxazole atau cefaclor, dan gentamicin topikal.

• Pembersihan liang telinga atau nasal airway akan meningkatkan fungsi eustachian tube, = tindakan tambahan penting dalam mengatasi berbagai gangguan pada telinga dan hidung

• Alergi pada gangguan nasal sering ada hubungannya dengan secretory otitis media

• Obat yang bersifat ototoksik– aminoglicoside antibacterial drugs – loop diuretics pada pasien yang ada

gangguan pada fungsi ginjal

Eye DiseasesVision = faktor penting dalam kehidupan

Managemen eye diseases yang optimum: screening (u/ diabetic retinopaty, open angle -glaucoma)

rapid diagnosis and treatment- Corneal ulcer- Injury- Narrow angle glaucoma

Memberi pengertian pada pasien - cataract- dry eye

Penting u/ pemilihan opsi yang paling memadai

Pada degenerative diseases of the eye sarankan pemberian nutritional suplementation (vitamin, zinc, mineral lain ....... )

Obat topikal pada mata: Bahan2 physicochemical obat (dan vehiclenya)Status fisiologik mata mempengaruhi penetrasi kedalam struktur mata

Konsentrasi obat dalam kornea dan aqueous humour dapat dipertahankan atau ditingkatkan dengan cara memperlama kontaknya dengan mata (bentuk ointments, gels, controlled-release insert, contact lenses atau collagen shields

Terapi pada gangguan okuler * administrasi topikal (tetes, unguenta, cream)* injeksi subconjuctival atau subtenon

* intravena (jarang)* terapi sistemik* kacamata, lensa kontak* operasi

Intervensi dengan Laser dan pembedahan = alternativ u/ cataract, glaucoma dan gangguan retinal tertentu. Pemilihan tergantung pada urgensi, biaya dan variasi individual.

Terapi dengan berbagai agen topikal ataupun administrasi sistemik dapat menimbulkan systemic adverse effect pada semua sistim tubuh termasuk mata

* Contoh: Kortikosteroid baik lokal dapat meningkatkan formasi katarak

Skin DiseasesRencana u/ rational treatment:

Tentukan apakah penyebabnya internal ataukah benar2 berasal dari kulit.

Bila berasal dari kulit, agen topikal, agen sistemik

Agen topikal : * losion dan pasta sangat baik u/ lesi basah * salep lemak u/ lesi kering* krim baik u/ keduanya

Terapi topikal kadang2 tdk memuaskan karena dapat timbul iritasi, alergi atau dosisnya tak cukup berpenetrasi ke kulit

Skin diseases • Terapi simptomatis• Agen sistemik• Agen topikal

• Banyak obat2 yang dapat menimbulkan gangguan pada kulit

Skin Biology

Epidermis:Outermost layer

Dermis:Contains small capillaries, glands, nerve fibres & hair follicles

Subcutaneous (Hypodermia):

Arterioles, fat, collagen, fibroblasts

• Epidermal layers:– Strateun corneum (epidermis layer) is 40%

protein, 40% water and 20% lipids (fat)• Keratinization – protective production of

keratin– Stratum lucidium – densely packed with keratin– Stratum granulosum – contains non-dividing

keratinocytes– Stratum spinosum – contains keratinocytes and

Langerhan cells (immunity)– Stratum germinativum – contact area between

epidermis and dermal layer

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Administration• Topically – outer layer of the skin

– Most act on the skin but are not absorbed (soften, disinfect or lubricate).

– Few contain enzymes to remove superficial debris (skin ulcerations)

– Others treat skin infections

• Transdermally – through a patch or inhaled– Readily absorbed with systemic effects– Patches – gradual release, reducing

toxicity effects– Fewer adverse reactions– Eg. Nitroglycerin (Cardiac Pts) and

Scopolamine (nausea)

Routes

• Sebaiknya dapat berpenetrasi ke lapisan cutaneous efek meningkat .

• Absorbsi Percutaneous melibatkan :– Disolusi obat dalam vehikulum– Difusi obat dari vehikulum ke permukaan kulit – Penetrasi melewati lapisan2 kulit

• NB: Passage is slowest in the stratum corneum

Factors that effect

cutaneous absorption

Transcellular Diffusion

Diffusion throughchannels between

epidermal cells

Diffusion through

sebaceous ducts

Diffusion through

hair follicles

Diffusion through

sweat ducts

Factors affecting absorption• Sifat alamiah kulit:

– Adanya lesi pada kulit, 80% dapat berpenetrasi, pada kulit utuh hanya 1% (hydrocortisone)

– Hidrasi meningkatkan kecepatan – stratum corneum tipis (infant & elderly)

• Sifat alamiah obat :– Konsentrasi obat aktiv, komposisi, bahan

physiochemical dan bahan dasar/vehicle– Lipid soluble > effective daripada water soluble

(20% fat)

Exogenous factors effecting efficacy

• Daluwarsa karena penurunan aktivitas obat ± 10%

• Lingkungan :– pH – mempengaruhi reaksi kimiawi dan tingkat

potensi – Temperatur – O2 degradation of agents– Cahaya menginduksi degradasi photochemical – Kelembabpan dehidrasi preparat

Terminology

Description Conditions

Astringents A coagulating protein that acts upon oozing discharge or bleeding

Dermatitis

Collodions Proxylin + ether/alcohol leaving a covering film

Minor wounds

Creams Water-soluble agents or oil based. Can contain water repellent agents

Irritation or rehydration

Emollients Fats or oils in a 2 phase system (1 dispersed over the other). Form a occlusive film over the skin to protect or soften.

Eczema and psoriasis

Gels Jelly-like solids or semi-solid perparations with a water (lubrication) or alcohol base (drying or cooling)

Dry scaling lesions in the skin and scalp

Humectants Substances to promote water retention

Dry lesions

Liniments Viscous agents contain pain-relieving analgesics

Pain intact skin lesions

Terminology

Description Conditions

Lotions Aqueous agents to cool areas Inflamed but still intact skin

Ointments Semi-solid, greasy and water insoluble preparations. Base vehicle is usually paraffin.

Fungal infections of the skin

Pastes High propotions of fine powder solids (zinc oxide)

Subacute lichenified or excoriated conditions

Suspensions Undissolved drugs in liquid vehicles

Various conditions

Topical Anti-infectives• = anti mikro organisme (bakteri, fungi,

virus) .• Antibiotik:– Efek: bakterisidal lokal atau bakteriostatik

• Bacitracin, Gentamicin (G-myticin), Erythromycin (Emgel) and neomycin

• Bacitracin (Baciguent) menhambat sintesis dining sel

– Mencegah infeksi superfisial pada luka, abrasi kulit, dan minor burns

• Antifungal:– Local inhibitory effect• Amphotericin B (Fungizone) used for mycotic

infections• Miconazole (Micatin), Ciclopirox (Loprox),

econazole (Spectazole) used for tinea pedis (athlete’s foot); tinea corporis (ringworm)• Clioquinol used for eczema and athletes'

foot

• Antiviral:– Acyclovir (Zovirax) and Penciclovir

(Denavir) the only available antiviral topical preparations

– Acyclovir used for initial presentation of genital herpes and herpes simplex in immunocomprised pts

– Penciclovir used for cold sores in adults

Adverse reactions to Anti-infectives

• Ringan, umum terjadi • Simptom : skin rash, itching, hives,

dermatitis, irritation and redness• Hypersensitive reactions• Penggunaan lama ‘Super-sized’

infection

Kontraindikasi• Hypersensitive pts• Hati2 pada pts dengan luka bakar

yang lebar – Nephrotoxicity

• Pada Bumil AB Topikal =kategori C, antiviral = kategori B

United States FDA Pharmaceutical Pregnancy Categories

Pregnancy Category A

Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

Pregnancy Category B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.

• Pregnancy Category C• Animal reproduction studies have shown an adverse effect on the fetus and

there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

• Pregnancy Category D• There is positive evidence of human fetal risk based on adverse reaction

data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

• Pregnancy Category X• Studies in animals or humans have demonstrated fetal abnormalities and/or

there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

• Pregnancy Category N• FDA has not classified this drug.

Topical Antiseptics and germicides• Antiseptic = menghentikan,

melambatkan atau mencegah pertumbuhan M.O.

• Germicide = membunuh bakteri

• Mekanisme tak jelas, hanya diketahui dapat berefek pd berbagai M.O.

• Efikasi: berkisar antara short-term dan long-term

• Benzalkonium (Zephiran)– Rapid acting, moderately long duration– Active against bacteria, fungi and protozoa– Tergantung konsentrasi dapat berefek

bakterisidal atau bakteriostatik

• Chlorhexidine gluconate (Hibiclens) : u/ bakteri gram positive dan negative.

• Iodine dikombinasikan dgn Povidone (Betadine) = antiseptik (iodine) dan kurang iritativ thd kulit

• Adverse reactions:– Jarang – reaksi alergi • Redness, itching etc

• K.I.:– Pts hipersensitiv– Penggunaan yang benar tak

menimbulkan K.I. yang signifikan

Topical Corticosteroids

• Potensi tgt konsetrasi obat, vehicle dan area aplikasi

• = anti-inflammatori lokal (reduction in oedema, irritation, vascular perfusion dannyeri)

• Psoriasis, dermatitis, rashes, eczema, 1st & 2nd degree burns

• Adverse reactions = irritation, dryness, secondary infections

Contraindications

• Hipersensitivitas• Tidak u/ penggunaan ophthalmic

(menginduksi glaucoma)• Category C for pregancy

• Eg: Hydrocortisone (Cort-Dome)

Keratolytics• Menhilangkan pertumbuhan

epidermis yang berlebihan (warts, calluses, corns

• Eg. Masoprocol (Actinex) & Diclofenac (Solaraze)

• Adverse reactions:– rare, burning sensation, rash, dry

skin or flu-like symptoms• Contra’s:– moles, birthmarks, warts with hair,

genital or facial warts, or warts on infected skin.

– Prolonged use leads to toxicity

Topical Local Anesthetics• Mekanisme Aksi: –Menghambat konduksi impuls

nociceptive dari saraf sensori • Eg. Benzocaine (Lanacane) &

lidocaine (Xylocaine)• Redakan gatal, nyeri, minor burns,

infeksi jamur, sengatan serangga, rashes, sunburn, plant poisoning.

• Adverse reactions:– Local irritation, dermatitis, rash, burning,

stinging, and tenderness may occur

• Contra’s:– Pts with known hypersensitivity