dermatology pharmacology and prescribing

route of administration

topically where possible

if oral, optimal absorption important

why is distribution and excretion important

in liver disease and renal disease

reducing doses or finding alternatives

what to think about in pharmacodynamics

-age of patient

-pregnancy risk

-drug interactions

-pharmacogenetics

topical therapy

•Medication applied to the skin

•Vehicle + active drug

Vehicle:  pharmacologically inert, physically and chemically stable substance that carries the active drug

what does the choice of vehicle affect

drug absorption

e.g. ointments more occlusive than creams

factor that affect topical absorption

•Concentration

•Base/vehicle

•Chemical properties of the drug

•Thickness and hydration of stratum corneum

•Temperature

•Skin site

Occlusion

vehicles

Solution  

Cream  

Lotion 

Gel 

Foam 

Tape

paste

spray powder

shampoo

ointment

paint

examples of drugs used topically

Corticosteroid 

Chemotherapy

Antibiotic 

Parasiticidals

Antiviral 

Coal Tar

Dithranol 

Anti-inflammatory

Vitamin analogues

Salicylic acid

topical steroids

•Anti- inflammatory and immunosuppressive properties

–Regulate pro inflammatory cytokines

–Suppress fibroblast, endothelial, and leukocyte function

–Vasoconstriction

Inhibit vascular permeability

finger tip unit

about 0.5 g

-treats area double the size of one hand

-useful in young children

side effects of topical steroids

•Thinning /atrophy

•Striae

•Bruising

•Hirsutism

•Telangiectasia

•Acne/rosacea/perioral dermatitis

•Glaucoma

•Systemic absorption, risk of adrenal suppression

•Cataracts

retinoids

•Vitamin A analogues

–Normalise keratinocyte function

–Anti inflammatory and anti cancer effects

•Four different molecules used orally in dermatology

isotretinoin

acitretin

bexarotene

alitretinoin

what are retinoids effective in

–Acne 

–Psoriasis 

–Cutaneous T cell lymphoma 

 Hand eczema

what can retinoids not be used in what do they require monitoring of

teratogenic

require monitoring of liver transaminases and triglycerides

retinoids side effects

–Cheilitis(dry lips) and xerosis (dry skin)

–↑transaminases, ↑triglycerides

–Rarely: psychiatric, eye, bone side effects

immunosuppressants

•Treatment of inflammatory skin disorders

•Oral steroids

•Azathioprine

•Ciclosporin

•Methotrexate

Mycophenolate mofetil

risk of immunosuppressants

•Risk of malignancy and serious infection

what do you need to do regularly in immunosuppressants

Need regular blood test monitoring, in particular

–FBC (esp in methotrexate and azathioprine)

–Renal function (esp ciclosporin)

–Liver function (esp methotrexate)

biologics

treat inflammatory conditions

–Genetically engineered proteins derived from human genes

–designed to inhibit specific components of the immune system

biologics that end in -cept

•'-cept’ indicates that it is a it is a Receptor fusion

–Etanercept -genetically engineered fusion protein

biologics that end in -mab

"-mab" is used to denote monoclonal antibodies

adalimumab

immunomodulator fully human monoclonal antibodies

Infliximab

immunomodulator  chimeric monoclonal antibodies

what dermatology conditions are biologics licensed for

Psoriasis – twelve

Hidradenitis suppurativa – three

 Chronic spontaneous urticaria – one

 Atopic eczema – four

 Pemphigus – one 

risks of biologics

•Risk of infection

–TB reactivation

–Serious infection

–Avoid live vaccines

•Risk of malignancy

•TNF inhibitors – risk of demyelination

treatment options for advanced myeloma

•Immunotherapy (IV)

–Metastatic disease stage 4

–Neoadjuvant or adjuvant for stage 3

–Adjuvant use for some stage 2B and 2C patients

•Targeted treatment (oral)

–BRAF 600 mutation (40-50%)

–BRAF inhibitor + MEK inhibitor

future options for melanoma

cancer vaccines

Tumour infiltrating lymphocytes