PCOL of Psoriasis (Maize) Flashcards
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.
hyperproliferation and incomplete differentiation
immune;autoimmune disease
Cytotoxic Agents – Coal tar
MOA:
- Suppresses ____ synthesis which ____ epithelial cell proliferation
- ____ agent
- DNA; decreases
- Photosensitizing
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 \_\_\_\_
- tar
- contact
- systemic
- odor
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 ____ ____
- effectiveness; safe; symptomatic
- irritating; photosensitizing
- eczema, rosacea, otitis externa
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
MOA:
Disruption, free radicals
Pharmacological effect
hyperplastic; growth
Side effects
- irritation
- erythema
- conjunctivitis
- systemic
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 ____
MOA:
- dihydrofolate reductase
- apoptosis; T-cells
Pharmacological effect
- Reduces
- Reduces
Side effects
- dyscrasias
- hair
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)
MOA:
- purine
- cytokine
Pharm effect:
- T-cells
- Anti-inflammatory
Side effects:
- bone marrow
- flu-like
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 ____
MOA:
- G0; cycle
- production and release
Pharmacological effect
- T-cells
- Anti-inflammatory
Side effects:
- nephrotoxicity
- hyper
- gingival
- CYP3A4
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
- Alefacept (Amevive)
- Efalizumab (Raptiva)
Antibody Therapy - TNFα inhibitors What drugs (3)
bind free TNFα and reduces inflammation
- Etanercept (Enbrel), Adalimumab (Humira), Infliximab (Remicade)
2 Types of Antibody Therapy
T-cell inhibitors
TNFα inhibitors
Antibody Therapy:
Pharmacological effect:
- Reduces the ____ and ____ of the plaques
Side Effects
- ____ reactions: chills, site pain, inflammation
- Serious infections and malignancies
- Blood ____
Pharm effect:
- number and size
Side effects:
- injection
- dyscrasias
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)
- RAR (Retinoic Acid Receptors) or RXR (Retinoid X Receptors)
- homodimer or heterodimer
- transcription factors
Nuclear Receptor Binder - Retinoids
Pharmacological effect:
- ____ proliferation and ____ differentiation of keratinocytes
- Acitretin does not suppress ____ ____ as effectively as the other retinoids
- Reduces; enhances
- sebum production
Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)
Kinetics:
- Half life is __ hours
- Drug is still ____ in the serum from _ to _ ____ after discontinuation
- 49
- detectable; 1 to 3 years
Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)
SIDE EFFECTS
- ____ effects
- ____ effects
- Pseudotumor ____
- Smaller changes in blood lipids than ____
- dermatological
- opthalmic
- cerebri
- isotretinoin
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
- peeling
- nose
- mouth
Nuclear Receptor Binder - Retinoids
Acitretin (Soriatane)
OPHTHALMIC Side Effects
- ____ irritation,
- dryness or thickening of conjunctiva,
- ____ vision,
- loss of ____/____
- eye
- blurred
- eyelashes/eyebrows
Benign intracranial hypertension associated with acitretin
Pseudotumor cerebri
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)
- peeling; dry
- photosensitivity
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
MOA:
- heterodimer; retinoid receptors
Pharm effect:
- proliferation; epidermal
- inflammation; inflammatory cytokine
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
corticosteroids; cortex
- Na+ retention - mineralocorticoids
- Hepatic glycogen storage – glucocorticoid
Nuclear Receptor Binders - Steroids
Mineralocorticoids:
- ____ is the endogenous steroid
- Acts on the ____ to retain ___ and thus retains water
- These usually have ____ anti-inflammatory activity
- Aldosterone
- kidneys; Na+
- little
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
- Cortisol and cortisone
- metabolism; stressful
- greater
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
Nuclear Receptor Binders - Steroids
MOA:
____ Mechanism – a homodimer binds to the ____ ____ ____ (___) in the DNA
Direct
- Glucocorticoid Response Element (GRE)
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
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
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
Effectiveness of Topical Glucocorticoids
Depends on (5):
- Concentration
- Efficacy
- Salt
- Vehicle
- Percutaneous absorption (Application)
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
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
Adrenal cortex will begin to ____ if no longer used.
atrophy
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
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)
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
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
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
