TOPICAL ANTIBIOTICS Topical Antibacterials - Most commonly isolated skin pathogens o GA Strep- beta hemolytic o Staph aureus o *For

surgical wounds, pathogens will be those common in that particular environment - Obtain in vitro culture and sensitivity studies are ideal - Common uses of Topical antibacterial: o Prophylactic use in clean wounds o For the early treatment of infected dermatoses and wounds o Treatment of acne vulagris o Axillary deodorization o Reduction of colonization of S. aureus in the anterior nares to prevent recurrent impetigo contagiosa ANTIBACTERIAL: 1. MUPIROCIN [Pseudomonic Acid A] 2. BACITRACIN 3. POLYMYXIN B 4. NEOMYCIN/GENTAMICIN 5. TRIPLE ANTIBIOTIC OINTMENT a. Bacitracin zinc b. Polymyxin B c. Neomycin sulfate - Advantage and rationale for use: o Effective for mixed infections and available in fixed dosages o Broader coverage especially if pathogens are undetermined o May prevent microbial resistance o Like any antibiotics, this must be used for 7 consecutive days;( some patient fail to comply) ECTOPARASITICIDES Lindane Permethrin Crotamiton Sulfur Kakawati

ANTIVIRALS Acyclovir Pencyclovir

ANTIFUNGAL Topical agents for Dermatophytic infxn Whitfields ointment Benzoic acid 6% Salicylic acid 3% Azoles : Imidazole Ketoconazoles Miconazole/ Tioconazole Clotrimazole Allylamines Terbinafine Naftifine Tolnafatate Undecyclenic/ Undecanoic Acid Akalpulko Systemic agents for Dermatophytic infxn Azole: Triazole Itraconazole Fluconazole Posaconazole Griseofulvin Terbinafine Superficial Candidiasis Nystatin Imidazole Pytiriasis Versicolor Imidazole Selenium sulfide Tolnaftate Zinc pyrithone Undeyclenic acid Whitfields ointment 12% Benzoic Acid 6% Salicylic Acid

ANTIBACTERIAL MUPIROCIN (pseudomonic acid) BACITRACIN

MOA Binds to ISOLEUCYL tRNA synthetase to inhibit CHON synthesis Inhibits the regeneration of phospholipid receptors involved in peptidoglycan synthesis Inhibits cell wall synthesis Increases cell wall permeability by interacting with phospholipid components of cell membrane

Absorption Minimal systemic absorption through skin

Distribution 95% protein bound

Metabolism Liver: Converted to MONIC ACID

Excretion Renal

POLYMYXIN B

Not absorbed from GIT, mucous membrane in the tissues

Renal: 60% unchanged in urine

NEOMYCIN/ GENTAMICIN

Binds to A site of 30S subunit of bacterial ribosomes to prevent elongation of peptide chain

Indication Gram (+) MRSA Used in Impetigo and eradication of nasal carriage S. aureus Pregnancy category B For superficial infection Gram (+) : Staph Strep Pneumococci Most Anaerobic cocci Diphtheria bacilli Tetanus Neisseria For Superficial infection Gram (-): Pseudomonas Klebsiella E. coli Enterobacter Note that most strain of serratia and proteus and all gram (+) are resistant to this drug Gram (-): E. coli Enterobacter Proteus Klebsiella Gram (+):*note genta > neomycin GA Strep Staph Pseudomonas Primary Skin Infection: Impetigo contagiosa Supf folliculitis Echtyma Furuncolosis Secondary Infection: Infected eczematoid Contact and postural dermatitis Bacterial superinfections of fungal and viral lesions

Others

Adverse reaction: Urticarial Allergic contact dermatitis Anaphylaxis(rare) * constituent of triple antibiotic ointment * constituent of triple antibiotic ointment

* constituent of triple antibiotic ointment

ANTIFUNGAL Topical agents for Dermatophytic infxn Whitfields ointment Benzoic acid 6% Salicylic acid 3% Azoles : Imidazole

MOA

Absorption

Distribution

Metabolism

Excretion

Indication

Others

keratolysis

reduction of ergosterol synthesis by inhibition of fungal CYT P450 Broad spectrum but toxic and hence limited to topical use

Tinea pedis Tinea cruris Tinea corporis (ringworm) Candida spp C. neoformans Dermatophytes Endemic mycoses Blastomycosis coccidiodomycosis

Selective toxicity: Azole has greater affinity for fungal than human CYTP450 Azole is grouped according to number of nitrogen: imidazole and triazole Also used as systemic agents Poorly selective: Interferes with mammalian P450 Interferes with steroid hormone syhthesis and ph1 drug metabolism

Ketoconazoles

Miconazole/ Tioconazole

Ihibits ergosterol biosythesis thus damaging fungal cell wall membrane and increases its permeability, allowing leakage of nutrients Broad spectrum Binds to phospholipids in the cell membrane altering cell wall permeability causing loss in essential intracellular elements

Minimal

Hepatic: Converted to inactive metabolites

Urine and feces

Vulvaginal candidiasis Tinea versicolor Oropharyngeal candidiasis Balanitis Pyityriasis versicolor

Only used as topical agents

Clotrimazole

Negligible through intact skin 3-10% vaginal

Hepatic: Converted to inactive metabolites

Urine Feces (as metabolites)

Only used as topical agents

Allylamines Terbinafine

Fungal cell death by inhibitng squalene epoxidase resulting in ergosterol deficiency of cell walls

Minimal absorption

Naftifine

Selectively inhibits squalene monooxygenase resulting in reduced synthesis of ergosterol within membrane Fungicidal and fungistatic

3-6% absorbed systemically after application of cream or gel

Distributed into stratum corneum of the skin, nail plate,hair and breast milk Extensive *conc higher than plasma Milk of rats(topical)

Hepatic: Converted to inactive metabolites

Urine Elimination: Normally, 17-36 hr Up to 400 hr(1/2 day) for prolonged therapy

Mucocutaneous fungal infection Fungicidal in dermatophytes and some yeast

Metabolised to at least 3 metabolites via oxidation of th phenyl and napthyl rings and Ndealkylation

Urine and feces (Unchanged drug or metabolites) Half life: Approx. 2-3 days

Synthetic allylamine

Tolnafatate

Inhibits growth of dermatophytes and M. furfur by distorting hyphae and stopping mycelial growth

Microsporum Epidermophyton Trichophyton Malassezia furfur Pityriasis versicolor Dermatomycosis furfuracea For athletes foot Jock itch Diaper rash Prickly heat, excessive sweating in groin area Itching, burning, chafing

Inactive against Candida spp or bacteria

Undecyclenic/ Undecanoic Acid

Unsaturated FA derived from castor oil(an emolient) WOF hypersensitivity reactions

Akalpulko

Tinea infections Insect bites Ringworms Ezema Scabies Itchiness Mouthwash in stomatitis

From plant Cassia alata Katanda, andadasi, palochina poultice Primarily used: Leaves Pounded and applied on affected areas 2x a day over several weeks

Systemic agents for Dermatophytic infxn Azole: Triazole

reduction of ergosterol synthesis by inhibition of fungal CYT P450 same as imidazole broad spectrum

Itraconazole

Fluconazole Posaconazole

Same MOA Same MOA No description given No description given

Candida Cryptococcus Blastomycosin Coccidiodomycosis Histoplasmosis Fungal meningitis ( by Cryptococcus)

More selective than ketoconazole

Griseofulvin Terbinafine Superficial Candidiasis Nystatin

Binds to ergosterol of the fungal membrane resulting in altered permeability and leakage of cellular contents

Negligible absorption from GIT following oral administration

For cutaneous and mucosal candida infection

Limited to topical use due to narrow spectrum and negligible absorption from GIT

Imidazole

Ketoconazole - Given 2-6 weeks 200 mg OD or BID Fluconazole - Long plasma half life - 100 mg OD or alternate days Itraconazole - For onchomycosis - Contraindicated in patient with ventricular dysfunction

CONTRAINDICATION: Patient taking HMG- CoA reductase inhibitor this will lead to rhabdomyosis

Pytiriasis Versicolor Imidazole Selenium sulfide See above Cytostatic effect on cells epidermis and follicular epithelium Antiseborrheic May involved transcription factors see info above (actually walang MOA n binigay) Keratolysis Currently withdrawn from the market Ketoconazole, clostrimazole, miconazole

Tolnaftate Zinc pyrithone

Undeyclenic acid

Whitfields ointment 12% Benzoic Acid 6% Salicylic Acid

Note the concentration is different from whitfields ointment for supf. dermatophytic infxn (6% BA, 3% SA)

cutaneous candidiasis o most common cuase of diaper rashin infants. The fungi take advantage of the warm, moist condition inside the diaper o Also common in obese diabetic patient o Patient using Birth control pills has inc risk o Onchomhycosis nail candida infection o Angular chelitis - candida infection around the mouth o

Versicolor o Causes the affected skin to the change color o Most commonly affected: Shoulder Back Chest Folds of skin such as the crook or arms, skin under the breast or the groin o Face is usually spared although sometime childeren can get it there o There may be just a few spots or many gives the appearance that the affected skin is normal while the unaffected skin around it seems to have a problem MOA Inhibits viral DNA syntehsis and replication by interfering with viral DNA polymerase Absorption 15-30% absrobed from GIT Slightly absorbed from the skin Absorbed from ophthalmic Distribution CSF- 50% of plasma concentration Crosses placenta Enters breast milk- 3x higher than maternal serum 9-33% protein bound Metabolism Intracellular conversion to active triphosphate by cellular enzyme Excretion Kidney (14% unchanged) Faces (2%) Half life: - 2-3 hr Indication HSV 1 HSV 2 Varicella Zoster Others

ANTIVIRALS Acyclovir

Pencyclovir

Active form inhibits viral DNA polymerase which will impair viral replication

Within the infected cell, viral thymidine kinase adds a phosphate grp to the pencyclovir leading to activation then is acted on by human kinase to add two more PO4, producing the active form

Initial form: inactive Slectivity is due to: 1. Active triphosphat concentration: virally infected cells > uninfected cells 2. affinity to DNA polymerase: viral > human *negligible toxicity on normal cells

ECTOPARASITICIDES Lindane

MOA No MOA given

Absorption Distribution Metabolism Concentrated in fatty acid tissue after absorption(including the brain) Small amount absorbed systemically Hepatic via ester hydrolysis and converted to inactive metabolites

Excretion

Indication Pediculosis capitis Pediculosis pubis

Others Adverse effect: Neurotoxic Hematotoxic Banned in some countries Adverse reaction: Can also cause hypersensitivity

Permethrin

Crotamiton

Sulfur

Pyrethroid pediculocide and scabicide cause paralysis and death of pest by inhibiting sodium ion influx through nerve cell membrane channels delaying repolarisation Scabicide with some antipruritic activities MOA is UNKNOWN NO MOA given

Urine

Pediculosis Scabies

Scabies

Sacbies

Kakawati

CONSTITUENTS: Aformosin (isoflavan) - antitumor Medicarpin(pterocarpan) - antifungal Tannin - antidiarrheal, antidysenteric, antimutagenic, antioxidant, bactericidal, hepatoprotective, pesticidal and viricidal Formononetin (isoflavan) Gliricidin-6a Gliricidol-9a trihydroxyflavonone Dihydorxy methoxyisoflavin Methylsepiol

Anti-scabies Anit-pruritic Anti-pseudomonas Anti-bacterial(staph) Insecticidal nematicidal

Safe but has an unpleasant smell and stain clothes Safe for infants and pregnant women Gliricidia maculata Gliricidia sepium Madre cacao St. Vincents plum Parts used: Leaves Barn roots