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Medicine Dermatology > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Major routes of administration for diseases of the skin

A

Topical, transdermal, subcutaneous/depot

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2
Q

Other epithelial routes for drug administration

A

Airways, conjunctival sac, nasal mucosa, vaginal

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3
Q

Most important barrier to drug penetration into the skin or diffusion across it

A

Stratum corneum

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4
Q

Brick and mortar model of stratum corneum

A

‘bricks’ - corneocytes containing keratin macrofilaments embedded in a filaggrin matrix surround by cornified envelop
‘mortar’ - multiple lamellar structures of intercellular lipids. Intercellular glue that can also act as a reservoir for lipid-soluble drugs

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5
Q

Drug delivery into and across the stratum corneum is a/an __ process, mediated by __ when the drug is applied topically

A

Active, diffusion

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6
Q

Topical route of administration

A

Drug is applied in a pharmacologically inactive vehicle to the skin

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7
Q

The topical route of administration is most often used local effects in the treatment of what?

A 
Superficial skin disorders (psoriasis, eczema)
Skin infections
Itching
Dry skin
Warts
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8
Q

Vehicles for topical route of administration from greatest water content to least

A 
Lotions
Creams
Ointments
Gels
Pastes
Powders
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9
Q

What is the choice of vehicle dilated by?

A

Physiochemical properties of the drug and the skin condition

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10
Q

Factors influencing the absorption of topically applied drugs

A

Rate of absorption
Nature of the skin
Drug/pharmaceutical preparation

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11
Q

What does rate of absorption depend on?

A

Permeability coefficient and concentration of drug in the vehicle

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12
Q

Lipophilic drug in a lipophilic base is soluble/insoluble in the vehicle and soluble/insoluble in the skin

A

Lipophilic drug in a lipophilic base is soluble in the vehicle and soluble in the skin and partitions between the two

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13
Q

Lipophilic drug in a hydrophilic base is more/less soluble in the skin

A

Lipophilic drug in a hydrophilic base is more soluble in the skin and so preferentially partitions into it

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14
Q

Hydrophilic drug in a lipophilic base has good/limited solubility in both the vehicle and the skin

A

Hydrophilic drug has limited solubility in both the vehicle and the skin and partitions into it weakly

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15
Q

Hydrophilic drug in hydrophilic base is soluble/insoluble in the vehicle and soluble/insoluble in the skin

A

Hydrophilic drug in hydrophilic base is soluble in the vehicle but insoluble in the skin and so remains on the surface

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16
Q

How can drug solubility and absorption be enhanced?

A

By inclusion of excipients within the vehicle

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17
Q

What provides the driving force for skin penetration for drugs applied topically?

A

The fraction within the vehicle solubilised

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18
Q

Advantage of using transdermal patches

A

They include excess, non-dissolved drug which can increase duration of effectiveness and provide a constant rate of delivery

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19
Q

Topically applied drugs are generally well/poorly absorbed

A

Poorly absorbed - only a small fraction partitions into the skin

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20
Q

Physical and chemical factors that can improve partitioning of topically applied drugs

A

Hydration of the skin by occlusion

Inclusion of excipients that increase solubility of hydrophobic drugs

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21
Q

Factors relating to nature of the skin that influence the absorption of topically applied drugs

A

Site of application (thickness of stratum corneum)
Hydration of the skin
Integrity of epidermis

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22
Q

Glucocorticoids are widely used topically in which conditions?

A

Eczema, psoriasis and pruritus

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23
Q

Formulations of topical glucocorticoids available

A

Lotion, cream, ointment

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24
Q

Adverse effects of long term use of high potency steroids

A 
Steroid rebound
Skin atrophy
Systemic effects
Spread of infection
Rosacea
Stretch marks and small superficial dilated blood vessels
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25
Q

Main nuclear receptor glucocorticoids signal via

A

GR alpha

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26
Q

What do glucocorticoids bind with once in the cytoplasm and what does this produce?

A

GR alpha producing dissociation of inhibitory heat shock proteins and the activated receptor translocates to the nucleus aided by importins

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27
Q

Subcutaneous route of administration

A

Drug delivered by a needle, inserted into the adipose tissue just beneath the surface of the skin

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28
Q

Advantages of subcutaneous route of administration

A

Absorption is fairly slow (advantage/disadvantage)
Relatively simple and fairly painless
Can be used to introduce a depot of drug under the skin that is very slowly released into circulation
Route of administration of many protein drugs and suitable for administration of oil-based drugs

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29
Q

Disadvantages of subcutaneous route of administration

A

Injection volume limited

Absorption is fairly slow (advantage/disadvantage)

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30
Q

Why is the skin an attractive route for drug administration for systemic effect

A

Application is simple and non-sterile
Avoids first pass metabolism
Potentially allows for a steady state concentration of drug to be achieved over a prolonged period of time

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31
Q

Transdermal drug delivery

A

The drug is usually incorporated into an adhesive patch applied to the epidermis

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32
Q

Features of drugs that make them suitable for transdermal drug delivery

A

Low molecular weight
Relatively lipophilic
Potent
Of relatively brief half-life

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33
Q

Advantages of transdermal drug delivery

A 
Steady rate of drug delivery
Decreased dosing frequency
Avoidance of first pass metabolism
Rapid termination of action (if half-life short)
User friendly
Convenient
Painless
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34
Q

Disadvantages of transdermal drug delivery

A

Few drugs suitable for this method
Allergies
Costly

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35
Q

Examples of drugs that can be used by the transdermal drug delivery method

A

GTN
Fentanyl
Buprenorphine
Estradiol

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36
Q

Advantages and disadvantages of topical treatments

A

Advantages - direct application, reduced systemic effects

Disadvantages - time consuming, correct dosing can be difficult, messy to use

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37
Q

What is a cream?

A

Semisolid emulsion in water, containing emulsifier and preservative

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38
Q

Creams have a high/low water content

A

High

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39
Q

Advantages of creams

A

Cool and moisturise
Non-greasy
Easy to apply
Cosmetically acceptable

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40
Q

What is an ointment?

A

Semisolid grease/oil (soft paraffin) with no preservative

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41
Q

Advantages and disadvantages of ointments

A

Advantages - occlusive and emollient, restrict transepidermal water loss
Disadvantage - greasy - less cosmetically acceptable

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42
Q

What is a lotion?

A

Suspension or solution of medication in water, alcohol or other liquids

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43
Q

What areas do lotions treat?

A

Scalp and hair-bearing areas

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44
Q

Disadvantage of lotions

A

May sting if they contain alcohol

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45
Q

What is a gel?

A

Thickened aqueous solution. Semi-solid containing high molecular weight polymers

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46
Q

Which areas are gels used to treat?

A

Scalp, hair-bearing areas, face

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47
Q

What is a paste?

A

A semisolid that contains finely powdered materials

48
Q

Advantages and disadvantages of pastes

A

Advantages - protective, occlusive, hydrating

Disadvantages - stiff, greasy, difficult to apply

49
Q

What is a foam?

A

Colloid with two-three phases. Usually a hydrophilic liquid in continuous phase with foaming agent dispersed gaseous phase

50
Q

Advantages of foams

A

Increased penetration of active agents, can spread over large areas of skin with no oily/greasy film

51
Q

Types of topical therapies

A 
Emollients
Topical steroids
Antinfective agents
Antipruritics
Kertolytics
Psoriasis therapies
Cytotoxic and antineoplastic therapies
52
Q

Benefit of emollients and which conditions they are used in

A

They enhance rehydration of the epidermis and are used in all dry/scaly conditions

53
Q

Dose of emollients prescribed

A

300-500g

54
Q

Tips to tell a patient when prescribing emollients

A

They need frequent application
Apply immediately after bathing
Apply in the direction of hair growth (prevent infection)
Use a clean spoon or spatula to remove from tub (prevent infection)
Can make skin and surfaces slippy - hazard
Fire risk if paraffin based
Avoid those containing SLS in leave-on products

55
Q

When is wet-wrap therapy used?

A

For xerotic skin

56
Q

Disadvantage of wet-wrap therapy

A

Very difficult and time consuming to apply

57
Q

Mode of action of corticosteroids

A

Vasoconstrictive, anti-inflammatory, anti-proliferative

58
Q

Examples of topical corticosteroids:

  • Mild
  • Moderate
  • Potent
  • Very potent
A

Mild = hydrocortisone 1%
Moderate = modrasone, clobetasone, butyrate 0.05%
Potent = mometasone, betamethasone, valerate 0.1%
Very potent = clobetasol propionate 0.05%

59
Q

Quantity of topical corticosteroids

A

1 application to whole body (adult) = 20-30g

1 fingertip unit = 1/2 gram - covers 2 hand areas

60
Q

Side effects of topical corticosteroids

A 
Thinning of skin
Purpura
Stretch marks
Steroid rosacea
Telangiectasia
Perioral dermatitis
May worsen or mask infections
Systemic absorption
Tachyphylaxis
Rebound flare of disease
Glaucoma and cataract
61
Q

Alternative to steroids

A

Calcineurin inhibitors

62
Q

How to calcineurin inhibitors work?

A

Suppress lymphocyte activation

63
Q

Disadvantages of calcineurin inhibitors

A

May cause burning sensation on application, perhaps risk of cutaneous infections and cancer

64
Q

Clinical uses for antiseptics

A

For recurrent infection, skin cleansing, wound irrigation

65
Q

Examples of antiseptics

A

Povidone iodine skin cleanser
Chlorohexadine
Triclosan
Hydrogen peroxide

66
Q

Clinical uses of antibiotics

A

Treatment of acne and rosacea
Treatment of skin infections
Treatment of infected eczematous process

67
Q

Caveats of antibiotics

A

Antibiotic resistance, sensitisation

68
Q

Antipruritics and how they work

A

Menthol - added to calamine and other lotions and creams to impart cooling sensation
Capsaicin - from red chilli peppers - depletes substance P at nerve endings and reduces neurotransmission
Camphor/phenol for pruritus ani
Crotamiton is used after scabies to relieve residual itch

69
Q

What do keratolytics do? Which conditions are they used in?

A 
Soften keratin
Viral warts
Hyperkeratotic eczema and psoriasis
Corns and calluses
To remove keratin plaque in scalp
70
Q

Treatment of warts

A

Mechanical paring plus:

  • Keratolytics
  • Formaldehyde
  • Glutaraldehyde
  • Silver nitrate
  • Cryotherapy
  • Podophyllin (for genital warts)
71
Q

Example of a keratolytic

A

Salicylic acid

72
Q

Topical psoriasis treatment

A

Emollients plus either:

  • Coal tar
  • Vitamin D analogue
  • Keratolytic
  • Topical steroid
  • Dithranol
73
Q

Advantages and disadvantages of coal tar

A

Advantages - effective, comes in mild solutions to strong crude coal tar
Disadvantages - messy and smelly

74
Q

Advantages and disadvantages to vitamin D analogue

A

Advantages - clean, no smell, easy to apply

Disadvantages - can be irritant, use limited to 100g weekly as can cause hypercalcaemia

75
Q

Advantages and disadvantages of dithranol

A

Advantages - effective

Disadvantages - difficult to use, irritant, stains normal skin

76
Q

Treatment for scalp psoriasis

A

Greasy ointments to soften scale
Tar shampoo
Steroids in alcohol base or shampoo
Vitamin D analogues

77
Q

Type I anaphylactic reaction presentation

A

Anaphylaxis and/or urticaria

78
Q

Type II cytotoxic reaction presentation

A

Blistering reactions - pemphigus and pemphigoid

79
Q

Type III immune complex mediated reaction presentation

A

Purpura/rash/vasculitis

80
Q

Type IV cell-mediated delayed hypersensitivity reaction presentation

A

Erythema/rash

81
Q

Examples of non-immunological cutaneous drug reactions

A 
Eczema
Drug induced alopecia
Phototoxicity
Skin erosion (topical 5-fluorouracil)
Atrophy (topical steroids)
Psoriasis
Pigmentation
Cheilitis
82
Q

Who to consider as having cutaneous drug eruptions

A

Any patient who is taking medication who suddenly develops a symmetrical skin eruption

83
Q

When does the effect of cutaneous drug eruptions usually resolve?

A

When the drug is withdrawn

84
Q

Factors that can cause cutaneous drug eruptions to continue on withdrawal of the drug

A

Half-life of drug
Ability of drug to be retained/accumulated in tissues plays a role
May cross react with a similar class of drugs

85
Q

Risk factors for drug eruptions

A 
Age - elderly > infants
Gender - females > males
Genetics
Concordant disease (e.g. viral infections, CF)
Immune status
86
Q

Most common type of drug eruption

A

Exanthematous drug eruptions

87
Q

What is an exanthematous drug eruption?

A

An idiosyncratic, T-cell mediated delayed hypersensitivity reaction

88
Q

Clinical presentation of exanthematous drug eruptions

A

Mild and self limiting widespread symmetrically distributed rash, which usually spares mucous membranes and is associated with itch.
Mild fever is common
Onset is 4-21 days after first taking drug

89
Q

Indicators of a potentially severe exanthematous drug eruption

A 
Involvement of mucous membrane and face
Facial erythema and oedema
Widespread confluent erythema
Fever
Skin pain
Blisters, purpura, necrosis
Lymphadenopathy, arthralgia
SOB, wheezing
90
Q

Drugs associated with exanthematous eruptions

A 
Penicillins
Sulphonamides
Erythromycin
Streptomycin 
Allopurinol
Anti-epileptics - carbamazepine, phenytoin
NSAIDs
Chloramphenicol
91
Q

Urticarial drug reactions

A

Usually an IgE mediated hypersensitivity reaction (type I) after rechallenge with drugs
or
Direct release of inflammatory mediators from mast cells on first exposure

92
Q

Acneiform

A

Looks like acne but there are no comedones or greasy skin

93
Q

In which people can acneiform be seen in?

A

Weightlifters who have taken steroids

94
Q

Drugs that can be associated with acneiform

A

Androgens
Lithium
Isoniazid
Pustulosis

95
Q

Acute generalised exanthematous pustulosis

A

Rare, sheets of monomorphic pustules

96
Q

Drugs that can be associated with acute generalised exanthematous pustulosis

A

Antibiotics, calcium channel blockers, antimalarials

97
Q

Drugs that can cause drug-induced bullous pemphigoid

A

ACE inhibitors, penicillin, furosemide

98
Q

Clinical presentation of fixed drug eruptions

A

Well demarcated round/oval plaques which are red and painful and often seen on hands, lips, genitalia, and occasionally oral mucosa.
Can present with eczematous lesions, papules, vesicles or urticaria

99
Q

What happens in fixed drug eruptions when the drug is stopped and then re-introduced?

A

When the drug is stopped, the fixed drug eruption resolves with persistent pigmentation
The reaction can re-occur at the same site on re-exposure to the drug

100
Q

Drugs associated with fixed drug eruptions

A

Tetracycline, doxycycline
Paracetamol
NSAIDs
Carbamezapine

101
Q

Severe cutaneous adverse drug reactions

A

Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Acute generalised exanthematous pustulosis (AGEP)

102
Q

Drugs that can cause toxic epidermal necrolysis

A 
Sulfonamides
Cephalosporins
Carbamezapine
Phenytoin
NSAIDs
Nevirapine
Lamotrigine
Sertraline
Pantoprazole
Tramadol
103
Q

Drugs that can cause drug reaction with eosinophilia and systemic symptoms

A 
Sulfonamides
Anticonvulsants
Allopurinol
Minocycline
Dapsone
NSAIDs
Abacavir
Nevirapine
Vancomycin
104
Q

Clinical presentation of drug reaction with eosinophilia and systemic symptoms

A

Facial oedema, lymphadenopathy, liver involvement, fevers ≥40˚C

105
Q

Consequences of severe cutaneous drug reactions

A 
Hypothermia
Fluid loss
Protein loss
Sepsis
Multi organ failure
Permanent sequelae
Death
106
Q

Acute phototoxic drug reactions

A

Skin toxicity - photosensitivity
Systemic toxicity
Photodegradation

107
Q

Chronic phototoxic drug reactions

A

Pigmentation
Photoageing
Photocarcinogenesis

108
Q

What is a phototoxic cutaneous drug reaction?

A

Non-immunological skin reaction due to light activation of a photo-reactive drug

109
Q

Patterns of skin phototoxicity

A

Immediate prickling with delayed erythema and hyperpigmentation
Exaggerated sunburn
Exposed telangiectasia
Delayed 3-5 days erythema and pigmentation
Increased skin fragility

110
Q

Which drugs cause immediate prickling and delayed erythema and pigmentation pattern of skin phototoxicity?

A

Chlorpromazine, amiodarone

111
Q

Which drugs cause exaggerated sunburn pattern of skin phototoxicity?

A

Quinine, thiazides, demeclocycline

112
Q

Which drugs cause exposed telangiectasia pattern of skin phototoxicity?

A

Calcium channel antagonists

113
Q

Which drugs cause delayed 3-5 days erythema and pigmentation pattern of skin phototoxicity?

A

Psoralens

114
Q

Which drugs cause increased skin fragility due to skin phototoxicity?

A

Naladixic acid, tetracycline, naproxen, amiodarone

115
Q

Drugs associated with phototoxicity

A 
Antibiotics
Thiazides
Chlorpromazine
NSAIDs
Quinine
Psoralens
Amiodarone
Poryphrins
BRAF inhibitors
Antifungals
Immunosuppressants
116
Q

Investigations for suspected cutaneous drug eruptions

A 
History and physical examination
Phototesting (for suspected phototoxic reactions)
Biopsies
Patch and photo patch tests
Skin prick/intradermal tests
117
Q

Management of cutaneous drug eruptions

A

Discontinue drug if possible and use an alternative
Topical corticosteroids
Antihistamines (help with type I or itch)
Allergy bracelets

Medicine Dermatology (19 decks)

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