L3 - Pharmacology of Skin Disorder Treatment Flashcards
Glucocorticoids treat ______ and _____ and modulate ____
Dermatitis, psoriasis and inflammation
General mechanism of action of glucocorticoids
Must be soluble enough to get into cell, Act on nuclear receptors, alter protein synthesis, inhibit or promote gene synthesis.
Describe the three prong effect of glucocorticoids!
- Interact with DNA ( glucocorticoid response element), stimulate synthesis of anti inflammatory genes
- Interact with DNA GRE to turn off inflammatory genes
- Affects gene transcription of other genes e.g pomC and ca2+ levels..
Glucocorticoid anti inflammatory mechanism - hint: purely anti-inflammatory effect.
Binds to intracellular steroid receptor
Steroid receptor hormone complex, translocated to nucleus,
Binds to to DNA = produces lipocortin 1 which turns off synthesis if inflammatory mediators
Glucocorticoid reduced inflammatory mechanism - hint: turns off decent branch of immune system.
Decreases immune response in skin
Binds to steroid receptor = turns things off
Reduces production of cytokines, chemokines, inflammatory proteins, enzymes and receptors.
Adverse effects: Glucocorticoids
Dose dependent, but can worsen infection or suppress HPA axis, stunt growth in children. AVOID ABSORPTION INTO MAIN BS.
Retinoids mechanism in terms of ACNE. Give an example of a retinoid to treat severe ACNE.
Vitamin derivative. Regulation of epidermal cell growth, turn it down. Reestablish regulation of sebaceous cell activity.
Acne = dysfunction in Vit A processes
ISOTRETINOIN
Adverse effects: VIT A RETANOIDS
dry, flaky skin, reduced activity of sebaceous glands.
Can be teratogenic
Calcipotriol is classified as a ______ treatment for psoriasis. Briefly describe what it does.
Hint: type of medicine
Vit D derivtive, retinoid. Primarly reduces TH2 mediated response (WBC activation). Has a +ve effect on differentiation.
Anti proliferation, pro differentiation.
Note: in psoriasis, skin replicates too fast and are pushed to the surface before maturation.
e.g Vit A > Retinal > retanoic acid > Nuclear transcription.
4 consequences of retinoids affecting nuclear transcription?
- Keratinocyte epithelial differentiation
- Reduce size of sebaceous glands
- Reduction in sebum
- Inhibition of leukocyte migration
Adverse effects: VIT D RETANOIDS
Dysfunction of calcium phosphate metabolism, bone disorder
What are the two classes of antibacterials that inhibit/kill protein synthesis?
Bacteriostatic: stops division, lets immune system catch up
Bactericidal - KILLS BACTERIA = good for immunocompromised
The three targets for antibacterials.
Briefly describe how each works with an example.
- Inhibition of cell wall synthesis: peptidoglycan bacteria wall, has sugars and amino acids cross linked mesh structure, B lactation, antibiotics inhibit enzymes involved in cross link mesh = disrupt cell wall = kill bacteria e.g flucloxacillin
- Inhibition of protein synthesis, act on bacteria enzyme ribosome 70s, generally bacteriostatic. e.g Doxycycline.
- Inhibition of DNA synthisis: Interfere with folic acid process, ANTIFOLATES e.g sulphonamides - cotrimoxazole.
Hown do antibacterials inhibit DNA synthesis?
Relate to folic acid process, referencing PABA and sulphonamides.
Cells need folic acid for DNA synthesis.
Mammalian cells get from diet, bacteria make their own.
So inhibit that process within bacteria = no folic acid = can’t replicate.
Sulphonamides are analogues of PABA, with compete with PABA to inhibit folic acid synthesis.
Humans also have dihydrofolate reductase but bacteria version slightly different
In terms of antibacterials:
Trimethoprim often used in combination with ___________ to inhibit dihydrofolate reducatase. Resulting a lesser chance for _________ as not being exposed to too much of the drug.
Sulphonamides, resistance
