2. The term retinoids includes all natural and synthetic
compounds that have structural or biological activities like
vitamin A There are more than 1500 retinoids have been developed
First generation(nonaromatic): Tretinone: all-trans retinoic acid ,
Isotretinoin : 13-cis retinoic acid, Alitretinoin: 9-cis retinoic
acid Second generation(monoaromatic): Etretinate, acitretin Third
generation(polyaromatic): Adapalene, Tazarotene, Bexarotene The
original second generation retinoid used for psoriasis, etretinate,
was superseded by its natural metabolite, acitretin, which was
shown to have similar efficacy with a better pharmacokinetic
profile
3. Approved Systemic Retinoids Chemical name Trade name Date
approval Indication (removal) Isotretinoin Accutane 5/7/1982
Amnesteem 11/2002 Sotret 12/2002 Claravis 4/2003 Etretinate Tegison
9/30/1986 (12/20/2002) Severe recalcitrant psoriasis Acitretin
Soriatane 10/26/1996 Severe psoriasis Bexarotene Targretin
12/29/1999 Refractory CTCL Severe recalcitrant nodular acne 4
4. Retinoids metabolism occurs in the liver They are excreted
in bile and urine
5. Mechanism of action These synthetic hormones bind to nuclear
retinoid receptors , thereby altering gene transcription and
returning keratinocyte proliferation and differentiation to normal.
As well as modification of inflammatory responses and neutrophil
function
6. Mayor Retinoid-Responsive Skin Diseases Acne: I,(T)
Psoriasis: E Disorders of keratinization:I,E,(T) NMSC:I,E
Precancerous lesions: T,E,(I) Skin aging:T
7. Psoriasis Retinoids , since they are not immunosuppressive,
retinoids have a role in the treatment of psoriasis in children,
patients with HIV infection and those who are prone to cancer. It
is generally safe for long-term use and has no time limit
restrictions. Retinoids are considered excellent for use in
combination with other treatments and when used with UVB or PUVA,
their dose and the number of phototherapy treatments can be
reduced, with the added benefit of a potential reduction in skin
carcinogenesis
8. Acitretin is as effective as etretinate . Plaque psoriasis :
variable response: 30% complete clearance, 50% significant
improvement (60-70% reduction of PASI score) Erythrodermic and
Pustular psoriasis: retinoids are the first-line therapy Complete
clearance usually requires a combination of therapy such as: 1.
Retinoids + topical steroids 2. Retinoids + topical vit D
derivatives 3. Retinoids + anthralin 4. Retinoids + PUVA (Re-PUVA):
retinoids are started for 14 days before starting PUVA 5. Retinoids
+ UVB
9. Psoriasis Within few days of initiating therapy at dose
30-70mg/day An initial worsening of the disease with increase of
erythema and/or extent of involvement Initial low dose: 10 mg/day
Followed by increasing of dose Efficacy of low-dose acitretin is as
placebo Effective doses 25,50,75 mg /day (0.5-1 mg/kg/day)
11. PRP Systemic Vitamin A had been used with considerable
effectiveness. The advent of synthetic retinoids has largely
supplanted vitamin A therapy Isotretinoin: Acitretin 1mg/kg/day
1mg/kg/day 80% of patients showed clearance of lesions after an
average 25 weeks treatment Alone or in combination with UVR
12. Acne vulgaris Isotretinoin is a systemic retinoid that is
highly effective in the treatment of acne vulgaris. Isotretinoin
causes normalization of epidermal differentiation, depresses sebum
excretion by 70%, is anti-inflammatory, and even reduces the
presence of P acnes. Treatment with isotretinoin can lead to both
marked improvement and long-lasting remission. Essentially,
isotretinoin has the capacity to cure acne.
13. Initially with the introduction of isotretinoin, only
patients with severe nodular cystic acne or severe inflammatory
acne, who were not responding to conventional therapy were given
the drug. Now, with more than 20 years of treatment experience,
expanded guidelines for its use include: 1. Moderate acne relapse
(
