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Pharm Exam 5 > Topicals > Flashcards

Topicals Flashcards

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1
Q

Describe the three absorption pathways of intact and diseased skin?

A

1) through appendages - down the hair follicle- shunt route
2) Through intracellular lipid domains
3) Transcellular route (through corneocytes of stratum corneum)
- hydrates keratin in corneocytes allows hydrophilic drugs to pass

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2
Q
  • What is rate limiting step of percutaneous absorption (PCA)?
  • What are the factors?
A
  • passage through stratum corneum
    1) [] of drug in the vehicle
    2) partitioning of drug from vehicle into stratum corneum (partition coefficient)
    3) molecular aspects of drug allowing diffusion across skin layers (drug diffusion coefficient)
    4) thickness of stratum corneum
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3
Q

What kind of process is conventional trandermal drug delivery?

A

passive process

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4
Q

what is name of equation to calculate rate of absorption or flux of substance across barrier

A

Fick’s Law

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5
Q

Drug variables for PCA?

A

1) concentration-directly related to PCA
2) lipophilicity-must be at least a little fat sol
3) Molecular size-most effective if <600daltons

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6
Q

Innate skin variables for PCA?

A

1) stratum corneum thickness - rate-limiting - inversely related
2) cutaneous vasculature-inc vaculature=inc local and systemic drug effects
3) area of absorptive surface-inc surface area=inc PCA (But concentration is still the more important variable)
4) mucosal surfaces-not much of a barrier compared to S. corneum-systemic effects with any mucosal barrier

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7
Q

What are vehicle factors?

A

1) how occlusive (hydrating) it is - the more=the greater hydration & absorption
2) how drug released from vehicle

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8
Q

Best occlusive vehicle for topical?

A

ointment

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9
Q

Best vehicle to use for transfering drug to stratum corneum lipids?

A

-Ointment

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10
Q

Dont use ointments where?

A

where skin rubs against skin - integrous areas

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11
Q

Which vehicle is best to prevent evaporation of topical?

A

ointment

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12
Q

Alergic reactions most often from what vehicle?

A

emulsifying agents

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13
Q

most penetration vs least penetration areas?

A

1) BEST ABSORPTION=MOST SYSTEMIC EXPOSURE = mucous membranes
2) scrotum
3) eyelids
4) face
5) chest and back
6) upper arms and legs
7) lower arms and legs
8) Dorsa of hands and feet
9) palmar and plantar skin
10) WORST = Nails

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14
Q

Psoriasis pathophysiology

  • describe disease?
  • what areas?
  • most common type?
A
  • autoimmune=inflammation and keratinocyte hyperproliferation
  • scalp, groin/genetalia, lower back, elbows & knees, nails
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15
Q

Acne

  • describe the disease?
  • steps?
A
  • hyperproliferation of epidermis + sebum secretion –> increased sensitivity to androgens
  • gram + bacteria –> perifollicular inflammation
    1) Microcomedone
    2) Comedone
    3) inflammatory pustule
    4) nodue - deeper inflammation
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16
Q

atopic dermatitis (eczema)

  • what is it?
  • secondary problems?
A
  • chronic inflammatory skin (unk mech but food, allergy, irritation related) disorder associated with intense pruritus and dried flaking skin
  • secondary S. Aureus infection
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17
Q

mechanism of itch (pruritus)

A
  • histamine released from dermal mast cells causes itch related to utricaria (hives) and insect dites
  • g-proteins on somatosensory nerves activated
  • Ca entry TRPV1 ligand activated
  • Substance P induced histamine release
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18
Q

types of pruritus

A

1) dermatologic (primary skin disorder)
- xerosis, atopic dermatitis, psoriasis..
2) systeic (affect other organ systems)
- CRF, liver disease, hematologic or lymphoproliferative, malignancy
3) neruologic (PNS or CNS issues like MS)
4) Psychogenic (psych disorders)
- depression, anxiety…
5) mixed - more than one cause

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19
Q

Benzoyl peroxide

  • type?
  • MOA?
  • used for?
A
  • topical antibiotic for non-inflammatory and inflammatory acne
  • broad cidal
  • non-specific oxydizing activity (no development of resistance)
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20
Q

Clindamycin?

  • type?
  • used for?
A

-topical antibiotic -broad cidal
-for acne
(Binds 50S subunit)

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21
Q

Erythromycin

  • type
  • used for?
A

-topical antibiotic -gram positive - cidal
-for acne
(Bind 50S subunit)

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22
Q

Metronidazole

  • type?
  • used for?
A

-topical antibiotic- gram + and - anaerobic coverage - static
-for acne
(disruption of DNA and inh of nucleic acid synth)

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23
Q

azelaic acid

  • type?
  • used for?
A

-topical antibiotic -against P Acnes –> cidal & static
-for acne
(disruption of mitochondiral respiration and DNA synth)

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24
Q

sodium sulfacetamide

  • type?
  • used for?
A

-topical antibiotic -against P acnes
-for acne
(inh dihydropteroate synthetase)

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25
- use of whcih topical antibiotic DOES NOT lead to resistance over time? - MOA?
- benzoyl peroxide | - non specific oxydizing agent
26
Retinoids - what are they? - what do they do generally?
- chemicals with activity like Vit A - binds retinoic acid receptors (RARs) and retoinoid X receptors (RXRs) - different isomer metabolites bind differentially to RARs and RXRs - direclty bind DNA and alter DNA transcription
27
Retinoids | -what do they do generally?
-direclty bind DNA and alter DNA transcription ==>decrease proinflammatory cytokines (Tol-Like receptors on monocytes that secrete cytokines) ==>reduce cellular proliferation and inflammation (AP-1 transcrpiton factor inhibited) ==>reduce obstruction within follicle ==> loosen corneocytes (inc abs of other agents treating acne) ==> promotes desquamation ==> promotes dermal collagen synthesis
28
tretinoin - what is it? type? - how does it work? - used for? - issues with this?
- naturally ocurring retinoic drug - binds to RARs and metabolic products binds RXRs - used for acne and photoaging - photosensitive - usually applied at night
29
first topical retinoid approved for acne?
tretinoin (all-trans retionic acid)
30
adapalene - what is it? type? - how does it work? - benefits to use? - used for?
- naturally ocurring retinoid - better than tretinoin bc more chemically stable and more lipophillic (trapped in sebum) - for acne
31
tazarotene - what is it? type? - how does it work? - used for?
- tpical pro-drug that becomes tazarotenic acid - binds to all RARs - treats psoriasis - treats mild to moderate acne
32
Which retinoid drug can be used to tx psoriasis?
tazarotene - tpical pro-drug that becomes tazarotenic acid - binds to all RARs
33
Which retinoid drugs cause teratogenic effects and which do not?
DO: Tretinoin, tazarotene, isotretinoin, Bexarotene, Acitretin DO NOT: adapalene
34
Which retinoid drug do you not prescribe with benzoyl peroxide? Which ok?
- DO NOT: Tretinoin | - OK WITH: Adapalene
35
Which retinoid drug is used specifically to treat AIDS-related kaposi's sarcoma?
-alitretinoin
36
Alitretinoin - type? - used for? - do not use with what drug/chemical?
- retinoid - treat AIDS-related kaposi's sarcoma - do not use with DEET (inc absorption of DEET)
37
isotretinoin - what type? - what used for?
- oral med for severe acne | - significant risk of teratogeneisis (extreme caution in women who might get pregnant - need birth control)
38
Bexarotene - what type? administration? - MOA? -what does it do/effects? - used for what? - risks?
- retinoid drug - oral and topical - selective RXR binding ==> inh cell cycle and inc apoptosis, decreases inflammation and reduces angiogenesis - tx cutaneous T-cell lymphoma - birth defects; hypothyroidism
39
Tx cutaneous T-cell lymphoma?
Bexarotene | --selective RXR binding ==> inh cell cycle and inc apoptosis, decreases inflammation and reduces angiogenesis
40
Acitretin - what type? administration? - risks? - used for what?
- retinoid - orally - highly teratogenic - do not get pregnant 3-years after stopping drug - with ETOH = prolonged storage in fat as etretinate - for severe psoriasis
41
Acetretin and alcohol should not be mixed why?
-converted to etretinate = liver toxicity - storage in fat
42
Absolute Acetretin contraindication
- pregnancy - liver failure - kidney failure - allergy to drug components
43
Dont get pregnant within 3 years of stopping this drug?
acetretin
44
Retinoid drugs and pregnancy risk? ok if used how theoretically?
- theoretically no teratogenic effects if used topically (but most docs dont prescribe if has risk) - Most are prego C category
45
Which retinoid drugs are prego category X?
- tazarotene | - isotretinoin
46
Retinoids adverse effects?
- pregnancy risks - photosensitivity - skin irritancy (first 3 weeks) - use synthetic soap
47
Vit D analogs | -what does it do?
- inh proliferation of keratinocytes - promotes formation of cornified envelope - inh production of IL 2 and IL6 by T-cells - blocks interferon gamma expression - inh t-cell and NK cell activity - causes hypercalcemina and hypercalcuria
48
Calcipotreiene - What type? - MOA? - used for? - risk?
- Vit D analog - binds Vit D receptor--> complexes with RXR-alpa receptor regulating gene trascription ==> dec keratinocyte proliferation and inflammation - some risk of hypercalcemia and hypercalcuria - mod to severe psoriasis
49
Pramoxine - type? - administration? - MOA?
- topical antipruritic | - blocks transmission of sensory nerve impulses - blocks cold pain but not warmth or heat pain
50
Menthol - -type? - administration? - MOA?
- topical antipruritic | - activates TRPM8 cation channel --> blocks cold pain
51
Doxepin
- topical antipruritic | - potent histamine antagonist (H1 and H2) --> sedation via anticholinergic properties
52
Photochemical therapy - used for? - how works?
- psoriasis - psoralen (methoxsalen & trioxsalen) plus Ultraviolet A - psoralen topical or oral and the expose skin to UVA light (intercalate with the DNA)
53
Methoxsalen & trioxsalen - type? - used how? - Tx?
- Psorlens - psoralen plus UVA photochemical therapy | - for psoriasis
54
Short term Photochemical therapy (psoralen) adverse effects?
- nausea - blistering - painful erythema
55
Chronic adverse Photochemical therapy (psoralen) adverse effects?
- photoaging - actinic keratoses - nonmelanoma skin cancer --> monitor closely for cutaneous carcinomas
56
Topical calcineurin inh
tacrolimus | pimecrolimus
57
tacrolimus & pimecrolimus - type? - used for?
- topical calcineurin inh - atopic dermatitis - psoriasis - pruritus - reduce inflammation - desnsitize peripheral nerve fibers (reduce itch - TRPV1 receptor) - reduce IL2 synthesis and secretion (prevent itch)
58
topical keratolytic agents: - name the drugs: - for what?
- salicylic acid - urea - propylene glycol - 5-fluorouracil -for stuff like psoriasis and ichthyoses (scaling and thickened areas of skin)
59
Salicylic acid - type? - does what? - caution where/how?
- topical keratolytic agent - reduces corneocyte adhesion and promotes softening of stratum corneum ==> desquamation - careful in children if in toxic systemic concentations
60
Urea - type? - does what? - used for (specific loaction)?
- topical keratolytic agent - inc solubilization of stratum corneum by altering keratin and breaking hydrogen bonds - used hyperkeratosis esp on palms and soles
61
propylene glycol - type - how used? - what for?
- topical keratolytic agent - used in combo with salicylic acid - for hyperkeratosis disorders (psoriasis and ichythyoses)
62
5-fluorouracil - type? - used for? - how works?
- topical keratolytic agent - for multiple actinic keratoses - inh thymidylate synthetase activity = DNA damage - redness--> ulceration --> necrosis --> reepitheliazation and healing
63
Hyperpigmentation drugs? | -MOA?
- hydroquinone - monobenzone -inh melanin production by melanocytes
64
hydroquinone - type? - MOA? - used for?
- anti-hyperpigmentation agent - -inh melanin production by melanocytes - temporary lightening of skin - used for melasma
65
monobenzone - type - MOA?
- anithyperpigmentation - -inh melanin production by melanocytes - Irreversible depigmentation - toxic to melanocytes

Pharm Exam 5 (10 decks)

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