How To Give A Drug To A Patient

Transcription

1 ( There's no need to refer to the slides) Note :don t memorize any numbers or any commercial name of a drug) Dermatologic pharmacology Today we will talk about a few names and a few drugs that's concern with skin diseases. Variables affecting pharmacologic response: 1- Regional variation in drug penetration:(different areas of the skin in the body). v If we give a drug to the palm of the hand it absorbs differentially that when we give to the the back of it.because we have more keratinized tissue. v So when we give a drug to a certain area, the amount of drug will be different depending on the variability of that region. Note: More obvious changes in fates. And it's completely different in the sole of the foot because of the difference in the thickness of the keratinized tissue. 2- Concentration gradient: v Increasing the concentration gradient increases the mass of drug transferred per unit time. 3-Dosing schedule (some drugs are given once a day, twice a day, etc). v Usually we like a drug to be given as little as possible because it will increase the patient complaints. v If we decrease the amount or the time we need for the drug it will be better for the patient. v It's hard to keep the topical drugs on it's place because of the contact and friction with the clothes and the body. 4- Vehicles and Occlusion. Vehicle: is a substance that's added to the drug to give it a dye of a cream or a lotion or whatever. 1

2 Percutaneous absorption o Here we can see the absorption of the drugs through different layers of the skin: A. In the stratum corneum most of the drug stay there as a reservoir and it's absorbed over time. B. Then it goes into the stratum spinosum and some of it will bind to it's receptor and have it's effect. C. Then it continues to the basement membrane to bind to it's receptor there and have it's effect. Dermatologic formulations for local drugs: Tinctures - are drugs that's administerd as a solution (for ex: mercurochrome, iodine) - are used to clean the wound area. - usually they have a high percent of a solvent like the alcohol. Wet dressings Lotions Gels 2

3 Powders Pastes Creams Ointments v Each one of the above has different water content and different properties. à Some drugs if it's given as cream, it's better than tincture because it have less alcohol so we will have less irritation for the tissue. v Depending on the patient condition: à If you want the affected area to be dry you must give a water based drug. à If you want the affected area to be moist you must give a cream or lotion to increase the moisture content in that area. Adverse effects of dermatologic preparations: Burning or stinging sensation: usually it has to do with the vehicle administer of the drug. Drying and irritation Pruritus (itching) Erythema Sensitization:can make an allergic reaction. Staining Superficial erosion Topical anti bacterial agents: Bacitracin: à It works on cell wall synthesis. à It's not from penicillin's. à It's Nephrotoxic if it's given systemically. Gramicidin. Note: Both Bacitracin and Gramicidin are active against Gram-Positive bacteria. Polymyxin B Neomycin Gentamicin. Note: Polymyxin B, Neomycin and Gentamicin all of them are active against Gram-Negative bacteria. 3

4 Bacitracin o Frequently used in combination with other agents(polymyxin B and neomycin) o Form: creams, ointments, aerosol preparations. o Usually steroidal anti-inflammatory agents are added (ex:hydrocortisone) Topical Antibacterials in Acne: v Clindamycin v Erythromycin Note: Both of Clindamycin and Erythromycin are macrolides which prevent protein synthesis. v Metronidazole à Can be considered as Antibacterial for anaerobic bacteria. à Also,can be considered as Antiparasitic for Amoeba. v Sodium sulfacetamide Note : à Acne is a bacterial infection. à The most causative factor for acne is stress. Clindamycin ü 10% absorbed, so, possibility of Pseudomembranous colitis. à Pseudomembranous colitis : it's the inflammation of bowels that s caused by Clostridia Difficle. ü The hydroalcoholic vehicle and foam formulation (Evoclin) may cause drying and irritation of the skin, with complaints of burning and stinging. ü The water-based gel and lotion formulations are well tolerated and less likely to cause irritation. Allergic contact dermatitis is uncommon. ü Clindamycin is also available in fixed-combination topical gels with benzoyl peroxide (Acanya, BenzaClin, Duac), and with tretinoin (Ziana). à Benzoyl peroxide: it peels the skin and kills the bacteria so it's very hard or very harsh on the skin. à Tretinoin: Ø It's one of the retinoid A antibiotics. 4

5 Metronidazole: Ø It's a very powerful antibiotic and the best available to treat acne. Ø It has many major side effects specially if it's given systemically. ü Effective in the treatment of Rosacea. à Rosacea is a bacterial infection that causes redness of the face and certain areas of the body. ü The mechanism of action is unknown, but it may relate to the inhibitory effects of metronidazole on Demodex brevis; This drug may act as an anti-inflammatory agent by direct effect on neutrophil cellular function. ü Adverse local effects of the water-based gel formulation (MetroGel) include dryness, burning, and stinging. ü Less drying formulations may be better tolerated (MetroCream, MetroLotion, and Noritate cream). ü Caution should be exercised when applying metronidazole near the eyes to avoid excessive tearing. Erythromycin: ü In topical preparations, erythromycin base rather than a salt is used to facilitate penetration Note: à Topically we use the erythromycin base. à Systemically we use the erythromycin salt. ü One of the possible complications of topical therapy is the development of antibiotic-resistant strains of organisms, including staphylococci. ü Adverse local reactions to erythromycin solution may include a burning sensation at the time of application and drying and irritation of the skin ü Erythromycin is also available in a fixed combination preparation with benzoyl peroxide (Benzamycin) for topical treatment of acne vulgaris. Note: the penetration or the mechanism of action of Erythromycin is increased when it's conjuncted with zink. 5

6 Topical Antifungal agents: Azole derivatives: ú clotrimazole ú econazole ú ketoconazole ú miconazole ú oxiconazole ú sulconazole. - All of these derivarives are active against dermatophytes and yeast, including candida albicans. Notes: è Azole :inhibits ergosterol synthesis.(which is a cholesterol in the fungi cell membrane) and we are not afraid from the interfering of these drugs with our cholesterol synthesis because of the absent of the ergosterol in our bodies and that means that we will have less side effects. è The differences between Dermatophytes and Yeast: Dermatophytes: they don't populate or live in living tissue and they live in dead tissue so they live in the nails and the keratinized layer of the skin.(nails and keratinized skin are non-nucleated) Yeast: part of normal flora in our body; so they live in the mucous membrane and the moist area of the skin. Oral antifungal agents: Azole derivatives:(used systemically not topically) ú fluconazole ú itraconazole ú ketoconazole è Affect the permeability of fungal cell membrane through alteration of sterol synthesis. è Effective in systemic mycosis, mucocutaneous candidiasis, and other cutaneous infections. è Might have systemic side effects: hepatitis and liver enzyme elevations, and interactions. - if they interact with other drugs, they will inhibit cytochrome p450 that metabolizes a lot of drugs ; so we will have more concentration of the active form of the drug. 6

7 Topical antifungal agents: Ciclopirox Olamine: Tinea versicolor. Naftifine and Terbinafine: tinea pedis, tinea cruris, and tinea corporis Tolnaftate (for all tinea infections). Nystatin and amphotericin B: è Only for Candida albicans. è Available as topical preparations, oral suspension, and vaginal tablets or suppositiries Notes: è Ciclopirox, naftifine and amphotericin B : unknown mechanism of action. è Candida: part of normal flora of our body in (oral cavity and genital areas); so if the patient is subjected to a low immnity conditions ; candida growth will increase over the growth of bacteria. è some of babies in delivery are exposed to candida albicans so they develop thrush; So they give them nystatin oral suspension ( usually one or two drops). è Nystatin: is toxic if it's given systemically. Oral anti fungal agents: Azole Derivatives: o Griseofulvin: - Effective against epidermophyton, microsporum, and trichophton. -Requires prolonged treatment ú 4-6 weeks for the scalp. ú 6 months for fingernails. ú 8-18 months for toenails. ú Has many side effects. o Terbinafine: -Recommended for onchomycosis (ringworm of the nail) ú 6 weeks for fingernails. ú 12 weeks for toenails.( they take a longer time because they are thicker) 7

8 Topical antiviral agents: Acyclovir. Valacyclovir. Penciclovir. Famciclovir. -Synthetic guanine analogs with inhibitory activity against herpes viruses. - Ointments and creams are useful for recurrent orolabial herpes simplex infection. Note: The causative agent is herpes simplex virus. Immunomodulators: - A new drugs that are used to treat skin infections o serious conditions like cancers. Imiquimod For external genital and perianal warts. Actinic keratosis on the face and scalp. (they decrease the keratinization of the skin by killing the cells gradually) Primary basal cell carcinoma. (one of the best malignant tumors and even though it's malignant; it's very well encapsulated and it doesn't metastize easily ; so it's easy to treat this cancer) Stimulates peripheral mononuclear cells to release interferon- ά and to stimulate macrophages to produce interleukins-1,-6, and -8 and tumor necrosis factor-ά. Tacrolimus. Pimecrolimus. - Useful for atopic dermatitis.( Eczema) - Inhibit T-lymphocyte activation and prevent release of inflammatory cytokines and mast cell mediators. Sorry for any mistakes, Done by: khaled al3nzi Best thanks for saqer alghais 8