Topical pharmacology Flashcards
What are the 3 main routes of absorption through the skin?
- Intercellular - Between cells
- Intracellular - Through cells
- Transappenageal - Through glands
What makes it hard for drugs to pass through the skin?
It is hard to navigate the stratum corneum due to its insoluble keratin matrix and intracellular lipid layers
What are some factors that affect absorption through the skin?
- Water solubility (More WS = More absorption)
- Molecular weight (Perfect = 100-500Da)
- Oil/water partition coefficient (LogP = 2 is perfect)
What is meant by topical drug delivery?
This is a method of delivery that involves applying the drug formulation directly onto intact and healthy skin
What are some skin conditions that can be treated topically?
- Psoriasis
- Eczema
- Skin infection
- Itching
- Dry skin
What are some advantages of topical drug absorption?
Advantages of topical drug administration are that the drugs can be applied directly to the affected tissue and reduce risk of systemic effects, especially in glucocorticoids
What are some disadvantages of topical drug absorption?
They can be messy and time consuming, however, and it is hard to ensure the correct dose
It can have systemic effects, moving through the dermis and subdermis and into systemic circulation
What are some formulations of topical drugs?
Ointments
Pastes
Creams
Topical solutions
Topical suspensions
Lotions
Gels
Foams
Sprays
Emollients
What are ointments?
Ointments are suspensions or emulsions containing <20% water and volatiles, and >50% hydrocarbons, waxes or polyethylene glycol
They may contain ethanol to disrupt the structure of the stratum corneum and increase permeability
What are some advantages of ointments?
They help to form an occlusive layer over the skin, preventing loss of heat and water, while also enhancing percutaneous absorption
What are some disadvantages of ointments?
They do have a greasy texture however, and are hard to wash off and spread
They can also be easily contaminated
Where are ointments most commonly used?
This is most commonly used in glabrous areas (Skin with sparse or short hair, dry areas such as trunk and extremities)
What are the 2 main types of ointments?
- Lipophilic ointments (Base of paraffins, vegetable oils, animal fats, synthetic glycerides or waxes)
- Water-soluble ointments (Base of polyethylene glycol)
What are pastes?
Pastes are stiff ointments which can be used as vehicles for insoluble powders
They contain a large proportion of solid component (>25%)
What are some advantages of pastes?
They can be used to restrict the active ingredient to the affected area without spread to the surrounding skin
The powder also acts as an absorbent for discharge
What is a disadvantage of pastes?
They are thicker and stiffer than other formulations, however, and so are hard to spread
What are creams?
Creams are emulsions containing >20% water and volatiles, and <50% hydrocarbons, waxes or polyethylene glycol
What are the advantages of creams?
They are useful in moisturising and have emoilient properties
They are also more spreadable than ointments and can be used on all areas of the body
What is a disadvantage of creams?
They are less hydrating that ointments
What are the 2 types of cream?
- W/O emulsions
- O/W emulsions
What are W/O emulsion creams?
W/O emulsions are oily creams (e.g. zinc oxide cream, sunscreens), with a lipophilic continuous phase
They contain W/O emulsifiers such as lanolin,, glyceryly stereate and lecithin
What are the O/W emulsion creams?
O/W emulsions are vanishing creams (e.g. topical steroid cream), with a hydrophilic continuous phase
They contain emulsifiers such as polysorbate, sorbitan laurate and cetearyl alcohol
What are topical solutions?
Topical solutions are a clear, homogeneous liquid dosage form for external application to the skin, composed of one or more solutes dissolved in aqueous, non-aqueous, or hydroalcoholic solvents
They can contain gelling agents to thicken
What are some advantages of topical solutions?
They are more spreadable than ointments and creams and can be used on all areas of the body, whilst also being very simple to make
What are some disadvantages of topical solutions?
They can be messy, however, and do not provide any protection or moisturisation to the skin
Alcohol-based solutions can cause stinging, dryness and irritation
What are topical suspensions?
Topical suspensions are a liquid dosage form that consists of a solid suspended in a liquid vehicles in a 2-phase system, containing up to 2-% of a finely divided, insoluble drug dispersed in an aqueous or alcoholic vehicle
What are some advantages of topical suspensions?
They are easy to apply and so are popular in children, providing a cooling and soothing after effect
What are some disadvantages of topical suspensions?
They do require shaking beforehand and require more drying than other formulations
Alcohol-based suspensions can cause stinging, dryness and irritation
What are lotions?
Lotions are an emulsion liquid dosage form, containing usually >50% water and volatiles, in which a finely dispersed drug is suspended or dispersed
What are some advantages of lotions?
They have moistening and emollient properties and ae more spreadable than ointments
They can be used on all areas of the body
What are some disadvantages of lotions?
They are less hydrating than ointments
Where are lotions usually used?
They are usually used in dry and exudative skin conditions and are commonly used on flexural or genital areas
What are gels?
Gels are transparent semi-solid emulsions that liquefy on contact with warm skin and dry to form a non-occlusive film
They contain water, volatile components (acetone or alcohol) and a gelling agent (Cellulose) to provide stiffness
What are some advantages of gels?
They are easy to apply and wash off and are non-greasy, which also providing a cooling sensation
What are some disadvantages of gels?
They can be removed by perspiration, however, and provide very little hydration
What are foams?
Foams are pressurised liquids added to a hydrocarbon propellant
What are some advantages of foams?
They do not contain fragrances or preservatives and are easy to apply
What are some disadvantages of foams?
They do not leave a residue
They may result in stinging or burning to excoriated skin and provide very little hydration
What are sprays?
Sprays are aerosols consisting of a solution (or suspension) of the drug in the pure propellant, or the propellant plus a suitable solvent
What are some advantages of sprays?
They can treat large areas of skin and are easy to app
Where are sprays usually used?
They should be used carefully in skin folds, where absorption can be higher
What are emollients?
Emollients are topic formulations used to enhance rehydration of the epidermis
What conditions are emollients used in?
They are used in all dry or scaly conditions, especially eczema
Patients are usually perscribed 300-500g in a patient with active eczema, which needs frequent application
What are some application tips for emollients?
- Apply immediately after bathing
- Apply in direction of hair growth
- Be careful of slippery skin and surfaces
- Use a clean spoon or spatula to remove from the tub
- Fire risk if paraffin-based
What is involved in wet wrap therapy?
They involve layering the body with topical drugs, and then placing cotton wool wraps over the top to keep the drug against the skin for longer periods of time
What conditions is wet wrap therapy used in?
Very dry (xerotic) skin
What are transdermal patches?
Transdermal patches are patches placed on the skin surface, allowing movement of a drug into the skin and then blood at a controlled rate
What are some transdermal patches used for analgesia?
Buprenorphine
Fentanyl
What is an example of a transdermal patch used for HRT?
Estradiol
What is an example of a transdermal patch used for contraception?
Ethinyloestradiol with norgelstromin
What is an example of a transdermal patch used for urinary incontinance?
Oxybutynin
What is an example of a transdermal patch used for angina?
Glyceryl nitrate
What is an example of a transdermal patch used for motion sickness?
Hyoscine
What is an example of a transdermal patch used for nausea and vomiting in chemotherapy?
Granisetron
What is an example of a transdermal patch used for Parkinson’s disease and restless leg syndrome?
Rotigotine
What is an example of a transdermal patch used for Alzheimer’s disease?
Rivastigmine
What is an example of a transdermal patch used for smoking cessation?
Nicotine
What is an example of a transdermal patch used for neuropathic pain?
Capsaicin
What are some advantages of transdermal patches?
Transdermal patches are simple, conveniant and painless, allowing for steady and prolonged administration of a drug overtime
There is also no 1st pass metabolism in the liver, unlike with oral administration
What are some disadvantages of transdermal patches?
Disadvantages include possible local irritation, slow delivery to site of action and they are only useful in lipophilic drugs with high skin permeability and low required dose
What are some chemical strategies to enhance transdermal absorption?
- Penetration enhancers:
- Water
- Alcohols
- Prodrugs
- Novel formulations containing nanoparticles and liposomes
How can water increase transdermal absorption?
Water in liquid preparations can accumulate in the stratum corneum, resulting in swelling of the corneocytes and the formation of pares that increase permeability
How can alcohol increase transdermal absorption?
Alcohols disrupt the lipid bilayer in the stratum corneum and increase flux
What are some physical strategies of increasing transdermal absorption?
- Electroporation - Use of electric pulses to create new pores and pathways in the skin
- Iontophoresis - Use of low voltage electric field to drive ionised drugs through the skin
- Sonophoresis - Use of ultrasound
What is a possible consequence of twice daily 40% salicylic acid ointment?
Salicylism
Death
What are some consequences of vitamin D analogue treatment?
Hypercalcaemia
Hypercalcuria
What are some consequences of topical steroid use?
Adrenal crisis and cushingoid features if stopped abruptly
What are some of the actions of glucocorticoids?
They suppress lymphocyte proliferation, collagen synthesis, fibroblast proliferation (Scar tissue formation) and release of chemical mediators of inflammation
They can also cause vasoconstriction
What skin conditions can glucocorticoids be used in?
Immune suppression is useful in allergic responses and eczema
Fibroblast and lymphocyte suppression is useful in psoriasis
Describe the movement of glucocorticoids into the cells?
Glucocorticoids bind to intracellular receptors (GCRs), belonging to the nuclear receptor family
GCRs are protein monomers containing DNA-binding domains that, in the absence of a ligand, reside in the cytoplasm
What are the 2 mechanisms of glucocorticoid pharmacodynamics?
Transactivation mechanism
Transrepression mechanism
Describe the transactivation mechanism of glucocorticoids
Upon binding with their glucocorticoid ligand, GCRs dimerise and translocate inside the nucleus, where they bind to specific DNA responsive elements (GREs) and up-regulate the transcription of genes encoding for regulatory proteins responsible for metabolic, anti-inflammatory, and immunosuppressive effects
Describe the transrepression mechanism of glucocorticoids?
GCRs can repress gene expression (e.g. genes encoding for pro-inflammatory proteins) by binding negative DNA responsive elements (nGREs) or transcription factors that constitutively drive the expression of these genes
How is glucocorticoid potency classified?
Glucocorticoids are classified in seven classes of potency (I-VII), with class I being the most potent and class VII the least potent
How much ointment could cover the whole body?
20-30 grams
How much body area can be covered by 1 fingertip unit of ointment (0.5g)?
2 hand areas
What are some possible side effects of topical glucocorticoids?
- Thinning of the skin
- Purpura
- Stretch marks
- Steroid rosacea
- Fixed telangectasia
- Perioral dermatitis
What is the action of calcineurin inhibitors?
Suppresses lymphocyte activation
What are some examples of calcineurin inhibitors?
- Tacrolimus
- Pimecrolimus
What are the uses of calcineurin inhibitors?
Topical treatment of atopic eczema, especially on the face and in children
What are some possible side effects of calcineurin inhibitors?
There is no risk of cutaneous atrophy, but may cause burning sensation of application
There is a risk of cutaneous infections and possible skin cancer risk
What is the action of anti-septics?
Bacteriostatic or bacteriocidal effects
What are some examples of anti-septics?
- Povidone iodine
- Chlorhexidine
- Triclosan
- Hydrogen peroxide
What are some uses of anti-septics?
Used in recurrent infection (Broad spectrum), skin cleansing and wound irrigation
For example, potassium permanganate is used to acute exudate eczema
What are some uses of antibiotics in dermatology?
- Treatment of acne and rosacea
- Treatment of skin infection (e.g. impetigo)
- Treatment of infected eczematous process (e.g. otitis externa)
What are some dermatological uses of anti-virals?
- Herpes simplex virus (Cold sore)
- Eczema herpeticum
- Herpes zoster (Shingles)
What are some examples of anti-fungals?
- Nystatin
- Clotrimazole
- Terbinafine
- Ketoconazole
What are some dermatological uses of anti-fungals?
- Candida (Thrush) - Nystatin or clotrimazole
- Dermatophytes (Ringworm) - Clotrimazole or terbinafine
- Pityriasis versicolor - Ketoconazole
What is the action of anti-pruritics?
Used to prevent itching
Capsaicin depletes substance P at nerve endings and reduces neurotransmission, building its affect
What are some examples of anti-pruritics?
- Menthol
- Capsaicin
- Camphor/phenol
- Crotamiton (E.g. eurax cream)
What are the uses of anti-pruritics?
Menthol is added to calamine and other lotions and creams to impart a cooling sensation
Camphor or phenol is used for pruritis ani
Crotamiton is used after treament of scabies to relieve residual itch
What is the action of keratolytics?
Used to soften keratin
What is an example of a keratolytic?
Salicylic acid ointment
What are some dermatological uses of keratolytics?
- Viral warts
- Hyperkeratotic eczema and psoriasis
- Corns and calluses
- Remove keratin plaques in the scalp
What is a possible side effect of dithranol?
Dithranol is effective, but difficult to use and can only be used on plaques as it can cause burning, irritation and stains on normal skin
How are warts treated?
Treatment of warts require mechanical pairing, alongside:
- Keratolytics (E.g. salicyclic acid)
- Formaldehyde
- Glutaraldehyde
- Silver nitrate
- Cryotherapy (Usually liquid nitrogen)
- Podophyllin (Genital warts)
What are some medications that can be used in psoriasis treatment?
- Coal tar
- Vitamin D analogue
- Keratolyics
- Topical steroids
- Dithranol
+ Emolient
How is stable chronic plaque psoriasis usually treated?
Coal tar, vitamin D analogues or dithranol
How is scalp psoriasis usually treated?
Greasy ointments, tar shampoo, steroid shampoo or vitamin D analogues
