Retinoic acid, also known as tretinoin or
all-trans-retinoic acid, is the acid form of vitamin A.
It is an effective topical treatment for acne
vulgaris.
Several analogs of vitamin A, e.g. 13-cis-retinoic
acid (isotretinoin), are effective in various dermatologic diseases when given
orally.
Vitamin A alcohol is the physiologic form of vitamin A.
The topical therapeutic agent, retinoic acid, is
formed by the oxidation of the alcohol group, with all four double bonds in the
side chain in the trans configuration .
Retinoic acid: Pharmacokinetics
Retinoic acid is insoluble in water but soluble in
many organic solvents.
It is
susceptible to oxidation, particularly when exposed to light, and ester
formation.
Topically applied retinoic acid remains chiefly in the
epidermis, with less than 10% absorption into the circulation.
The small quantities of retinoic acid absorbed
following topical application are metabolized by the liver and excreted in bile
and urine.
Retinoic acid: Mechanism of
action
Retinoic acid has several effects on epithelial
tissues.
It stabilizes
lysosomes,
Increases RNA polymerase activity,
Increases prostaglandin E2, cAMP, and cGMP levels,
Increases the incorporation of thymidine into DNA.
Retinoic acid: Mechanism of
action
Its action in
acne has been attributed to decreased cohesion between epidermal cells and
increased epidermal cell turnover.
This leads to
the expulsion of open comedones and the
transformation of closed comedones into open ones.
Retinoic acid: Cautions
in Administration
Topical retinoic acid is applied initially in a
concentration sufficient to induce slight erythema with mild peeling.
The concentration or
frequency of application may be decreased if too much irritation occurs.
Topical retinoic acid should be applied to dry skin
only
Care should be
taken to avoid contact with the corners of the nose, eyes, mouth, and mucous
membranes.
Retinoic acid: Cautions
in Administration
During the first 4–6 weeks of therapy, comedones not
previously evident may appear and give the impression that the acne has been
aggravated by the retinoic acid.
However, with continued therapy, the lesions will
clear, and in 8–12 weeks optimal clinical improvement should occur.
A timed-release formulation of tretinoin containing
microspheres (Retin-A Micro) delivers the medication over time and may be less
irritating for sensitive patients.
Retinoic acid: Other uses
The effects of tretinoin on keratinization and
desquamation offer benefits for patients with photodamaged skin.
Prolonged use
of tretinoin promotes dermal collagen synthesis, new blood vessel formation,
and thickening of the epidermis, which helps diminish fine lines and wrinkles.
A specially
formulated moisturizing 0.05% cream (Renova) is marketed for this purpose.
Retinoic acid: Adverse effects
The most common adverse effects of topical retinoic
acid are erythema and dryness that occur in the first few weeks of use,
However, these usually
resolve with continued therapy.
Retinoic acid: Adverse effects
Animal studies suggest that this drug may increase the
tumorigenic potential of ultraviolet radiation.
Therefore, patients
using retinoic acid should be advised to avoid or minimize sun exposure and use
a protective sunscreen.
Allergic contact dermatitis to topical retinoic acid
is rare.
RETINOIDS:ASSIGNMENT
Describe the
classification of the retinoids (6 marks)
Describe the
effects of the retinoids on gene expression (5 marks)
Describe pharmacological effects and therapeutic uses of the following retinoids
(14 marks):
Tretinoin
Tazarotene
Isotretinoin
Bexarotene
Alitretinoin
Describe the therapeutic role of retinoids in skin cancers (5 marks)
Adapalene
Adapalene is a
derivative of naphthoic acid that resembles retinoic acid in structure and
effects.
It is applied as a 0.1% gel once daily.
Adapalene is photochemically
stable and shows little decrease in efficacy when used in combination with
benzoyl peroxide.
Adapalene is less irritating than tretinoin and is
most effective in patients with mild to moderate acne vulgaris.
Benzoyl Peroxide
Benzoyl peroxide is an effective topical agent in the
treatment of acne vulgaris.
It penetrates the stratum corneum or follicular
openings unchanged
It is then converted metabolically to benzoic acid
within the epidermis and dermis.
Less than 5% of an applied dose is absorbed from the
skin in an 8-hour period.
Benzoyl peroxide: Mechanism of
action
The mechanism
of action of benzoyl peroxide in acne is related to:
Its antimicrobial
activity against P acnes
Its peeling and comedolytic effects.
Benzoyl peroxide: Adverse
effects
Irritation:
To decrease the
likelihood of irritation, application should be limited to a low concentration
(2.5%) once daily for the first week of therapy
This is then increased
in frequency and strength if the preparation is well tolerated.
Benzoyl peroxide is a potent contact sensitizer in
experimental studies, and this adverse effect may occur in up to 1% of acne
patients.
Benzoyl peroxide: Adverse
effects
Care should be taken to avoid contact with the eyes
and mucous membranes.
Benzoyl peroxide is an oxidant and may rarely cause
bleaching of the hair or colored fabrics.
Benzoyl peroxide combination therapy
Fixed-combination formulations of 5% benzoyl peroxide
with 3% erythromycin base (Benzamycin)
or 1% clindamycin (BenzaClin) are more effective than individual agents alone.
Azelaic Acid
Azelaic acid is a straight-chain saturated
dicarboxylic acid that has been demonstrated to be effective in the treatment
of acne vulgaris and acne rosacea .
It is active
against P acnes
It has also been found
to inhibit the conversion of testosterone to dihydrotestosterone.
Initial therapy
is begun with once-daily applications of the 20% cream or 15% gel to the
affected areas for 1 week and twice-daily applications thereafter.
Clinical
improvement is noted in 6–8 weeks of continuous therapy.
Azelaic acid: Adverse effects
Most patients experience mild irritation with redness
and dryness of the skin during the first week of treatment.
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