Subject: Pharmacology Topic: Dermatologic Pharmacology 2 Lecturer: Dra.

Dela Cruz Date of Lecture: 22/7/11 Transcriptionist: ior Editor: ior Pages: 8

Antiseptics / Disinfectants Antisepsis application of chemical agents that inhibit growth and multiplication of microorganisms in living tissues to prevent infection applied to the skin surface or mucous membrane generally static

Lower concentration is necessary for use as Antiseptics to avoid adverse effects e.g. 3%-6% H2O2 for cleansing wounds >30% H202 for use as bleaching and oxidizing agent ** Those with high concentrations are used as disinfectants to avoid adverse reaction Types of Antiseptics/Disinfectants 1. Alcohol (may either be): Ethyl alcohol Isopropyl alcohol

Disinfection application of chemical agents to inhibit the growth or kill microorganisms in inanimate objects usually stronger and too toxic to be used in living tissues generally cidal Sterilization Chemical or physical process that completely destroys or remove all types of microorganisms including spores and viruses with a low probability of survival General Uses: 1. Cleansing of skin and wound surfaces after injury 2. Preparation of skin surface prior to injection or surgical procedures 3. Routine disinfection of body cavities E.g. bladder, urethra, vagina 4. Treatment of mouth and throat infection 5. Surgical scrub 6. Hand sanitizers (usually contain antiseptic)

Spectrum of activity: Bacteria, mycobacteria, fungi and lipophilic viruses No activity against spores and hydrophilic viruses Not effective for sterilization

Mechanism of Action: cause cell membrane damage and rapid denaturation of proteins

Uses: Applied to the skin prior to injections For hard surface disinfection no residual action because they evaporate completely drying effect on the skin, may be alleviated by adding emollients or moisturizers to the formulation highly flammable 30-90% concentration for antimicrobial activity 70% is optimum concentration for antiseptic purposes at <50% concentration - used as preservative or in combination to enhance antimicrobial activity of other antiseptics

Most chemicals may be used as Antiseptics and Disinfectants

SY 2011-2012

o o Differences between Isopropyl and Ethyl Alcohol Isopropyl Alcohol Source and synthesis combination of water and propylene gas (petroleum) more effective vs bacteria oxidized to acetone Ethyl Alcohol

Greater sporicidal activity than Formaldehyde but less tuberculocidal Lethal action against spores and mycobacteria will require longer exposure

3. Iodine compounds May either be Tincture of Iodine or Povidone Iodine the later as the most popular and commonly used in the medical field aka Betadine. broadest spectrum among all topical antiinfectives cidal to all skin pathogens including spores far better tolerated does not interfere with wound healing leaves a depot of active iodine, creating a persistent effect up to 3% solution does not stain the skin inactivated by organic materials such as blood or sputum

fermentation of sugars and distillation

Antiseptic efficacy

more effective vs viruses metabolized readily to CO2 and H20 USP Ethanol can be taken internally more likely to induce rusting

Metabolism

Tincture of Iodine Other characteristics not given internally o o o Contains 2% Iodine and 2.4% Sodium Iodide in alcohol Most active Antiseptic for intact skin Not commonly used because of serious hypersensitivity reaction and stains clothing and dressing

greater lipophilic properties

Povidone-Iodine o 2. Aldehydes May either be a Formaldehyde or a Glutaraldehyde Used for disinfection or sterilization of instruments that cannot withstand exposure to high temperature or steam broad spectrum of antimicrobial action bactericidal, tuberculocidal, fungicidal, virucidal and sporicidal (it can cover all microorganisms and their spores) o o o An Iodophor complex of Iodine with a surface active agent Polyvinyl pyrrolidone (Povidone) Sporicidal with prolonged exposure Contains about 10% active Iodine require up to 2 minutes of contact time to release free iodine, which is the active chemical once released the free iodine has rapid killing action used as either Disinfectant or Antiseptic less irritating and less likely to produce hypersensitivity reaction than Tincture of Iodine Formulations and Uses: 2.5% Ophthalmic Solution prevent eye infection in the newborn, eye infection 7.5% Cleansing Solution Skin Cleanser (bubbles like a soap) 10% Antiseptic Solution Surgical scrub , wound care

o o o

Formaldehyde o o A monoaldehyde Used for high level disinfection of hemodialyzers, preparation of vaccines, preservation and embalmimg of tissues o

Glutaraldehyde o o A dialdehyde Alkalinized to pH 7.4-8.5 for activation

5% Cream/10% Ointment Wound care, burns 1% Oral Solution -for prophylaxis, during and after oral surgery; for regular oral hygiene; as a disinfectant soak for dentures and toothbrushes 7.5% Feminine wash regular female hygiene, during menstruation, postepisiotomy, postpartum vaginal wash

concentrations from 0.22.0% have moderate antimicrobial activity against gram-positive cocci, mycobateria and yeast not effective vs. gram-negative bacilli, especially P. aeruginosa bacteriostatic resistance can readily develop minimally affected by organic matter Safety concern dioxin, chloroform gas (triclosan is metabolized to dioxin and chloroform gas which are toxic to our environment)

4. Chlorhexedine gluconate Spectrum of activity: Active against bacteria including mycobacteria, moderate activity vs fungi and viruses Sporostatic (but spores of bacteria only) Strongly adsorbs to bacterial membranes causing leakage of small cytoplasmic proteins

(some examples of triclosan) 6. Hydrogen Peroxide broad spectrum of antimicrobial activity sporicidal activity will require higher concentration and longer contact time has the advantage of producing decomposition products that are not toxic or harmful to the environment antiseptic action of hydrogen peroxide is produced by the release of oxygen bubbling, effervescent action of oxygen affords a mechanical means for the removal of debris from a wound used as a 6% solution to clean and deodorize wounds and ulcers 1% or 3% solutions - used in household first aid for abrasion, laceration and dirty wounds not commonly recommended for typical wound care as the strong oxidation causes scar formation and increases healing time

Mechanism of action: Cause damage to the cell membrane followed by leakage of intracellular constituents Also cause precipitation of cytoplasmic proteins

Other Characteristics: Residual effect Safe even for use on newborn infants Inactivated by soap Usually available in 2-4% concentration Expensive slower in onset of action than alcohol but has longer duration of action bactericidal action equivalent to Alcohol if used repeatedly

Uses: Oral rinse Skin cleanser Preservative Feminine wash

7. Mercury containing compounds Merbromin (Mercuchrome) Thiomerosal (Merthiolate) one used in nail hygiene Organic form of mercury limited bacteriostatic activity poor tissue penetration and tissue fixation

5. Triclosan a colorless substance incorporated into soaps , feminine washes, toothpaste, deodorants, mouth washes useful as antibacterial and antifungal

Keratolytics Therapeutic Uses: Acne (0.5% - 2%) Warts, callus, corn Hyperkeratotic state xerosis, ichthyosis vulgaris, etc Tinea versicolor

Types of Keratolytics are: Salicylic acid (prototype of keratolytics) same with aspirin Benzoyl peroxide Propylene glycol Urea

Salicylic acid Mechanism of action: promote shedding of the keratinized epithelial cells on the surface of the skin preventing closure of the pilosebaceous orifice and formation of follicular plugs, and facilitating the flow of sebum used as keratolytic in 3%-6% conc. destructive to tissues in concentrations greater than 6% may be absorbed if given in large amounts for prolonged period

1.Retinol is taken up from the blood and bound to CRBP (cellular retinol-binding protein) in the cytoplasm. 2. The retinol dehydrogenase (RoDH) enzymes metabolize retinol to retinal, and then retinal is metabolized to RA by the retinaldehyde dehydrogenases (RALDHs). 3. RA is bound in the cytoplasm by CRABP (cellular RA-binding protein). 4. RA enters the nucleus and binds to the RA receptors (RARs) and the retinoid X receptors (RXRs) 5. Binding to a sequence of DNA known as the RARE (RA-response element). 6. Activation of transcription of the target gene. Anti Acne Agents Preparation: 1. First generation Retinoids Retinoic acid (Tretinoin) Isotretinoin

Retinoids 1. First Generation (for acne) Retinoic acid (Tretinoin) Isotretinoin

2. Adapalene 3. Azelaic acid 4. Antibacterials Benzoyl peroxide Clindamycin Erythromycin Tetracycline Metronidazole

2. Second generation (for psoriasis) Acitretin

3. Third Generation (for psoriasis) Tazarotene Bexarotene

(the items listed above are some of the components used in anti acne preparation) Etiopathogenisis of Acne plugging of follicles accumulation of sebum growth of Propionibacterium acnes inflammation

Mechanism of action: Activation of retinoid receptors: 1. Retinoic acid receptors (RARs) 2. Retinoid X receptors (RXRs) The cellular mechanism of retinoid action

Retinoid Therapy in Acne

corrects the altered pattern of follicular keratinization suppress sebaceous gland activity decrease P. acnes (implicated in nodular acne) anti-inflammatory

Retinoid Therapy in Acne (Isotretinoin) 13-cis-retinoic acid; Accutane is the brand name FDA-approved in 1982 for the treatment of severe recalcitrant nodular acne has been a life-altering medication this is used for BIG acnes sebum production is reduced by at least 90% through competitive inhibition of retinol dehydrogenase-4, the enzyme that mediates the skin's production of dihydrotestosterone and androstenedione

Adverse effects of Retinoids: 1. Skin and mucous membranes Cheilitis, dryness, epistaxis, blepharoconjunctivitis, erythematous eruptions and xerosis 2. Hyperlipidemia Increase triglycerides, total cholesterol and LDL cholesterol, decrease HDL cholesterol 3. Myalgia, arthralgia 4. Pseudotumor cerebri headache 5. Transient elevation of liver enzymes 6. Teratogenic Pregnancy is an absolute contraindication

Pharmacokinetics of Isotretinoin available in soft gel capsules and 0.5% cream and gel absorption from GIT is enhanced when administered with a high-fat meal 2x increase in peak plasma concentration following administration with a high-fat meal versus fasting conditions highly lipophilic more than 99.9% bound to plasma proteins, primarily albumin oral Isotretinoin remains the most effective treatment for acne reserved for severe cases that are unresponsive to conventional therapy due to: o potential for significant side effects o need for close monitoring during treatment

7. Skeletal side effects on long term therapy diffuse idiopathic skeletal hyperosteoses extraskelatal ossification premature epiphyseal closure in children

Topical Retinoid Therapy for Acne (Tretenoin) used as first-line therapy for most cases of mild to moderate inflammatory acne preferred agent for maintenance therapy has immunomodulatory properties and efficacy against the inflammatory component of acne useful in photodamaged human skin available in 0.01% to 0.1% concentrations as cream, gel and solution applied once daily at bedtime maximum response within one year avoid sun exposure poor systemic absorption topical application for acne treatment is unlikely to produce systemic drug levels and increase risk for congenital malformations applying the drug to more than 15% of the body surface area may produce detectable levels. Used to prevent wrinkles caused by sun damage

Teratogenic effects of Isotretinoin: occurs if drug is given during the first 3 weeks of gestation women with child bearing potential must be screened thoroughly Pregnancy test must be done 1 month prior to therapy and 1 month after completion of therapy Treatment is initiated at the beginning of a normal menstrual period after getting and informed consent and obtaining 2 negative pregnancy tests on the 2nd and 3rd day of the next menstrual period contraception is advised 1 month before, throughout and for 1-2 more menstrual cycle following discontinuation of treatment Patients are restricted to donate blood during treatment and 1 month after treatment 5

Baseline CBC, liver function tests, lipid profile must be done and repeated after 1 month; subsequent test would depend on initial results Teratogenic effects include CNS, cardiac, thymus and craniofacial abnormalities in some cases, these abnormalities have resulted in fetal death spontaneous abortion occurs in 1/3 of patients

first retinoid indicated for topical treatment of psoriasis anti-inflammatory and anti-proliferative effect percutaneous absorption occur teratogenic concentrations if applied to more than 20% of total body surface area may produce photosensitivity other adverse effects: 1. sensory irritation burning or stinging sensation 2. erythema 3. peeling 4. irritant dermatitislg

Sunscreens and Sunblocks block the penetration of ultraviolet radiations through the epidermis by acting as filters that absorb and reflect high energy UV radiation helps prevent skin damage, wrinkles and reduces the risk for developing skin cancer greatest sun damage occurs between 10 AM to 3 PM

Benefits of Isotretinoin in Acne: Lasting response in a disfiguring disease Short duration of treatment Long-term improvement in self-esteem and function

Distinction: Sunscreens (Chemical sunscreens) work by absorbing the energy of UV radiation before it affects the skin Sunblocks (Physical sunscreens) reflect or scatter UV radiation before it reaches the skin

Anti-Psoriasis Preparations Second and Third Generation Retinoids 1. Systemic Acitretin

2. Topical Sunblocks Tazarotene Calcipotriene provide broad spectrum UVA and UVB protection and are gentle enough for everyday use not chemicals so especially useful for individuals with sensitive skin, as they rarely cause skin irritation

Acitretin a metabolite of the retinoid Etretinate effective for pustular and erythrodermic forms of psoriasis improvement occurs in 3-6 months teratogenic adverse effects resemble hypervitaminosis A produce elevation of cholesterol and triglycerides and liver enzymes

Sunscreens composed of several active ingredients to block the entire UV spectrum most chemicals only block a narrow region of the UV spectrum (usually the UVB region) combining several chemicals, with each one blocking a different region of UV light to provide broad spectrum protection

Tazarotene hydrolyzed to an active metabolite Tazarotenic acid which bind to the retinoid receptor

SPF (sun protection factor):

refers to the strength of protection and the length of time a sun-screening product will allow your skin to be in the sun without burning, given that the average person can remain in the sun for 10 minutes only without burning. provides valuable information regarding UVB protection but not UVA no standard measurement for UVA protection indicates how long a sunscreen remains effective on the skin can determine how long the sunblock will be effective by multiplying the SPF factor by the length of time it takes for a person to suffer a burn without sunscreen. E.g. o Given: a person normally develops sunburn in 10 minutes without wearing a sunscreen A sunscreen with an SPF of 15 will protect that person from having sunburn for 150 minutes 10 x SPF 15 = 150 minutes a sunscreen with SPF 15 will absorb more than 92% of incident UVB radiation a sunscreen with SPF 30 may absorb 96.7% and an SPF 40 may absorb 97.5% UVB the higher the SPF, the greater the protection from sunburn caused mostly by UVB

Paraaminobenzoic acid potent absorber of UVB but not UVA no longer use because of higher risk for contact and photocontact sensitvity reactions Octyl dimethyl paraaminobenzoic acid now commonly used Oldest type of sunscreen used

Salicylates first cosmetic sunscreen used in the US have been used as a standard for determining protection factors because of their safety profile Octyl salicylate major salicylate component of sunscreens

Components of Nivea Sunscreen Octyl methoxycinnamate 8.0% w/w (UVB) Titanium dioxide 5.0% w/w (UVA/UVB) Octyl triazone 4.0% w/w (UVB) Butyl methoxydibenzoylmethane 3.0% w/w (UVA) Phenylbenzimidazole sulfonic acid 2.0% w/w (UVB)

Recommendations to Protect Skin from Overexposure to the Sun and Minimize Skin Damage: Use of a "broad spectrum" sunblock SPF of at least 30 that is applied daily to all sun exposed areas, then reapplied every two hours Wear sun protective clothing Avoid sun exposure from 10 a.m. to 3 p.m.

Components of Coppertone Sunscreen Avobenzone 2% (UVA) Homosalate 13% (UVB) Octisalate 5% (UVB) Octocrylene 2% (UVB) Oxybenzone 4% (UVA/UVB)

Avobenzone Parsol 1789 (4-tert-butyl-4-methoxydibenzoylmethane) most common dibenzolmethane found in sunscreen products in the USA also function as preservatives protect against sunlight induced discoloration of cosmetic products one of the most common cause of photocontact allergy

Skin Whitening or Bleaching Agents: 1. Hydroquinone acts by inhibition of enzyme tyrosinase to interfere with synthesis of melanin reduce hyper pigmentation of the skin with resultant temporary lightening

Depigmentation of the skin is reversible

2. Monobenzones monobenzyl ether of Hydroquinone causes irreversible depigmentation of the skin toxic to melanocytes may cause local irritation

a specific Type II 5-alpha reductase inhibitor to suppress both serum and scalp dihydrotestorone this enzyme is responsible for conversion of testosterone to dihydrotestosterone Two Types of 5-alpha reductase: 1. Type I found in sebaceous glands 2. Type II found in hair follicles

Trichogenic: Minoxidil first developed as an antihypertensive was found to be associated with hypertrichosis developed into a topical formulation enhances follicular size, resulting in thicker hair shafts and stimulates and prolongs the anagen phase of the hair cycle may produce allergic and irritant contact dermatitis

approved for use only in males because it can lead to masculinizing effect in females

Response to Treatment: 1. Increase hair counts in both the vertex and frontal scalp 2. Increase hair growth in 80% of males over a 2 year period 3. Increase hair growth in 3 months of therapy Adverse Effects: 1. Decrease libido 2. Erectile dysfunction 3. Ejaculation disorder with decrease volume of ejaculate

Finasteride

-----------------------------------------------------end of transcription-------------------------------------------------------------------TABLE OF ACTIVE INGRIDIENTS OF SUNBLOCKS (take note of the asterisk as well as those that can block both uv-a and uv-b Active Ingredient Aminobenzoic acid Avobenzone Cinoxate Homosalate Menthyl anthranilate Octocrylene Octyl methoxycinnamate Octisalate Oxybenzone Phenylbenzimidazole sulfonic acid Sulisobenzone Titanium dioxide* Trolamine salicylate Zinc oxide* Type of UV radiation blocked UV-B UV-A UV-B UV-B UV-A UV-B UV-B UV-B UV-B, UV-A UV-B UV-B, UV-A UV-A/B, broad spectrum UV-B UV-A/B, broad spectrum

I have loved you with an everlasting love: therefore I have continued my faithfulness to you. Jeremiah 31:3