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imed3004 > Skin Pharmacology 1 > Flashcards

Skin Pharmacology 1 Flashcards

1
Q

What is the preferred modality of treatment for most dermatoses? Why?

A

Topical therapy, due to direct contact between drug and target tissue and without the systemic side effects.

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2
Q

What are the uses of topical drugs? Name 5

A

Barriers (eg moisturisers)

Antiinflammatories (Topical steroids)

Anti infective

Immune modulators (Imiquimod and tacrolimus)

Cytotoxic (5-fluorouracil)

Keratolytic

Retinoids

Depigmentary creams

Sunscreen

Camouflage

Depilatory (removing hairs)

Antiperspirants

Insect repellants

Others

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3
Q

What does the effectiveness of topical drugs depend on?

A

Nature of skin (Stratum corneum integrity, anatomical site, skin metabolism (inflammation))

Nature of topical preparation

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4
Q

How does stratum corneum integrity affect effectiveness of topical drug therapy?

A

Skin damage may increase permeability

Adherent scale may reduce drug penetration

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5
Q

How does anatomical site affect drug permeability?

A

Thicker skin (eg feet or palms) less permeable

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6
Q

What are the types of topical preparation vehicles (or bases)?

A

Monophasic (Powder, liquid, greasy base)

Biphasic (Shake lotions, creams, ointments, pastes)

Triphasic (Cooling paste, cream paste)

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7
Q

How are powders used?

A

Contain active ingredients

Used in cosmetics and sunscreens

Can promote drying

If skin weeping, abrasive in the flexures (should be used with caution near these areas)

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8
Q

What are the types of monophasic liquids?

A

Wet dressings (Burow’s, normal saline, H2O2)

Baths

Tinctures

Lotions (sprays/aerosols)

Gels (transparent colloidal dispersions that liquify on contact with skin)

Greasy bases (Oils and Petrolatum)

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9
Q

What are tinctures?

A

Organic solvents that evaporate rapidly to leave film of active ingredients

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10
Q

What are oils for?

A

They do not adhere to skin and are used to remove adherent materials

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11
Q

What is petrolatum (vaseline) used for?

A

It is a stable, occlusive and emollient made up of a purified semisolid hydrocarbon ointment base.

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12
Q

What are the types of biphasic vehicles?

A

Shake lotions: Powder in solution

Creams (oil in water base)

Ointments (water in oil base)

Pastes (powder in ointment base)

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13
Q

What are creams needed for?

A

Emulsifying agents necessary to increase the surface area of the dispersed phase.

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14
Q

What are ointments good for?

A

Better moisturisers than creams

They are better moisturisers than creams

No preservatives are necessary

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15
Q

What is a possible side effect of using ointments?

A

Can cause occlusive folliculitis

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16
Q

How are pastes different to ointments?

A

They are more viscid and less greasy than ointments.

Powder is added into ointment base

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17
Q

What are triphasic vehicles used for?

A

They are used as cooling pastes (oil - water - powder mixtures)

Creamy pastes (Burow’s emulsion)

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18
Q

What ingredients are commonly used in topical preparations?

A

Emollients (petrolatum, cetyl alcohol, stearyl alcohol)

Humectants (glycerin)

Solvents (alcohol, propylene glycol)

Emulsifying agents (Polysorbates and sorbitan (can cause contact dermatitis))

Stabilisers (preservatives, antioxidants, and chelating agents)

Thickening agents

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19
Q

What are the factors affecting local action of topical therapy?

A

Pharmaceutical phase (Drug-vehicle) = Concentration, frequency, quantity

Pharmacokinetic phase = Penetration and permeation of drug into skin

Pharmacodynamic phase = interaction with drug receptors in the skin

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20
Q

What factors are important to consider with topical pharmacology?

A

Concentration of active drug - dose response

Frequency

Quantity/amount applied

Permeability differences with body sites

Occlusion increases penetration 10 - 100 times

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21
Q

What are fingertip units?

A

A fingertip unit describes amount of cream squeezed out of tube onto fingertip

1 male adult = 0.5g, 1 female adult = 0.4g

Child <4 = 1/3 adult, infant 1/4 of adult quantity

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22
Q

What are the types of eczema?

A

Endogenous and exogenous.

Endogenous includes atopic, seborrhoeic, discoid, asteatotic, venous, pompholyx, hyperkeratotic, and lichen simplex.

Exogenous is irritant, allergic, photoallergic or phototoxic

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23
Q

What is atopic eczema?

A

Chronic relapsing condition characterized by intense pruritis, dry skin, and inflammation.

Sets in primarily at 2 to 6 months of age

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24
Q

What is the cause of atopic eczema?

A

Genetics, environmental, and immune dysfunction. Result of altered skin barrier and immune deregulation; Th2 lymphocyte cytokines particularly IL-4 and 13

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25
Q

What is the incidence of atopic dermatitis today compared to 1981?

A

Incidence (258/10000 compared to 11/10000 in 1981) has doubled and prevalence has also doubled

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26
Q

What is atopic dermatitis associated with?

A

Mostly in children before 5 years of age and can continue into adulthood.

AD is associated with other allergic or atopic diseases including asthma, allergic rhinitis, and food allergies.

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27
Q

How is atopic eczema diagnosed?

A

Onset < 2 years

History of skin crease involvement

History of generally dry skin

Personal history of other atopic disease

Visible flexural dermatitis

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28
Q

How is eczema managed?

A

Basic therapy: Educate, avoid contact irritants, moisturiser-humectants and emollients, baths, avoid overheating.

Topical therapy includes topical corticosteroids, tars, and topical calcineurin inhibitors.

Systemic therapy

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29
Q

Why are moisturisers the cornerstone of treating eczema?

A

Restores and preserves skin barrier integrity

Improves clinical signs and symptoms of AD

Corticosteroid sparing effect

Alone or complementary to treatment enhances treatment efficacy and may prevent disease exacerbation.

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30
Q

How do moisturisers help treat eczema?

A

They restore fatty components of skin outer layer

Occlusive effect reduces water loss

Some attract and retain transepidermal water

And in irritant contact dermatitis they prevent dryness or chapping of the skin

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31
Q

How are emollients chosen for treating eczema?

A

Skin dryness

Climate (Not used in hot weather)

Adverse effects

Cost

Patient preference

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32
Q

What emollients are most commonly used for eczema?

A

Sorbolene cream with glycerol 10% (medium strength inexpensive and readily available)

Wool alcohols ointments (in severe xerosis)

Emulsifying ointment

Aqueous cream (medium strength pleasant feel and can be varied by mixing with paraffin, peanuts or olives)

White soft paraffin (very greasy, rarely stings, vary strength, rarely accepted)

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33
Q

Why are corticosteroids used for atopical eczema?

A

It is the most effective treatment (must know which one for where)

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34
Q

What are the problems with using topical corticosteroids?

A

Adverse effects

Encouraging treatment compliance can be difficult

Steroid phobia may affect compliance (Alleviate concern over long-term side effects, educate because people are misinformed about this)

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35
Q

How are corticosteroids categorized?

A

Mild, moderate, potent and very potent

If too potent: Perioral deramatitis, skin atrophy, striae

If not potent enough: Inadequate treatment and prolonged use increases risk of adverse effects

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36
Q

What are the most commonly used mild topical corticosteroids?

A

Hydrocortisone 0.5% to 1%

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37
Q

What moderate corticosteroids are used commonly?

A

Triamcinolone acetonide 0.02% and betamethasone valerate 0.02%

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38
Q

What potent corticosteroids are used commonly?

A

methylprednisolone aceponate 0.1%

Mometasone furoate 0.1%

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39
Q

What are the very potent topical corticosteroids?

A

Betamoethasone dipropionate 0.05% in optimised vehicle, clobetasol propionate 0.05%

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40
Q

How is the vehicle chosen for topical medication?

A

Nature of affected skin: (Acute, weeping: Cream base; Dry or lichenified: Ointment; Hair areas: Lotion)

Patient preferences

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41
Q

What are the adverse effects of topical corticosteroids?

A

Local (>4 weeks of use or applied to large area on the body):

Skin atrophy (Erythematous red skin in area where topical steroids are applied)

Perioral dermatitis

Telangeictasia

Striae

Folliculitis

Systemic (Systemic effects are rare though):

HPA-axis suppression

Glaucoma or cataract in peri-ocular areas

42
Q

What is used when corticosteroids can’t or are undesired?

A

Tars

43
Q

Why aren’t tars used more often?

A

They stain and are foul smelling

44
Q

What effects do tars have?

A

They are steroid sparing

Anti-inflammatory

Available predominantly as extemporaneous products

45
Q

What are the types of topical immunomodulators?

A

Immunosuppressive topical agents

46
Q

Give an example of an immunosuppressive topical agent and how it works?

A

Topical calcineurin inhibitors: tacrolimus and pimecrolimus work by inhibiting T cell activation

Topical phosphodiesterase (PD4 inhibitor) - PD4 inhibition -> increase in cAMP suppresses TNFallpha, IL-12, 23 and other cytokine release resulting in TH2 inactivation available as crisaborole 2% ointment

47
Q

When should topical calcineuran inhibitors be used?

A

Facial atopic dermatitis on face or eyelids where topical steroids are contraindicated.

48
Q

What types of drugs are used for skin systemically?

A

Treatment of secondary infections (Staph aureus, or viral infections)

Phototherapy

Systemic immunosuppressive agents such as prednisolone, azathioprine, methotrexate, cyclosporin, mycophenolate mofetil.

Biologics - Dupilumab (IL-4R alpha antagonist) inhibits IL-4 and IL-13 cytokines (In USA) and IL-13 & 31 inhibitors (Phase II and III trials)

Others - JAK inhibitors, leukotriene inhibitors

49
Q

What is psoriasis?

A

A T-cell mediated inflammatory disease where pathogenic memory T cells infiltrate lesiional skin in response to multiple undetermined epidermal antigens

50
Q

What is the most common type of psoriasis?

A

Chronic plaque type

51
Q

How is the severity of psoriasis assessed?

A

PASI

BSA

PGA

DLQI (patient subjective experience important for this assessment)

52
Q

What are the comorbidities associated with psoriasis?

A

Psoriatic arthritis (especially if nails are affected)

Diabetes

Hypertension

Cardiovascular disease

53
Q

How is psoriasis treated?

A

Keratolytic agent

Tar

Dithranol

Calcipotriol

Corticosteroids

Combined calcipotriol/corticosteroid

Tazarotene

54
Q

When are topical therapies used for psoriasis?

A

For localised or mild chronic plaque psoriasis and as adjunct to moderate/severe disease.

55
Q

Are emollients and keratolytics used for psoriasis?

A

They can be useful

56
Q

How are topical steroids applied for psoriasis?

A

Mild to potent and tailored to areas of application

Ointments are used instead of creams.

Once daily is prescribed to improve patient compliance.

Topical steroids are first line in combination with other therapies

57
Q

How is dithranol used for psoriasis?

A

Useful for thick plaque psoriasis, SCDT with 0.5 - 2% with 2 - 5% salicylic acid

10 minutes increasing to 30 minutes with 0.1% used in Ingram’s regime, SE’s used in combination with topical steroids

58
Q

How is calcipotriol used?

A

Slower onset of action compared with topical steroids, od/bd, SE’s, combined with steroids

59
Q

What is tazarotene?

A

A synthetic retinoid that is used in combination with topical steroids to redcue local irritant effect. (not used commonly due to staining and high vitD which results in hypercalcaemia.

60
Q

How is psoriasis treated systemically?

A

Phototherapy

Retinoids - acitretin

Methotrexate

Cyclosporin A

Biologicals (In Aus: etanercept, infliximab, adalimumab, ustekinumab, secukinumab - all injectables)

Apremilast (Otezla) - Oral agent phosphodiesterase inhibitor, efficacy similar to methotrexate.

61
Q

What are the types of phototherapy and how do they work?

A

NBUVB phototherapy - narrow band or broad band (Narrow band prevents carcinogenic effect)

PUVA phototherapy - 8-methoxsalen and UVA

Topical phototherapy for localised disease

62
Q

Which kinds of phototherapy are more commonly used?

A

NBUVB is most commonly used with 3x/week regimes according to skin type

PUVA is no longer used due to risk of SCC and possible mu

63
Q

How effective is NBUVB?

A

20 - 25 treatments produce PASI 75 in 60 - 80% of patients.

64
Q

What is the drawback to NBUVB?

A

Has potential of skin carcinogenicity and photoaging with multiple therapies in fair skinned patients.

65
Q

When is systemic therapy used for psoriasis?

A

Poor or no response to topical therapy and phototherapy

Severe and widespread disease, BSA >10 - 15%, PASI > 15

Severe inflammatory forms of psoriasis - generalised pustular psoriasis and erythrodermic psoriasis

Psoriatic arthritis

Psoriasis impacting on quality of life or affecting gainful employment

66
Q

What is acitretin? How is it used?

A

Affects mechanisms of proliferation and differentiation and is anti-inflammatory

2 ways to use:

Monotherapy with palmoplantar, pustular, eryhtrodermic or atypical psoriasis

To increase efficacy of NBUVB or PUVA therapy and reduce the dosage of phototherapy

67
Q

What is the daily dosage of acitretin?

A

0.25 - 0.5 mg/kg/day

68
Q

What are the limitations to using acitretin?

A

Dryness of skin

Peeling of lips

Tiredness

Myalgia

Not advised in women of child bearing age.

69
Q

How does methotrexate work?

A

Slows epidermal cell proliferation

Immunosuppressant

Inhibits dihydrofolate reductase

70
Q

What is the most commonly prescribed oral antipsoriatic?

A

Methotrexate

71
Q

What are the contraindications of using methotrexate?

A

Pregnant/breastfeeding

Underlying infection/malignancy

Renal impairment

Alcoholics

Unreliable patients

Patients considering conception within 3 months

72
Q

How ss methotrexate effectiveness measured?

A

If PASI 60 at 12 weeks. Repeat blood tests fortnightly for the first month, monthly for 6 months, and then every 2 months after that.

73
Q

What are the adverse effects of methotrexate?

A

GI upset

Fatigue

Bone marrow toxicity

Hapatotoxicity

Cirrhosis

Pneumonitis

Drug interactions

74
Q

How is methotrexate therapy stopped?

A

After adequate clearance (75 - 80%), dose is reduced by 2.5mg/month

Rotation therapy is used to reduce side effects and cumulative dose problems.

75
Q

What does cyclosporin do?

A

Immunosuppressive that inhibits production and liberation of cytokines and function of APC

It has an effective, more rapid onset relative to Methotrexate

76
Q

What is the dosage of cyclosporin?

A

3 - 5 mg/kg/day with a higher initial dose

77
Q

What kinds of psoriasis is cyclosporin most effective for?

A

Erythrodermic and pustular psoriasis

78
Q

What are the side effects of cyclosporin?

A

Hypertension

Nephrotoxicity (with prolonged use)

Tremors

GI upset

Gingival hyperplasia

Hirsutism (excess hair growth)

Drug interactions

79
Q

How are systemic therapies done?

A

Rotiational therapies - To reduce side effects from 1 form of therapy (Including phototherapy)

Combination therapies - combine phototherapy with acitretin, acitretin with cyclosporin, cyclosporin with methotrexate

These treatments were often used before biologics took over.

80
Q

What are biologics used for psoriasis?

A

3 main types:

Recombinant cytokines or growth factors

Monoclonal antibodies

Fusion proteins (cept - combines TNF receptor to human IgG1 FC or LFA3)

81
Q

What are the 4 major ways in which biologics are active in psoriasis?

A

Elimination of pathogenic Th (CD4) cells - Alefacept

Blockade of T-cell activation/costimulation/migration

Alteration of T cell proliferation

Blocking of proinflammatory effector cytokines

82
Q

What drug is used for elimination of pathogenic CD4 T cells?

A

Alefacept

83
Q

What does Efalizumab do?

A

Blocks T cell activation/costimulation/migration

Alters T-cell proliferation

84
Q

Which biologics target TNFalpha?

A

Etanercept

Infliximab

Adalimumab

85
Q

Which biologics target IL-12/23 inhibitor?

A

Usketinumab

86
Q

Which biologics target IL-17 inhibitor?

A

Secukinumab

Ixekizumab

87
Q

Which biologics target IL-23 inhibitor?

A

Guselkumab

88
Q

How is a patient started on biologics?

A

If patient meets the criteria and is on no current treatment for psoriasis. These criteria include:

Chronic infections/diseases that can be exacerbated by them.

Baseline investigations (FBP, U&E/Creatinine, LFT, HepB/C, HIV, ANA)

Vaccinations

89
Q

What diseases are screened for before using biologics?

A

Patient is also screened for:

Chronic infections such as TB,HIV, Hep B or C.

CHF

Demyelinating diseases (MS)

Liver disease - Abnormal LFTs, alcoholics, cirrhosis

Pregnancy and contraception

Breastfeeding not recommended

90
Q

What baseline investigations are done before prescribing biologics?

A

FBP

U&E/creatinine

LFT

91
Q

What live vaccinations are screened for before using biologics?

A

MMR

Varicella

Oral typhoid

Yellow fever

92
Q

Which vaccines are ok?

A

Influenza and pneumococcal vaccines

93
Q

What is the cause of acne related problems?

A

Androgen response in sebocytes and keratinocytes.

Keratinocytes desquamate and sebocytes produce lots of sebum.

Follicular millieu is altered and colonised with propionibacterium acnes resulting in inflammation

94
Q

What are the features of acne?

A

Seborrhoea

Non inflammatory lesions - comedones

Inflammatory lesions - papules pustules, nodules and cysts

Severity classified into mild, moderate, and severe depending on numbers of lesions and whether or not they are inflammatory

95
Q

How is acne managed?

A

Explanation of pathogenesis

Depends on severity of disease

96
Q

What topical agents are used for acne?

A

Benzoyl peroxide

Azelaic acid

Topical antibiotics

Topical retinoids

Combination of topical antibiotics/benzoyl peroxide or topical retinoid/benzoyl peroxide

Topical dapsone

Extemporaneous agents

97
Q

What systemic agents are used for treatment of acne?

A

Oral antibiotics (doxycycline, minocycline, erythromycin, trimethoprim-sulphamethoxazole)

Antiandrogens (Oestrogens, cyproterone acetate, drosperinone, spironolactone)

Isotretinoin (For severe cystic acne when not responsive to other therapies)

98
Q

How is mild acne treated?

A

Topical retinoids (reduce comedone activity)

Combination adapalene, benzoyl peroxide (Epiduo)

99
Q

How is moderate acne treated?

A

Benzoyl peroxide and azelaic acid

Combination topical adapalene, benzoyl peroxide

Topical antibiotics or topical dapsone

Oral antibiotics

Hormonal treatments

100
Q

How is severe acne treated?

A

Systemic isotretinoin (vitA derivative that inhibits sebaceous gland activity and is comedolytic and anti-inflammatory, teratogenic)

Hormonal therapy

Systemic steroids

Oral antibiotics such as erythromycin or roxithromycin

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