PPM2 Dermatologic Agents

Required Reading:

Note:  Brenner does not have a chapter on dermatologic medications.  Therefore, you will need to search elsewhere for reading to match the learning objectives.  Your best resource is Katzung, BG, Basic & Clinical Pharmacology, either the 7^th or 8^th edition.  The learning objectives are set up to follow Katzung.  Some, but not all, of the information can also be found in Current.

Katzung          Chp. 62:  “Dermatologic Pharmacology”

CMDT 2003    Chp. 6: “Skin, Hair, & Nails,” pp. 80-86.

Objectives:

1.         List typical dermatologic vehicles, and identify which are better used as drying preparations versus lubricating preparations.  Describe the general indications for choosing a drying vehicle versus a lubricating vehicle.

Brent Katzung 7^th ed. 999

Appropriate vehicles maximize the ability of the drug to penetrate the outer layers of the skin.  Depending upon the vehicle, dermatologic preparations include tinctures, wet dressings, lotions, gels, aerosols, powders, pastes, creams, and ointments.  This list is organized by those vehicles which are less likely to retard evaporation (tinctures) to those that are most likely (ointments)

Generally acute inflammation with oozing, vesiculation, and crusting is best treated with drying preparations (eg, tinctures, wet dressings, lotions), while chronic inflammation with xerosis, scaling, and lichenification is best treated with lubricating preps (eg, creams, ointments).  

Tinctures, lotions, gels, and aerosols are good for the scalp and hairy areas.

Jam, Katzung 7^th ed      999

•     drying agents: tinctures, wet dressings, & lotions. Used in acute inflammation with oozing, vesiculation, & crusting.

•     Lubricating agents: creams, & ointments. Used in chronic inglammation with xerosis, scaling, & lichenification.

•     Other vehicles: gels, aerosols, powders, pastes.      

Anonymous

Generalized indications: First of all, medications are incorporated into a vehicle that facilitates cutaneous application.

• solubility of active agent in vehicle

• rate of release of agent

• ability of vehicle to hydrate stratum corneum (enhancing penetration)

• stability of the therapeutic agent in vehicle

• interactions: chemical and physical of vehicle

• traditionally considered inert - many therapeutically beneficial themselves

Drying versus lubricating vehicles:

• Tincture (drying) - convenient for hair and scalp. used in acute inflammation with oozing vesiculation and crusting.

• Wet dressing (drying) - convenient for hair and scalp. used in acute inflammation with oozing vesiculation and crusting.

• Lotion (drying) - convenient for hair and scalp. used in acute inflammation with oozing vesiculation and crusting.

• Gel  -  convenient for hair and scalp

• Aerosol  -  convenient for hair and scalp

• Powders  -  

• Pastes  -  

• Creams  -  Emulsified vanishing creams can be used in intertriginous areas without causing maceration. Chronic inflammation w/xerosis, scaling, lichenification.

• Ointments  -  greater retarding of evaporation. Chronic inflammation w/xerosis, scaling, lichenification

*The ability of the above agents to retard evaporation from the skin surfaces runs in order - with tincture being least and ointments having the greatest effect.

*Emulsifying agents can cause irritation. Substituting different preparations or using a lower concentration may help.

Anonymous  

Generalized indications: First of all, medications are incorporated into a vehicle that facilitates cutaneous application.

*  solubility of active agent in vehicle

*  rate of release of agent

*  ability of vehicle to hydrate stratum corneum (enhancing penetration)

*  stability of the therapeutic agent in vehicle

*   interactions: chemical and physical of vehicle

*  traditionally considered inert - many therapeutically beneficial themselves

Drying versus lubricating vehicles:

Tincture (drying) - convenient for hair and scalp. used in acute inflammation with oozing vesiculation and crusting.

Wet dressing (drying) - convenient for hair and scalp. used in acute inflammation with oozing vesiculation and crusting.

Lotion (drying) - convenient for hair and scalp. used in acute inflammation with oozing vesiculation and crusting.

Gel  -  convenient for hair and scalp

Aerosol  -  convenient for hair and scalp

Powders  -  

Pastes  -  

Creams  -  Emulsified vanishing creams can be used in intertriginous areas without causing maceration. Chronic inflammation w/xerosis, scaling, lichenification.

Ointments  -  greater retarding of evaporation. Chronic inflammation w/xerosis, scaling, lichenification

*The ability of the above agents to retard evaporation from the skin surfaces runs in order - with tincture being least and ointments having the greatest effect.

*Emulsifying agents can cause irritation. Substituting different preparations or using a lower concentration may help.

Anonymous Katzung pg 999

Typical dermatologic vehicles- tinctures, wet dressings, lotions, gels, aerosols, powders, pastes, creams and ointments.

Acute inflammation with oozing, vesiculation, and crusting is best treated with drying preparations such as tinctures, wet dressings, and lotions.

Chronic inflammation with xerosis (dry skin), scaling and lichenification is best treated with more lubricating preparations such as creams and ointments.

2.         List indications for the use of topical antibacterial agents.  (representative OTC drugs:  bacitracin, polymyxin B, neomycin)

Brent Katzung 7^th ed. 1000-01

Indications for topical antibacterial agents:

-preventing infections in clean wounds

-in the early treatment of infected dermatoses and wounds

-reducing colonization of the nares by staphylococci

-axillary deodorization

-management of acne vulgaris

jam, Katzung 7^th ed      1000 Preventing infections in clean wounds, early tx of infected dermatoses & wounds, in reducing colonization of nares by staph (bacitracin), in axillary deodorization, & in management of acne

•     bacitracin - works on gram+ like strep, staph & anaerobic cocci, neisseria, tetanus bacilli, diptheria bacilli

•     polymyxin B - works on gram- like P. aeruginosa, E. coli, Enterobacter, Klebsiella

•     neomycin - aminoglycoside effective against gram- like E. coli, Kleb, Enterobacter

Anonymous Noble, p. 756

Acne and minor bacterial skin problems. Bactroban can be used for gram + cocci.

Anonymous  

Acne and minor bacterial skin problems. Bactroban can be used for gram + cocci. Noble, p. 756

Anonymous Katzung pg 1000

Topical antibacterial agents may be useful in preventing infections in clean wounds, in the early treatment of infected dermatoses and wounds, in reducing colonization of the nares by staphylococci, in axillary deodorization, and in the management of acne vulgaris.

Bacitracin: a peptide antibiotic active against gram-positive organisms such as streptococci, pneumococci, and staphylococci.  In addition, most anaerobic cocci, neisseriae, tetanus bacilli, and diphtheria bacilli are sensitive.

Polymyxin B, Neomycin: Bacitracin is compounded in an ointment base alone or in combination with neomycin, ploymyxin B, or both.

3.         Identify mupirocin as a prescription, topical antibacterial used in the treatment of impetigo.

Brent Katzung 7^th ed. 1000

Mupirocin is structurally unrelated to other currently available topical antibacterials.  Most gram + aerobic bacteria, including MRSA, are sensitive to mupirocin.  It is also effective in the Tx of impetigo caused by S aureus and group A beta-hemolytic strep.

Jam, Katzung 7^th ed      1000 effective against impetigo caused by S. aureus, including MRSA, & grp A beta-hemolytic strep; a.k.a. pseudomonoc acid A

Anonymous Brenner 425

Mupirocin (Bactroban) is a bacterial protein synthesis inhibitor that is used as a topical antibacterial agent against staph and strep., which are the most common causes of impetigo.

Anonymous  

Mupirocin ( Bactroban) is a bacterial protein synthesis inhibitor that is used as a topical antibacterial agent against staph and strep., which are the most common causes of impetigo. Brenner 425

Anonymous Katzung pg 1000

Most gram-positive aerobic bacteria, including methicillin-resistant S aureus, are sensitive to mupirocin.  It is effective in the treatment of impetigo caused by S aureus and group A beta-hemolytic streptococci.

4.         List topical agents used in the treatment of mild to moderate acne vulgaris.   (representative drugs:  benzoyl peroxide, clindamycin, erythromycin, tetracycline)  (Note:  Katzung does not cover the use of systemic antibiotics or oral contraceptives for acne vulgaris.  These may be discussed in class.)

Brent Katzung 7^th ed. 1001,1007

The effectiveness of topical therapy is less than that achieved by systemic therapy, but topical therapy is generally suitable in mild-moderate cases of acne.

Clindamycin, erythromycin, tetracycline, and benzoyle peroxide all have an inhibitory action, in some way or another, against Propionibacterium (Corynebacterium) acnes.

jam, Katzung 7^th ed      1001 text lists metronidazole for acne rosacea.

•     Erythromycin- may develop resistance; also available as a fixed combination prep with benzoyl peroxide called Benzamycin

•     clindamycin - 10% applied dose is absorbed; rarely causes pseudomembranous colitis; water-based gel causes less drying or stinging

•     tetracycline - available in 2 forms, Topicycline & Meclan; may temporarily stain skin yellow; contraindicated in pregnancy, hx of significant renal or hepatic dysfunction

•     1007 benzoyl peroxide - <5% applied dose is absorbed from skin; has peeling & comedolytic effect

Anonymous See Table 83-4 in Noble, pp. 756 for more info.

• Benzoyl peroxide 5% and Erythromycin 3%: brand name Benzamycin gel

• Clindamycin phosphate 1% (noted for acne vulgaris, not  rosacea): Cleocin-T soln., gel

• Tetracycline HCl: Achromycin ointment, Topicycline alcohol soln.

Anonymous  

See Table 83-4 in Noble, pp. 756 for more info.  This brief info from there, possibly more from class.

Benzoyl peroxide 5% and Erythromycin 3%: brand name Benzamycin gel

Clindamycin phosphate 1% (noted for acne vulgaris, not a. rosacea): Cleocin-T soln., gel

Tetracycline HCl: Achromycin ointment, Topicycline alcohol soln.

Anonymous

Topical antibiotics including erythromycin and clindamycin are effective in decreasing the P. acnes skin population.  These preparations in solution, lotion, and gel are used bid, often in conjunction with comedolytics or benzoyl peroxide (a potent bactericidal agent).  Topical antibiotics are not quite as effective as systemic antibiotics, but they do alleviate the many side effects of oral antibiotics. Noble pg759-60

Tetracycline- Two topical TCN antibiotics are currently available for treatment of acne vulgaris:

1. TCN hydrochloride in hydroalcoholic base containing n-decyl methyl sulfoxide (Topicycline)

2. Miclocycline sulfosalicylate in a cream base (Meclan). Katzung pg 1001

Systemic antibiotics: Tetracycline and erythromycin are effective in controlling mild to moderate popular or nodular inflammatory acne.  TCN 500mg bid or E-mycin 500mg bid is commonly used. GI upset is common with both drugs, and TCN must be taken on an empty stomach. Noble pg759-60

OBC: Ortho Tri-Cyclen has been approved for the treatment of acne in women.  However, hormone treatment introduces another dimension of possible side effects, plus the risk for a flare on introduction and a possible rebound flare on discontinuation.  The possible interaction between oral antibiotics and oral contraceptives and the need for additional forms of birth control should be discussed with patients. Goroll pg. 1029

5.         Describe the use and most common adverse effects of topical retinoic acid in acne vulgaris.

Brent Katzung 7^th ed. 1006

Retinoic acid (Accutane) is the acid form of Vit A and is currently reserved for the treatment of severe cystic acne.  Common side effects resemble hypervitaminosis A and  include dryness and itching of the skin and mucous membranes.  Birth defects are a significant risk; therefore, women of childbearing age must use effective contraception 1 month prior to initiating therapy, throughout therapy, and for one or more menstrual cycles following discontinuation of Tx.  A serum pregnancy test must be obtained 2wks before starting Tx.  

Less common side effects are HA’s, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, and muscle and joint pains.  Lipid abnormalities are frequent.  Also, premature closure of epiphyses have been noted in children.

Jam, Katzung 7^th ed      1006-7

remains chiefly in epidermis, with <10% systemic absorption. Applied to dry skin only, initially in a concentration sufficient to induce slight erythema with mild peeling; avoid corners of nose, mouth, eyes, mucous membranes. Adverse effects: erythema & dryness in 1st few weeks most common

Anonymous

• The Use: The action in acne has been attributed to decreased cohesion between epidermal cells and increased epidermal cell turnover. i.e. in the expulsion of open comedones and the transformation of close comedones into open ones.

• Adverse effects: The most common adverse effects are the erythema and dryness that occur in the first few weeks of use. Also, may increase the tumorigenic potential of ultraviolet radiation.

Anonymous  Katzung Ch. 62

The Use: The action in acne has been attributed to decreased cohesion between epidermal cells and increased epidermal cell turnover. i.e. in the expulsion of open comedones and the transformation of close comedones into open ones.

Adverse effects: The most common adverse effects are the erythema and dryness that occur in the first few weeks of use. Also, may increase the tumorigenic potential of ultraviolet radiation.

Anonymous Goroll pg. 1028

Retinoic acid (Avita, Retin-A, Retin-A Micro) is the main comedolytic agent currently available.  Retinoids normalize desquamation of the follicular epithelium, promote drainage of existing comedones, and prevent the formation of new comedones.  Irritation is the primary adverse reaction.  Frequency of application can be adjusted to produce minimal desquamation.

6.         Describe the indications, common adverse effects, and teratogenicity of isotretinoin in acne vulgaris.

Greg  Katzung Basic and Clinical Pharmacology, Ch. 62 “Acne Preps” sectiononline UW library.  Sorry this one doesn’t give page numbers.

Indication:

Isotretinoin (Accutane) is a synthetic retinoid currently restricted to the treatment of severe cystic acne that is recalcitrant to standard therapies. The precise mechanism of action of isotretinoin in cystic acne is not known, although it appears to act by inhibiting sebaceous gland size and function. The drug is well absorbed, extensively bound to plasma albumin, and has an elimination half-life of 10-20 hours.
Most cystic acne patients respond to 1-2 mg/kg, given in two divided doses daily for 4-5 months. If severe cystic acne persists following this initial treatment, after a period of 2 months, a second course of therapy may be initiated.

Common adverse effects:

Common adverse effects resemble hypervitaminosis A and include dryness and itching of the skin and mucous membranes. Less common side effects are headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, and muscle and joint pains. These effects are all reversible on discontinuance of therapy. Skeletal hyperostosis has been observed in patients receiving isotretinoin with premature closure of epiphyses noted in children treated with this medication. Lipid abnormalities (triglycerides, HDL) are frequent; their clinical relevance is unknown at present.
Teratogenicity:
Teratogenicity is a significant risk in patients taking isotretinoin; therefore, women of childbearing potential must use an effective form of contraception for at least 1 month before, throughout isotretinoin therapy, and for one or more menstrual cycles following discontinuance of treatment. A serum pregnancy test must be obtained within 2 weeks before starting therapy in these patients, and therapy should be initiated only on the second or third day of the next normal menstrual period.

Paul, Did not find in Katzung

Sung

Very teratogenic. Special labels required on prescriptions. And female patients are required to go on birth control pills, too. It is that serious.

Anonymous  Noble 760  Katzung 1007

•        Isotretinoin (Acutane) is a useful therapy in severe nodular acne that is unresponsive to other treatment regimens.  

•        Common side effects include: dryness and itching of the skin and mucous membranes, cheilitis.  Less common side effects include: headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, epistaxis, eye irritation, myalgias and bony hyperkeratosis.  Dose related increases in triglycerides, and night blindness are seen.

•        This drug is a potent teratogen (extremely high risk of congenital anomalies) and is contraindicated in pregnancy.  Effective form of contraception must be used one month prior to taking medication, throughout isotretinoin therapy, and for one ore more menstrual cycles following treatment.  A serum pregnancy test must be obtained within 2 weeks before starting therapy, and therapy should be initiated only on the second or third day of the next normal menstrual period.

•        While on this drug, a patient’s CBC, LFT”s, and lipids are monitored as well as checking for pregnancy in females.

Anonymous   Goroll, pg. 913.

13-cis-Retinoic acid (isotretinoin, Accutane) is a powerful systemic agent for the tx of nodulocystic inflammatory acne. One or two 15-20-week courses often bring severe acne under complete control, with little, or no further therapy. However, it is also a potent teratogen.  The guidelines of Care for Acne Vulgaris published by the American Academy of Dermatology clearly state that this should not be therapy of first choice and that it must be demonstrated that the pt is unresponsive to other standard therapies.  In the tx of women of childbearing potential, it should be used only in pts with severe, disfiguring, cystic acne. Printed guidelines are provided by the manufacturer with a detailed informed consent protocol.  She must use effective contraception, including abstinence, for at least 1 month before starting the therapy and must have a negative blood test for pregnancy 2 weeks before initiating therapy.  After the negative pregnancy test, the pt should be instructed to initiate therapy during the second or third day of the next menstrual period.  She should be seen monthly thereafter and have a recommended monthly pregnancy test. Contraceptive use must continue for at least 1 month after completion of therapy, and a blood pregnancy test should be done 1 month after completion of therapy. Other side effects include hypertriglyceridemia, pseudotumor cerebri, idiopathic skeletal hyperostosis, cheilitis, nasal mucosal dryness, nosebleeds, conjunctivitis, skin fragility, arthralgia, HA and transaminase elevations, most of these are reversible.

Anonymous Katzung pg 1007

Indications: Restricted to the treatment of severe cystic acne that is unresponsive to standard therapies.

Adverse Effects: common adverse effects resemble hypervitaminosis A and include dryness and itching of the skin and mucous membranes.  Less common side effects are headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, and muscle and joint pains.  These effects are all reversible on discontinuance of therapy.  Lipid abnormalities are frequent; their clinical relevance is unknown at present.

Teratogenicity is a significant risk in patients taking Accutane; therefore, women of childbearing potential must use an effective form of contraception for at least 1 mo. before, throughout therapy, and for one or more menstrual cycles following discontinuance of treatment.  A serum pregnancy test must be obtained within 2 weeks before starting therapy in these patients, and therapy should be initiated only on the second or third day of the next normal menstrual period.

7.         Recognize the following as topical antifungal agents, and distinguish whether they are effective against superficial Candida infections, dermatophyte infections, or both:  azole derivatives (representative drugs: miconazole, clotrimazole), terbinafine added 2004, tolnaftate replaced 2004, nystatin.

Zen Seeker  Brenner 442

*terbinafine has fungistatic activity against Candida but are not approved for he treatment of candidiasis.

Miconazole not in Brenner

Greg  Katzung Basic and Clinical Pharmacology, Ch. 62 online UW library. “Anti-fungal Agents”.  

Note that these four drugs are all for this graph are topical antifungal agents.

Paul, Katzung pg 1047

Drug                             superficial Candida                  dermatophyte infections

Miconazole                             yes                                           yes

Clotrimazole                           yes                                           yes

Tolnaftate                               no                                            yes

Nystatin                                  yes                                           no

Anonymous Brenner 442Noble 757

Anonymous  Brenner, p.442

miconazole - Vaginal candidiasis, severe systemic fungal infections

clotrimazole - candida, dermatophyte infections of the skin

Tolnaftate (Tinactin) - dermatophyte infections (tinea pedis, tinea unguium, tinea capitis, tinea corporis, tinea cruris, tinea versicolor)

Nystatin - intestinal candida or thrush (oral candida)

Anonymous Katzung pg 1002

Axole Derivatives: have a wide range of activity against both dermatophytes and yeasts, including Candida albicans and Pityrosporum orbiculare, the cause of tinea versicolor

1. Miconazole- (Monistat, Micatin) is available for topical application as a cream or lotion and as vaginal cream or suppositories for use in vulvovaginal candidasis

2. Clotrimazole- (Lotrimin, Mycelex) is available for tpical application to the skin as a cream or lotions and as vaginal cream and tablets for use in vulvovaginal candidiasis.

Tolnaftate: is a synthetic antifungal compound that is effective topically against dermatophyte infections caused by Epidermophyton, Microsporum, and Trichophyton.  It is also active against P orbiculare but NOT against Candida.

Nystatin: is useful in the topical therapy of Candida albicans infections but ineffective against dermatophytes.  Nystatin is limited to topical treatment of cutaneous and mucosal Candida infections because of its narrow aspectrum and negligibile absorption from the GI tract following oral administration.

8.         Describe the indications for use and adverse effects of oral griseofulvin.

Greg  Katzung Basic and Clinical Pharmacology, Ch. 62 online UW library. “Anti-fungal Agents”.  

Indications:

-Griseofulvin is effective orally against dermatophyte infections caused by epidermophyton, microsporum, and trichophyton. It is ineffective against candida and P orbiculare.

-It is most effective in treating tinea infections of the scalp and glabrous (nonhairy) skin.

Adverse Effects:

Headaches, nausea, vomiting, diarrhea, photosensitivity, peripheral neuritis, and occasionally mental confusion. Cross-sensitivity with penicillin may occur. It is contraindicated in patients with porphyria or hepatic failure or those who have had hypersensitivity reactions to it in the past. Safety in pregnant patients has not been established. Leukopenia and proteinuria have occasionally been reported. Therefore, in patients undergoing prolonged therapy, routine evaluation of the hepatic, renal, and hematopoietic systems is advisable. Coumarin anticoagulant activity may be altered by griseofulvin, and anticoagulant dosage may require adjustment.

Paul, Katzung pg 1049-1050

Indications:  effective orally against dermatophyte infections caused by epidermophyton, microsporum, and trichophyton.  Most effective in treating tinea infections of the scalp and glabrous (nonhairy) skin.  Dermatophyte infections of the nails respond only to prolonged administration.  Fingernails may respond to 6 months of therapy, whereas toenails may require 8-18 months of therapy

Adverse effects:  Headache, nausea, vomiting, diarrhea, photosensitivity, peripheral neuritis, and occasionally mental confusion.  Derived from penicillin mold, and cross-sensitivity may occur.  Contraindicated in patients with porphyria or hepatic failure.  Leukopenia and proteinuria have occasionally been reported.  Coumarin anticoagulant activity may be altered by griseofulvin.

Anonymous Brenner 446

Griseofulvin is derived from penicillium griseofulvum.  It is fungistatic against numerous dermatophytes including E. flocosum, Microsporum audouinii, M. canis, M. gypseum, T. rubrum, T. tonsurans, and trichohyton verrucosum, but it is not active against candida

The adverse effects of this drug are: dizziness, headache, insomnia, GI bleeding, hepatitis, skin rash or leukopenia).

Anonymous  

Indications- main use is in treatment of tinea capitis in children. Noble, p. 757

Adverse Effects- Abdominal pain, erythema multiforme, headache, mixed drug reactions, nausea and vomiting, photosensitivity, urticaria. Habif: Clinical Dermatology, 3rd ed p. 389

Anonymous Katzung pg 1003

Indications:

Griseofulvin is effective orally against dermatophyte infections cause by Epidermophyton, Microsporum, and Trichophyton and ineffective against yeasts. Griseofulvin is active only against growing cells. It is most effective in treating tinea infections of the scalp and glabrous (nonhairy) skin. Dermatophyte infections of the nails respond only to prolonged administration of griseofulvin (fingernails= 6 mo of therapy, toenails=8-18 mo of therapy)

Adverse Effects:

Headache, n/v, diarrhea, photosensitivity, peripheral neuritis, and occasionally mental confusion may occur.  Griseofulvin is derived from a PCN mold, and cross-sensitivity with PCN may occur. It is contraindicated in patients with porphyria or hepatic failure or those who have had hypersensitivity reactions to it in the past.  Routine evaluation of the hepatic, renal, and hematopoietic systems is advisable in long term therapy. Coumadin anticoagulant activity may be altered by griseofulvin, and anticoagulant dosage may require adjustment.

9.         Describe the indications for use, adverse effects, and contraindications of oral azole derivatives.  (representative drugs: ketoconazole dropped 2004, fluconazole)  

Greg  Katzung Basic and Clinical Pharmacology, Ch. 62 online UW library. “Anti-fungal Agents”.  Sorry guys, this material wasn’t laid out very well, hopefully lecture will clear things up a bit.

Azole derivatives currently available for oral treatment of systemic mycosis (fungal dz) include fluconazole (Diflucan) and ketoconazole (Nizoral). Imidazole derivatives act by affecting the permeability of the cell membrane of sensitive cells through alterations of the biosynthesis of lipids, especially sterols, in the fungal cell.

Indications:
Ketoconazole was the first imidazole derivative used for oral treatment of systemic mycoses. Patients with chronic mucocutaneous candidiasis respond well to a once-daily dose of 200 mg of ketoconazole, with a median clearing time of 16 weeks. Most patients require long-term maintenance therapy. Variable results have been reported in treatment of chromomycosis.
Ketoconazole has been shown to be quite effective in the therapy of cutaneous infections caused by epidermophyton, microsporum, and trichophyton species. Infections of the glabrous skin often respond within 2-3 weeks to a once-daily oral dose of 200 mg. Palmar-plantar skin is slower to respond, often taking 4-6 weeks at a dosage of 200 mg twice daily. Infections of the hair and nails may take even longer before resolving with low cure rates noted for tinea capitis. Tinea versicolor is very responsive to short courses of a once-daily dose of 200 mg.
Adverse Effects:
Nausea or pruritus has been noted in approximately 3% of patients taking ketoconazole. More significant side effects include gynecomastia, elevations of hepatic enzyme levels, and hepatitis. Caution is advised when using ketoconazole in patients with a history of hepatitis. Routine evaluation of hepatic function is advisable for patients on prolonged therapy.
Indications:
Fluconazole is well absorbed following oral administration, with a plasma half-life of 30 hours. In view of this long half-life, daily doses of 100 mg are sufficient to treat mucocutaneous candidiasis; alternate-day doses are sufficient for dermatophyte infections.

Contraindictions:
Administration of oral azoles with terfenadine, astemizole, or cisapride may increase the plasma concentration of the latter drugs by inhibiting their metabolism. This may result in severe cardiac dysrhythmias, including ventricular tachycardia and death. Administration of oral azoles with midazolam or triazolam has resulted in elevated plasma concentrations and may potentiate and prolong hypnotic and sedative effects of these agents. Therefore, administration of the oral azoles with terfenadine, astemizole, cisapride, midazolam, or triazolam is absolutely contraindicated.

Paul, Katzung pg 1050

Indications:  Ketoconazole: systemic mycosis, chronic mucocutaneous candidiasis responds to 200 mg QD with a median clearing of 16 weeks,  cutaneous infections caused by epidermophyton, microsporum, and trichophyton species.  Infections of the glabrous skin often respond within 2-3 weeks to a QD oral dose of 200 mg.  Palmar-plantar skin is slower to respond, often taking 4-6 weeks of 200 mg BID.  Infections of the hair and anils mayt ake even longer before resolving with low cure rates natoed for tinea capitis.  Tinea versicolor is very responsive to short courses of a QD dose of 200 mg.  Fluconazole: Due to long plasma half-life, treat mucocutaneous dandidiasis with 100 mg QD and dermatophyte infections with alternate day doses.

Adverse effects:  Ketoconazole: nausea or pruritus noted in approximately 3% with more significant side effects of gynecomastia, elevations of hepatic enzyme levels, and hepatitis.  Caution advised in use with known hepatitis history.  Routine evaluation of hepatic function is advisable for patients on prolonged therapy.

Contraindications:  Administration or oral azoles with terfenadine, astemizole, or cisparide may increase the plasma concentration of the latter drugs by inhibiting their metabolism which may result in severe cardiac dysrrhythmias (V-tach and death).  Administration of oral azoles with midazolam or triazolam may result in elevated plasma concentrations and may potentiate and prolong hypnotic and sedative effects of these agents.  Therefore, administration of the oral azoles with terfenadine, astemizole, cisapride, midazolam, or triazolam is absolutely contraindicated.

Anonymous Brenner 446

Anonymous   Katzung, pg 937

Indications are for systemic mycoses or cutaneous infections caused by Epidermphyton, Microsporum and Trichophyton species (glabrous skin, palmar-pantar skin, onchomycosis, tinea versicolor).  Adverse effects include nausea, puritus, gynecomastia, elevtions of hepatic enzyme levels and hepatitis.  Coadministration with either terfenadine or astemizole is absolutely contraindicated as plasma concentrations of both can rise causing cardiac dysrhythimias, particularly v-tach.

Anonymous Katzung pg 1004

Ketoconazole:

Indications- was the first to be used for the oral treatment of systemic mycoses. Has also been shown to be quite effective in the therapy of cutaneous infections caused by Epidermophyton, Microsporum, and Trichophyton species.

Adverse Effects- Nausea or pruritis has been noted in approximately 3% of patients. More significant side effects include gynecomastia, elevations of hepatic enzyme levels, and hepatitis.

Fluconazole:

Indications- systemic mycoses

Adverse Effects- nausea, H/A, vomiting, rash, diarrhea, dyspepsia, dizziness, hepatotoxicity

Coadministration of the oral azoles with terfenadine, astemizole, cisapride, midazolam, or triazolam is absolutely contraindicated. May cause severe cardiac dysrhythmias, including ventricular tachycardia and death

10.       Identify lindane and permethrin as topical pediculicides and scabicides.  Describe the concerns about the use of lindane in infants, children, and pregnant women.

Greg  Katzung Basic and Clinical Pharmacology, Ch. 62 online UW library. “Ectoparasiticides”.  

Lindane & Permethrin are topical pediculicides and scabicides.  Lindane is available as  shampoo, lotion, or cream.  Permethrin is available as a cream rinse.

Lindane concerns:

Much controversy exists about the possible systemic toxicities of topically applied lindane used for medical purposes. Concerns about neurotoxicity and hematotoxicity have resulted in warnings that lindane should be used with caution in infants, children, and pregnant women. The current USA package insert recommends that it not be used as a scabicide in premature infants and in patients with known seizure disorders. The risk of adverse systemic reactions to lindane appears to be minimal when it is used properly and according to directions in adult patients. However, local irritation may occur, and contact with the eyes and mucous membranes should be avoided.

Greg.   CDMT p130.

The FDA has issued a warning re: potential neurotoxicity, and any use of lindane in infants and pregnant women or in any patient with wide-spread excoriations and open skin-as well as overuse in adults-is discouraged.

Paul, Katzung pg 1051-1052

Lindane is an effective pediculicide and scabicide.  Permethrin is neurotoxic to Pediculus humanus, Pthirus pubis, and Sarcoptes scabiei.

Concerns about neurotoxicity and hematotoxicity have resulted in warnings that lindane should be used with caution in infants, children, and pregnant women.  The current USA package insert recommends that it not be used as a scabicide in premature infants and in patients with known seizure disorders.  The risks with adult patients is minimal when used properly and according to directions.

Anonymous Brenner 471, Noble 233-234Katzung 1004-1005

• Both Noble and Brenner agree that permethrin and lindane are treatments for pediculosis and scabies.  Brenner says that permethrin is the treatment of choice for both.

• Concerns about neurotoxicity and hematotoxicity have resulted in warnings that lindane be used with caution in infants, children and pregnant women.  There is much controversy about systemic toxicities when applied topically.

(Noble said it is not recommended to use either drug in infants, children and pregnant women)

(Katzung only mentioned the caution with lindane)

Anonymous  Saunders,

 Ch. 298, pp. 1293.  

Permethrin is the agent of choice.  Destroys both lice and eggs.

Lindane is an alternate agent due to organism resistance.  Lindane also causes neurotoxicity in infants, children, and pregnant women, usually due to misuse or over-dose applications.  Lindane should not be used in lactating women.

Anonymous Katzung pg 1004

Lindane and permethrin are effective pediculicides and scabicides. (good to know J)

Concerns about neurotoxicity and hematotoxicity have resulted in warning that lindane should be used with caution in infants, children, and pregnant women.  The risk of adverse systemic reactions to lindane appears to be minimal when it is used properly and according to directions in adult patients.  However, local irritation may occur, and contact with the eyes and mucous membranes should be avoided.

11.       Identify calcipotriene as a synthetic vitamin D₃ derivative that is used in the topical treatment of psoriasis, and describe potential adverse effects.

Jenn, Katzung Chap 62

Calcipotriene is a synthetic vitamin D₃ derivative that has been shown to be effective in the treatment of plaque type psoriasis vulgaris of moderate severity. Approximately 6% of the 0.005% topically applied ointment is absorbed through psoriatic plaques, resulting in a transient elevation of serum calcium in less than 1% of subjects treated in clinical trials. Improvement of psoriasis was generally noted following 2 weeks of therapy, with continued improvement for up to 8 weeks of treatment. Less than 10% of patients demonstrate total clearing while on calcipotriene as single-agent therapy. Adverse effects include burning, itching, and mild irritation, with dryness and erythema of the treatment area. Care should be taken to avoid facial contact, which may cause ocular irritation.

Dustin, Katzung online.

Calcipotriene is a synthetic vitamin D₃ derivative that has been shown to be effective in the treatment of plaque type psoriasis vulgaris of moderate severity. Approximately 6% of the 0.005% topically applied ointment is absorbed through psoriatic plaques, resulting in a transient elevation of serum calcium in less than 1% of subjects treated in clinical trials. Improvement of psoriasis was generally noted following 2 weeks of therapy, with continued improvement for up to 8 weeks of treatment. Less than 10% of patients demonstrate total clearing while on calcipotriene as single-agent therapy. Adverse effects include burning, itching, and mild irritation, with dryness and erythema of the treatment area. Care should be taken to avoid facial contact, which may cause ocular irritation.

Anonymous Noble 762Katzung1008

            Calcipotriol (calcipotriene, Dovonex) is a vitamin D3 derivative that affects keratinocyte differentiation.  It has been effective in treating the plaques of psoriasis vulgaris of moderate severity.  

            Adverse effects include: burning, itching and mild irritation, with dryness and erythema of the treated area.  Avoid facial contact because of possible ocular irritation.

Anonymous  Goroll, page 1034-5

Vitamin D derivatives control epidermal growth and inflammation by binding to vitamin D receptors which are members of the superfamily of steroid hormone receptors (has something to do with modulation of gene transcription activity).  Calcipotriene is a first or second line agent for mild to moderate plaque psoriasis and is highly effective in most patients for flattening plaque and decreasing scales.  Ointment formulation is more effective than short-contact anthralin cream and is more cosmetically acceptable.  Response starts within 2 weeks.  Adverse effects include: peirlesional or lesional irritation and erythema.  Dermatitis of the face by self-inocculation or inadvertent spreading may occur.  Immediate hand washing following application should reduce incidence.  If weekly dosage exceeds 100g, hypercalcemia and hypercalciuria can occur therefore caution in using this cream with patients who have a history of hypercalcemia or kidney stones.

Anonymous Katzung pg 1008

Calcipotriene is a synthetic vitamin D₃ derivative that has been shown to be effective in the treatment of plaque type psoriasis vulgaris of moderate severity.

Adverse Effects: include burning, itching, and mild irritation, with dryness and erythema of the treatment area.  Care should be taken to avoid facial contact, which may cause ocular irritation.

12.       Identify coal tar preparations as useful in the treatment of seborrheic dermatitis and psoriasis, and describe potential adverse effects.

Jenn, Katzung Chap 62

Tar preparations are used mainly in the treatment of psoriasis, dermatitis, and lichen simplex chronicus. The phenolic constituents endow these compounds with antipruritic properties, making them particularly valuable in the treatment of chronic lichenified dermatitis. Acute dermatitis with vesiculation and oozing may be irritated by even weak tar preparations, which should be avoided. However, in the subacute and chronic stages of dermatitis and psoriasis, these preparations are quite useful and offer an alternative to the use of topical corticosteroids.
The most common adverse reaction to coal tar compounds is an irritant folliculitis, necessitating discontinuance of therapy to the affected areas for a period of 3-5 days. Phototoxicity and allergic contact dermatitis may also occur. Tar preparations should be avoided in patients who have previously exhibited sensitivity to them. Care should be exercised when using tar compounds in patients with erythrodermal or generalized pustular psoriasis, because of the risk of total body exfoliation.

Dustin, Katzung online.

Tar preparations are used mainly in the treatment of psoriasis, dermatitis, and lichen simplex chronicus. The phenolic constituents endow these compounds with antipruritic properties, making them particularly valuable in the treatment of chronic lichenified dermatitis. Acute dermatitis with vesiculation and oozing may be irritated by even weak tar preparations, which should be avoided. However, in the subacute and chronic stages of dermatitis and psoriasis, these preparations are quite useful and offer an alternative to the use of topical corticosteroids.

The most common adverse reaction to coal tar compounds is an irritant folliculitis, necessitating discontinuance of therapy to the affected areas for a period of 3-5 days. Phototoxicity and allergic contact dermatitis may also occur. Tar preparations should be avoided in patients who have previously exhibited sensitivity to them. Care should be exercised when using tar compounds in patients with erythrodermal or generalized pustular psoriasis, because of the risk of total body exfoliation.
Anonymous Katzung 1009

• Coal tar is actually a by-product of the distillation of bituminous coal that is mixed with several other agents.  It is available OTC and may be compounded in concentrations of 2-10% in creams, ointments and shampoos.  

• Tar preparations are useful in treating dermatitis and psoriasis.  They have an antipuritic effect that can be an alternative to corticosteroids.  

• The adverse effects of coal tar include: irritant folliculitis is the most common and requires immediate discontinuation of the treatment.  Phototoxicity and allergic contact dermatitis may also occur.  

• Care should be taken when using this compound in patients with erythrodermal or pustular psoriasis because of the risk of total body exfoliation.

Anonymous  Behrman: Nelson Textbook of Pediatrics, Sixteenth Edition, p. 1969

Tars are antipruritic and astringent and appear to promote normal keratinization. They may be useful for chronic eczema and psoriasis, and their efficacy may be increased if the affected area is exposed to ultraviolet (UV) light after the tar has been removed. Tars should not be used in acute inflammatory lesions. Tars are often messy and unacceptable because they may stain and they have an odor. Tars may be incorporated into shampoos, bath oils, lotions, and ointments.

Anonymous Katzung pg 1009

Tar preparations are used mainly in the treatment of psoriasis, dermatitis, and lichen simplex chronicus.

Adverse Effects: most common is an irritant folliculitis, necessitating discontinuance of therapy to the affected areas for a period of 3-5 days.  Phototoxicity and allergic contact dermatitis may also occur. Avoid in patients with a sensitivity to tar preparations.

13.       Describe the uses of topical corticosteroids as anti-inflammatory agents, and identify dermatologic disorders which are very responsive to their use (see Katzung, Table 62-2).

Jenn, Katzung Chap 62

The remarkable efficacy of topical corticosteroids in the treatment of inflammatory dermatoses was noted soon after the introduction of hydrocortisone in 1952. Subsequently, numerous analogs have been developed that offer extensive choices of potencies, concentrations, and vehicles. The therapeutic effectiveness of topical corticosteroids is based primarily on their anti-inflammatory activity. Definitive explanations of the effects of corticosteroids on endogenous mediators of inflammation such as histamine, kinins, lysosomal enzymes, prostaglandins, and leukotrienes await further experimental clarification. The antimitotic effects of corticosteroids on human epidermis may account for an additional mechanism of action in psoriasis and other dermatologic diseases associated with increased cell turnover

Dustin, Katzung online

The remarkable efficacy of topical corticosteroids in the treatment of inflammatory dermatoses was noted soon after the introduction of hydrocortisone in 1952. Subsequently, numerous analogs have been developed that offer extensive choices of potencies, concentrations, and vehicles. The therapeutic effectiveness of topical corticosteroids is based primarily on their anti-inflammatory activity. Definitive explanations of the effects of corticosteroids on endogenous mediators of inflammation such as histamine, kinins, lysosomal enzymes, prostaglandins, and leukotrienes await further experimental clarification. The antimitotic effects of corticosteroids on human epidermis may account for an additional mechanism of action in psoriasis and other dermatologic diseases associated with increased cell turnover.

Table 62-2 lists major dermatologic diseases in order of their responsiveness to these drugs. In the first group of diseases, low- to medium-efficacy corticosteroid preparations often produce clinical remission. In the second group, it is often necessary to use high-efficacy preparations, occlusion therapy, or both. Once a remission has been achieved, every effort should be made to maintain the patient with a low-efficacy corticosteroid.

Anonymous see Katzung Ch 62, pg 1008 and, Table 62-2, pg 1011.

Remarkable efficacy of topical corticosteroids in treatment of inflammatory dermatoses was noted soon after introduction of hydrocortisone in 1952. Therapeutic effectiveness of topical corticosteroids is based primarily on their anti-inflammatory activity. Definitive explanations of the effects of corticosteroids on endogenous mediators of inflammation such as histamines, kinins, lysosomal enzymes, prostaglandins, and leukotrienes await further experimental clarification. The antimitotic effects of corticosteroids on human epidermis may account for an additional mechanism of action in psoriasis and other dermatologic diseases associated with increased cell turnover.

Very responsive to use:  Atopic dermatitis, seborrheic dermatitis, lichen simplex chronicus, pruritis ani, later phase of allergic contact dermatitis, later phase of irritant dermatitis, nummular eczematous dermatitis, stasis dermatitis, psoriasis especially of genitalia and face.

Anonymous  see Katzung, Table 62-2.

Topical corticosteroids provide effective local anti-inflammatory and antipruritic effects. They cause immediate and profound cutaneous vasoconstriction, which prevents mobilization of polymorphonuclear leukocytes and monocytes into the reaction site, and also interfere with the inflammatory activities of already-present cells (e.g., mast cells). Topical corticosteroids are intrinsically active and have a rapid therapeutic effect. They slow the mitotic rate of fibroblasts, decrease collagen synthesis, and possibly enhance collagen catabolism.

The most potent topical agents are useful for Recalcitrant psoriasis, discoid lupus, recalcitrant lichen planus, nummular eczema. Intermediate potency useful for Dermatitis--allergic-contact, atopic eczema, neurodermatitis. Low potency useful for Intertrigo, pruritus ani, seborrheic dermatitis. Goldman, Cecil’s Textbook of Medicine, 21^st edition, p. 2273

Anonymous see Katzung, Table 62-2. Katzung pg 1008,1011

The therapeutic effectiveness of topical corticosteroids is based primarily on their anti- inflammatory activity. (ya don’t say)

Table 62—2. Dermatologic disorders responsive to topical corticosteroids ranked in order of sensitivity.

Very responsive

Atopic dermatitis

Seborrheic dermatitis

Lichen simplex chronicus

Pruritus ani

Later phase of allergic contact dermatitis

Later phase of irritant dermatitis

Nummular eczematous dermatitis

Stasis dermatitis

Psoriasis, especially of genitalia and face

chronica helicis

14.       Describe variation in topical corticosteroid penetration by vehicle, use of occlusion, and anatomy (e.g. face vs. extremities vs. genitals), and the importance of using low- to medium-efficacy corticosteroid preparations whenever possible.

Jenn, Katzung Chap 62

The limited penetration of topical corticosteroids can be overcome in certain clinical circumstances by the intralesional injection of relatively insoluble corticosteroids, eg, triamcinolone acetonide, triamcin-olone diacetate, triamcinolone hexacetonide, and betamethasone acetate-phosphate. When these agents are injected into the lesion, measurable amounts remain in place and are gradually released for 3-4 weeks. This form of therapy is often effective for the lesions listed in Table 62-2 that are generally unresponsive to topical corticosteroids.

Occlusion and Anatomny:  Corticosteroids are only minimally absorbed following application to normal skin; for example, approximately 1% of a dose of hydrocortisone solution applied to the ventral forearm is absorbed. Long-term occlusion with an impermeable film such as plastic wrap is an effective method of enhancing penetration, yielding a tenfold increase in absorption. There is a marked regional anatomic variation in cortico-steroid penetration. Compared with the absorption from the forearm, hydrocortisone is absorbed 0.14 times as well through the plantar foot arch, 0.83 times as well through the palm, 3.5 times as well through the scalp, 6 times as well through the forehead, 9 times as well through vulvar skin, and 42 times as well through scrotal skin. Penetration is increased severalfold in the inflamed skin of atopic dermatitis; and in severe exfoliative diseases, such as erythrodermic psoriasis, there appears to be little barrier to penetration.

In the first group of diseases, low- to medium-efficacy corticosteroid preparations often produce clinical remission. In the second group, it is often necessary to use high-efficacy preparations, occlusion therapy, or both. Once a remission has been achieved, every effort should be made to maintain the patient with a low-efficacy corticosteroid.

Dustin, Katzung online

The limited penetration of topical corticosteroids can be overcome in certain clinical circumstances by the intralesional injection of relatively insoluble corticosteroids, eg, triamcinolone acetonide, triamcin-olone diacetate, triamcinolone hexacetonide, and betamethasone acetate-phosphate. When these agents are injected into the lesion, measurable amounts remain in place and are gradually released for 3-4 weeks. This form of therapy is often effective for the lesions listed in Table 62-2 (Katzung online through healthlinks) that are generally unresponsive to topical corticosteroids. The dosage of the triamcinolone salts should be limited to 1 mg per treatment site, ie, 0.1 mL of 10 mg/mL suspension, to decrease the incidence of local atrophy

Corticosteroids are only minimally absorbed following application to normal skin; for example, approximately 1% of a dose of hydrocortisone solution applied to the ventral forearm is absorbed. Long-term occlusion with an impermeable film such as plastic wrap is an effective method of enhancing penetration, yielding a tenfold increase in absorption. There is a marked regional anatomic variation in cortico-steroid penetration. Compared with the absorption from the forearm, hydrocortisone is absorbed 0.14 times as well through the plantar foot arch, 0.83 times as well through the palm, 3.5 times as well through the scalp, 6 times as well through the forehead, 9 times as well through vulvar skin, and 42 times as well through scrotal skin. Penetration is increased severalfold in the inflamed skin of atopic dermatitis; and in severe exfoliative diseases, such as erythrodermic psoriasis, there appears to be little barrier to penetration.

Experimental studies on the percutaneous absorption of hydrocortisone fail to reveal a significant increase in absorption when applied on a repetitive basis compared to a single dose, and a single daily application may be effective in most conditions. Ointment bases tend to give better activity to the corticosteroid than do cream or lotion vehicles. Increasing the concentration of a corticosteroid increases the penetration but not to the same degree. For example, approximately 1% of a 0.25% hydrocortisone solution is absorbed from the forearm. A tenfold increase in concentration causes only a fourfold increase in absorption. Solubility of the corticosteroid in the vehicle is a significant determinant of the percutaneous absorption of a topical steroid. Marked increases in efficacy are noted when optimized vehicles are used, as demonstrated by newer formulations of betamethasone dipropionate and diflorasone diacetate.

Anonymous Katzung Ch 62, pg 1008-09; Noble Ch 83, pg 754-5

• The vehicle containing a corticosteroid can be as important as the steroid itself. Creams and lotions are composed of a combination of oil and water. Higher the ratio of oil to water, the thicker the preparation. The presence of water in the vehicle may contribute to skin drying through evaporation. Vehicles containing water must also contain preservatives to prevent contamination with bacteria and fungi. In general, patients tolerate creams and lotions better than ointments, but ointments have some inherent occlusive properties that enhance penetration of steroids. Creams and lotions seem to be more effective in intertriginous or moist areas because of drying properties. Ointments preferably on dry skin because of occlusive properties and retard drying. Solutions usually contain alcohol and best used on the scalp.

• Steroids have increased effectiveness when they are occluded. Use of ointment provides some natural occlusion, but additional occlusion can be provided with use of plastic or synthetic dressing such as Duoderm. Even simple tape increases penetration of steroid. Although occlusion increases effectiveness, it also increases chances of side effects.

• There are marked regional anatomic variation in corticosteroid penetration. Compared with absorption from the forearm, hydrocortisone is absorbed 0.14 times as well through the plantar foot arch, 0.83 times as well through the palm, 3.5 times as well through the scalp, 6 times as well through the forehead, 9 times as well through vulvar skin, and 42 times as well through scrotal skin. Penetration is increased several-fold in the inflamed skin of atopic dermatitis, and in severe exfoliative diseases, such as erythodermic psoriasis, there appears to b little barrier to penetration.

• Experimental studies on pecutaneous absorption of hydrocortisone fail to reveal a significant increase in absorption when applied on a routine basis compared to a single dose, and a single daily application may be as effective in most conditions. Ointment bases tend to give better activity to the corticosteroid than do cream or lotion vehicles. Increasing the concentration of a corticosteroid increases the penetration but not to the same degree. For example, approximately 1% of a 0.25% hydrocortisone solution is absorbed from the forearm. A tenfold increase in concentration causes only a fourfold increase in absorption. Solubility of the corticosteroid in the vehicle is a significant determinant of the percutaneous absorption of a topical steroid.

• Marked increases in efficacy are noted when optimized vehicles are used. Low-to-medium efficacy corticosteroid preparations often produce clinical remission. Once remission has been achieved, every effort should be made to maintain patient with low-efficacy corticosteroid.

Anonymous  Noble, p. 755

Vehicle- Generally, patients tolerate creams and lotions better than ointments, but ointments have some inherent occlusive properties that enhance the penetration of steroids. Creams and lotions tend to be more effective in intertriginous or moist areas because of their drying properties. Ointments are used preferably on dry skin because their occlusive properties retard drying. Solutions usually contain alcohol and are best used on the scalp.

Occlusion- occlusion increases effectiveness of steroids. Ointments provide some natural occlusion, but additional occlusion can be provided by use of plastic or other synthetic dressing (ie Duoderm). Although occlusion increases effectiveness, it also increases side effects.

Anatomy- Class I steroids should generally not be used on face. Class II-V can be used on open areas of the skin for up to several months, but should be avoided in intertriginous areas. Class VI and VII are generally safe on face and in intertriginous areas.

Choice of strength- chronic use of potent steroids can cause skin atrophy with thinned dermis, prevalent telangiectasis and increased friability. Changes can lead to development of straie. On face, can cause rosacea-like popular and pustular dermatitis. Therefore, you should reserve use of potent steroids only for short term therapy for dermatoses unresponsive to other treatments.

Anonymous Katzung pg 1008

1. Ointment bases tend to give better activity to the corticosteroids than do cream or lotion vehicles.

2. Long-term occlusion with an impermeable film such as plastic wrap is an effective method of enhancing penetration, yielding a tenfold increase in absorption. (ointments usually are not occluded because folliculitis may develop)

3. There is a marked regional anatomic variation in corticosteroid penetration. Compared with the absorption from the forearm, hydrocortisone is absorbed 0.14 times as well through the plantar foot arch, 0.83 times as well through the palm, 3.5 times as well through the scalp, 6 times as well through the forehead, 9 times as well through vulvar skin, and 42 times as well through scrotal skin. (Basically, the thinner the skin, the more cortisone is absorbed). Thin-skinned areas are especially susceptible to the development of atrophy.  Less potent formulations should also be used on areas such as the face, dorsum of the hands, and the scrotum. (Goroll pg 1024)

4. low- to medium- efficacy corticosteroids should be used whenever possible in order to avoid the adverse local effects and possible systemic effects (see the next 2 questions)

15.       List or recognize potential systemic adverse effects of topical corticosteroids.

Jenn, Katzung Chap 62

Adverse Effects
All absorbable topical corticosteroids possess the potential to suppress the pituitary-adrenal axis (Chapter 39). Although most patients with pituitary-adrenal axis suppression demonstrate only a laboratory test abnormality, cases of severely impaired stress response can occur. Iatrogenic Cushing's syndrome may occur as a result of protracted use of topical corticosteroids in large quantities. Applying potent corticosteroids to extensive areas of the body for prolonged periods, with or without occlusion, increases the likelihood of systemic side effects. Fewer of these factors are required to produce adverse systemic effects in children, and growth retardation is of particular concern in the pediatric age group.

Adverse local effects of topical corticosteroids include the following: atrophy, which may present as depressed, shiny, often wrinkled “cigarette paper”-appearing skin with prominent telangiectases and a tendency to develop purpura and ecchymosis; steroid rosacea, with persistent erythema, telangiectatic vessels, pustules, and papules in central facial distribution; perioral dermatitis, steroid acne, alterations of cutaneous infections, hypopigmentation, hypertrichosis, and increased intraocular pressure; and allergic contact dermatitis, which may be confirmed by patch testing with high concentrations of cortico-steroids, ie, 1% in petrolatum, because topical corticosteroids are not irritating. Screening for allergic contact dermatitis potential is performed with tixicortol pivalate, budesonide, and hydrocortisone valerate or butyrate. Topical corticosteroids are contraindicated in individuals who demonstrate hypersensitivity to them. Some sensitized subjects develop a generalized flare when dosed with ACTH or oral prednisone.

Dustin, Katzung online

All absorbable topical corticosteroids possess the potential to suppress the pituitary-adrenal axis. Although most patients with pituitary-adrenal axis suppression demonstrate only a laboratory test abnormality, cases of severely impaired stress response can occur. Iatrogenic Cushing's syndrome may occur as a result of protracted use of topical corticosteroids in large quantities. Applying potent corticosteroids to extensive areas of the body for prolonged periods, with or without occlusion, increases the likelihood of systemic side effects. Fewer of these factors are required to produce adverse systemic effects in children, and growth retardation is of particular concern in the pediatric age group.

Anonymous Katzung CH 62, pg 1009

All absorbable topical steroids have the potential to suppress the pituitary-adrenal axis. Although most patients with pituitary-adrenal axis suppression demonstrate only a laboratory test abnormality, cases of severely impaired stress response can occur. Iatrogenic Cushing’s syndrome may occur (in as little as 2 weeks) as a result of protracted use of topical corticosteroids in large quantities. Applying potent corticosteroids to extensive areas of body for prolonged periods, with or without occlusion, increases likelihood of systemic effects. Fewer of these factors are required to produce adverse systemic side effects in children, and growth retardation is of particular concern in pediatric age group.

• Other systemic adverse effects with long-term use include hyperglycemia, glucose intolerance, HTN, and osteoporosis.  There may also be sodium retention or potassium loss with use of cortisone or hydrocortisone.  (Brenner 348)

• Glucocorticoids are contraindicated or should be used with caution in patients with psychoses, peptic ulcers, heart diseases, HTN, diabetes, osteoporosis, and certain infections.

Anonymous  Noble p. 754-755

Graded from class I (most potent) to class VII (least potent). Generally safe in short course – chronic use can result in side effects if the steroid is stronger than class VII. Main effect: skin atrophy with thinned dermis with prevalent telangiectasis and increased friability, which can lead to development of striae. When potent steroids are used on the face, a rosacea-like papular and pustular dermatitis, referred to as steroid-induced rosacea, can occur.

Anonymous Current pg 85

All absorbable topical corticosteroids possess the potential to suppress the pituitary-adrenal axis.  Although most patient with pituitary-adrenal axis suppression demonstrate only a laboratory test abnormality, cases of severely impaired stress response can occur.   Iatrogenic Cushing’s syndrome may occur as a result of protracted use of topical corticosteroids in large quantities.  Applying potent corticosteroids to extensive areas of the body for prolonged periods, with or without occlusion, increases the likelihood of systemic side effects. (Katzung pg 1009)

Systemic absorption does occur, but adrenal suppression, diabetes, hypertension, osteoporosis, and other complications of systemic steroids are very rare with topical steroid therapy

16.       List or recognize adverse local effects of topical corticosteroids.

Suzy “Dermatologic Pharmacology” Katzung pg 1056

•        Atrophy, which may present as depressed, shiny, often wrinkled “cigarette paper” appearing skin with prominent telangeiectases and tendency to develop purpura and ecchymosis.

•        Steroid rosacea, with persistent erythema, telangiectatic vessels, pustules, and papules in central facial distribution.

•        Perioral dermatitis

•        Steroid acne

•        Alterations of cutaneous infections

•        Hypopigmentation

•        Hypertrichosis

•        Increased intraocular pressure

•        Allergic contact dermatitis, which may be confirmed by patch testing.

All absorbable topical corticosteroids possess the potential to:

•        Suppress the pituitary-adrenal axis (Mostly abnormal lab tests)

•        Iatrogenic Cushing’s syndrome (protracted use of large quantities of topical)

Shauna CMDT pg 86

Allergyà can cause allergic contact dermatitis

Irritationà may cause acne eruption

Absorptionà drugs may be absorbed through the skin, esp near mucous membranes, through broken skin or inflamed skin, or from under occlusive dressings causing a systemic reaction (ie: suppress pituitary, cushing’s syndrome). Systemic absorption has special implications in pregnant women. Podophyllum resin, lindane, and tretinoin are CI in pregnant women.

Over useà over use may induce acne-like lesions (steroid rosacea)

Suzy “Dermatologic Pharmacology” Katzung pg 1056

•        Atrophy, which may present as depressed, shiny, often wrinkled “cigarette paper” appearing skin with prominent telangeiectases and tendency to develop purpura and ecchymosis.

•        Steroid rosacea, with persistent erythema, telangiectatic vessels, pustules, and papules in central facial distribution.

•        Perioral dermatitis

•        Steroid acne

•        Alterations of cutaneous infections

•        Hypopigmentation

•        Hypertrichosis

•        Increased intraocular pressure

•        Allergic contact dermatitis, which may be confirmed by patch testing.

All absorbable topical corticosteroids possess the potential to:

•        Suppress the pituitary-adrenal axis (Mostly abnormal lab tests)

•        Iatrogenic Cushing’s syndrome (protracted use of large quantities of topical)

Anonymous Katzung Ch 62, pg 1009

Main side effect seen with chronic use of potent steroids is skin atrophy with thinned dermis with prevalent telangiectasis and increased friablility. These changes can lead to development of striae. When potent steroids use to face, a rosacea-like popular and pustular dermatitis, referred to as steroid-induced rosacea, can occur. Noble Ch 83, pg 755

• Adverse local side effects of topical corticosteroids include the following:

  • Atrophy, which may present as depressed, shiny often wrinkled “cigarettes paper” appearing skin with prominent telangiectases and a tendency to develop purpura and ecchymosis

  • Steroid rosacea, with persistent erythema, telangiectatic vessels, pustules, and papules in central facial distribution

  • Perioral dermatitis

  • Steroid acne

  • Alterations of cutaneous infections

  • Hypopigmentation

  • Hypertrichosis

  • Increased intraocular pressure, cataracts & glaucoma

  • Allergic contact dermatitis

Anonymous  Katzung Chp. 62

Adverse local effects include:

atrophy- presents as depressed, shiny, often wrinkled “cigarette paper” appearing skin w/prominent telangiectases, + tendency to develop purpura + ecchymosis;

steroid roacea- w/ persistent erythema, telangiectatic vessels, pustules + papules in central facial distribution;

perioral dermatitis

steroid acne

alterations of cutaneous infections

hypopigmentation

hypertrichosis

increased intraocular pressure

allergic contact dermatitis

Anonymous Goroll pg 1024

The potent corticosteroids are the most likely to cause atrophy, telangiectasia, purpura, striae, and an acneiform eruption.   

17.       Describe the use of podophyllum resin and podofilox and imiquimod added 2004 for condyloma accuminatum.  Identify potential adverse effects, and describe patient instructions.

Zen Seeker

     web

imiquimod added 2004

ADVERSE REACTIONS

Healthcare providers and patients may contact 3M or FDA’s Medwatch to report adverse reactions by calling 1-800-814-1795 or 1-800-FDA-1088, or on the internet at http://www.fda.gov/medwatch. Dermal safety studies involving induction and challenge phases produced no evidence that Aldara Cream causes photoallergenicity or contact sensitization in healthy skin; however, cumulative irritancy testing revealed the potential for Aldara Cream to cause irritation, and in the clinical studies application site reactions were reported in a significant percentage of study patients. Phototoxicity testing was incomplete as wavelengths in the UVB range were not included and Aldara Cream has peak absorption in the UVB range (320 nm) of the light spectrum.

External Genital Warts

In controlled clinical trials for genital warts, the most frequently reported adverse reactions were local skin and application site reactions. These reactions were usually mild to moderate in intensity; however, severe reactions were reported with 3X/week application. These reactions were more frequent and more intense with daily application than with 3X/week application. Some patients also reported systemic reactions. Overall, in the 3X/week application clinical studies, 1.2% (4/327) of the patients discontinued due to local skin/application site reactions. The incidence and severity of local skin reactions during controlled clinical trials are shown in the following table.

Remote site skin reactions were also reported in female and male patients treated 3X/week with Aldara Cream. The severe remote site skin reactions reported for females were erythema (3%), ulceration (2%), and edema (1%); and for males, erosion (2%), and erythema, edema, induration, and excoriation/flaking (each 1%).

Adverse events judged to be probably or possibly related to Aldara Cream reported by more than 5% of patients are listed below; also included are soreness, influenza-like symptoms and myalgia.

Adverse events judged to be possibly or probably related to Aldara Cream and reported by more than 1% of patients included: Application Site Disorders: Wart Site Reactions (burning, hypopigmentation, irritation, itching, pain, rash, sensitivity, soreness, stinging, tenderness); Remote Site Reactions (bleeding, burning, itching, pain, tenderness, tinea cruris); Body as a Whole: fatigue, fever, influenza-like symptoms; Central and Peripheral Nervous System Disorders: headache; Gastro- Intestinal System Disorders: diarrhea; Musculo-Skeletal System Disorders: myalgia.

Patient information -

How Does ALDARA Cream Work?

ALDARA cream is an immune response modifier that stimulates the body's own immune response system and helps the body fight the virus.

How Do I Use ALDARA Cream?

ALDARA cream is rubbed directly on the wart(s). It should not be taken by mouth or used in or near the eyes.

How To Use ALDARA Cream:

1. Wash hands and open a new packet of ALDARA cream just before bedtime

2. Apply a thin layer of cream on the wart(s)

3. Rub the cream in until it vanishes

4. Discard the open packet and wash hands

5. Leave the cream on the wart(s) for 6 to 10 hours

6. After 6 to 10 hours, wash the area where ALDARA cream was applied with mild soap and water.

Always apply ALDARA cream as directed by your health care provider.

When Should I Use ALDARA Cream?

It is important to use ALDARA cream as directed by your health care provider. Typically, dosing is once a day, 3 days a week:

• Monday, Wednesday, and Friday, or

• Tuesday, Thursday, and Saturday

Apply ALDARA cream at bedtime, after bathing, so you do not wash off the cream. Treatment with ALDARA cream should continue until the warts are completely gone, or up to 16 weeks. Your health care provider can tell you how often and for how long you need to use ALDARA cream.

Can I Have Sex While Using ALDARA Cream?

Sexual contact should be avoided while the cream is on the skin. If you decide to have sexual relations, apply ALDARA cream after - not before - sexual activity. If you have already applied the cream, it should be washed off before sexual activity. In addition, ALDARA cream may weaken condoms and diaphragms; therefore the cream should not be left on during sexual activity. The effect of ALDARA cream on the transmission of genital warts is unknown.

What If I Forget A Dose?

Apply the missed dose of cream as soon as you remember and then continue on the regular schedule.

What Can I Expect From ALDARA Cream?

Results vary from person to person. Many people see reddening or swelling on or around the warts during the course of treatment.

In clinical trials, about one-half of patients completely cleared their warts. In most patients, the warts disappeared in 8 to 12 weeks. However, some patients got rid of their warts in 4 weeks and others took up to 16 weeks. Patients should be aware that new warts may develop during therapy, as ALDARA cream is not a cure. For best results with ALDARA cream, follow your health care provider's instructions closely.

Will I Get Any Side Effects From ALDARA Cream?
There are some side effects associated with ALDARA cream. Side effects are most often at the wart area and are usually mild to moderate.

Most common side effects are redness, peeling, and swelling in the area where ALDARA cream is applied.

Some patients have also experienced burning, itching, and pain where ALDARA cream was applied. These may be caused by the response of your body's immune system to the drug. However, if you experience a severe skin reaction, contact your health care provider.

What Should I Avoid While Using ALDARA Cream?
Do not cover warts with bandages or other closed dressings. Avoid using overly large amounts of cream. A thin layer that completely covers each wart is enough.

Who Should Not Use ALDARA Cream?
ALDARA cream has not been studied in pregnant women. If you are pregnant, check with your health care provider. Additionally, ALDARA cream should not be applied to warts inside the vagina or anus.

As with any prescription medicine, there are some general rules you should follow:

• Always use ALDARA cream as directed by your doctor or health care provider

• Try to stick to your dosing schedule

• Discard any unused cream after each application

• Do not share ALDARA cream with anyone else; it was prescribed only for you

• Keep ALDARA cream and all medicines out of the reach of children.

3M Pharmaceuticals wants you to know about the medicine you use. However, this information does not replace advice given by your doctor or health care provider. If you have any questions about ALDARA cream, your health care provider can discuss them with you.

Suzy “Dermatologic Pharmacology” Katzung pg 1059

Podophyllum resin, an alcoholic extract of Podophyllum peltatum, commonly known as mandrake root or May apple, is used in the treatment of condyloma acuminatum and other verrucae. Percutaneous absorption occurs, particularly in intertriginous areas and from applications to large moist condylomas.

Application: By provider only. 25% concentration should be restricted to wart tissue only, to limit the total amount of medication used to prevent severe erosive changes in adjacent tissue. Limit application to minimize systemic absorption. 3-5 applications have not resulted in significant resolution, other methods of treatment should be considered.

Patient instructions: Wash off the preparation 2-3 hours after the initial application, since the irritant reaction is variable. Depending on the individual reaction, this period can be extended to 6-8 hours on subsequent applications.

Adverse affects: It is soluble in lipids and therefore is distributed widely throughout the body, including the central nervous system.

Toxic symptoms associated with excessively large applications include: nausea, vomiting, alterations in sensorium, muscle weakens, neuropathy with diminished tendon reflexes, coma, and even death. Local irritation is common, and inadvertent contact with the eye may cause severe conjunctivitis. Contraindicated in pregnancy.

Podofilox, pure podophyllotoxin is approved for use as a 0.5% podophyllotoxin preparation (Condylox) for treatment of genital warts.

Application: by the patient. Apply 0.5% solution or gel twice-daily application for 3 consecutive days followed by a 4-day drug-free period. Repeat Q wk x 4

Apply with supplied cotton-tip applicator, allow to dry thoroughly

Neither gel nor solution is indicated for mucous membrane warts; solution NOT for perianal warts.

Adverse affects: Low dose reduces the potential for systemic toxicity. Local effects include inflammation, erosions, burning pain, and itching.

Shauna CMDT pg 124 and 704

Podophyllum resin- paint each wart carefully (protect normal skin) every 2-3 weeks with 25% podophyllum resin in compound tincture of benzoin. CI in pregnant patients. It must be washed off after 2-4 hours. Podophyllum must be applied be a provider.

Podofilox- it is the purified active component of the resin and can be applied by the patient. Patient is to use BID for three consecutive days a week for cycles of 4-6 weeks. It is less irritating and more effective than podophyllum resin. After a single 4 week cycle, 45% of patients were wart-free; but of these, 60% relapsed at 6 weeks. Thus multiple cycles of treatment are often necessary.

Anonymous katzung Ch 62, pg 1012

• Podophyllum resin: Major use of podophyllum resin is in the treatment of condyloma acuminatum. Podophyllotoxin and its derivatives are active cytotoxic agents with specific affinity for the microtubule protein of the mitotic spindle. Normal assembly of the spindle is prohibited. 25% concentration of podophyllum resin in compound tincture of benzoin recommended for treatment. Application restricted to wart tissue only to limit total amount of medication used and prevent erosive changes in adjacent tissue. In treating large condlyomas, it is advisable to limit application to sections of affected area to avoid minimize systemic absorption.

• Patient should be instructed to wash off preparation 2-3 hours after initial application since irritant reaction is variable. Depending on pt reaction, this period can be extended to 6-8 hours on subsequent applications. If 3-5 applications have not resulted in significant resolution, other methods of treatment should be considered.

• Toxic symptoms associated with excessively large applications include nausea, vomiting, alterations in sensorium, muscle weakness, neuropathy with diminished tendon reflexes, coma, and even death. Local irritation is common, and inadvertent contact with the eye may cause severe conjunctivitis. Use during pregnancy is contraindicated in view of possible cytotoxic effects on fetus.

Podofilox (pure pdophyllotoxin) is approved for use as a 0.5% podophyllotoxin preparation for application in treatment for genital condylomas. Low concentration of podofilox significantly reduces the potential for systemic toxicity. Most men with penile warts may be treated with less than 70ul per application. At this dose, podofilox is not routinely detected in the aerum. Treatment is self administered in treatment cycles of twice daily application for 3 consecutive days followed by a 4-day drug-free period. Local adverse effects include inflammation, erosion, burning pain, and itching.

Anonymous  

A preparation of 20%-40% podophyllin in compound tincture of benzoin is used to treat macerated genital warts.  It must be applied sparingly, only to the wart, and allowed to dry thoroughly before the patient dresses.  The medication is washed off by the patient 1-4 hours after application.  Repeated treatment is the rule.  Podophyllum is contraindicated in pregnancy.  Podofilox .2% (condylox) solution and gel are available for the treatment of external genital warts in both men and women.  Podofilox is a purified fraction of podophyllum resins and is the first prescription product for the treatment of warts that is safe for self-application at home.  It is applied for 3 days consecutively, followed by 4 days of no treatment; treatment is repeated if the warts persist.  GOROLL 1058

Podophyllum is toxic and can be a severe irritant and thus should not be dispensed.  Podofilox is less irritating and more potent than podophyllum.  NOBLE 790

Anonymous  Katzung pg 1012

Podophyllum resin:

Use is in the treatment of condyloma acuminatum.

Adverse effects associated with excessively large applications include nausea, vomiting, alterations in sensorium, muscle weakness, neuropathy with diminished tendon reflexes, coma, and even death.  Local irritation is common, and inadvertent contact with the eye may cause severe conjunctivitis.

Pt Instructions are to wash off the preparation 2-3 hrs after the initial application, since the irritant reaction is variable.  Depending on the individual patient’s reaction, this period can be extended to 6-8 hours on subsequent applications.  If 3-5 applications have not resulted in significant resolution, other methods of treatment should be considered.

Podofilox:

Use is approved for application by the patient in the treatment of genital condylomas.

Adverse effects include inflammation, erosions, burning pain, and itching.

Pt Instructions Treatment is self administered in treatment cycles of twice-daily application for 3 consecutive days followed by a 4-day drug-free period.