Skin ISU Flashcards
what are some of the benefits of produgs
increased solubility in lipid or water
improved taste
improved stability
reduced toxicity
modify time of duration of action
deliver drug to specific site
differences between bio precursor and carrier prodrugs
bio contain the embryo of the active species within their structure and require metabolic modification through a step or series of steps to become active e.g. oxidation or reduction via enzymes.
carrier is a combination of active drug and carrier species which are linked by a functional group which can easily be metabolised such as ester or amide.
how is the protide approach used in nucleoside analogues?
- Add a phosphate or phosphonate group to the NA prodrug
- this eliminates the slow rate limiting step in vivo
how do photoactivated prodrugs work
-they are activated by certain wavelengths of light (visible or UV) to an excited state in order for them to react with a substrate. Generally results in destruction of target cell
- molecule can decay with phosphorescence or fluorescence
important points about the structure of steroids
- all share common tetracyclic structure but have different functional groups and substituents.
- have a chair conformation where stereochemistry of the three 6 membered rings are all identical in all steroids
-only one stereoisomer occurs naturally for any particular steroid.
-double bonds are identified using delta symbol and carbon number.
-they are hydrophobic in nature
what is the main glucocorticoids and what are they used for
corticosterone, cortisone, cortisol
carb,fat,protein metabolism
mainly in liver, muscles and brain cells
excess= Cushing’s syndrome
deficit = Addison’s disease
what is the main mineralocorticoid and what it is used for
Aldosterone
regulates electrolyte balance (sodium ion retention in kidney cells)
Excess = Conn’s disease
what do all adrenocorticoids have in their structure
pregnane skeleton (2C side chain at C17)
what structural features of cortisol are important for its activity
essentially all of them, the removal of groups reduces/eliminates activity
However additional groups can enhance the activity which allows for one of the original functional groups to be removed
for example adding 9alpha-fluoro substituent gives fludrocortisone which has 10 times activity, but also 300-600 increased mineralocorticoid activity
where is the origin of cortisol
released from adrenal cortex above the kidneys
what are some clinical uses for topical corticosteroids (TCS)
-atopic eczema
-contact dermatitis
-Psoriasis
MOA of TCS for anti-proliferative effect
- Increased Lipocortin 1 reduces keratinocytes proliferation and collagen synthesis in epidermis + dermis.
- stops migration of T cells, dendritic cells and macrophages to epidermis
MOA of TCS for anti-inflammatory effects
-TCS synthesise lipocortin 1
-this inhibits phospholipase A enzyme (which converts phospholipids to arachidonic acid) –> decreases production of prostaglandins and leukotrienes.
-TCS directly inhibit COX-2 enzymes which inhibits production of prostaglandins
-resulting in reduced inflammation.
MOA of TCS for immunosuppressive effect
- inhibit humoral factors involved in the inflammatory response as well as suppression of maturation, differentiation, and proliferation of all immune cells
MOA of TCS for vasoconstrictive effect
unknown
-thought to be related to inhibiting vasodilators, histamine,bradykinins)
- vasoconstriction of the blood vessels in the upper dermis decreases inflammatory mediators to the region.
cutaneous adverse effects of TCS
- atrophy - epidermal thinning (reversible with cessation of TCS)
-Striae - appear as scars and permanent
-rosacea due to topical fluorinated steroids
-less common are hypertrichosis (excessive hair growth) and purpura (delayed wound healing)
systemic adverse effects of TCS
-HPA axis suppression
-Cushing’s syndrome
-Hypertension
-Hyperglycaemia
-Glaucoma
contraindications related to TCS
- bacterial infections as they mask infection
- delaying diagnosis and treatment
why are anabolic steroids not topical corticosteroids?
-manufactured from male hormone testosterone
-usually abused and taken without medical advice to increase muscle mass and improve athletic performance
Define Eczema and it’s causes and symptoms
- Chronic inflammation of the skin (atopic increased immune response to an allergen or trigger.
- Causes: genetic link with patients if FHx of atopic disease. Mutation of Filaggrin gene in 50% of cases
Discuss management and treatment options for Eczema
- self care: use of emollients, avoid exacerbating triggers
- mild: emollients + mild potency topical corticosteroid in red areas (hydrocortisone 1%)
- moderate: Betamethasone val 0.025% or clobetasone 0.05%, dressings, non-sedative antihistamine for itching
- severe: very potent TCS betamethasone val 0.1%. Moderate potency for delicate skin areas max 5 days use. Not used in children under 12mo.
-For infected eczema 1st line is Flucloxacillin
-Clarithromycin if penicillin allergy.
-emollients used at least 4 times a day and applied 15-30 mins before TCS
-Weekend regiment for TCS is apply on consecutive days, nothing in the week or twice weekly apply on 2 days per week.
Define Psoriasis and it’s causes and symptoms
systemic immune-mediated inflammatory skin disease. Well-defined plaques caused by hyperproliferation and abnormal differentiation of immune cells.
-triggered by step infection, drugs, hormonal changes, HIV, smoking, alcohol, obesity
Discuss management and treatment options in Psoriasis
- Emollients
- vit D preparations e.g. Calcipotriol, Calcitriol, Tacalcitol (not to be used on face and avoid sunlight + contraindicated with calcium disorders, kidney +liver disease and hypersensitivity)
-corticosteroids
-salicylic acid
-coal tar
-Calcipotriol OD/BD max 100g per week, 60mL scalp solution
-if used in combination with Betamethasone OD for 4 weeks (1-4g OD) DONT EXCEED 30% BODY SURFACE
-Calcitriol Apply BD, max 30g/day
-Tacalcitol OD, max 10g/10mL day
define cellulitis and its causes and symptoms
acute bacterial infection of dermis
pain, warmth, swelling, redness of infected area, fever, nausea.
Caused by microorganisms entering skin e.g. strep pyogenes
management and treatment of cellulitis
-urgent hosp admission if class III or IV suspected or really young or frail or orbital cellulitis
- First line Flucloxacillin
- pen allergy Clarithromycin
-Metronidazole if anaerobe cause, avoid alcohol
define acne and its causes and symptoms
chronic inflammatory skin condition, blocked inflamed pilosebaceous unit. Affects face back chest.
-non inflam comedones (whiteheads and blackheads)
-can develop to papules, nodules and cysts.
-excess sebum produced + follicular plugs.
-Causes are genetics + diet
define Rosacea and its causes and symptoms
-chronic inflammatory skin condition which affects the centrofacial region
-symptoms include facial flushing, erythema, papules ,pustules
-genetic link, immune system dysregulation and dysregulation in inflammatory response
Management and treatment options for acne
6-8 weeks before any improvement
Mild - benzoyl peroxide + clindamycin(topical)
Moderate - topical adapalene (retinoids) + benzoyl peroxide, PLUS oral lymecycline/doxycycline OD
Severe - Combination Azelaic acid BD PLUS oral lymecycline/doxycycline OD
oral antibiotics used if topical fail
Tetracyclines can’t be used in pregnancy so use Erythromycin
LFT needed before treatment for oral antibiotics review treatment @6 weeks then every 12 weeks
- oral contraceptives (combined) used in acne with patients who have PCOS (use if first line not successful)
discuss management and treatment of Rosacea
what are the layers of the skin from outside to inside?
stratum corneum, viable epidermis, dermis, subcutaneous fat
what is the difference between topical and transdermal drug delivery?
topical - we want the drug to act within the stratum corneum or epidermis locally.
transdermal - we want the drug to enter the bloodstream after permeating the skin and act more systemically
