Skin pharmacology Flashcards
What pharmologcial methods can we use to treat skin conditions?
Topical
Systemic
Drugs that induce reactions in the skin, e.g. psoralen
What ways can we use the skin to deliver drugs to the body?
Transdermal application
Topical
What is the difference between transdermal and topical administration?
Transdermal: application of drug to the skin with the intent that the drug will act elsewhere in the body
Topical: application of the drug to the damaged skin, the drug acts locally
What methods of transdermal administration are there?
Transdermal patch: a sticker
Iontopheresis: use of electric currents to get the drug through the skin
Micro-needles: the future, tiny needles that help drug bypass the skin barrier
How do transdermal patches work?
Apply to skin, the drug passes through the skin slowly providing a slow release of the drug over a long time period
The skin is a highly effective barrier, how does the drug get across it from a transdermal patch?
The drugs used need to be lipophilic
The stratum corneum (outer layer) is lipid rich, so the drug can get through it and into the body
What features must a drug given transdermically have?
Lipid soluble
High affinity
What are the advantages of transdermal patches?
This route bypasses the first-pass effect
Self-administration
Lasts over long periods of time
What is the first-pass effect?
When a drug is given orally, its concentration is greatly reduced because it is metabolised by the liver before it can act
What drugs are given transdermically?
HRT Contraception Nicotine replacement Angina Pain relief
What drug is used to treat angina transdermically?
GTN: glyceryl trinitrate
Name some factors that affect the delivery of the drug via a transdermal patch?
The skin type
How much fact there is
The placement of the patch
Body temperature
How does glyceryl trinitrate help treat angina?
Nitroglycerin converts to NO
Affects the smooth muscle
A vasodilator
More blood flow to heart, less ischaemia and pain
What drug is often given for pain relief via a transdermal patch?
Fentanyl, an opiate
What are the side effects of fentanyl?
Fever
Breathing problems
These usually resolve when you take off the patch
In what ways is a fentanyl transdermal patch better and worse than oral morphine?
Better:
- much lower dose is required to get the same effect
- great for chronic pain due to slow release
Worse:
- slow onset of action
What is iontopheresis?
A transdermal patch that uses electrical currents to get the drug in through the skin more efficiently
What are micro-needles?
Apart from sounding really cute!
They are tiny needles that allow the drug to pass the skin barrier and get into the body
Currently in development still
What forms can you get drugs in to give topically?
Ointment: made with grease
Pastes: powder suspended in ointment
Cream: made with water and grease
Lotion: liquid, wet
Which form of topical drug is best for very potent drugs that may cause damage to surrounding healthy tissue?
Pastes: they stay where they are put
What do emollients do to the skin?
Hydrate, soothe, reduce itching
They can help repair the damaged epithelial barrier
What is the benefit of having urea in an emollient?
Urea dissolves the intercellular matrix of the cells of the stratum corneum, promoting desquamation of scaly skin,
It helps to soften hyperkeratotic areas.
Name some ‘barrier cream’?
What do they do?
Silicones and Zinc oxide
They help create a barrier on the skin, to prevent pathogens and allergens getting in
When given topically, what does salicylic acid do?
What type of drug is it?
Facilitates breakdown of keratin to soften skin
It is a keratolytic
Different drugs target receptors in different regions of the body’s cells. Name some common targets?
Cytoplasmic receptors
Nuclear receptors
Cell membrane receptors
What drugs target cytoplasmic receptors? (skin only)
Glucocorticoids
Mineralocorticoids
How do glucocorticoids help skin disease? How do they work?
Vasoconstriction
Anti-inflammatory
Immunosuppressive
Anti-proliferative
They inhibit NFkB pathway
By doing this they inhibit pro-inflammatory cytokine expression
And stimulate anti-inflammatory cytokine production
Name some pro and anti-inflammatory cytokines?
Pro: IL1, 2, 6, TNFa
Anti: IL-10
Which skin diseases are glucocorticoids used in?
Which diseases are they not recommended and why?
Used in eczema, insect stings, etc.
Not used in acne + psoriasis due to rebound effect on withdrawal of drug
Not used in widespread infections since it’s an immunosupressive
Adverse affects of topical corticosteroids?
Atrophy of skin
Glaucoma if used around eye
Infection
Acne + rosacea
Which drugs target nuclear receptors?
Vitamin D analogues
Vitamin A analogues
Name a vitamin D analogue?
Calcipotriol (dovonex!)
How do vit D analogues help in skin disease?
They are anti-inflammatory and anti-proliferative
Which diseases are vitamin D analogues used to treat?
Psoriasis, especially plaque
Who should you not give vit D analogues to?
People who are known to be hypercalcaemic
An adverse effect of these drugs is hypercalcaemia, but it is rare
Name a vitamin A analogue?
Isotretinoin: a systemic vitamin A analogue
There are many more
What is retinol?
Vitamin A
How do vitamin A analogues help in skin disease?
They inhibit cell proliferation by affecting the cell’s DNA
Prevent hyperkeratosis, and skin proliferation
What is the problem with vitamin A analogues?
They are teratogenic
Drying and irritating to skin and mucous membranes
What is calcineurin?
An enzyme that activates chain reactions to promote IL-2 synthesis
IL-2 is a pro-inflammatory cytokine
How do calcineurin inhibitors help in skin disease?
Inhibiting calcineurin inhibits the promotion of IL-2 synthesis, reducing inflammation
Name some calcineurin inhibitors?
Tacrolimus
Ciclosporin
How does methotrexate help treat psoriasis?
Inhibits the metabolism of folic acid
Which inhibits proliferation, inflammation
Problems with methotrexate?
Hepatotoxic
Need to supplement folic acid
Needs to be an injection once a week
Which drug is given as an adjuvant to phototherapy? Why?
Psoralen
Because it further increases the damage done to nucleic acids in DNA by UVA
It enhances the damage
How does PUVA therapy work?
Psoralen combined with UVA
UVA and psoralen act to damage nucleic acids in DNA
This prevents replication, reducing hyperproliferation
Which monoclonal antibodies are used to treat psoriasis?
TNF-a antibodies
- infliximab
- adalimumab
There are 4 types of immune reactions that can occur to drugs. Name them?
TYPE 1: allergic
TYPE 2: antibody mediated
TYPE 3: immune complex
TYPE 4: delayed hyper-sensitivity
Describe and give an example of a type 1 drug reaction?
IgE against the drug/antigen already exists in the body
When the drug is given an immune reaction occurs straight away
Anaphylaxis
Describe and give an example of a type 2 drug reaction?
Antibody dependent
Host cells take up the drug antigen (APCs)
IgG and M binds to the host cells and destroys them
Penicillin causing haemolytic anaemia (destruction of RBCs due to this mechanism)
Describe and give an example of a type 3 drug reaction?
Deposition of immune complexes (drug antigen-antibody) in skin and microcirculation
Causes rashes and damage to organs
Describe and give an example of a type 4 drug reaction?
T cell mediated
The T cells mount a response against the drug antigen
Eczema caused by topical anti-histamine
What kind of reactions occur in the skin to drugs?
Exanthematous: eruptive skin rash, burning, itching
Urticaria: raised itchy red blotches (like nettle rash)
Angioedema: oedema of face
Fixed skin eruptions: blisters
Steven-Johnson syndrome
What is Steven-Johnson syndrome?
Skin blistering, mucosal erosion
Systemic features: fever, malaise, arthralgia
Caused by a drug reaction
Name some variants of Steven-Johnson syndrome?
Erythema multiforme
Toxic epidermal necrosis
What type of drug is ciclosporin?
A calcineurin inhibitor
What type of drug is methotrexate?
Anti-folic acid
What type of drug is Calcipotriol?
Vitamin D analogue
What type of drug is isotretinoin?
Vitamin A analogue
What type of drug is tacrimolus?
A calcineurin inhibitor
