Drugs- Dermatologic Pharm (Kinder)

Question 1

what are the major variables determining pharm response of skin

Answer 1

drug penetrance

concentration gradient

dosing schedule

vehicles and occlusion
-occlusion is trapping of a liquid within cavities on the skin, which can be extremely effective in maximizing drug efficacy

Question 2

what are the three routes that molecules can penetrate the skin

Answer 2

through intact stratum corneum

sweat ducts

sebaceous follicles

Question 3

what is the rate of absorption

Answer 3

J = Cveh * Km * D/x

i) Where J is the rate of absorption, Cveh is the concentration of drug in vehicle, Km is the partition coefficient, D is the diffusion coefficient, and x is the thickness of the stratum corneum (Piacquadio and Kligman, 1998).
ii) The rate of absorption is directly related to the concentration of drug, the partition coefficient, and the diffusion coefficient and inversely related to the thickness of the stratum corneum.

corneum is the rate limiting step

Question 4

what is the partition coefficient

Answer 4

release of drug from the vehicle

Question 5

what is the diffusion coefficient

Answer 5

drug diffusion across the layers of the skin reaching its site of action

Question 6

what are the preferable characteristics of topical drugs

Answer 6

low molecular mass

adequate solubility in oil/lipids and water

high lipid:water partition coefficient

Question 7

in order of their ability to retard evaporation from the surface of skin, name some dermatological vehicles

Answer 7

tinctures < wet dressings < lotions < gels < aerosols < powders < pastes < creams < ointments

wet - pulls excess moisture from the skin

acne preps
-if the pt has oily skin, using a wet dressing are good for oily skin
dry skin- use cream or ointment to prevent evaporation

Question 8

i) Acute inflammation with oozing, vesiculation, and crusting is best treated with what?

Answer 8

drying preparations such as tinctures, wet dressings, and lotions.

picks up excess moisture from the skin

Question 9

ii) Chronic inflammation with xerosis, scaling, and lichenification is best treated with what ?

Answer 9

more lubricating preparations such as creams and ointments.

prevents excess evaporation

Question 10

where is drug penetrance of skin higher

Answer 10

face

intertriginous areas

perineum

axilla, grow

Question 11

how does water content of the stratum corneum affect absorption

Answer 11

i) Absorption of pharmaceutical agents is increased as the water content of the stratum corneum is increased (i.e., the more hydrated the skin the more drug absorption will occur).
iii) Methods of hydration include occlusion with an impermeable film, application of lipophilic occlusive vehicles such as ointments, and soaking dry skin before occlusion.

Question 12

how does age affect absorption of drugs via skin

Answer 12

i) Due to the fact that children have a greater surface area to mass ratio than adults, a given amount of topical drug will result in a greater systemic dose in children.
ii) Research studies have shown that term infants possess a stratum corneum with barrier properties comparable with adults; however, preterm infants have markedly impaired barrier function.

Question 13

MOA of bacitracin and gramicidin

Answer 13

i) MOA: inhibits cell wall synthesis (bacitracin); binds phospholipids and increases permeability of cell wall (gramicidin).

Question 14

spectrum of bacitracin and gramicidin

Answer 14

ii) Spectrum: gram-positive organisms (streptococci, pneumococci, staphylococci) and most anaerobic cocci, neisseriae, tetanus bacilli, and diphtheria bacilli.

Question 15

MOA mupirocin (pseudomnonic acid A)

Answer 15

i) MOA: inhibits protein synthesis (binds to bacterial isoleucyl-tRNA synthetase).

Question 16

spectrum of Mupirocin

Answer 16

ii) Spectrum: most gram-positive aerobic bacteria, including methicillin-resistant S. aureus (MRSA).
iii) Effective treatment for impetigo caused by S. aureus and group A β-hemolytic streptococci.

Question 17

Polymyxin B sulfate MOA

Answer 17

i) MOA: binds phospholipids and increases permeability of cell wall membrane.
iii) Among main ingredients in Neosporin (with bacitracin and neomycin).

Question 18

Polymyxin B sulfate spectrum

Answer 18

ii) Spectrum: gram-negative organisms including P. aeruginosa, E. coli, Enterobacter, Klebsiella.

Question 19

high levels of polymyxin B sulfate can cause what?

Answer 19

neurotoxicity and nephrotoxicity

Question 20

MOA neomycin and gentamicin

Answer 20

i) MOA: irreversibly binds 30S subunit and inhibits protein synthesis.

Question 21

Spectrum of Neomycin and Gentamicin

Answer 21

gram-negative organisms including E. coli, Enterobacter, Klebsiella, Proteus, P. aeruginosa (gentamicin), staphylococci (gentamicin), group A β-hemolytic streptococci (gentamicin).

Question 22

if a pt has renal failure and is taking neomycin and gentamicin , what might happen

Answer 22

renal failure may cause nephrotoxicity, neurotoxicity, ototoxicity if serum levels become detectable (rare).

Question 23

Clindamycin
Erythromycin
Metronidazole

Answer 23

used as topical antibiotics in treatment of acne

Question 24

MOA and spectrum of Clindamycin

Answer 24

ii) Clindamycin
(1) MOA: inhibits protein synthesis by reversibly binding to 50S ribosomal subunit.

(2) Activity against Propionibacterium acnes thought to be beneficial effect in acne treatment.

Question 25

MOA of erythromycin

Answer 25

iii) Erythromycin | (1) MOA: inhibits protein synthesis by reversibly binding to 50S ribosomal subunit.

Question 26

what complications might occur with the use of topical erythromycin for acne

Answer 26

(2) Complications include development of antibiotic resistant staphylococci; if this occurs, discontinue topical treatment and begin systemic antibiotic therapy.

Question 27

Metronidazole | MOA and spectrum

Answer 27

(1) MOA: interacts with DNA resulting in strand breakage; anti-inflammatory effects. (2) Effective in the treatment of acne rosacea.

Question 28

in what pt's is metronidazole contraindicated

Answer 28

(3) Not recommended during pregnancy or nursing due to carcinogenic nature.

Question 29

Topical antifungal: | azole MOA

Answer 29

(1) MOA: inhibits synthesis of ergosterol (an essential component of the fungal cell membrane) by inhibiting fungal cytochrome P450 activity (lanosterol 14-α-demethylase).

Question 30

what are the uses of azoles

Answer 30

(2) Used for tinea corporis (ring worm), tinea pedis (athlete’s foot), tinea cruris (jock itch), tinea versicolor, and cutaneous candidiasis, such as vaginal yeast infections, infections of the skin, diaper rash, and thrush (candidiasis of the oral mucosa and tongue, and sometimes the palate, gingivae, and floor of the mouth). (3) Clotrimazole and miconazole are the prototype azoles used for Candidiasis infections that can be treated topically (topical formulations not suitable for oral, vaginal, or ocular use).

Question 31

Ciclopierox olamine

Answer 31

topical antifungal (1) Broad-spectrum antimycotic agent. (2) MOA: inhibits the uptake of precursors of macromolecular synthesis disrupting synthesis of DNA, RNA, and protein.

Question 32

uses for ciclopirox olamine

Answer 32

(3) Used to treat topical dermatomycosis, candidiasis, and tinea versicolor and mild to moderate onychomycosis of fingernails and toenails at higher topical concentrations (poor efficacy with overall cure rate approximately 12%).

Question 33

allylamines (terbinafine and naftifine) MOA and uses

Answer 33

topical antifungal (1) MOA: inhibits squalene epoxidase, a key enzyme in ergosterol biosynthesis. (2) Effective for topical treatment of tinea corporis, tinea cruris, and tinea pedis.

Question 34

Butenafine

Answer 34

(1) Similar to allylamines in MOA and use. topical antifungal

Question 35

Tolnaftate MOA and uses what is this ineffective against ?

Answer 35

Topical antifungal (1) Effective in the treatment of most cutaneous mycoses but is ineffective against candida. (2) MOA: exact antifungal MOA unknown. (3) Used for tinea pedis, tinea cruris, and tinea corporis.

Question 36

Nystatin and amphotericin B MOA

Answer 36

(1) MOA: binds to ergosterol in fungal cell membrane and alters membrane permeability, leading to the loss of potassium and other cell constituents (ineffective against dermatophytes). (2) Nystatin is limited to topical cutaneous and mucosal uses (poor oral bioavailability), which includes its use as an oral suspension for the treatment of oral candidiasis (thrush). (3) Amphotericin B has a broader antifungal spectrum and is used intravenously (lesser applications topically; may cause yellowing of the skin if used in a cream vehicle).

Question 37

ADR's of amphotericin B

Answer 37

topical antifungal (4) Amphotericin B causes infusion related toxicity (fever, shills, muscle spasms, vomiting, headache, and hypotension) and cumulative organ toxicity (kidney in almost all patients, liver, anemia), which has given this drug the nickname ‘ampho-terrible’

Question 38

what are the oral antifungal agents

Answer 38

azoles - fluconazole - itraconazole Griseofulvin Terbinafine

Question 39

what are the uses of oral azoles and what are the drug drug interactions

Answer 39

(1) Applicable in cases of vaginal, urinary, oropharyngeal or esophageal candida infections, onychomycosis. (2) Systemic yeast infections are more common in immune compromised patients, such as those with type 1 diabetes, leukemia, or AIDS. (4) Involved in numerous drug-drug interactions by decreasing rate of drug metabolism (e.g., results in increased INR in patients receiving warfarin and co-administration with statins increases risk of rhabdomyolysis).

Question 40

what are the topical antivirals used?

Answer 40

acyclovir penciclovir docosanol (Abreva)

Question 41

MOA of acyclovir and penciclovir

Answer 41

(1) Randomized trials of patients with sporadic recurrences of HSV-1 infection showed that antiviral therapy with topical creams or ointments are of modest benefit. (2) Synthetic guanine analogs; inhibitory activity against members of herpesvirus family (HSV1 & 2) (3) MOA: converted to pharmacologically active triphosphate metabolites, inhibit viral DNA synthesis and viral replication topically used for recurrent orolabial HSV infections (immunocompetent)

Question 42

Docosanol MOA

Answer 42

(1) MOA: inhibits fusion between the plasma membrane and the HSV envelope, thereby preventing viral entry and replication. can shorten duration of orolabial herpes

Question 43

Imiquimod MOA uses

Answer 43

Immunomodulator i) Approved for the treatment of external genital and perianal warts in adults, actinic keratoses on the face and scalp, biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities. ii) MOA: may be related to stimulation of peripheral mononuclear cells to release interferon-α and macrophage stimulation to produce interleukins-1, -6, -8, and tumor necrosis factor-α (TNF-α).

Question 44

Tacrolimus and Pimecrolimus MOA

Answer 44

immunomodulators iii) MOA: inhibit T-lymphocyte activation and prevent release of inflammatory cytokines and mediators from mast cells.

Question 45

uses of Tacrolimus

Answer 45

i) Macrolide immunosuppressant beneficial in treatment of atopic dermatitis as a second-line agent.

Question 46

what are the ADR's of tacrolimus and which patients do you NOT use this drug

Answer 46

iv) Common topical adverse effects include transient erythema, burning, and pruritus (systemic adverse effects are hypertension, nephrotoxicity, neurotoxicity, GI symptoms, hyperglycemia, hyperlipidemia). do not use in immunocompromised patients or children < 2 years.

Question 47

Exposure to what is responsible for most of the erythema and sunburn associated with sun exposure and tanning

Answer 47

a) Exposure to UVB rays responsible for most of the erythema and sunburn associated with sun exposure and tanning. b) Chronic exposure to UVB rays (280-320 nm) induces aging of the skin and photocarcinogenesis. c) Long-wave UVA rays (320-400 nm) associated with skin cancer and aging.

Question 48

what three classes of chemicals are most often used in sunscreens

Answer 48

i) p-aminobenzoic acid (PABA) ii) Benzophenones (oxybenzone, dioxybenzone, sulisobenzone) iii) Dibenzoylmethanes (Parasol, Eusolex)

Question 49

how long is sunscreen effective period.

Answer 49

2 hours i) Sunscreens should be uniformly applied approximately 15-30 minutes before sun exposure. ii) The American Academy of Dermatology recommends a sunscreen of SPF 30 or higher be used in most circumstances. iii) Most adults need one ounce of sunscreen. Reapply every 2 hours.

Question 50

Tretinoin (all trans retinoic acid) (Acid form of Vitamin A) MOA

Answer 50

(a) MOA: exact mechanism in the treatment of acne unknown; may decrease cohesion between epidermal cells and increase epidermal cell turnover, thought to result in the expulsion of open comedones and the transformation of closed comedones into those that are open (also marketed as an anti-wrinkle cream).

Question 51

what are Adapalene and Tazarotene

Answer 51

retinoic acid derivatives

Question 52

Adapalene | uses

Answer 52

retinoic acid derivative (a) Photo-chemically more stable and less irritating than tretinoin. (b) Used to treat mild to moderate acne vulgaris.

Question 53

tazarotene uses

Answer 53

retinoic acid derivative (a) Approved for psoriasis, photoaging, acne

Question 54

in what pt's are topical retinoids NOT recommended

Answer 54

pregnant women

Question 55

Adverse effects of tretinoin

Answer 55

(c) Common adverse events include erythema, mild peeling, and dryness; patients advised to avoid or minimize sun exposure (patients may experience photosensitivity reactions because of enhanced reactivity to UV radiation, increases their risk for severe sunburn). (d) Initial therapy may aggravate acne but continual treatment increases the likelihood of optimal clinical improvement.

Question 56

(1) Isotretinoin what is this? MOA uses

Answer 56

oral acne preparation (b) MOA: reduces sebaceous gland size and reduces sebum production. (a) Use restricted to the treatment of unmanageable severe cystic acne, disorders of keratinization, psoriasis, and cutaneous and extracutaneous malignant neoplasms.

Question 57

Adverse effects of isotretinoin

Answer 57

(a) Use restricted to the treatment of unmanageable severe cystic acne, disorders of keratinization, psoriasis, and cutaneous and extracutaneous malignant neoplasms. (f) Severe side effects include headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, muscle and joint pains, suicide risk.

Question 58

in what pt's is isotretinoin contraindicated

Answer 58

pregnancy (g) Teratogen; serum pregnancy test MUST be obtained within 2 weeks before starting therapy.

Question 59

MOA of Benzoyl peroxide

Answer 59

i) MOA: releases free-radical oxygen which oxidizes bacterial proteins in the sebaceous follicles decreasing the number of anaerobic bacteria and decreasing irritating-type free fatty acids. ii) Prodrug converted to benzoic acid within the epidermis and dermis. used for P. acnes

Question 60

``` Acitretin Tazarotene Calcipotriene cyclosporine TNF inhibitors ```

Answer 60

Drugs for psoriasis

Question 61

acitretin

Answer 61

i) Retinoic acid derivative given orally for the treatment of severe psoriasis, especially pustular form

Question 62

contraindications of acitretin

Answer 62

v) Contraindicated in any women who are pregnant or may become pregnant during treatment or at any time for at least 3 years after treatment (patient must commit to using two effective forms of birth control starting 1 month prior to treatment and for 3 years after discontinuation); similar restrictions for blood donation. iv) Combination with ethanol can form etretinate, a highly teratogenic compound that may be found in plasma and subcutaneous fat for up to 3 years.

Question 63

b) Tazarotene

Answer 63

i) Topical retinoid prodrug used in the treatment of psoriasis, acne, photoaging. ii) Active metabolite binds to retinoic acid receptors; may affect expression of genes that modulate cell differentiation, proliferation, and inflammation.

Question 64

Calcipotriene

Answer 64

i) Synthetic vitamin D3 analog that regulates skin cell production and proliferation. ii) Used alone or in fixed combination with betamethasone dipropionate for the topical treatment of plaque-type psoriasis. Combination more effective than either agent used alone. iii) Adverse effects include burning, itching, mild irritation, dryness, erythema; avoid contact with face and eyes.

Question 65

cyclosporine | MOA

Answer 65

i) MOA: inhibits calcineurin (phosphatase that enhances cytokine transcription) and thereby inhibits transcription of interleukin-1 and -2 receptors; blocks T-cell activation (immunosuppressant agent). ii) PO dosing approved for treatment of psoriasis, rheumatoid arthritis, and liver, heart, kidney, and bone marrow transplants.

Question 66

what are the side effects of cyclosporine

Answer 66

iii) Side effects include significant nephrotoxicity, hypertension, hepatotoxicity, gingival hyperplasia, and hirsutism.

Question 67

Etanercept infliximab adalimumab

Answer 67

Biologic response modifiers TNF inhibitors

Question 68

Etanercept MOA

Answer 68

(a) Dimeric fusion protein of the extracellular ligand-binding portion of the human tumor necrosis factor (TNF) receptor linked to the Fc portion of human IgG1. (b) MOA: binds to TNF α and β and prevents TNF-mediated immune response. treat psoriasis

Question 69

infliximab MOA

Answer 69

(a) Chimeric IgG1 monoclonal antibody. (b) MOA: binds to soluble and transmembrane forms of TNF-α and inhibits TNF receptor activation. psoriasis treatment

Question 70

adalimumab MOA

Answer 70

(a) Recombinant IgG1 monoclonal antibody (b) MOA: binds to TNF-α and inhibits TNF receptor activation. psoriasis treatment

Question 71

ADR;s of TNF alpha inhibitors

Answer 71

(4) TNF-α inhibitors can cause serious life-threatening infections (e.g., sepsis, pneumonia), exacerbate congestive heart failure, and cause demyelinating disease in predisposed patients. (5) Evaluate for tuberculosis risk factors and latent disease prior to initiating therapy. (6) There is a possible association between the use of TNF blockers and the development of lymphoma and other cancers.

Question 72

what are the adverse effects of topical corticosteroids

Answer 72

(1) Suppression of the pituitary-adrenal axis, Cushing’s syndrome and other systemic effects with long-term use. (2) Atrophy, steroid rosacea, perioral dermatitis, steroid acne, increased intraocular pressure, allergic contact dermatitis.

Question 73

what are some examples of common topical corticosteroids

Answer 73

hydrocortisone (among the lowest efficacy), (methyl)prednisolone, dexamethasone, betamethasone, mometasone, triamcinolone, and clobetasol propionate (among the highest efficacy).

Question 74

what is a keratolytic agent

Answer 74

a) A keratolytic agent is a peeling agent that causes softening/dissolution or peeling of the stratum corneum of the epidermis.

Question 75

salicylic acid

Answer 75

keratolytic agent i) Approved for treatment of acne, seborrheic dermatitis, psoriasis, hyperkeratosis (corns, plantar warts, calluses); in combination with antifungal sodium thiosulfate for tinea versicolor. ii) Can be destructive to tissues at concentrations greater than 6% (keratolytic at 3-6%).

Question 76

what are the adverse effects of salicylic acid and in what pt's must you use caution

Answer 76

iii) Salicylate toxicity can occur (nausea, vomiting, dizziness, loss of hearing, tinnitus, lethargy, diarrhea, psychic disturbances). iv) Use care in patients with diabetes or peripheral vascular disease.

Question 77

MOA of Fluorouracil

Answer 77

keratolytic agent i) Fluorinated pyrimidine antimetabolite resembling uracil used in the topical treatment of multiple actinic keratosis. ii) MOA: inhibits thymidylate synthetase and interferes with DNA synthesis (effects most pronounced on rapidly proliferating cells). iii) Adverse topical effects include pain, pruritus, burning, residual post-inflammatory hyperpigmentation; avoid excessive exposure to sun during treatment.

Question 78

first generation antihistamines as antipruitic agents examples? uses?

Answer 78

iv) First generation H1-receptor antagonists (1) Examples include diphenhydramine and promethazine (2) Have some anticholinergic activity and are sedating, making them useful for the control of nocturnal pruritus.

Question 79

2nd generation antihistamines as antipruitic agents examples uses

Answer 79

v) Second generation H1-receptor antagonists (1) Lack anticholinergic side effects, do not cross blood-brain barrier, and are nonsedating. (2) Examples include cetirizine, loratadine, desloratadine, fexofenadine hydrochloride. (3) Second generation blockers are metabolized by CYP3A4 and CYP2D6 and should not be co-administered with medications that inhibit these enzymes (e.g., imidazole antifungals, macrolide antibiotics). i) H¬1-receptor antagonists are useful in the treatment of pruritus.

Question 80

what is a trichogen

Answer 80

an agent that promotes the growth of hair

Question 81

minoxidil (rogaine)

Answer 81

used for androgenic alopecia MOA not known iii) Response rate better for vertex balding than frontal balding. iv) Treatment must be continued or any drug-induced hair growth will be lost. v) Percutaneous absorption is minimal but systemic effects on blood pressure should be monitored in patients with cardiac disease.

Question 82

finasteride MOA

Answer 82

i) Used for treatment of androgenic alopecia and benign prostatic hypertrophy. ii) MOA: competitive and selective inhibitor of steroid 5α-reductase; blocks the conversion of testosterone to dihydrotestosterone (DHT). iv) Treatment must be continued to sustain benefit.

Question 83

what are the predictable adverse effects of finasteride

Answer 83

iii) Predictable adverse effects: decreased libido, ejaculation disorders, erectile dysfunction. v) Pregnant women should not be exposed to drug, either by use (not approved for use in women) or handling, due to risk of hypospadias in male fetus.

Question 84

Which two topical antimicrobials cover group A β-hemolytic streptococci and S. aureus (including MRSA)?

Answer 84

retapamulin | mupirocin

Question 85

general treatment approach for non-bullous impetigo

Answer 85

Non-bullous impetigo – topical therapy with mupirocin or retapamulin for 5 days More extensive forms of impetigo and bullous forms – oral antimicrobials for 7 days why can't we used bacitracin-neomycin-polymyxin B? -not as effective can cause contact dermatitis

Question 86

increased sebum production in acne creates a lipid rich micro-aerobic environment favorable to what organism

Answer 86

gram positive rod --> propionbacterium acne

Question 87

what are the options for treatment of dermatophyte infections ?

Answer 87

Tinea capitis (scalp) – oral griseofulvin, terbinafine, itraconazole Tinea pedis (feet) – topical antifungals Tinea cruris (groin) – topical antifungals Tinea corporis (body) – topical antifungals, oral antifungals

Question 88

what are the treatment options for candida

Answer 88

Thrush (oropharyngeal candidiasis) – oral nystatin, clotrimazole troche, oral fluconazole Esophageal candidiasis – systemic antifungals Vulvovaginitis – topical antifungals, oral fluconazole Invasive infection – systemic antifungals

Question 89

mild acne?

Answer 89

few lesions, little or no inflammation

Question 90

moderate acne

Answer 90

many lesions | signficiant inflammation

Question 91

severe acne

Answer 91

numerous lesions | extreme inflammation, signficant scarring

Question 92

treatment for comedonal (non-inflammatory acne)

Answer 92

topical retinoid

Question 93

mild papulopustural and mixed acne treatment

Answer 93

topical retinoid AND topical antimicrobial (BPO alone or BPO +/- antibiotic)

Question 94

treatment for moderate papulopustular and mixed acne or moderate nodular acne?

Answer 94

topical retinoid AND oral antibiotic AND topical BPO

Question 95

treatment for Severe nodular/conglobate acne

Answer 95

Oral isotretinoin

Question 96

in the treatment of mild/moderate psoriasis, what are the first line agents

Answer 96

emollients - reduce scaling, itching keratolytics - reduce hyperkeratosis topical glucocorticoids - control inflammation and itching topical!

Question 97

treatment of systemic psoriasis (>5% of body surface area)

Answer 97

methotrexate- don't use in kidney or liver dysfunction acitretin -don't use in pregnancy and heavy alcohol use cyclosporine - don't use in kidney dysfunction and HTN