Pharmacology Flashcards
1
Q
Major routes of administration for diseases of the skin
A
Topical, transdermal, subcutaneous/depot
2
Q
Other epithelial routes for drug administration
A
Airways, conjunctival sac, nasal mucosa, vaginal
3
Q
Most important barrier to drug penetration into the skin or diffusion across it
A
Stratum corneum
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
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
6
Q
Topical route of administration
A
Drug is applied in a pharmacologically inactive vehicle to the skin
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
8
Q
Vehicles for topical route of administration from greatest water content to least
A
Lotions Creams Ointments Gels Pastes Powders
9
Q
What is the choice of vehicle dilated by?
A
Physiochemical properties of the drug and the skin condition
10
Q
Factors influencing the absorption of topically applied drugs
A
Rate of absorption
Nature of the skin
Drug/pharmaceutical preparation
11
Q
What does rate of absorption depend on?
A
Permeability coefficient and concentration of drug in the vehicle
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
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
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
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
16
Q
How can drug solubility and absorption be enhanced?
A
By inclusion of excipients within the vehicle
17
Q
What provides the driving force for skin penetration for drugs applied topically?
A
The fraction within the vehicle solubilised
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
19
Q
Topically applied drugs are generally well/poorly absorbed
A
Poorly absorbed - only a small fraction partitions into the skin
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
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
22
Q
Glucocorticoids are widely used topically in which conditions?
A
Eczema, psoriasis and pruritus
23
Q
Formulations of topical glucocorticoids available
A
Lotion, cream, ointment
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
25
Main nuclear receptor glucocorticoids signal via
GR alpha
26
What do glucocorticoids bind with once in the cytoplasm and what does this produce?
GR alpha producing dissociation of inhibitory heat shock proteins and the activated receptor translocates to the nucleus aided by importins
27
Subcutaneous route of administration
Drug delivered by a needle, inserted into the adipose tissue just beneath the surface of the skin
28
Advantages of subcutaneous route of administration
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
29
Disadvantages of subcutaneous route of administration
Injection volume limited
| Absorption is fairly slow (advantage/disadvantage)
30
Why is the skin an attractive route for drug administration for systemic effect
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
31
Transdermal drug delivery
The drug is usually incorporated into an adhesive patch applied to the epidermis
32
Features of drugs that make them suitable for transdermal drug delivery
Low molecular weight
Relatively lipophilic
Potent
Of relatively brief half-life
33
Advantages of transdermal drug delivery
```
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
```
34
Disadvantages of transdermal drug delivery
Few drugs suitable for this method
Allergies
Costly
35
Examples of drugs that can be used by the transdermal drug delivery method
GTN
Fentanyl
Buprenorphine
Estradiol
36
Advantages and disadvantages of topical treatments
Advantages - direct application, reduced systemic effects
| Disadvantages - time consuming, correct dosing can be difficult, messy to use
37
What is a cream?
Semisolid emulsion in water, containing emulsifier and preservative
38
Creams have a high/low water content
High
39
Advantages of creams
Cool and moisturise
Non-greasy
Easy to apply
Cosmetically acceptable
40
What is an ointment?
Semisolid grease/oil (soft paraffin) with no preservative
41
Advantages and disadvantages of ointments
Advantages - occlusive and emollient, restrict transepidermal water loss
Disadvantage - greasy - less cosmetically acceptable
42
What is a lotion?
Suspension or solution of medication in water, alcohol or other liquids
43
What areas do lotions treat?
Scalp and hair-bearing areas
44
Disadvantage of lotions
May sting if they contain alcohol
45
What is a gel?
Thickened aqueous solution. Semi-solid containing high molecular weight polymers
46
Which areas are gels used to treat?
Scalp, hair-bearing areas, face
47
What is a paste?
A semisolid that contains finely powdered materials
48
Advantages and disadvantages of pastes
Advantages - protective, occlusive, hydrating
| Disadvantages - stiff, greasy, difficult to apply
49
What is a foam?
Colloid with two-three phases. Usually a hydrophilic liquid in continuous phase with foaming agent dispersed gaseous phase
50
Advantages of foams
Increased penetration of active agents, can spread over large areas of skin with no oily/greasy film
51
Types of topical therapies
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Emollients
Topical steroids
Antinfective agents
Antipruritics
Kertolytics
Psoriasis therapies
Cytotoxic and antineoplastic therapies
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52
Benefit of emollients and which conditions they are used in
They enhance rehydration of the epidermis and are used in all dry/scaly conditions
53
Dose of emollients prescribed
300-500g
54
Tips to tell a patient when prescribing emollients
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
When is wet-wrap therapy used?
For xerotic skin
56
Disadvantage of wet-wrap therapy
Very difficult and time consuming to apply
57
Mode of action of corticosteroids
Vasoconstrictive, anti-inflammatory, anti-proliferative
58
Examples of topical corticosteroids:
- Mild
- Moderate
- Potent
- Very potent
Mild = hydrocortisone 1%
Moderate = modrasone, clobetasone, butyrate 0.05%
Potent = mometasone, betamethasone, valerate 0.1%
Very potent = clobetasol propionate 0.05%
59
Quantity of topical corticosteroids
1 application to whole body (adult) = 20-30g
| 1 fingertip unit = 1/2 gram - covers 2 hand areas
60
Side effects of topical corticosteroids
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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
Alternative to steroids
Calcineurin inhibitors
62
How to calcineurin inhibitors work?
Suppress lymphocyte activation
63
Disadvantages of calcineurin inhibitors
May cause burning sensation on application, perhaps risk of cutaneous infections and cancer
64
Clinical uses for antiseptics
For recurrent infection, skin cleansing, wound irrigation
65
Examples of antiseptics
Povidone iodine skin cleanser
Chlorohexadine
Triclosan
Hydrogen peroxide
66
Clinical uses of antibiotics
Treatment of acne and rosacea
Treatment of skin infections
Treatment of infected eczematous process
67
Caveats of antibiotics
Antibiotic resistance, sensitisation
68
Antipruritics and how they work
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
What do keratolytics do? Which conditions are they used in?
```
Soften keratin
Viral warts
Hyperkeratotic eczema and psoriasis
Corns and calluses
To remove keratin plaque in scalp
```
70
Treatment of warts
Mechanical paring plus:
- Keratolytics
- Formaldehyde
- Glutaraldehyde
- Silver nitrate
- Cryotherapy
- Podophyllin (for genital warts)
71
Example of a keratolytic
Salicylic acid
72
Topical psoriasis treatment
Emollients plus either:
- Coal tar
- Vitamin D analogue
- Keratolytic
- Topical steroid
- Dithranol
73
Advantages and disadvantages of coal tar
Advantages - effective, comes in mild solutions to strong crude coal tar
Disadvantages - messy and smelly
74
Advantages and disadvantages to vitamin D analogue
Advantages - clean, no smell, easy to apply
| Disadvantages - can be irritant, use limited to 100g weekly as can cause hypercalcaemia
75
Advantages and disadvantages of dithranol
Advantages - effective
| Disadvantages - difficult to use, irritant, stains normal skin
76
Treatment for scalp psoriasis
Greasy ointments to soften scale
Tar shampoo
Steroids in alcohol base or shampoo
Vitamin D analogues
77
Type I anaphylactic reaction presentation
Anaphylaxis and/or urticaria
78
Type II cytotoxic reaction presentation
Blistering reactions - pemphigus and pemphigoid
79
Type III immune complex mediated reaction presentation
Purpura/rash/vasculitis
80
Type IV cell-mediated delayed hypersensitivity reaction presentation
Erythema/rash
81
Examples of non-immunological cutaneous drug reactions
```
Eczema
Drug induced alopecia
Phototoxicity
Skin erosion (topical 5-fluorouracil)
Atrophy (topical steroids)
Psoriasis
Pigmentation
Cheilitis
```
82
Who to consider as having cutaneous drug eruptions
Any patient who is taking medication who suddenly develops a symmetrical skin eruption
83
When does the effect of cutaneous drug eruptions usually resolve?
When the drug is withdrawn
84
Factors that can cause cutaneous drug eruptions to continue on withdrawal of the drug
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
Risk factors for drug eruptions
```
Age - elderly > infants
Gender - females > males
Genetics
Concordant disease (e.g. viral infections, CF)
Immune status
```
86
Most common type of drug eruption
Exanthematous drug eruptions
87
What is an exanthematous drug eruption?
An idiosyncratic, T-cell mediated delayed hypersensitivity reaction
88
Clinical presentation of exanthematous drug eruptions
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
Indicators of a potentially severe exanthematous drug eruption
```
Involvement of mucous membrane and face
Facial erythema and oedema
Widespread confluent erythema
Fever
Skin pain
Blisters, purpura, necrosis
Lymphadenopathy, arthralgia
SOB, wheezing
```
90
Drugs associated with exanthematous eruptions
```
Penicillins
Sulphonamides
Erythromycin
Streptomycin
Allopurinol
Anti-epileptics - carbamazepine, phenytoin
NSAIDs
Chloramphenicol
```
91
Urticarial drug reactions
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
Acneiform
Looks like acne but there are no comedones or greasy skin
93
In which people can acneiform be seen in?
Weightlifters who have taken steroids
94
Drugs that can be associated with acneiform
Androgens
Lithium
Isoniazid
Pustulosis
95
Acute generalised exanthematous pustulosis
Rare, sheets of monomorphic pustules
96
Drugs that can be associated with acute generalised exanthematous pustulosis
Antibiotics, calcium channel blockers, antimalarials
97
Drugs that can cause drug-induced bullous pemphigoid
ACE inhibitors, penicillin, furosemide
98
Clinical presentation of fixed drug eruptions
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
What happens in fixed drug eruptions when the drug is stopped and then re-introduced?
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
Drugs associated with fixed drug eruptions
Tetracycline, doxycycline
Paracetamol
NSAIDs
Carbamezapine
101
Severe cutaneous adverse drug reactions
Stevens-Johnson syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Acute generalised exanthematous pustulosis (AGEP)
102
Drugs that can cause toxic epidermal necrolysis
```
Sulfonamides
Cephalosporins
Carbamezapine
Phenytoin
NSAIDs
Nevirapine
Lamotrigine
Sertraline
Pantoprazole
Tramadol
```
103
Drugs that can cause drug reaction with eosinophilia and systemic symptoms
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Sulfonamides
Anticonvulsants
Allopurinol
Minocycline
Dapsone
NSAIDs
Abacavir
Nevirapine
Vancomycin
```
104
Clinical presentation of drug reaction with eosinophilia and systemic symptoms
Facial oedema, lymphadenopathy, liver involvement, fevers ≥40˚C
105
Consequences of severe cutaneous drug reactions
```
Hypothermia
Fluid loss
Protein loss
Sepsis
Multi organ failure
Permanent sequelae
Death
```
106
Acute phototoxic drug reactions
Skin toxicity - photosensitivity
Systemic toxicity
Photodegradation
107
Chronic phototoxic drug reactions
Pigmentation
Photoageing
Photocarcinogenesis
108
What is a phototoxic cutaneous drug reaction?
Non-immunological skin reaction due to light activation of a photo-reactive drug
109
Patterns of skin phototoxicity
Immediate prickling with delayed erythema and hyperpigmentation
Exaggerated sunburn
Exposed telangiectasia
Delayed 3-5 days erythema and pigmentation
Increased skin fragility
110
Which drugs cause immediate prickling and delayed erythema and pigmentation pattern of skin phototoxicity?
Chlorpromazine, amiodarone
111
Which drugs cause exaggerated sunburn pattern of skin phototoxicity?
Quinine, thiazides, demeclocycline
112
Which drugs cause exposed telangiectasia pattern of skin phototoxicity?
Calcium channel antagonists
113
Which drugs cause delayed 3-5 days erythema and pigmentation pattern of skin phototoxicity?
Psoralens
114
Which drugs cause increased skin fragility due to skin phototoxicity?
Naladixic acid, tetracycline, naproxen, amiodarone
115
Drugs associated with phototoxicity
```
Antibiotics
Thiazides
Chlorpromazine
NSAIDs
Quinine
Psoralens
Amiodarone
Poryphrins
BRAF inhibitors
Antifungals
Immunosuppressants
```
116
Investigations for suspected cutaneous drug eruptions
```
History and physical examination
Phototesting (for suspected phototoxic reactions)
Biopsies
Patch and photo patch tests
Skin prick/intradermal tests
```
117
Management of cutaneous drug eruptions
Discontinue drug if possible and use an alternative
Topical corticosteroids
Antihistamines (help with type I or itch)
Allergy bracelets
