[PF] DERMATOLOGICAL PHARMACOLOGY Flashcards
Two purposes of dermatological pharmacology:
- To directly treat disorders of the skin
2. To deliver drugs to other tissues
After application of a drug to the surface of the skin (stratum corneum), __________ and __________ may occur that affect the drug’s ultimate bioavailability.
evaporation
structural/compositional alterations
__________ limits drug diffusion into the lower layers and hence into the body
Stratum corneum
between the cells of the stratum corneum
Intercellular
across the corneal cellular layer
Transcellular
across the corneal cellular layer
Follicular
*with its associated sebaceous glandular cells and arrector pili muscle that is innervated by the sympathetic branch of the autonomic nervous system
Permeation to the _____ brings a drug in contact with lymphatics and cutaneous vessels carrying arterial and venous blood.
dermis
*These vessels provide an absorptive route into the general circulation.
Deeper permeation to the _______ may also occur.
hypodermis
Important considerations when a drug is applied to the skin:
- What are the absorption pathways of intact and diseased skin?
- How does the chemistry of the drug affect the penetration?
- How does the vehicle affect the penetration?
- How much of the drug penetrates the skin?
- What are the intended pharmacological targets?
- What host and genetic factors influence drug function in the skin?
- What are the predicted adverse effects?
immunosuppressive and anti-inflammatory properties
Glucocorticoids
measured using a vasoconstrictor assay in which an agent is applied to skin under occlusion, and the area of skin blanching is assessed.
Topical Glucocorticoids
*suppression of erythema and edema and the psoriasis bioassay
selected on the basis of its potency, the site of involvement, and the severity of the skin disease
Topical Glucocorticoids
Often, a more potent steroid is used initially, followed by a less potent agent.
Topical Glucocorticoids
daily application of topical glucocorticoids suffices; more frequent application does not improve response.
Twice
Chronic use of class 1 glucocorticoids:
- Skin atrophy
- Striae
- Telangiectasias
- Purpura
- Acneiform eruptions
________ and _______ develop after the use of fluorinated compounds on the face, therefore should not be used on this site.
perioral dermatitis and rosacea
________ increases the risk of HPA axis suppression
Occlusion
For severe dermatological illnesses and generally is reserved for allergic contact dermatitis to plants (e.g., poison ivy) and for life-threatening vesiculobullous dermatoses
Systemic Glucocorticoids
Daily morning dosing with ________ generally is preferred, although divided doses occasionally are used to enhance efficacy.
prednisone
Most side effects are _____________-.
dose dependent
Natural and synthetic compounds that exhibit vitamin A– like biological activity or bind to nuclear receptors for retinoids.
Retinoids
Retinoids exert their effects on gene expression by activating two families of receptors, ______ and ______, members- steroid receptor superfamily.
RARs and RXRs
*RAR: retinoic acid receptor
RARE: retinoic acid–responsive element
RXR: retinoid X receptor
On binding to a retinoid, RARs and RXRs form heterodimers (RAR-RXR) that bind specific DNA sequences (RAREs) that activate _______ of genes whose products produce both the desirable pharmacological effects
transcription
Retinoids that target _____ predominantly affect cellular differentiation and proliferation.
RARs
_______, _______ and _______ which target RARs, are used in acne, psoriasis, and photoaging (disorders of differentiation and proliferation).
Tretinoin
Adapalene
Tazarotene
Retinoids that target _____ predominantly induce apoptosis.
RXRs
_________ and ________ which target RXRs are used
Bexarotene
Alitretinoin
Retinoid Toxicity is similar to vitamin A intoxication:
dry skin, nosebleeds from dry mucous membranes, conjunctivitis, reduced night vision, hair loss, alterations in serum lipids and transaminases, hypothyroidism, inflammatory bowel disease flare, musculoskeletal pain, pseudotumor cerebri, and mood alterations
Photolabile (susceptible of change under the influence of radiant energy and especially of light)
Tretinoin
Should be applied once nightly for acne and photoaging
Tretinoin
_______ inactivates tretinoin and should not be applied simultaneously.
Benzoyl peroxide
Approved for the treatment of acne, psoriasis, and Cutaneous T Cell lymphoma
Systemic Retinoids
Recalcitrant (unresponsive to treatment) and nodular acne vulgaris (efficacy in severe acne) and may induce prolonged remissions after a single course of therapy.
Isotretinoin
Topical vitamin D analogue for the treatment of psoriasis.
Calcipotriene
Applied twice daily to plaque psoriasis on the body, often in combination with topical corticosteroids.
Calcipotriene
Hypercalcemia and hypercalciuria may develop when the cumulative weekly dose exceeds the recommended ________ limit and resolves within days of discontinuation of calcipotriene
100 g/week
precursor of vitamin A (green and yellow vegetables)
β-Carotene
Dietary supplementation used to reduce skin photosensitivity in patients with erythropoietic protoporphyria
β-Carotene
decreases the production of free radicals or single oxygen
β-Carotene
Maximum recommended therapeutic dose (MRTD) for β-carotene is _________.
0.05 mg/kg/d
UV or visible radiation induce a therapeutic response either alone (__________) or in the presence of an exogenous photosensitizing drug (__________)
phototherapy
photochemotherapy
(340–400 nm)
UVA1
(320–340 nm)
UVA2
(290–320 nm)
UVB
most erythrogenic and melanogenic, major action spectrum for sunburn, tanning, skin cancer, photoaging, and cutaneous vitamin D synthesis
UVB
(100–290 nm)
UVC
almost completely absorbed by the ozone layer and atmosphere so that measurable amounts do not reach Earth’s surface.
UVC
sunburns, photoaging, and skin cancer development, cause photoimmune suppression, an effect that is utilized for therapy of certain dermatological conditions.
UVA and UVB
a thousandth as erythrogenic as UVB but penetrates more deeply into the skin and contributes substantially to photoaging and photosensitivity diseases
UVA
able to penetrate clouds and glass, so exposure may occur even in the shade or while indoors.
UVA
combines UVA light with photosensitizing compounds called ________.
psoralens
Orally administered __________ followed by _______ is FDA approved for vitiligo and psoriasis, off label in several other inflammatory or lymphoproliferative cutaneous disorders
methoxsalen (8-methoxypsoralen)
UVA (PUVA)
stimulate melanocytes and induce antiproliferative, immunosuppressive, and anti-inflammatory effects, between 320 and 340 nm
PUVA: Psoralens and UVA
Oral methoxsalen dose is _____ capsule depending on weight (__________) taken about 1.5–2 h before UVA exposure.
10–70 mg
0.4–0.6 mg/kg
Lotion containing ________ is available for topical application for vitiligo.
1% methoxsalen
Approximately 70%–100% of psoriatic patients have clearing or virtual clearing of skin disease within about 24 treatments
PUVA
Remission typically lasts __________, often require maintenance therapy with intermittent PUVA or other agents.
3–6 months
between 150 and 300 treatments.
VITILIGO
Topical PUVA and more extensive disease with systemic administration.
Localized vitiligo
Risk of __________ dose dependent, greatest risk at more than 200–250 treatments
nonmelanoma skin cancer
Extracorporeal peripheral blood mononuclear cells separated using a leukapheresis-based method then exposed to UVA radiation in the presence of methoxsalen
Extracorporeal photopheresis (ECP)
_________ injected directly into the extracorporeal plasma before radiation and reinfusion
Methoxsalen
Treated lymphocytes are returned to the patient undergoing apoptosis over ________.
48–72 hr
Combines the use of photosensitizing drugs and visible light for the treatment of dermatological disorders, aminolevulinic acid and methylaminolevulinate.
Photodynamic Therapy
Provide temporary photoprotection from the acute and chronic effects of sun exposure
Sunscreens
Comprehensive sun protection approach along with minimizing sun exposure and using photoprotective gear.
Sunscreens
Reduces photocarcinogenesis and photoaging
Sunscreens
Ratio of the minimal dose of incident sunlight that will produce erythema (sunburn) on skin with the sunscreen in place to the dose that evokes the same reaction on skin without the sunscreen.
SPF (Sun protection factor)
Primarily a measure of UVB protection and does not provide information regarding UVA coverage.
SPF (Sun protection factor)
UVA protection assessed using the CW (critical wavelength) method, and products with a CW of 370 nm or greater may be labeled as ___________
“broad spectrum”
Sunscreens broad-spectrum coverage with an ______ or greater may include a claim on their labeling that use “decreases risk of skin cancer and early aging caused by the sun.”
SPF 15
Sunscreens should be applied liberally ________ prior to sun exposure and reapplied every ______.
15–30 min
2 hr
Activities involve swimming or sweating, water-resistant sunscreens are recommended and should be reapplied every _______ depending on their labeling.
40 or 80 min
Potent vasodilator, bronchial smooth muscle constrictor, and stimulant of nociceptive itch receptors
Antihistamines
Human skin mast cells express H1, H2, and H4 receptors but not ________.
H3 receptors
_____ and _______ receptors in wheal formation and erythema
H1 and H2 receptors
H1 receptor agonists cause ________.
pruritus
Blockade of H1 receptors does not totally relieve itching, and combination therapy with _____ and _______ may be superior to the use of H1 antagonists alone.
H1 and H2 antagonists
First-generation sedating H1 receptor antagonists:
- hydroxyzine
- diphenhydramine
- promethazine
- cyproheptadine
Lack anticholinergic side effects and are described as nonsedating largely because they do not cross the blood-brain barrier
Second-generation H1 receptor antagonists
Second-generation H1 receptor antagonists:
cetirizine levocetirizine loratadine desloratadine fexofenadine
Most common dermatological disorder treated with either topical or systemic antibiotics
Acne
Gram-positive anaerobe ___________ - component of normal skin flora that proliferates in the obstructed, lipid-rich lumen of the pilosebaceous unit, where O2 tension is low, generates free fatty acids from sebum and interacts with toll-like receptors, which promotes microcomedo formation and inflammatory lesions.
Propionibacterium acnes
Topical antimicrobials:
benzoyl peroxide
clindamycin
erythromycin
antibiotic–benzoyl peroxide combinations
Topical monotherapy with ________ or _________ is not recommended due to a slower onset of action and potential for development of bacterial resistance
clindamycin or erythromycin
Addition of ________ or use of combination antibiotic–_________ is recommended to improve efficacy and decrease emergence of antibiotic-resistant bacteria
benzoyl peroxide/benzoyl peroxide products
Systemic therapy for patients with acne vulgaris that is more extensive or resistant to topical therapy are antibiotics:
- Tetracyclines (doxycycline, minocycline, tetracycline)
- Macrolides (azithromycin, erythromycin)
- Trimethoprim-sulfamethoxazole
Usually administered once or twice daily, and _______ is required for visible clinical results, with maximum effect sometimes requiring _______.
6–8 weeks
3–6 months
Concomitant use with topical ________ may decrease development of antibiotic-resistant bacteria.
benzoyl peroxide
_________ and ________ have better GI absorption than tetracycline and may be given with food to minimize GI side effects
Minocycline and doxycycline
Inhibits protein synthesis by binding to bacterial isoleucyl-tRNA synthetase; effective for treatment of S. aureus and S. pyogenes, but it is inactive against normal skin flora or anaerobes.
Mupirocin
Mupirocin is available as a ____ ointment or cream, applied two or three times daily for ______.
2%
5–10 days
Inhibits staphylococci, streptococci, and gram-positive bacilli.
Bacitracin
Against staphylococci and most gram-negative bacilli.
Neomycin
Against aerobic gram-negative bacilli, including Pseudomonas aeruginosa.
Polymyxin B
Relatively common causes of allergic contact dermatitis, especially in patients with stasis dermatitis or otherwise disrupted skin
Both bacitracin and neomycin
Aminoglycoside that inhibits protein synthesis by binding to the 30S subunit of bacterial ribosomes; with activity from S. aureus, and gram-negative bacteria, including P. aeruginosa.
Gentamicin
Gentamicin sulfate ____ cream or ointment may be applied three or four times daily to affected areas.
0.1%
Binds to bacterial DNA and inhibits replication.
Silver Sulfadiazine
Bactericidal against gram-positive bacteria, including MRSA, and gram-negative bacteria, including P. aeruginosa
Silver Sulfadiazine
For partial-thickness burns or lower extremity venous stasis ulcers. However, recent studies have failed to demonstrate efficacy in these settings
Silver Sulfadiazine
SSTIs only caused by streptococcal and staphylococcal species, _________ and ________ are the systemic antibiotics used most frequently in their treatment.
penicillins (especially β-lactamase–resistant β-lactams) and cephalosporins
MRSA
clindamycin
doxycycline
trimethoprim-sulfamethoxazole
When coverage for both MRSA and streptococci is needed, _______ alone or the combination of either ________ or ________ with a β-lactam may be used
clindamycin
doxycycline or trimethoprim-sulfamethoxazole
Dermatophyte infections of the skin (Tinea Corporis, Cruris, and Pedis) generally respond to topical antifungals, including:
- Allylamines (naftifine, terbinafine)
- Benzylamines (butenafine)
- Azoles (econazole, luliconazole)
- Ciclopirox
Systemic therapy with ________, _______, _______ or ________ is used when there is more extensive cutaneous involvement or a poor response to topical therapy.
terbinafine
fluconazole
itraconazole
griseofulvin
________ for Tinea capitis
Griseofulvin
Dermatophyte infections of the hair (Tinea capitis) and follicles (Majocchi granuloma) require systemic therapy:
Terbinafine
Fluconazole
Itraconazole
fungal infection of the nails that is commonly caused by dermatophytes or candida.
Onychomycosis
________ is the most effective treatment of dermatophyte onychomycosis, adult dosing of 250 mg daily for _____ for fingernails and _____ for toenails.
Terbinafine
6 weeks
12 weeks
Cutaneous candidiasis localized
topical azole antifungals or nystatin
Systemic _________ or ________ for more recalcitrant or severe cases of cutaneous candidiasis
azole-fluconazole or itraconazole
Pityriasis versicolor and seborrheic dermatitis by Malassezia (pityrosporum) species is treated with _____ antifungals in cream or shampoo formulations.
azole
Are often used systemically to treat HSV and VZV infections
Acyclovir, famciclovir, and valacyclovir
For mucocutaneous HSV; however, they are less effective than systemic therapies
Acyclovir
Docosanol
Penciclovir
Combination of acyclovir/hydrocortisone
______ off label topically or intralesionally as treatment of anogenital warts caused by HPV.
Cidofovir
Topical cidofovir ___ gel or cream and applied once daily for 5 consecutive days every other week for a maximum of six cycles.
1%
Synthetic pyrethroid that interferes with insect Na+ transport proteins causing neurotoxicity and paralysis
Permethrin
Treatment of scabies
5% Permethrin
OTC for the treatment of lice; approved for use in infants 2 months or older.
1% lotion or cream rinse Permethrin
Organochloride compound that induces neuronal hyperstimulation and eventual paralysis of parasites.
Lindane
Second-line for pediculosis and scabies
Lindane
Potential for neurotoxicity in children and adults weighing less than 50 kg and patients with underlying skin disorders such as atopic dermatitis and psoriasis
Lindane
Lindane is contraindicated in _______ and patients with _______.
premature infants
seizure disorders
Organophosphate that inhibits acetylcholinesterase in lice, causing paralysis and death.
Malathion
For treatment of head lice in children 6 years and older.
Malathion
Formulation of malathion lotion contains _________, flammable.
78% isopropyl alcohol
Treatment of lice in patients 6 months and older.
Benzyl alcohol 5% lotion
Inhibits lice from closing their respiratory spiracles, which allows the vehicle to obstruct the spiracles and causes the lice to asphyxiate.
Benzyl alcohol 5% lotion
Antihelmintic drug approved for oral treatment of onchocerciasis and strongyloidiasis.
Ivermectin
Treatment of lice in patients 6 months or older
Topical ivermectin 0.5% lotion
Treat rosacea
1% cream ivermectin
Effective in the off-label treatment of scabies
Ivermectin
Both scabies and lice, Ivermectin is given at an oral dose of _______, which may be repeated in 1 week.
200 μg/kg
_________, longer treatment cycles of oral ivermectin sometimes in addition to topical keratolytics and scabicides.
Crusted scabies
Ivermectin should not be used in children weighing ________.
less than 15 kg
Are used in dermatology to treat dermatoses such as cutaneous lupus erythematosus, cutaneous dermatomyositis, polymorphous light eruption, porphyria cutanea tarda, and sarcoidosis.
Chloroquine, hydroxychloroquine, and quinacrine
Only _________ is FDA approved for treating lupus erythematosus.
hydroxychloroquine
Anti-inflammatory therapeutic effects of anti-malarial agents are uncertain but may involve inhibition of
endosomal toll-like receptor signaling, resulting in ________ and _________.
reduced B-cell
dendritic cell activation
Hydroxychloroquine
200 mg twice a day (maximum of 6.5 mg/kg/d)
Chloroquine
250–500 mg/d (maximum of 3 mg/kg/d)
Quinacrine
100–200 mg/d
_______ decreases the effectiveness of antimalarials in the treatment of cutaneous lupus erythematosus
Smoking
_______________ occurs with chloroquine more often than hydroxychloroquine.
Dose-dependent ocular toxicity
Chronic immune-mediated inflammatory disorder involving the innate and adaptive immune systems, with resultant abnormal keratinocyte proliferation
Psoriasis
Psoriasis is primarily ________, also with Th17/IL-17 pathway plays the most significant role.
Th1 mediated
Are key targets for therapy for Psoriasis
IL-23, TNF-α, and IL-17
Chronic skin disorder characterized by epidermal barrier dysfunction and immune-mediated inflammation.
Atopic dermatitis
Atopic dermatitis is ____ cell mediated, associated with cytokines ____, ____ and ____.
Th2
IL-4, IL-5, and IL-13
Chronic atopic dermatitis also involves ___ cell-mediated activity, associated with cytokines ____ and _____.
Th1
IL-12 and IFN-γ
________ and ________ are common therapies for atopic dermatitis and several of the traditional immunosuppressants
Topical corticosteroids and calcineurin inhibitors
Binds both TNF-α and TNF-β for plaque psoriasis and psoriatic arthritis in adults, safe and efficacious for pediatric psoriasis at dosing of 0.8 mg/kg (maximum
50 mg) once weekly.
Etanercept
For chronic severe plaque psoriasis and psoriatic arthritis; onset of action may be faster and efficacy greater compared to TNF-a. Concomitant administration of methotrexate or glucocorticoids may suppress this neutralizing antibody formation.
Infliximab
IL-12/23 Inhibitors
Ustekinumab
For moderate-to-severe plaque psoriasis and psoriatic arthritis.
Ustekinumab
After initial doses of Ustekinumab at weeks 0 and 4, it is administered every ______ for the maintenance phase of therapy, which may be ideal for some patients
12 weeks
IL-17 Inhibitors
Secukinumab
Fully human IgG1κ monoclonal antibody against IL-17A approved for the treatment of moderate-to-severe plaque psoriasis in adults
Secukinumab
most common adverse effects for IL-17 inhibitors
nasopharyngitis, upper respiratory tract infection, and diarrhea.
potential for increased mucocutaneous candidiasis infections, although this was not common during clinical trials.
Secukinumab
PDE4 Inhibitors
Apremilast
increases intracellular cyclic AMP levels, thereby decreasing expression of inflammatory cytokines such as TNF-α and IL-23 and increasing expression of anti-inflammatory cytokines such as IL-10.
Apremilast
For moderate- to-severe plaque psoriasis and psoriatic arthritis in adults.
Apremilast
Side effects of Apremilast are:
weight loss and depression.
_________ are tyrosine kinases involved in cytokine receptor signaling.
Janus kinases
______ leads to decreased downstream activity of STAT which modulates transcription of genes involved in cell growth, proliferation, and differentiation.
Jak inhibition
__________ is an oral Jak inhibitor approved for use in rheumatoid arthritis in adults.
Tofacitinib
IL-4 Inhibitors
Dupilumab
_________ shown promising results in clinical trials, demonstrating significant improvement in disease severity and fewer skin infections compared to placebo in atopic dermatitis
Dupilumab
The most frequent adverse effects of Dupilumab are ________ and ________.
nasopharyngitis and headache
Genetically inherited trait for male and female pattern
baldness
Androgenic Alopecia
Most common cause of hair loss in adults older than 40 years.
Androgenic Alopecia
__________ binds to the androgen receptor, and the hormone receptor complex activates the genes responsible for the gradual transformation of large terminal follicles into miniaturized vellus follicles.
Dihydrotestosterone (DHT)
________ is originally developed as an antihypertensive agent was noted to be associated with hypertrichosis in some patients.
Minoxidil
___ solution and a ___ solution or ______, enhances follicular size, resulting in thicker hair shafts, and stimulates and prolongs the anagen phase of the hair cycle, resulting in longer and increased numbers of hair.
2%
5%
foam
________ and __________ can occur, and care should be taken in applying the drug because hair growth may emerge in undesirable locations.
Allergic and irritant contact dermatitis
*reversible on stopping the drug
Patients with increased _________ enzyme activity - most likely to respond to minoxidil treatment; this may be a useful predictive test in the future.
sulfotransferase
________ inhibits the type II isozyme of 5α-reductase, the enzyme that converts testosterone to DHT and that is found in hair follicles.
Finasteride
Orally administered finasteride (______) variably increases hair growth in men over a 2-year period.
1 mg/d
___________ is approved for use only in men but has been used off label for female pattern hair loss
Finasteride
_____ use in women limited by its teratogenicity, inducing genital abnormalities in male fetuses.
Finasteride
Adverse effects of Finasteride:
decreased libido
erectile dysfunction
ejaculation disorder
decreased ejaculate volume
As with _________, new hair growth will be lost when
finasteride is discontinued.
minoxidil
______________ is a combined type I and type II isozyme 5α-reductase inhibitor that has similar or greater efficacy, but side effects may be more common
Dutasteride (0.5 mg/day)
____________ is an aldosterone antagonist and K+-sparing diuretic.
Spironolactone
it also has antiandrogen activity
Spironolactone
Spironolactone is used off label for female pattern alopecia at dosages of _________.
50–200 mg/d
Women of reproductive potential should not receive ______________ without reliable contraception because it can cause feminization of a male fetus
spironolactone
