3. Pharmacology of Skin Disorder Treatment Flashcards
1. Describe the mechanism(s) of action 2. Therapeutic outcome, and 3. Main adverse effects For the main pharmacological treatments of: – dermatitis (eczema), – psoriasis, – acne, – fungal infections of the skin – actinic keratosis
Corticosteroids - basic info
Produced in adrenal glands (cortex)
Primary use is reduction of inflammation
Glucocorticoids & Mineralcorticoids
Glucocorticoid - effect on cell signalling
- trans-Activation of Gre (anti-inflammatory)
- cis-Repression - negative GRE (side-effects)
- trans-Repression (decreases inflammation)
Glucocorticoid - Mechanism of Action
Binds to intracellular steroid receptor
Steroid hormone receptor complex (SHRC) translocated to nucleus
- Anti-inflammatory effect: Binds to DNA & increases the production of Lipocortin 1 (Annexin 1) - Lipocortin 1 suppresses conversion of phospholipids to arachidonic acid, suppresses production of inflammatory mediators
- Reduced inflammation: Forms complex with CPB & NFk-B; inhibits activation of NFk-B, thereby reducing production of cytokines, chemokine, inflammatory proteins, enzymes & receptors
Glucocorticoids - Adverse effects
- Worsen infection of skin/acne
- Suppression of Hypothalamic-Pituitary Axis (HPA)
- Stunted growth in children
- Usually dose dependent
Retinoids: Vitamin A derivatives - basic info
- Treat acne/psoriasis (severe)
- Modulates epidermal cell growth & keratinocyte differentiation
- Regulates sebaceous cell activity & anti-inflammatory
- Actions via RXR/RAR intracellular receptors
Retinoids - Mechanisms of Action
Retinoids interact with RXR/RAR nuclear receptor to produce changes in genes that modulate keratinocyte differentiation, reduce size & output of sebaceous glands & exert an anti-inflammatory effect
Retinoids - Adverse effects
- Dry, flaky skin
- Stinging or burning sensation
- Teratogenic
Vitamin D - basic info
- Treat psoriasis
- A group of compounds
- Vit D3 is synthesised in skin in response to sunlight
- Primarily reduces Th2-mediated effects
Vitamin D - effects
- Act via VDR intracellular receptors
- Keratinocytes, sebaceous gland cells, Langerhans’s cells
- Anti-proliferation
- Pro differentiation in keratinocytes
- Increased apoptosis in plaque keratinocytes
- Inhibit T-cell activation
Vitamin D - Adverse effects
- Dysfunction of calcium/phosphate metabolism
- Bone disorders
Biologics - basic info
- Treat psoriasis & dermatitis
- Targets TNF-α - decreases activity of immune system
Antibacterials - basic info
- Treats dermatitis & acne
- Designed to target “non-host” cells e.g. Cell wall. Ribosome structure, Folic acid synthesis
Antibacterials - inhibition of cell wall synthesis
- β-lactam antibiotics inhibit transpeptidase enzymes involved in cross linking peptidoglycan during cell wall formation
- Kills bacteria by disrupting its cell wall structure
- E.g. Flucloxacillin
Antibacterials - inhibition of protein synthesis
- Act on bacteria ribosome (70S) to inhibit bacterial protein synthesis (Bacteriostatic)
- E.g. Doxycycline, clindamycin
Antibacterials - inhibition of DNA synthesis
- Antifolates (sulphonamides) inhibit folic acid synthesis as they are analogues of PABA
- Bacterial cells required folic acid for nucleic acid synthesis
- Trimethoprim inhibits DHFR - less chance of resistance
- E.g. Sulphonamide + Trimethoprim = Cotrimoxazole
