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Pharmacology Flashcards

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Dermatology Board Prep flashcards
1
Q

Name and describe the 3 major routes of drug administration through the skin

A

Topical
- applied to the skin to treat skin disease and underlying tissues

Transdermal drug delivery (TDD)
- the drug diffuses across the skin to have a systemic effect

Subcutaneous
- the drug is injected into the skin to have a systemic effect

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2
Q

What is a major advantage of topical administration of a drug?

A

It can produce a relatively high local concentration of drug and minimise adverse systemic effects

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3
Q

Give an example of a drug in each category of the 3 major routes of drug administration through the skin

A

Topical - topical NSAIDs

Transdermal drug delivery (TDD) - nicotine patch

Subcutaneous - insulin

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4
Q

List 4 epithelial routes of drug administration that allow for a local effect

A

Airways
Conjunctival sac
Nasal mucosa
Vaginal

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5
Q

What is the main barrier for topical drug absorption?

A

The stratum corneum

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6
Q

Describe the structure of the stratum corneum using the ‘brick and mortar’ analogy

A

‘Bricks’ - corneocytes containing keratin are highly cross-linked by corneodesmosomes to provide tensile strength

‘Mortar’ - hydrophobic, intercellular lipids hold the corneocytes together and act as a reservoir for lipid-soluble drugs, prolonging their time of action

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7
Q

By what method do drugs applied to the skin cross the stratum corneum?

A

Simple diffusion from an area of high conc. on the skin surface to an area of low conc. deeper in the skin

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8
Q

State the 2 main routes of drug diffusion through the stratum corneum

A
  • Intercellular

- Transcellular

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9
Q

Describe the intercellular route of drug diffusion

A
  • This is the main route of drug administration
  • It is hydrophobic
  • The drug diffuses between the corneocytes
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10
Q

Describe the transcellular route of drug diffusion

A
  • It is hydrophilic

- The drug diffuses through the corneocytes

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11
Q

What pathologies are topical drugs mainly used to treat?

A
  • Superficial skin disorders
  • Skin infections
  • Pruritis
  • Dry skin
  • Warts
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12
Q

What is meant by a drug’s vehicle?

A

A pharmacologically inactive substance combined with the drug which helps the drug to be absorbed at the site of administration

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13
Q

List some common drug vehicles from highest to lowest water content

A 
Lotions
Creams
Ointments
Gels
Pastes
Powders
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14
Q

The choice of drug vehicle is dictated by…

A
  • Properties of the drug

- The clinical condition

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15
Q

Factors that influence the rate of absorption of topical drugs can be describes using…

A

Fick’s Law of Diffusion

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16
Q

Referring to Fick’s Law, what factors influence the rate of absorption of topical drugs?

A
  • Permeability coefficient (Kp)
  • Dissolved concentration of drug in vehicle (Cv)
  • Partition coefficient (Km)
  • Diffusion coefficient (D)
  • Length of the diffusion pathway (L)
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17
Q

Why are drug vehicles so important?

A

Dissolved concentration of the drug in the vehicle (Cv) and the partition coefficient (Km) are highly dependent on the vehicle

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18
Q

How will the drug partition in the following scenario…

  • Lipophilic drug
  • Lipophilic base
A

Drug is soluble in both vehicle and skin so partitions between the two

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19
Q

How will the drug partition in the following scenario…

  • Lipophilic drug
  • Hydrophilic base
A

Drug is more soluble in skin so partitions into it

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20
Q

How will the drug partition in the following scenario…

  • Hydrophilic drug
  • Lipophilic base
A

Drug has limited solubility in both vehicle and skin so partitions into the skin weakly

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21
Q

How will the drug partition in the following scenario…

  • Hydrophilic drug
  • Hydrophilic base
A

Drug is more soluble in the vehicle so remains on the surface on the skin

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22
Q

What is the driving force for diffusion of topical drugs?

A

The concentration of dissolved drug in the vehicle (Cv)

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23
Q

What are excipients?

A

Substances included in the vehicle that can enhance drug solubility and absorption

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24
Q

Why is excess, non-dissolved drug included in transdermal patches?

A

As dissolved drug is absorbed, undissolved drug solubilises

This increases duration of effectiveness and provides a constant rate of delivery

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25
Q

Topically applied drugs are generally well/poorly absorbed

A

Poorly

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26
Q

Describe 2 ways in which drug partitioning can be improved

A
  • Hydration of the skin by occlusion i.e., preventing water loss by evaporation (e.g., choice of vehicle, cling film/waterproof dressings)
  • Inclusion of excipients
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27
Q

Methods of improving drug partitioning results from a reduction in the barrier function of…

A

The stratum corneum

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28
Q

What factors influence the absorption of topically applied drugs?

A
  • Site of application
  • Hydration of skin
  • Integrity of epidermis
  • Drug concentration and properties
  • The drug salt
  • The vehicle
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29
Q

List these drug application sites from most to least permeable:

Palm/sole
Trunk/extremities
Nail
Scrotum

A

Scrotum
Trunk/extremities
Palm/sole
Nail (impermeable)

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30
Q

What effects do topical corticosteroids have on the skin?

A

Anti-inflammatory
Immunosuppressant
Vasoconstricting
Anti-proliferating towards keratinocytes and fibroblasts

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31
Q

List 3 dermatological pathologies that can be treated with topical corticosteroids

A
  • Atopic eczema
  • Psoriasis
  • Pruritis
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32
Q

Duration of use of topical corticosteroids depends on…

A

Whether they are categorised as mild, moderate, potent or very potent

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33
Q

List some adverse effects of long-term use of high potency topical steroids

A
  • Steroid rebound (glucocorticoid receptor down-regulation)
  • Skin atrophy
  • Systemic effects
  • Spread of infection
  • Skin reddening/pimples (steroid rosacea)
  • Stretch marks
  • Superficial dilated blood vessels
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34
Q

Describe the molecular action of glucocorticoids (from Principles)

A
  • Lipophilic glucocorticoid enters the cell by simple diffusion
  • Binds to glucocorticoid receptor (GR) in cytoplasm
  • Inhibitory heat shock proteins dissociate from GR\
  • GR travels to nucleus
  • Two GR’s join together in the nucleus and bind to glucocorticoid response elements (GRE)
  • The transcription of specific genes and expression of their proteins is altered
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35
Q

How is a drug administered via the subcutaneous route?

A

A needle inserts the drug into the adipose tissue beneath the surface of the skin

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36
Q

How do subcutaneously administered drugs reach systemic circulation?

A

By diffusion into either…

  • Capillaries
  • Lymphatic vessels (esp. high molecular weight compounds)
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37
Q

What are the advantages of subcutaneous drug administration?

A
  • Drug is absorbed and released slowly due to poor vascular supply to adipose tissue
  • Simple and painless
  • Ideal route of administration for many protein (e.g., insulin) and oil-based (e.g., steroid) drugs
  • Avoids degradation of the drug in the GI tract and first pass metabolism by the liver
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38
Q

What are the disadvantages of subcutaneous drug administration?

A
  • Injection volume is limited

- Needle needs to be sterilised

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39
Q

How does transdermal drug delivery (TDD) work?

A

The drug is held in a drug reservoir between an external backing and a drug-release membrane in contact with the skin
(drug patches)

The membrane controls the rate of administration of the drug across the skin

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40
Q

What sort of drugs is transdermal drug delivery (TDD) most suitable for?

A
  • Low molecular weight
  • Moderately lipophilic
  • Potent
  • Relatively brief half-life
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41
Q

What are the advantages of transdermal drug delivery (TDD)?

A
  • Steady state of drug delivery
  • Decreased dosing frequency
  • Avoids first-pass metabolism
  • Rapid termination of action
  • User friendly
  • Painless
42
Q

What are the disadvantages of transdermal drug delivery (TDD)?

A
  • Relatively few drugs are suitable (GTN, nicotine etc)
  • Expensive
  • Adhesive patch can cause skin irritation
43
Q

What strategy can be used to improve transdermal drug delivery (TDD)?

A

The addition of chemical enhancers

44
Q

How do chemical enhancers work?

A

They interact with lipids in the stratum corneum to increase permeability (mainly to lipophilic drugs which already cross the skin reasonably well)

45
Q

List 3 agents that may be used as chemical enhancers

A
  • Water (prolongs occlusion by increasing stratum corneum hydration)
  • Solvents e.g., ethanol
  • Surfactants
46
Q

What are the advantages of chemical enhancers?

A
  • Cheap

- Can be incorporated into vehicles or patches

47
Q

What are the disadvantages of chemical enhancers?

A
  • Skin irritation/toxicity

- Not effective for hydrophilic drugs or macromolecules

48
Q

Name 6 bases or vehicles that topical therapies can come in

A 
Creams
Ointments
Lotions
Gels
Pastes
Foams
49
Q

Name 7 different types of topical therapies

A 
Emollients (common)
Topical steroids (common)
Anti-infective agents
Anti-pruritics
Keratolytics
Psoriasis therapies
Cytotoxic & anti-neoplastic agents
50
Q

List some general side effects of topical therapies

A
  • Burning
  • Irritation
  • Contact allergic dermatitis
  • Local toxicity
  • Systemic toxicitiy
51
Q

What is the function of emollients and how many grams are supplied for one week’s use?

A

Used for all dry/scaly skin conditions (esp. eczema) to enhance rehydration of the epidermis

300-500g

52
Q

What are the risks associated with emollients?

A
  • Makes skin and surfaces slippery
  • Risk of bacterial contamination so use spoon/spatula to remove from tub
  • Fire risk if paraffin-based
  • SLS in ‘leave-on’ products can cause skin irritation
53
Q

When are wet wraps used?

A

After moisturising in cases of extremely dry and itchy skin e.g., atopic eczema in young children to prevent itching and cool the skin

54
Q

What are the 3 modes of action of topical steroids?

A

Vasoconstrictive
Anti-inflammatory
Anti-proliferative

55
Q 
Give an example of a...
- mild
- moderate
- potent 
- very potent
... topical steroid
A

Mild -> hydrocortisone
Moderate -> modrasone
Potent -> mometasone
Very potent -> clobetasol

56
Q

What type of skin conditions are topical steroids used for?

A

Non-infective inflammatory skin diseases e.g., eczema, psoriasis, lichen planus, keloid scars

57
Q

Why should steroids be used with caution for psoriasis?

A

There is risk of rebound flare ups of a disease if a potent steroid is stopped suddenly

58
Q

How much ointment is required to cover the whole adult body?

How much ointment is in one fingertip unit and how much of the body can be covered by this?

A

20-30g

1-2g -> 2 hand areas

59
Q

List as many possible side effects of topical steroids as you can

A
  • Skin thinning/atrophy
  • Purpura
  • Stretch marks
  • Telangectasia
  • Steroid rosacea
  • Perioral dermatitis
  • Masking of infections (by getting rid of erythema and itch)
  • Adrenal suppression or Cushing’s syndrome
  • Tachyphylaxis
  • Rebound flare of disease (esp. psoriasis)
  • Glaucoma and cataract
60
Q

What is tachyphylaxis?

A

Reduced response to steroids even when dose is increased

61
Q

What are Calicneurin Inhibitors?

A

Non-steroidal topical treatments sometimes used for atopic eczema and psoriasis - esp. for the face and for children

62
Q

Give an example of antiseptics being used for skin pathology

A

Potassium permanganate can be used to soak acute exudative eczema or pompholyx

63
Q

What is pompholyx?

A

Exudative eczema with blisters which is restricted to the hands and feet

64
Q

What skin conditions are antibiotics used for?

A
  • Acne
  • Rosacea
  • Skin infection e.g., impetigo
  • Infected eczematous process
65
Q

List 3 diseases which are treated with antivirals

A
  • Herpes simplex (cold sore)
  • Eczema herpeticum (herpes in a patient with atopic eczema)
  • Herpes zoster (shingles)
66
Q

List 3 diseases which are treated with antifungals

A
  • Candida (thrush)
  • Dermatophytes (ringworm)
  • Pityriasis versicolor (scaly erythema all over torso)
67
Q

Why are shampoo antifungals sometimes more useful than topical?

A

It’s easier to cover the entire body

68
Q

Name 2 anti-pruritics and describe how they work

A

Menthol -> added to calamine and other lotions/creams to give a cooling sensation

Capsaicin -> reduces neurotransmission, may burn initially but benefits are felt gradually

69
Q

What are keratolytics used for? Give an example of one

A

Used to soften keratin e.g., viral warts, hyperkeratotic eczema & psoriasis, corns, calluses

E.g., salicylic acid

70
Q

Give 2 examples of cytotoxic and anti-neoplastic therapies used for solar damage and superficial basal cell carcinoma

A

5-Fluorouacil

Imiquimod

71
Q

Give a list of possible topical treatments that can be used alongside an emollient to treat psoriasis

A
  • Coal tar
  • Vitamin D analogue
  • Keratolytic
  • Topical steroid
  • Dithranol
72
Q

What are the disadvantages of vitamin D analogues?

A
  • Can be an irritant

- Use limited to 100g weekly due to hypercalcaemia risk

73
Q

What are the disadvantages of dithranol?

A

Irritant and stains normal skin so must be applied directly to the affected area

74
Q

Immunological drug reactions are dose/non-dose dependent

Non-immunological drug reactions are dose/non-dose dependent

A

Immunological = Non-dose dependent

Non-immunological = Dose dependent

75
Q

What are the 4 types of immunologically mediated drug reactions?
Give an example of each

A

Type 1 - immediate IgE hypersensitivity e.g., anaphylaxis

Type 2 - cytotoxic reactions e.g., blistering reactions

Type 3 - immune complex mediated reactions e.g., vasculitis

Type 4 - T cell-mediated delayed hypersensitivity e.g., erythema

76
Q

List examples of conditions caused by non-immunological drug reactions

A 
Eczema
Psoriasis
Atrophy
Alopecia
Phototoxicity
Pigmentation
77
Q

What are the most common presentations of drug eruptions?

A

Exanthematous/morbilliform/maculopapular (75-95%) – an extensive, red, maculopapular rash

Urticarial (5-10%) – hives, nettle rash

Purpuric, vasculitic

Papulosquamous/pustular/bullous

78
Q

Cutaneous drug eruptions are usually symmetrical/asymmetrical and do/don’t resolve when the drug is withdrawn

A

Cutaneous drug eruptions are usually symmetrical and do resolve when the drug is withdrawn

(but there are exceptions to this rule)

79
Q

What are the patient risk factors for drug eruptions? (5)

A

Ageing (take more drugs and are predisposed)

Female gender

Genetic predisposition

Certain underlying disease e.g., HIV, CF

Immune status e.g., previous drug reaction

80
Q

What are the drug risk factors for adverse drug reactions? (4)

A

Chemistry e.g., b-lactam compounds, NSAIDs, high molecular weight/hapten-forming drugs

Route of administration

Dose (non-allergic = dose dependent)

Kinetics/half-life

81
Q

Which investigations may be used for a drug eruption?

A

History and physical examination are usually sufficient

In less clear situations, blood test, biopsy, phototesting, patch testing or skin prick may be used

82
Q

How is a drug reaction halted?

A
  • Discontinue drug use (if possible)

- Use an alternative drug or drug class

83
Q

How is a cutaneous skin eruption treated?

A
  • Topical steroids
  • Antihistamines (for type 1 hypersensitivity or itch)
  • Supportive care for severe drug reactions
84
Q

What further precautions can be taken to prevent drug eruptions?

A
  • Allergy bracelets (so people know which drugs not to administer if the patient is unconscious and unable to tell them)
  • Report reactions to the Yellow Card scheme
85
Q

Describe exanthematous drug eruptions

A
  • Most common type of drug eruption (90%)
  • Idiosyncratic T-cell mediated type 4 hypersensitivity reactions
  • Symmetry is a hallmark feature
  • Usually mild, self-limiting and spares the mucous membranes
  • Fever and pruritis may also be seen
  • Onset 4-21 days after taking the drug
86
Q

Which drugs are associated with exanthematous drug eruptions?

A 
Penicillins
Sulphonamides
Erythromycin
Streptomycin
Allopurinol
Anti-epileptics
NSAIDs
Chloramphenicol
87
Q

List some indicators of severe exanthematous drug eruptions

A

Involvement of mucous membranes and face

Facial erythema & oedema or ulceration of the mouth/lips

Widespread confluent oedema

Fever (>38.5)

Skin pain (rash is usually itchy but not painful)

Blisters, purpura, necrosis

Lymphadenopathy, arthralgia (joint stiffness)

SOB, wheezing

88
Q

What are the 2 ways by which urticarial drug eruptions occur?

A
  1. As an IgE mediated type 1 hypersensitivity reaction after re-challenge with a drug (most of the time)

OR

  1. As direct release of inflammatory mediators from mast cells on first exposure (uncommon)
89
Q

How long does an urticarial drug reaction usually last?

A

<12 hours

90
Q

What may an urticarial drug reaction be associated with?

A

Angioedema or anaphylaxis

91
Q

Give examples of pustular/vesicular/bullous drug eruptions (3)

A

Steroid acne

Acute generalised exanthematous pustulosis (AGEP)

Drug-induced bullous pemphigoid

92
Q

Describe fixed drug eruptions

A
  • Usually well demarcated round/ovoid plaques
  • Red and painful
  • Singular lesions or occur in a small number
  • Hands, genitalia and oral mucosa most commonly affected
93
Q

What are the lasting effects of fixed drug eruptions once the lesion has resolved? (2)

A
  • Persistent pigmentation

- The lesion can re-occur at the same site on re-exposure to the drug

94
Q

Which drugs are associated with fixed drug eruptions?

A 
Tetracycline
Doxycycline 
Paracetamol
NSAIDs
Carbamazepine
95
Q

Describe drug-induced photosensitivity reactions

A
  • Non-immunological skin reactions caused by light reaction of a photo-reactive drug
  • Usually caused by UVA light
  • Can also be caused by visible or UVB light
  • The effects can usually be reversed by stopping the drug
96
Q

List some possible presentations of skin phototoxicity (6)

A
  • Immediate prickling with delayed erythema and pigmentation (can even occur on a cold day)
  • Exaggerated easy sunburning
  • Telangiectasia on sun exposed sites e.g., Ca2+ channel blockers
  • Delayed 3-5 days erythema and pigmentation
  • Increased skin fragility
  • Pigmentation
97
Q

Which drugs are associated with drug-induced phototoxicity?

A 
Antibiotics (esp. doxycycline)
Thiazides
Chlorpromazine
NSAIDs
Quinine
Amiodarone
Porphyrins
BRAF inhibitors
Antifungals
Azathioprine
98
Q

Name 4 severe and life-threatening drug reactions

A
  • Steven-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Acute generalised exanthematous pustulosis (AGEP)
99
Q

Give a brief description of the following drug reactions:
- Steven-Johnson syndrome (SJS)

  • Toxic epidermal necrolysis (TEN)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Acute generalised exanthematous pustulosis (AGEP)
A
  • Steven-Johnson syndrome (SJS) - severe mucosal rash
  • Toxic epidermal necrolysis (TEN) - life-threatening blistering and peeling of the skin
  • Drug reaction with eosinophilia and systemic symptoms (DRESS) - extensive skin rash with eosinophilia and visceral organ involvement
  • Acute generalised exanthematous pustulosis (AGEP) - sheets of coalescing pustules, extensive systemic rash, sluffing off of the skin
100
Q

List some consequences of severe cutaneous drug reactions (7)

A
  • Hypothermia
  • Fluid loss
  • Protein loss
  • Sepsis
  • Multi-organ failure (due to involvement of whole skin and loss of skin function)
  • Permanent sequalae e.g., ocular & mucosal scarring & strictures, psychological impact
  • Death

LR Dermatology (11 decks)

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