PCOL of Psoriasis (Maize) Flashcards

(38 cards)

1
Q

Psoriasis is a disease characterized by keratinocyte ____ and incomplete ____ caused by cytokines (IL-1 & TNFa) released from infiltrating activated T-cells.

Evidence points to an ____-mediated disorder, possibly an organ-specific ____ ____ of skin.

A

hyperproliferation and incomplete differentiation

immune;autoimmune disease

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2
Q

Cytotoxic Agents – Coal tar
MOA:
- Suppresses ____ synthesis which ____ epithelial cell proliferation
- ____ agent

A
  • DNA; decreases

- Photosensitizing

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3
Q
Cytotoxic Agents - Coal tar 
Side Effects:
- Irritation, stinging, burning (\_\_\_\_ smarts)
- Folliculitis (bumps around hair follicles) particularly of the axilla and groin (tar acne)
- \_\_\_\_ dermatitis 
- Photosensitizing
- Carcinogenic (rare)
- No \_\_\_\_ side effects
- Will stain light skin and hair
- Unpleasant \_\_\_\_
A
  • tar
  • contact
  • systemic
  • odor
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4
Q

Cytotoxic Agents - Shale tar (ichthammol)

  • Cytotoxic but the exact mechanism of action is unknown
  • No clinical studies have demonstrated its ____, but it is ____ and gives ____ relief
  • It is less ____ and has no ____ activity unlike coal tar
  • Also used for treatment of ____, ____, and acute ____ ____
A
  • effectiveness; safe; symptomatic
  • irritating; photosensitizing
  • eczema, rosacea, otitis externa
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5
Q

Cytotoxic Agents - Anthralin
MOA:
____ of the DNA alpha helix by ____ ____

Pharmacological effect
suppresses ____ keratinocyte cell ____

Side effects:

  • Local ____, mainly to normal skin
  • ____ on normal skin around lesions
  • Severe ____ with eye contact
  • No ____ side effects
  • Will stain skin, hair, clothes a dark brown/black color
A

MOA:
Disruption, free radicals

Pharmacological effect
hyperplastic; growth

Side effects

  • irritation
  • erythema
  • conjunctivitis
  • systemic
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6
Q

T-cell and cytokine suppressors - Methotrexate

MOA:

  • Inhibits ____ ____
  • Promotes the ____ of activated _-____

Pharmacological effect

  • ____ keratinocyte hyperproliferation
  • ____ the number of T-cells

Side effects:

  • GI: diarrhea, ulcerative stomatitis
  • Blood ____ (anemia)
  • Cirrhosis (liver scarring)
  • Teratogenic
  • loss of ____
A

MOA:

  • dihydrofolate reductase
  • apoptosis; T-cells

Pharmacological effect

  • Reduces
  • Reduces

Side effects

  • dyscrasias
  • hair
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7
Q
T-cell and cytokine suppressors - 
Mycophenolate mofetil (Myfortic)

MOA:

  • Inhibits ____ synthesis
  • Inhibits ____ production

Pharmacological effect:

  • reduces the number of _-_____
  • ____ action

Side effects

  • ____ ____ suppression
  • GI upset
  • ____ symptoms (achy, low grade fever)
A

MOA:

  • purine
  • cytokine

Pharm effect:

  • T-cells
  • Anti-inflammatory

Side effects:

  • bone marrow
  • flu-like
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8
Q

T-cell and cytokine suppressors - Cyclosporine

MOA:

  • Arrests keratinocytes in the __ stage of the cell ____
  • Inhibits ____ and ____ of cytokines

Pharmacological effect

  • reduces the number of _-_____
  • ____ action

Side effects

  • ____ after long term use
  • ____tension
  • ____ hyperplasia (gum overgrowth)
  • Multiple drug interactions through ____
A

MOA:

  • G0; cycle
  • production and release

Pharmacological effect

  • T-cells
  • Anti-inflammatory

Side effects:

  • nephrotoxicity
  • hyper
  • gingival
  • CYP3A4
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9
Q

Antibody Therapy - T-cell inhibitors
Which drug (MOA):
____ - binds to the antigen on psoriatic plaques preventing T-cells from binding

____ - binds CD 11a to inhibit T-cell activation and migration

A
  • Alefacept (Amevive)

- Efalizumab (Raptiva)

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10
Q
Antibody Therapy - TNFα inhibitors
What drugs (3)

bind free TNFα and reduces inflammation

A
  • Etanercept (Enbrel), Adalimumab (Humira), Infliximab (Remicade)
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11
Q

2 Types of Antibody Therapy

A

T-cell inhibitors

TNFα inhibitors

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12
Q

Antibody Therapy:

Pharmacological effect:
- Reduces the ____ and ____ of the plaques

Side Effects

  • ____ reactions: chills, site pain, inflammation
  • Serious infections and malignancies
  • Blood ____
A

Pharm effect:
- number and size

Side effects:

  • injection
  • dyscrasias
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13
Q

Nuclear Receptor Binder - Retinoids

MOA:

  • Binds to either ____ or ____ retinoid receptors
  • A ____ or ____ is formed which alters DNA transcription (direct)
  • A single receptor complex binds ____ ____ to alter DNA transcription (indirect)
A
  • RAR (Retinoic Acid Receptors) or RXR (Retinoid X Receptors)
  • homodimer or heterodimer
  • transcription factors
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14
Q

Nuclear Receptor Binder - Retinoids

Pharmacological effect:

  • ____ proliferation and ____ differentiation of keratinocytes
  • Acitretin does not suppress ____ ____ as effectively as the other retinoids
A
  • Reduces; enhances

- sebum production

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15
Q

Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)

Kinetics:

  • Half life is __ hours
  • Drug is still ____ in the serum from _ to _ ____ after discontinuation
A
  • 49

- detectable; 1 to 3 years

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16
Q

Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)

SIDE EFFECTS

  • ____ effects
  • ____ effects
  • Pseudotumor ____
  • Smaller changes in blood lipids than ____
A
  • dermatological
  • opthalmic
  • cerebri
  • isotretinoin
17
Q

Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)

DERMATOLOGICAL Side Effects

  • lip inflammation
  • alopecia (hair loss)
  • ____ on palms, soles, and fingertips
  • dry ____ and epitaxis
  • dry ____ and stomatitis
A
  • peeling
  • nose
  • mouth
18
Q

Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)

OPHTHALMIC Side Effects

  • ____ irritation,
  • dryness or thickening of conjunctiva,
  • ____ vision,
  • loss of ____/____
A
  • eye
  • blurred
  • eyelashes/eyebrows
19
Q

Benign intracranial hypertension associated with acitretin

A

Pseudotumor cerebri

20
Q

Nuclear Receptor Binder - Retinoids
Tazarotene (Tazorac)

SIDE EFFECTS

  • Pruritis, burning, stinging, erythema, irritation, rash, ____ and ____ skin
  • ____
  • No known systemic side effects
  • Teratogenic (Do not use in pregnancy)
A
  • peeling; dry

- photosensitivity

21
Q

Nuclear Receptor Binder - Vitamin D derivative
Calcipotriene (Dovonex)

MOA:
- Calcipotriene-VDR complex forms a ____ with ____ ____ to alter DNA function

Pharmacological effect:

  • Inhibits ____ and promotes ____ differentiation
  • Decreases ____ by decreasing ____ ____ release
A

MOA:
- heterodimer; retinoid receptors

Pharm effect:

  • proliferation; epidermal
  • inflammation; inflammatory cytokine
22
Q

Nuclear Receptor Binders - Steroids

Steroids are called ____ because they are formed in the adrenal ____

Corticosteroids have two main effects:

Most corticosteroids have a mixture of these activities

A

corticosteroids; cortex

  1. Na+ retention - mineralocorticoids
  2. Hepatic glycogen storage – glucocorticoid
23
Q

Nuclear Receptor Binders - Steroids

Mineralocorticoids:

  • ____ is the endogenous steroid
  • Acts on the ____ to retain ___ and thus retains water
  • These usually have ____ anti-inflammatory activity
A
  • Aldosterone
  • kidneys; Na+
  • little
24
Q

Nuclear Receptor Binders - Steroids

Glucocorticoids:

  • ____ and ____ are the endogenous steroids
  • Have significant effect on ____ to help the body through ____ times
  • These compounds usually have ____ anti-inflammatory action
A
  • Cortisol and cortisone
  • metabolism; stressful
  • greater
25
Nuclear Receptor Binders - Steroids MOA: - modulate inflammation either ____ or ____ by increasing the transcription of anti-inflammatory proteins or decreasing the transcription of inflammatory proteins
directly; indirectly
26
Nuclear Receptor Binders - Steroids MOA: ____ Mechanism – a homodimer binds to the ____ ____ ____ (___) in the DNA
Direct - Glucocorticoid Response Element (GRE)
27
Nuclear Receptor Binders - Steroids MOA: ____ Mechanism: a single receptor/steroid complex binds __-_ and __-__ and prevent ____ to the ____
Indirect - AP-1 and NF-kB; binding TRE
28
Nuclear Receptor Binders - Topical Glucocorticoids Relative Potency (Efficacy) - A ____ assay is used to measure efficacy - 7 degrees of potency - Steroids in each class have the same relative ____
- vasoconstrictor | - efficacy
29
Effectiveness of Topical Glucocorticoids Percutaneous absorption - - Proportional to the (3): - ____ or ____ skin is more permeable - ____ dressing can enhance percutaneous absorption by as much as __ ____ - The skin acts as a ____ so frequent dosing is not needed
- duration of use - area of coverage and - thickness of skin - Abraded or inflamed - Occlusive; 10 fold - reservoir
30
Effectiveness of Topical Glucocorticoids Depends on (5):
- Concentration - Efficacy - Salt - Vehicle - Percutaneous absorption (Application)
31
Topical Glucocorticoids Side Effects Immediate side effects of topical steroids - Increased risk of ____ ____ and ____ of infection Long term use of topical steroids (7)
- local infection and masking Long Term: - Atrophy of the dermis and epidermis - Striae - Purpura - Telangiectasia (spider veins on the face) - Acne - Hypertrichosis - Cataracts and glaucoma
32
Topical/Oral Glucocorticoids Systemic Side Effects: - Topical glucocorticoids can be absorbed in sufficient quantities to produce systemic side effects - Usually only occurs under ____ ____ like when ____ potency with ____ dressing are used over a large area of the body for a long period of time - Adrenal suppression affects the ____ - Cushing's Syndrome - Addison's Syndrome - Growth suppression in ____
- extreme use high occlusive - HPA (Hypothalamus-Pituitary-Adrenal) axis - children
33
Adrenal cortex will begin to ____ if no longer used.
atrophy
34
Effectiveness of Topical Glucocorticoids Permeability of the skin - (High/Low) - scalp, axilla, face, eyelids, neck, perineum & genitalia - (High/Low) - back, palms, and soles ``` A comparison of absorption hydrocortisone (1) from the forearm Sole of foot - 0.14 times Palm - 0.83 Scalp - 3.5 Forehead - 6 Vulva - 9 Scrotal skin – 42 ```
- High | - Low
35
Topical/Oral Glucocorticoids | Systemic Side Effects - Cushing's Syndrome (4)
- Rounding, puffiness, plethora (redness) of the face ("moon face") - Fat redistributes to the face and trunk ("buffalo hump") - Fine hair grows over the thighs, face, trunk - Alopecia (hair loss on head)
36
Phototherapy - Methoxsalen MOA: - Belongs to the chemical class ____ - ____ – a drug that is excited by a specific wavelength of light - The drug does not have activity until excited - After exposure to ____, methoxsalen combines with the ____ in epidermal cells by forming ____ linkages with ____
MOA: - psoralens - Chromophore - UVA, DNA, covalent, pyrimidines
37
Phototherapy - Methoxsalen Pharmacological effect: - Normalizes ____ and ____ of keratinocytes - ____ cutaneous blood vessels - Cytotoxic to _-____ - Increases ____ pigmentation Side Effects (7)
Pharmacological effect: - number and arrangement - Reorganizes - T-cells - melanin Side Effects: - Pruritus - Nausea - Erythema & Blistering - Hyperpigmentation - Increased skin aging - Increased risk of skin cancer - Cataracts
38
Topical/Oral Glucocorticoids | Systemic Side Effects - Addison's Syndrome (6)
- Weakness & fatigue - Weight loss - Hyperpigmentation (tan color) - Hypotension - Electrolyte imbalance - Possible death if discontinued to rapidly