Dermatologic Pharmacology Summary

Dermatologic Pharmacology Summary Drug MOA Route of Uses Administration Topical use Against Gram positive bacteria Bacitracin (Antibacterial) Inhibitor of cell wall synthesis Mupirocin (Pseudomonic acid A) Protein synthesis inhibitor (targets tRNA) -Topical use Retapamulin Protein synthesis inhibitor -Topical use Polymyxin B (Peptide antibiotic) Affects the cell membrane -Topical use Neomycin & Gentamicin Affects protein synthesis -Topical use -Most gram positive bacteria including MRSA -Treatment of impetigo (S. aureus, group A β-hemolytic strep) -Internasal ointment for eliminating nasal carriage of S aureus -Uncomplicated superficial skin infection caused by group A β-hemolytic strep. and S. aureus excluding MRSA -Treatment of impetigo - Against gramnegative organisms, including Pseudomonas aeruginosa, Escherichia coli, enterobacter, and klebsiella - Against gramnegative organisms, including E coli, proteus, klebsiella, and Enterobacter. -Gentamicin generally shows greater activity against P aeruginosa than neomycin Side Effects - Internasal ointment for eliminating nasal carriage of S aureus may be associated with irritation of mucous membrane caused by the polyethylene glycol vehicle -Well tolerated with only occasional local irritation of the treatment site Notes -Used in combination with Polymyxin B and Neomycin -Anti-inflammatory agents are usually added (Hydrocortisone) -Not absorbed systemically so it’s safe. -A semisynthetic pleromutilin derivative - Most strains of proteus and serratia are resistant, as are all gram-positive organisms. -Long term use of gentamicin causes appearance of gentamicin-resistant organisms -Nephrotoxicity & neurotoxicity -Aminoglycosides -Not used systemically (very toxic) - Gentamicin is more active against staphylococci and group A β-hemolytic streptococci Dermatologic Pharmacology Summary Drug MOA Route of Uses Administration -Topical use -Treatment of acne (Propionibacterium) -Available in fixedcombination topical gels with benzoyl peroxide and with tretinoin Clindamycin Protein synthesis inhibitor (50S) Metronidazole -The nitro group accepts electrons forming reduced cytotoxic compounds that bind to proteins and DNA resulting in cell death -Topical use Erythromycin Protein synthesis inhibitor (50S) -Topical use (base rather than salt) Miconazole & Clotrimazole Inhibition of Ergosterol synthesis (inhibits 14-a demethylase) -Topical use -Treatment of acne -May act as an antiinflammatory agent by direct effect on neutrophil cellular function -Against anaerobic bacteria and protozoa -Effective in the treatment of rosacea -Treatment of acne -In patients allergic to penicillin -Available in a fixed combination preparation with benzoyl peroxide (Benzamycin) for topical treatment of acne vulgaris -Ringworm -Tinea versicolor -Mucocutaneous candidiasis Side Effects Notes -10% absorbed → possibility of Pseudomembranous colitis and bloody diarrhea -The hydroalcoholic vehicle and foam formulation (Evoclin) may cause drying, irritation of the skin, burning and stinging -Adverse local effects include dryness, burning, and stinging -Caution should be exercised when applying metronidazole near the eyes to avoid excessive tearing -The water-based gel and lotion formulations are well tolerated and less likely to cause irritation. -Allergic contact dermatitis is uncommon -Development of antibiotic-resistant strains of organisms, including staphylococci -Burning sensation at the time of application and drying and irritation of the skin -Inhibitor of cytochrome p450 (we need to check if the patient takes warfarin) → causes severe bleeding -Metronidazole nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa -Imidazoles (antifungal) -Miconazole is a potent inhibitor of cytochrome p450 (warfarin metabolism) Dermatologic Pharmacology Summary Drug MOA Ciclopirox Olamine Route of Uses Administration -Topical use -Tinea versicolor Naftifine & Terbinafine Inhibition of Ergosterol synthesis (inhibits squalene monooxygenase) -Topical use -Terbinafine can be used orally Amphotericin B Bind to ergosterol and disrupt membrane integrity (Loss of cellular K+) -Topical & IV use Nystatin Bind to ergosterol and disrupt membrane integrity (Loss of cellular K+) -Topical use only Tolnaftate -Topical use -Tinea pedis, tinea cruris, tinea corporis -Oral use of terbinafine is recommended for onychomycosis (ringworm of the nail) -To treat serious disseminated yeast and dimorphic fungal infections in immunocompromised hospitalized patients -C. albicans -IV injections are used as an alternative therapy for visceral leishmaniasis especially is areas with high resistance -Superficial infections cause by C. albicans -Oral candidiasis (thrush), mild esophageal candidiasis and vaginitis Side Effects Notes -Antifungal agent -Allylamines (antifungal) -IV (common) → Fever, chills, and tachypnea -Anaemia, hypokalaemia, liver damage, thrombocytopenia and anaphylatic reactions -Very toxic (main toxicity is renal) -Nephrotoxicity is the most common and the most serious longterm toxicity of amphotericin B administration -Polyene antifungal -Produced by the actinomycete Streptomyces - The polyene macrolides are very poorly absorbed orally and they are reluctant to pass through mucous membranes -80% of patients get reduction in kidney function which generally recovers after treatment -More toxic than amphotericin B -Polyene antifungal -Too toxic for systemic use -Antifungal agent Dermatologic Pharmacology Summary Drug MOA Route of Uses Administration -Oral use -Effective in systemic mycosis, mucocutaneous candidiasis, and other cutaneous infections -Oral use -Effective against epidermophyton, microsporum, and trichophton Fluconazole Itraconazole Ketoconazole Inhibition of ergosterol synthesis Griseofulvin Disrupts microtubule aggregation during mitosis Acyclovir Valacyclovir Penciclovir Famciclovir Synthetic guanine analogs, inhibits DNA synthesis by inhibiting viral DNA polymerase -Topical use -Against herpes viruses -Ointments and creams are useful for recurrent orolabial herpes simplex infection Tacrolimus & Pimecrolimus -Bind to FK binding protein inside the Tlymphocyte creating a complex -Eventually, they decrease IL-2 production and inhibit Tlymphocyte proliferation -Topical & systemic use -Used systematically after organ transplant -Used topically for the treatment of atopic dermatitis, and psoriasis Side Effects Notes -Might have systemic side effects: hepatitis and liver enzyme elevations, and interactions -Ketoconazole is an imidazole -Itraconazole & Fluconazole are triazoles -Has many side effects. -An antifungal -Requires prolonged treatment -Antiviral agents -Nephrotoxic -hepatotoxic -Seizures -Increase LDL which increases the risk for developing atherosclerosis -Immunosuppressants -The complex created inhibits calcineurin preventing the dephosphorylation & translocation of transcription factor NFAT to the nucleus → decrease in the production of IL-2 → inhibition of Tlymphocyte proliferation -Tacrolimus is a substrate for Cyt. P450 -High levels of LDL are treated by statins which are inhibitors of cytochrome p450 Dermatologic Pharmacology Summary Drug Imiquimod MOA -Stimulates peripheral mononuclear cells to release INF- ά -Stimulates macrophages to produce IL-1,-6, and -8 and TNF-ά Permethrin Lindane Route of Uses Administration -Topical use -Used topically for external genital and perianal warts (condyloma acuminatum) which is caused by HPV -Actinic keratosis -Primary basal cell carcinoma -Topical use -Toxic to Pediculus humanus (lyse infection), Pthirus pubis, and Sarcoptes scabiei -Topical use -Used to treat pediculosis Crotamiton -Topical use Sulfur & Malathion Hydroquinone -Topical use Monobenzone Mequinol Reduce hyperpigmentation of skin by inhibiting the enzyme tyrosinase → inhibition of melanin Reduce hyperpigmentation of skin by inhibiting the enzyme tyrosinase → inhibition of melanin Reduce hyperpigmentation of skin by inhibiting the enzyme tyrosinase → inhibition of melanin -Topical use Notes -An immunomodulator -An ectoparasiticide - 10% absorbed and concentrated in fatty tissues -Very toxic if absorbed, can cause neurotoxicity and hematotoxicity -Treating scabies -A general antipruritic (decreases itching) -Hexachlorocyclohexane - An ectoparasiticide -An ectoparasiticide -Ectoparasiticides -Skin whitening to reduce the color of skin -Temporary lightening -Topical use -Topical use Side Effects -May be toxic to melanocytes resulting in permanent depigmentation -Results in temporary lightening Dermatologic Pharmacology Summary Drug MOA Trioxsalen & Methoxsalen Re-stimulate the melanocytes to produce melanin and induce pigmentation Sunscreens Absorb UV light Route of Uses Administration -Topical use -Repigmentation of depigmented macules of vitiligo -Topical use Sunshades Opaque materials that reflect light -Topical use Retinoic Acid (Tretinoin) -Stabilizes lysosomes. -Increases RNA polymerase activity. -Increases PGE2, cAMP, and cGMP levels. -Increases the incorporation of thymidine into DNA. -Gets rid of comedones -Thickens the epidermis helping in fine lines and wrinkles diminishment. -Systemic use Side Effects Notes -They can cause cataract or skin cancer, because they intercalate with DNA -Both drugs are psoralens, meaning that they require activation by light to perform their action -Useful in polymorphous light eruption, lupus erythematosus, and drug –induced photosensitivity. -Useful in polymorphous light eruption, lupus erythematosus, and drug –induced photosensitivity -Useful in acne treatment. -Examples are para amino benzoic acid (PABA) and its esters -Example: titanium dioxide – Can cause erythema and dryness –Tumorigenic in animals -Gets rid of comedones through decreasing the cohesion between epidermal cells and increasing epidermal cell turnover. This will result in expulsion of open comedones and the transformation of closed comedones into open ones -Thickens the epidermis by promoting dermal collagen synthesis and new blood vessel formation. Dermatologic Pharmacology Summary Drug MOA Isotretinoin (Accutane) – Inhibits sebaceous gland size and function Benzoyl Peroxide Penetrates the stratum corneum or follicular openings and is converted to benzoic acid within the epidermis and dermis generating free radicals. Route of Uses Administration -Oral use -Restricted for severe cystic acne resistant to standard treatment. -Topical use Azelaic Acid Acitretin Tazarotene Calcipotriene -Oral use -It has antiinflammatory and anti-proliferative actions -Topical use -Useful in acne treatment -Has antimicrobial activity against P. acnes, as well as peeling and comedolytic effects (inhibits formation of comedones) -Has activity against anaerobic bacteria -Useful in acne treatment. -useful in psoriasis treatment. -useful in psoriasis treatment. -useful in psoriasis treatment. Side Effects -Toxicity: dryness, itching, headache, corneal opacities, pseudotumor cerebri (increase in intracranial pressure), inflammatory bowel disease, anorexia, alopecia, muscle and joint pain, and lipid abnormalities. ✓ -Teratogenic drug -Can cause bleaching of hair or colored fabrics -Hepatotoxic and teratogenic Notes Given orally: 1–2 mg/kg, given in two divided doses daily for 4–5 months. -Can be combined with erythromycin or clindamycin. -Has antimicrobial activity. -Related to isotretinoin (similar side effects) -Patients should not become pregnant for 3 years after stopping treatment, and also should not donate blood. -Teratogenic. Also, can cause burning, stinging, peeling, erythema, and localized edema of skin -A synthetic vitamin D3 derivative. Dermatologic Pharmacology Summary Drug MOA Route of Administration Uses Alefacept -useful in psoriasis treatment. Efalizumab -used to be useful in psoriasis treatment. Etanercept - useful in psoriasis treatment. Side Effects Notes -One of the biologic agents involved in psoriasis treatment. -It is an immunosuppressive dimer fusion protein of CD2 linked to the Fc portion of human IgG1 -Progressive multifocal leukoencephalopathy (PML) → withdrawn. -Can cause thrombocytopenia. -One of the biologic agents involved in psoriasis treatment. -Recombinant humanized IgG1 monoclonal antibody -Was withdrawn - One of the biologic agents involved in psoriasis treatment. -Dimeric fusion protein of TNF receptor linked to the Fc portion of human IgG1. Dermatologic Pharmacology Summary Drug MOA Topical Corticosteroids (Hydrocortisone, Prednisolone, Methylprednisolone, Dexamethasone, Betamethasone, Triamcinolone, Fluocinonide) Tar compounds Salicylic Acid -Solubilizes cell surface proteins resulting in desquamation of keratotic debris Propylene Glycole - Increases the hydration of the outer layers of skin Route of Uses Administration -Topical -Useful as antiinflammatory agents. -Used in dermatologic disorders that are very responsive to steroids: • Atopic dermatitis. • Seborrheic dermatitis. • Lichen simplex chronicus. • Pruritus ani. • Allergic contact dermatitis. • Eczematous dermatitis. • Psoriasis -Used alongside chemotherapeutic agents - often used in allergic conditions of the skin. -Mainly used in psoriasis, dermatitis, and lichen simplex chronicus - Topical use - used to prevent the development of acne or to clear the skin from black heads -Usually used as a vehicle for organic compounds Side Effects -Suppression of pituitary-adrenal axis. - Systemic effects: e.g. fat redistribution (buffalo hump, moon face). -Skin atrophy. -Erythema. -Pustules. -Acne. -Infections. -Hypo/Hyperpigmentation. -Allergic contact dermatitis. - Can cause irritant folliculitis, phototoxicity, and allergic contact dermatitis. -Locally, can cause urticaria, anaphylactic and erythema multiforme reactions, irritation, inflammation, and ulceration Minimally absorbed, oxidized in liver to lactic acid and pyruvic acid. Notes - Used alongside chemotherapeutic agents: 1) Hydrocortisone with Miconazole (in tinea infections). 2) Hydrocortisone with Bacitracin. -Triamcinolone is used in the treatment of keloid scars - prednisolone and dexamethasone might also be used as inhalers -One of the Keratolytic agents - Keratolytic in 3-6% concentration, but destructive in higher concentrations. -It increases the hydration of the outer layers of the skin as it develops an osmotic gradient through the stratum corneum. Dermatologic Pharmacology Summary Drug MOA Route of Administration Propylene Glycole (Cont.) Uses -Minimally absorbed, oxidized in liver to -One of the keratolytic agents -Has a humectant activity, i.e. softening and moisturizing effect on the stratum corneum. -Increases water content as a result of its hygroscopic characteristics. -When absorbed, it is excreted in urine -One of the keratolytic agents -Considered to be an antimetabolite. -It attracts water causing wetting and hydration of the skin. -It is used to decrease the unpleasant oily feel of dermatologic preparations Flurouracil -Resembles uracil and inhibits thymidylate synthetase, thus interferes with DNA and may be RNA synthesis - Used in multiple actinic keratosis Aminolevulinic Acid -Topical use Notes -Used alone as a keratolytic agent in concentrations of 40%- 70%, with plastic occlusion, or in gel with 6% salicylic acid. Urea Nonsteroidal antiinflammatory drugs Side Effects -When used as a gel (3% get formulation diclofenac), they have the ability to act as keratolytic agents -Used in actinic keratosis. lactic acid and pyruvic acid. -Examples: diclofenac sodium and diclofenac potassium. After topical application (20%) and exposure to light, it produces a cytotoxic superoxide and hydroxyl radicals which can harm the skin. -One of the keratolytic agents. Dermatologic Pharmacology Summary Drug MOA Doxepine -Potent H1 and H2 – receptor antagonist Pramoxine -It causes anesthesia in the applied area, causing loss of itching sensations Route of Administration Uses Side Effects - Can cause drowsiness and anticholinergic effects. -Topical use. Minoxidil (Rogaine) Notes -One of the Antipruritic Agents. -One of the Antipruritic Agents. -Considered to be a local anesthetic agent. Finasteride (Propecia) - 5ά-reductase -Oral use inhibitor which (tablets) blocks the conversion of testosterone to dihydrotestosterone. - Designed as an antihypertensive agent. - Used to regrow hair on the scalp since it has trichogenic properties -Effective in reversing the progressive miniaturization of terminal scalp hairs associated with androgenic alopecia - Serves as both a trichogenic (in men) and antitrichogenic agent (in women). - Also used to treat prostate hyperplasia Eflornithine – Is an irreversible inhibitor of ornithine decarboxylase, therefore, inhibits polyamine synthesis. - Effective in reducing facial hair growth in 30% of women when used for 6 months - Vertex balding is more responsive than frontal balding. -Can cause decreased libido, ejaculation disorders, and erectile dysfunction. -One of the antitrichogenic agents -Polyamines are important in cell division and hair growth. Dermatologic Pharmacology Summary Drug Sodium Stibogluconate MOA - Binds to SH groups found on parasite’s proteins disrupting their 3D structures. - Inhibits phosphofructokinase Miltefosine Pentamidine - Inhibits DNA replication. - Also, it is considered to be a DHF reductase inhibitor. Route of Uses Administration -Topical use - Drug of choice for -IM injection all forms of -IV infusion leishmaniasis Side Effects -Cough, Vomiting, Diarrhea, myalgia, arthralgia, ECG changes, Rash, Pruritus. Notes -One of the Pentavalent antimonials -IV infusions must be given slowly, because it is irritant. - Given for 20-28 days. - Resistance is increasing, especially in India. - Typical preparations contain 30% to 34% pentavalent antimony by weight as well as mchlorocresol added as a preservative. - Given for 28 days. -Oral use - Drug of choice For visceral leishmaniasis -Causes vomiting & diarrhea, hepatotoxicity, nephrotoxicity, and it is teratogenic. - IM or IV injection - Inhalation - Leishmaniasis: Alternative to Na stibogluconate -Pneumocystis jiroveci: Treatment and prophylaxis of patients who cannot tolerate or fail other drugs. -Trypanosomiasis: For early hemolymphatic stage. -Rapid Infusion: - Binds avidly to Hypotension, tissues, not the CNS. tachycardia, dizziness. -Low lipid solubility -Pain at the injection site. -Others: Pancreatic, Renal, and Hepatic toxicity. Dermatologic Pharmacology Summary Drug MOA Route of Administration Uses Dapsone and Sulphones Inhibit folate synthesis - One of the Antilepromatous drugs. -Also used for Pn. Jeroveci in AIDS patients Rifampin -Induces Cytochrome P450 - One of the Antilepromatous drugs Clofazimine -Binds to DNA -Given for sulphoneresistant or intolerant cases Side Effects Notes -Hemolysis, particularly in G-6-PD deficiency. -GIT intolerance -Fever, Pruritus, Rashes. - Erythema Nodosum Leprosum - Related to sulfonamides. - Combined with Rifampin and Clofazimine to overcome resistance. - Well absorbed and distributed. - Retained in the skin, muscle, liver and kidney ENL is suppressed by steroids or thalidomide. - Discussed with antituberculosis drugs. - Causes skin discoloration (redbrown to black) and GIT intolerance -Stored widely in RES and skin. -Released slowly from storage sites, t1/2 = 2 months.