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)

ANTIFUNGAL

Topical agents for Dermatophytic infxn

Whitfield’s 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

Whitfield’s ointment

12% Benzoic Acid

6% Salicylic Acid

ECTOPARASITICIDES

Lindane

Permethrin

Crotamiton

Sulfur

Kakawati

ANTIVIRALS

Acyclovir

Pencyclovir

ANTIBACTERIAL MOA Absorption Distribution Metabolism Excretion Indication Others

MUPIROCIN (pseudomonic acid)

Binds to ISOLEUCYL tRNA synthetase to inhibit CHON synthesis

Minimal systemic absorption through skin

95% protein bound

Liver: Converted to MONIC ACID

Renal Gram (+)

MRSA Used in Impetigo and eradication of nasal carriage S. aureus Pregnancy category B

BACITRACIN Inhibits the regeneration of phospholipid receptors involved in peptidoglycan synthesis Inhibits cell wall synthesis

For superficial infection Gram (+) :

Staph

Strep

Pneumococci

Most Anaerobic cocci

Diphtheria bacilli

Tetanus

Neisseria

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

POLYMYXIN B Increases cell wall permeability by interacting with phospholipid components of cell membrane

Not absorbed from GIT, mucous membrane in the tissues

Renal: 60% unchanged in urine

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

* constituent of triple antibiotic ointment

NEOMYCIN/ GENTAMICIN

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

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

* constituent of triple antibiotic ointment

ANTIFUNGAL MOA Absorption Distribution Metabolism Excretion Indication Others

Topical agents for Dermatophytic infxn

Whitfield’s ointment

Benzoic acid 6%

Salicylic acid 3%

keratolysis Tinea pedis Tinea cruris Tinea corporis (ringworm)

Azoles : Imidazole reduction of ergosterol synthesis by inhibition of fungal CYT P450

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

Ketoconazoles Broad spectrum but toxic and hence limited to topical use

Also used as systemic agents Poorly selective: Interferes with mammalian P450 Interferes with steroid hormone syhthesis and ph1 drug metabolism

Miconazole/ Tioconazole

Ihibits ergosterol biosythesis thus damaging fungal cell wall membrane and increases its permeability, allowing leakage of nutrients

Minimal Hepatic: Converted to inactive metabolites

Urine and feces

Vulvaginal candidiasis Tinea versicolor Oropharyngeal candidiasis Balanitis Pyityriasis versicolor

Only used as topical agents

Clotrimazole Broad spectrum Binds to phospholipids in the cell membrane altering cell wall permeability causing loss in essential intracellular elements

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

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

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

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

Milk of rats(topical)

Metabolised to at least 3 metabolites via oxidation of th phenyl and napthyl rings and N-dealkylation

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

Inactive against Candida spp or bacteria

Undecyclenic/ Undecanoic Acid

For athlete’s foot Jock itch Diaper rash Prickly heat, excessive sweating in groin area Itching, burning, chafing

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

Itraconazole broad spectrum Candida Cryptococcus Blastomycosin Coccidiodomycosis Histoplasmosis

More selective than ketoconazole

Fluconazole Same MOA Fungal meningitis ( by Cryptococcus)

Posaconazole Same MOA

Griseofulvin No description given

Terbinafine No description given

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 See above Ketoconazole, clostrimazole, miconazole

Selenium sulfide Cytostatic effect on cells epidermis and follicular epithelium

Tolnaftate

Zinc pyrithone Antiseborrheic May involved transcription factors

Currently withdrawn from the market

Undeyclenic acid see info above (actually walang MOA n binigay)

Whitfield’s ointment

12% Benzoic Acid

6% Salicylic Acid

Keratolysis

Note the concentration is different from whitfield’s 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

ANTIVIRALS MOA Absorption Distribution Metabolism Excretion Indication Others

Acyclovir Inhibits viral DNA syntehsis and replication by interfering with viral DNA polymerase

15-30% absrobed from GIT Slightly absorbed from the skin Absorbed from ophthalmic

CSF- 50% of plasma concentration Crosses placenta Enters breast milk- 3x higher than maternal serum 9-33% protein bound

Intracellular conversion to active triphosphate by cellular enzyme

Kidney (14% unchanged) Faces (2%) Half life:

- 2-3 hr

HSV 1 HSV 2 Varicella Zoster

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 MOA Absorption Distribution Metabolism Excretion Indication Others

Lindane No MOA given Concentrated in fatty acid tissue after absorption(including the brain)

Pediculosis capitis Pediculosis pubis

Adverse effect: Neurotoxic Hematotoxic Banned in some countries

Permethrin Pyrethroid pediculocide and scabicide cause paralysis and death of pest by inhibiting sodium ion influx through nerve cell membrane channels delaying repolarisation

Small amount absorbed systemically

Hepatic via ester hydrolysis and converted to inactive metabolites

Urine Pediculosis Scabies

Adverse reaction: Can also cause hypersensitivity

Crotamiton Scabicide with some antipruritic activities MOA is UNKNOWN

Scabies

Sulfur NO MOA given Sacbies Safe but has an unpleasant smell and stain clothes Safe for infants and pregnant women

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

Gliricidia maculata Gliricidia sepium Madre cacao St. Vincent’s plum Parts used: Leaves Barn roots