Pharmacology Flashcards
(100 cards)
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
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
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
4
Q
List 4 epithelial routes of drug administration that allow for a local effect
A
Airways
Conjunctival sac
Nasal mucosa
Vaginal
5
Q
What is the main barrier for topical drug absorption?
A
The stratum corneum
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
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
8
Q
State the 2 main routes of drug diffusion through the stratum corneum
A
- Intercellular
- Transcellular
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
10
Q
Describe the transcellular route of drug diffusion
A
- It is hydrophilic
- The drug diffuses through the corneocytes
11
Q
What pathologies are topical drugs mainly used to treat?
A
- Superficial skin disorders
- Skin infections
- Pruritis
- Dry skin
- Warts
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
13
Q
List some common drug vehicles from highest to lowest water content
A
Lotions Creams Ointments Gels Pastes Powders
14
Q
The choice of drug vehicle is dictated by…
A
- Properties of the drug
- The clinical condition
15
Q
Factors that influence the rate of absorption of topical drugs can be describes using…
A
Fick’s Law of Diffusion
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)
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
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
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
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
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
22
Q
What is the driving force for diffusion of topical drugs?
A
The concentration of dissolved drug in the vehicle (Cv)
23
Q
What are excipients?
A
Substances included in the vehicle that can enhance drug solubility and absorption
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
25
Topically applied drugs are generally well/poorly absorbed
Poorly
26
Describe 2 ways in which drug partitioning can be improved
- 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
27
Methods of improving drug partitioning results from a reduction in the barrier function of...
The stratum corneum
28
What factors influence the absorption of topically applied drugs?
- Site of application
- Hydration of skin
- Integrity of epidermis
- Drug concentration and properties
- The drug salt
- The vehicle
29
List these drug application sites from most to least permeable:
Palm/sole
Trunk/extremities
Nail
Scrotum
Scrotum
Trunk/extremities
Palm/sole
Nail (impermeable)
30
What effects do topical corticosteroids have on the skin?
Anti-inflammatory
Immunosuppressant
Vasoconstricting
Anti-proliferating towards keratinocytes and fibroblasts
31
List 3 dermatological pathologies that can be treated with topical corticosteroids
- Atopic eczema
- Psoriasis
- Pruritis
32
Duration of use of topical corticosteroids depends on...
Whether they are categorised as mild, moderate, potent or very potent
33
List some adverse effects of long-term use of high potency topical steroids
- Steroid rebound (glucocorticoid receptor down-regulation)
- Skin atrophy
- Systemic effects
- Spread of infection
- Skin reddening/pimples (steroid rosacea)
- Stretch marks
- Superficial dilated blood vessels
34
Describe the molecular action of glucocorticoids (from Principles)
- 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
35
How is a drug administered via the subcutaneous route?
A needle inserts the drug into the adipose tissue beneath the surface of the skin
36
How do subcutaneously administered drugs reach systemic circulation?
By diffusion into either...
- Capillaries
- Lymphatic vessels (esp. high molecular weight compounds)
37
What are the advantages of subcutaneous drug administration?
- 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
38
What are the disadvantages of subcutaneous drug administration?
- Injection volume is limited
| - Needle needs to be sterilised
39
How does transdermal drug delivery (TDD) work?
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
40
What sort of drugs is transdermal drug delivery (TDD) most suitable for?
- Low molecular weight
- Moderately lipophilic
- Potent
- Relatively brief half-life
41
What are the advantages of transdermal drug delivery (TDD)?
- Steady state of drug delivery
- Decreased dosing frequency
- Avoids first-pass metabolism
- Rapid termination of action
- User friendly
- Painless
42
What are the disadvantages of transdermal drug delivery (TDD)?
- Relatively few drugs are suitable (GTN, nicotine etc)
- Expensive
- Adhesive patch can cause skin irritation
43
What strategy can be used to improve transdermal drug delivery (TDD)?
The addition of chemical enhancers
44
How do chemical enhancers work?
They interact with lipids in the stratum corneum to increase permeability (mainly to lipophilic drugs which already cross the skin reasonably well)
45
List 3 agents that may be used as chemical enhancers
- Water (prolongs occlusion by increasing stratum corneum hydration)
- Solvents e.g., ethanol
- Surfactants
46
What are the advantages of chemical enhancers?
- Cheap
| - Can be incorporated into vehicles or patches
47
What are the disadvantages of chemical enhancers?
- Skin irritation/toxicity
| - Not effective for hydrophilic drugs or macromolecules
48
Name 6 bases or vehicles that topical therapies can come in
```
Creams
Ointments
Lotions
Gels
Pastes
Foams
```
49
Name 7 different types of topical therapies
```
Emollients (common)
Topical steroids (common)
Anti-infective agents
Anti-pruritics
Keratolytics
Psoriasis therapies
Cytotoxic & anti-neoplastic agents
```
50
List some general side effects of topical therapies
- Burning
- Irritation
- Contact allergic dermatitis
- Local toxicity
- Systemic toxicitiy
51
What is the function of emollients and how many grams are supplied for one week's use?
Used for all dry/scaly skin conditions (esp. eczema) to enhance rehydration of the epidermis
300-500g
52
What are the risks associated with emollients?
- 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
When are wet wraps used?
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
What are the 3 modes of action of topical steroids?
Vasoconstrictive
Anti-inflammatory
Anti-proliferative
55
```
Give an example of a...
- mild
- moderate
- potent
- very potent
... topical steroid
```
Mild -> hydrocortisone
Moderate -> modrasone
Potent -> mometasone
Very potent -> clobetasol
56
What type of skin conditions are topical steroids used for?
Non-infective inflammatory skin diseases e.g., eczema, psoriasis, lichen planus, keloid scars
57
Why should steroids be used with caution for psoriasis?
There is risk of rebound flare ups of a disease if a potent steroid is stopped suddenly
58
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?
20-30g
1-2g -> 2 hand areas
59
List as many possible side effects of topical steroids as you can
- 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
What is tachyphylaxis?
Reduced response to steroids even when dose is increased
61
What are Calicneurin Inhibitors?
Non-steroidal topical treatments sometimes used for atopic eczema and psoriasis - esp. for the face and for children
62
Give an example of antiseptics being used for skin pathology
Potassium permanganate can be used to soak acute exudative eczema or pompholyx
63
What is pompholyx?
Exudative eczema with blisters which is restricted to the hands and feet
64
What skin conditions are antibiotics used for?
- Acne
- Rosacea
- Skin infection e.g., impetigo
- Infected eczematous process
65
List 3 diseases which are treated with antivirals
- Herpes simplex (cold sore)
- Eczema herpeticum (herpes in a patient with atopic eczema)
- Herpes zoster (shingles)
66
List 3 diseases which are treated with antifungals
- Candida (thrush)
- Dermatophytes (ringworm)
- Pityriasis versicolor (scaly erythema all over torso)
67
Why are shampoo antifungals sometimes more useful than topical?
It's easier to cover the entire body
68
Name 2 anti-pruritics and describe how they work
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
What are keratolytics used for? Give an example of one
Used to soften keratin e.g., viral warts, hyperkeratotic eczema & psoriasis, corns, calluses
E.g., salicylic acid
70
Give 2 examples of cytotoxic and anti-neoplastic therapies used for solar damage and superficial basal cell carcinoma
5-Fluorouacil
| Imiquimod
71
Give a list of possible topical treatments that can be used alongside an emollient to treat psoriasis
- Coal tar
- Vitamin D analogue
- Keratolytic
- Topical steroid
- Dithranol
72
What are the disadvantages of vitamin D analogues?
- Can be an irritant
| - Use limited to 100g weekly due to hypercalcaemia risk
73
What are the disadvantages of dithranol?
Irritant and stains normal skin so must be applied directly to the affected area
74
Immunological drug reactions are dose/non-dose dependent
Non-immunological drug reactions are dose/non-dose dependent
Immunological = Non-dose dependent
Non-immunological = Dose dependent
75
What are the 4 types of immunologically mediated drug reactions?
Give an example of each
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
List examples of conditions caused by non-immunological drug reactions
```
Eczema
Psoriasis
Atrophy
Alopecia
Phototoxicity
Pigmentation
```
77
What are the most common presentations of drug eruptions?
Exanthematous/morbilliform/maculopapular (75-95%) – an extensive, red, maculopapular rash
Urticarial (5-10%) – hives, nettle rash
Purpuric, vasculitic
Papulosquamous/pustular/bullous
78
Cutaneous drug eruptions are usually symmetrical/asymmetrical and do/don't resolve when the drug is withdrawn
Cutaneous drug eruptions are usually symmetrical and do resolve when the drug is withdrawn
(but there are exceptions to this rule)
79
What are the patient risk factors for drug eruptions? (5)
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
What are the drug risk factors for adverse drug reactions? (4)
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
Which investigations may be used for a drug eruption?
History and physical examination are usually sufficient
In less clear situations, blood test, biopsy, phototesting, patch testing or skin prick may be used
82
How is a drug reaction halted?
- Discontinue drug use (if possible)
| - Use an alternative drug or drug class
83
How is a cutaneous skin eruption treated?
- Topical steroids
- Antihistamines (for type 1 hypersensitivity or itch)
- Supportive care for severe drug reactions
84
What further precautions can be taken to prevent drug eruptions?
- 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
Describe exanthematous drug eruptions
- 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
Which drugs are associated with exanthematous drug eruptions?
```
Penicillins
Sulphonamides
Erythromycin
Streptomycin
Allopurinol
Anti-epileptics
NSAIDs
Chloramphenicol
```
87
List some indicators of severe exanthematous drug eruptions
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
What are the 2 ways by which urticarial drug eruptions occur?
1. As an IgE mediated type 1 hypersensitivity reaction after re-challenge with a drug (most of the time)
OR
2. As direct release of inflammatory mediators from mast cells on first exposure (uncommon)
89
How long does an urticarial drug reaction usually last?
<12 hours
90
What may an urticarial drug reaction be associated with?
Angioedema or anaphylaxis
91
Give examples of pustular/vesicular/bullous drug eruptions (3)
Steroid acne
Acute generalised exanthematous pustulosis (AGEP)
Drug-induced bullous pemphigoid
92
Describe fixed drug eruptions
- 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
What are the lasting effects of fixed drug eruptions once the lesion has resolved? (2)
- Persistent pigmentation
| - The lesion can re-occur at the same site on re-exposure to the drug
94
Which drugs are associated with fixed drug eruptions?
```
Tetracycline
Doxycycline
Paracetamol
NSAIDs
Carbamazepine
```
95
Describe drug-induced photosensitivity reactions
- 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
List some possible presentations of skin phototoxicity (6)
- 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
Which drugs are associated with drug-induced phototoxicity?
```
Antibiotics (esp. doxycycline)
Thiazides
Chlorpromazine
NSAIDs
Quinine
Amiodarone
Porphyrins
BRAF inhibitors
Antifungals
Azathioprine
```
98
Name 4 severe and life-threatening drug reactions
- Steven-Johnson syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Acute generalised exanthematous pustulosis (AGEP)
99
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)
- 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
List some consequences of severe cutaneous drug reactions (7)
- 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
