L3 - Pharmacology of Skin Disorder Treatment

Question 1

Glucocorticoids treat ______ and _____ and modulate ____

Answer 1

Dermatitis, psoriasis and inflammation

Question 2

General mechanism of action of glucocorticoids

Answer 2

Must be soluble enough to get into cell, Act on nuclear receptors, alter protein synthesis, inhibit or promote gene synthesis.

Question 3

Describe the three prong effect of glucocorticoids!

Answer 3

1. Interact with DNA ( glucocorticoid response element), stimulate synthesis of anti inflammatory genes
2. Interact with DNA GRE to turn off inflammatory genes
3. Affects gene transcription of other genes e.g pomC and ca2+ levels..

Question 4

Glucocorticoid anti inflammatory mechanism - hint: purely anti-inflammatory effect.

Answer 4

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

Question 5

Glucocorticoid reduced inflammatory mechanism - hint: turns off decent branch of immune system.

Answer 5

Decreases immune response in skin

Binds to steroid receptor = turns things off
Reduces production of cytokines, chemokines, inflammatory proteins, enzymes and receptors.

Question 6

Adverse effects: Glucocorticoids

Answer 6

Dose dependent, but can worsen infection or suppress HPA axis, stunt growth in children. AVOID ABSORPTION INTO MAIN BS.

Question 7

Retinoids mechanism in terms of ACNE. Give an example of a retinoid to treat severe ACNE.

Answer 7

Vitamin derivative. Regulation of epidermal cell growth, turn it down. Reestablish regulation of sebaceous cell activity.

Acne = dysfunction in Vit A processes

ISOTRETINOIN

Question 8

Adverse effects: VIT A RETANOIDS

Answer 8

dry, flaky skin, reduced activity of sebaceous glands.

Can be teratogenic

Question 9

Calcipotriol is classified as a ______ treatment for psoriasis. Briefly describe what it does.

Hint: type of medicine

Answer 9

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.

Question 10

e.g Vit A > Retinal > retanoic acid > Nuclear transcription.

4 consequences of retinoids affecting nuclear transcription?

Answer 10

1. Keratinocyte epithelial differentiation
2. Reduce size of sebaceous glands
3. Reduction in sebum
4. Inhibition of leukocyte migration

Question 11

Adverse effects: VIT D RETANOIDS

Answer 11

Dysfunction of calcium phosphate metabolism, bone disorder

Question 12

What are the two classes of antibacterials that inhibit/kill protein synthesis?

Answer 12

Bacteriostatic: stops division, lets immune system catch up

Bactericidal - KILLS BACTERIA = good for immunocompromised

Question 13

The three targets for antibacterials.

Briefly describe how each works with an example.

Answer 13

1. 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
2. Inhibition of protein synthesis, act on bacteria enzyme ribosome 70s, generally bacteriostatic. e.g Doxycycline.
3. Inhibition of DNA synthisis: Interfere with folic acid process, ANTIFOLATES e.g sulphonamides - cotrimoxazole.

Question 14

Hown do antibacterials inhibit DNA synthesis?

Relate to folic acid process, referencing PABA and sulphonamides.

Answer 14

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

Question 15

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.

Answer 15

Sulphonamides, resistance

Question 16

1. What is mean target for ANTIFUNGALS
2. Human and fungi versions of these targets?
3. Briefly describe general mechanism.

Answer 16

Steroles

Human = cholesterol
Fungi = ergosterol 

Target sterols in cell membranes, disrupt integrity of fungal cell wall = affects how well fungus attaches to each other and replicate

Question 17

Antifungals

Clotrimazole inhibits and reduces fungi _____.

Adverse effects?

Answer 17

reduces fungi ergosterol

Can inhibit CYP3a4, lots of DDI, GI disturbance and hepatotoxicity.

Question 18

Terbinafine is an azalea, which is classed as an anti-______

Answer 18

anti fungal

Question 19

Methotrexate is an ___________ medicine used for treatment of psoriasis and dermatitis. Works by altering immune system.

Adverse effects:

Answer 19

pancytopenia (low RBC), GI epithelium damage and photosensitivity.

Immune system weak = opportunistic infection.

Question 20

ALCAR > ADENOSINE > STRONG ANTI-INFLAMMATORY EFFECTS

Briefly describe MTX mechanism.

Answer 20

MTX inhibits enzyme which results in more ALCAR, decreasing immune response

MTX similar to human version of folic acid, inhibits DNA synthesis. Targets rapidly dividing cells (non-specific)

Question 21

Cytotoxic chemotherapy medication for cancer, 5-FU mechanism?

Answer 21

5-FU mimics uricil structure, gets incorporated into DNA, false substrate = cells can’t divide properly.

Question 22

Adverse effects: MTX

Answer 22

opportunistic infection, pancytopenia (reduction in blood cells, dec immune system response) GI epithelium damage and photosensitivity

Question 23

Imiquimod ____ -regulates the immune response.

Main treatment for _____ ______

Mechanism of action:

Adverse effects:

Answer 23

UPREGULATE

Actinic keratosis

Immune modifier via TLR7 - inc. TH1 pathway

erythema, oedema, scaling and ulceration (increased immune response)