1 - TOPICAL RETINOIDS Flashcards
Tretinoin (all-trans retinoic acid) is an oxidised form of all-trans retinol and is synthesised endogenously from all-trans retinol after delivery of the compound to basal keratinocytes from the bloodstream
True
Alitretinoin (9-cis retinoic acid) is a naturally occurring endogenous retinoid
True (same as tretinoin and all-trans retinol)
All topical retinoids should be avoided during pregnancy due to risk of teratogenecity
True (although topical absorption of retinoids is generally slight, there is concern when large surface areas are treated)
A pregnancy test is recommended before the use of Tazarotene and Bexarotene (third generation retinoids) in women of child bearing potential, and appropriate birth control measures in place for the duration of treatment
True
All-trans retinol and all-trans retinoic acid are naturally occurring retinoids
True
Cytosolic all-trans retinoic acid-binding protein (CRABP) is predominantly in human skin and may be the determining factor in the bioavailability of retinoids
True (all-trans retinoic acid binds to CRABP)
All-trans retinol is oxidised to all-trans retinoic acid when needed by the cell
True
All-trans retinol is the natural alcohol form of vitamin A that is transported in the blood stream from storage in the liver to the peripheral target tissues bound to the serum transport protein retinol-binding protein
True
All-trans retinol traverses the interstitial spaces in the papillary dermis and is taken up by basal keratinocytes
True
When all-trans retinol is topically applied to the skin, the drug is taken up by the keratinocytes in the outer epidermis and diffuses through the skin as a fat soluble drug
True
Within the keratinocytes, excess all-trans retinol is esterified to long chain fatty acids to form retinyl esters which form lipid droplets (similar to how vitamin A is stored in the liver)
True
Acyl CoA - retinol acyltransferase is an enzyme system that is involved in direct esterification and hydrolysis of retinyl esters important for topically applied all-trans retinol
True
Lecithin - retinol acyltransferase is an enzyme system that is involved in direct esterification and hydrolysis of retinyl esters important for endogenously supplied all-trans retinol
True
All-trans retinoic acid (first generation retinoid Tretinoin) induce genes which are involved in cell proliferation and anti-apoptosis, leading to inhibition of cell growth
True
All-trans retinol and all-trans retinoic acid causes epidermal hyperplasia in thin or atrophic photo damaged epidermis
True
All-trans retinol and all-trans retinoic acid causes normalisation of epidermal thickness in hypertrophic skin
True
Topical application of All-trans retinol and all-trans retinoic acid causes irritation, erythema and desquamation
True
All-trans retinol do not bind to any retinoid receptors
True
All-trans retinoic acid/Tretinoin (first generation retinoid) binds to RAR receptors
True
Alitretinoin (third generation retinoid) binds to all RAR and RXR retinoid receptors
True
Bexarotene (third generation retinoid) binds to RXR retinoid receptors
True
Both Adapalene and Tazarotene (third generation retinoid) bind to RAR retinoid receptors and not RXR retinoid receptors
True (in contrast to third generation Bexarotene which binds to RXR and not RAR retinoid receptors)
Tazarotene (third generation retinoid) is converted to its active metabolite tazarotenic acid
True (Tazarotene is a prodrug)
All-trans retinol, all trans-retinoic acid (both first generation retinoids), Adapalene and Tazarotene (both third generation retinoids) result in comedolysis in acne
True
Topical Adapalene and Tazarotene (both third generation retinoids) may result in irritation, erythema, desquamation, pruritus and burning
True
Adapalene (third generation retinoid) is similar to all-trans retinoic acid (first generation retinoid) in its effects on acne, though it is more stable chemically, less photolabile, more lipophilic which enables it to penetrate follicles quickly
True
Adapalene (third generation retinoid) is more chemically stable than all-trans retinoic acid (first generation retinoid)
True
Adapalene (third generation retinoid) is less photolabile than all-trans retinoic acid (first generation retinoid)
True (however it is still recommended that patients on Adapalene exercise caution with respect to UV exposure with photoprotection)
Adapalene (third generation retinoid) is more lipophilic than all-trans retinoic acid (first generation retinoid)
True (enable it to penetrate follicles more quickly in acne and contribute to Adapalene’s success in treating acne)
Adapalene (third generation retinoid) has selective affinity for RAR beta and gamma receptors
True
Adapalene (third generation retinoid) suppresses/inhibits polymorphonuclear (neutrophil) chemotaxis and release of oxygen free radicals from neutrophils
True (neutrophils commonly found in acne)
Adapalene is systemically absorbed
False (only trace amounts systemically absorbed and excreted through the hepatobiliary route, otherwise excreted via skin desquamation)
Systemically absorbed Adapalene (only trace amounts) are excreted through the hepatobiliary route
True
Adapalene is carcinogenic
False (only trace amounts absorbed systemically)
Adapalene is mutagenic
False (only trace amounts absorbed systemically)
Adapalene is teratogenic
False (only trace amounts absorbed systemically) - although still recommended that Adapalene be discontinued during pregnancy as there are no controlled studies in pregnant women
Adapalene is genotoxic
False (only trace amounts absorbed systemically)
It is still recommended that Adapalene be discontinued during pregnancy although no significant teratogenic effects of topical Adapalene have been observed
True (as there are no controlled studies in pregnant women)
There are no clinical studies that show that Adapalene is photosensitising
True (Adapalene more photostable than Tretinoin, however it is still recommended that patients on Adapalene exercise caution with respect to UV exposure with photoprotection)
Adapalene (third generation retinoid) is active without metabolic transformation
True
Adapalene (third generation retinoid) is mainly excreted through skin desquamation
True (only trace amounts systemically absorbed)
All-trans retinoic acid becomes the active metabolite of all-trans retinol
True
All-trans retinol and all-trans retinoic acid are excreted through the hepatobiliary route and skin desquamation
True (so does Adapalene)
There is increased systemic absorption of All trans-retinoic acid (first generation retinoid Tretinoin) in dermatitic skin
True (1-2% systemically absorbed in normal skin, and up to 31% absorbed in dermatitic skin)
Both all-trans retinol and all-trans retinoic acid are absorbed by the keratinocytes with minimal dermal uptake
True
Tazarotene (third generation retinoid) results in normalisation of differentiation and proliferation of the epidermal keratinocytes in psoriasis
True (also comedolysis in acne)
Tazarotene (third generation retinoid) suppresses and downregulate the inflammatory markers in psoriasis
True
Tazarotene (third generation retinoid) blocks induction of ornithine decarboxylase activity resulting in decreased cell proliferation and hyperplasia
True
The systemic absorption of topical Tazarotene (third generation retinoid) is practically non-existent because of its rapid skin metabolism to tazarotenic acid
True (although up to 5% systemically absorbed when applied to normal skin, up to 15% systemically absorbed in psoriatic skin)
Total systemic absorption of Tazarotene (third generation retinoid) is up to 5% in normal skin and 15% in psoriatic skin
True
The small amounts systemically absorbed Tazarotene (third generation retinoid) which are not degraded, are excreted in both urine and faeces
True (in contrast to degradation of tazarotenic acid to inactive metabolites being excreted in urine)
Tazarotene (third generation retinoid) is absorbed by keratinocytes with dermal penetration and uptake into the bloodstream
True
Even though teratogenicity in topical Tazarotene (third generation retinoid) was not observed in animal models, the oral administration of Tazarotene resulted in teratogenicity
True (reason for topical Tazarotene to be absolutely contraindicated in pregnancy with pregnancy category X)
Tazarotene (third generation retinoid) is also excreted via skin desquamation
True (also in urine and faeces)
Bexarotene (third generation retinoid) is a synthetic retinoid which bind selectively to RXR retinoid receptors
True
Adapalene (third generation retinoid) is a synthetic retinoid
True
Tazarotene (third generation retinoid) is a synthetic retinoid
True
Alitretinoin (third generation retinoid) is a natural retinoid
True (same as all-trans retinol and all-trans retinoic acid)
There are 3 natural topical retinoids: all-trans retinol, all-trans retinoic acid and Alitretinoin
True
There are 3 synthetic topical retinoids: Adapalene, Tazarotene and Bexarotene (all third generation retinoids)
True
Tazarotene (third generation retinoid) may worsen psoriasis
True (although it is use in psoriasis)
Bexarotene (third generation retinoid) inhibits the cell cycle leading to decreased proliferation and increased apoptosis
True (used in Mycosis Fungoides)
Tazarotene (third generation retinoid) may be used in both acne vulgaris and psoriasis
True
Topical Bexarotene (third generation retinoid) may be used in early stage persistent or refractory mycosis fungoides
True
Bexarotene (third generation retinoid) has antitumour effects
True (used in mycosis fungoides)
Oral Bexarotene (third generation retinoid) induces tumour regression and inhibits growth of tumour cell lines of haematopoetic and keratinocytes
True (used in mycosis fungoides)
Bexarotene (third generation retinoid) increases cellular differentiation and decreased cellular growth
True (used in mycosis fungoides)
The metabolism of topical Bexarotene is primarily unknown as in contrast to oral Bexarotene, studies and results are not available with respect to drug-drug interactions, renal or hepatic insufficiency
True (Oral Bexarotene is highly bound to plasma proteins and metabolised through the CYP3A4 pathway)
Many of the precautions for topical Bexarotene were derived from studies of oral Bexarotene
True
Topical Bexarotene is considered pregnancy category X
True (derived from studies of oral Bexarotene)
Better efficacy of topical Bexarotene for mycosis fungoides has been associated with an increased frequency of application to affected areas
True
There are no studies to indicate that topical Bexarotene results in central hypothyroidism from decreased thyrotropin levels as reported with oral Bexarotene
True
Even though Clinical studies have failed to demonstrate topical Bexarotene may be photosensitising, patients are still advised to exercise precaution with regards to UV exposure
True
Trace amounts of topical Bexarotene may be absorbed systemically (< 5 Ng/mL)and the increases in plasma concentration of Bexarotene are directly related to the percentage of body surface area treated
True
Topical Alitretinoin (third generation retinoid) is used for the treatment of AIDS related Kaposi’s sarcoma
True
Alitretinoin (third generation retinoid) binds to all RAR and RXR retinoid receptors
True
In general, the RAR retinoid receptors are associated with cellular differentiation
True (Tretinoin for photoaging and acne vulgaris, Adapalene for acne vulgaris, Tazarotene for acne vulgaris and psoriasis)
In general, the RXR retinoid receptors are associated with apoptosis
True (Alitretinoin for AIDS relate Kaposi’s sarcoma and Bexarotene for mycosis fungoides)
Systemic absorption of topical Alitretinoin (third generation retinoid) is minimal
True (though still pregnancy category D)
Tretinoin (first generation retinoid) may cause temporary worsening of acne and photosensitivity
True
There is possible neutralisation of Tretinoin with simultaneous benzoyl peroxide
True
Photosensitising drugs I.e. Thiazides, tetracyclines, fluoroquinolones, Phenothiazines antipsychotic agents, sulfonamides may increase the photosensitivity to topical Tretinoin
True
Concomitant skin irritants may precipitate the irritation, erythema, peeling with topical Tretinoin
True
Pregnancy is relatively contraindicated in use of topical all-Trans retinol and all-trans retinoic acid
True
Pregnancy is absolutely contraindicated in topical Tazarotene and Bexarotene
True
Topical Tazarotene may cause Koebnerisation of psoriasis
True
All topical retinoids may cause skin irritation I.e. Erythema, pruritus
True
Topical Sulfur, resorcinol and salacylic acid may interact with topical Adapalene
True
Products with high % alcohol, astringents, spices and lime may interact with topical Adapalene
True
Dermatologic medications and cosmetics with a strong drying effect should be avoided in patients on topical Tazarotene
True
Photosensitising medications should be avoided in patients using topical Tazarotene
True
Co-administration of products containing the insect repellent DEET should be avoided in patients using Alitretinoin and a bexarotene due to increased potential for DEET toxicity
True
Patients on topical retinoids notice a decreased tolerance to UV radiation, leading to photosensitivity reactions
True
It is helpful for patients on all topical retinoids to avoid concomitant use of irritating topical products I.e. Medicated/abrasive soaps and cosmetics, products with high concentrations of alcohol, astringents, spices or lime, topical products containing Sulfur, resorcinol or Salicylic acid
True (to minimise risk of skin irritancy)
Topical retinoids do not play a direct inhibitory role on excess sebum
True
Topical retinoids are first line treatment for non-inflammatory acne
True
Topical retinoids are also helpful in the management of inflammatory acne where they may be used in combination with topical or systemic antimicrobials or hormone therapies
True
Topical retinoids are generally not used in severe nodular acne vulgaris
True
Once the acne is controlled, the topical retinoid should be continued to maintain the favourable results
True
Topical retinoid therapy consists of once daily application to the entire region of the face prone to develop acne lesions
True (not used as spot treatment of individual lesions)
Topical Tretinoin is photolabile and should be applied at bedtime
True
Topical Adapalene and Tazarotene are more photostable than Tretinoin and may be applied morning or night
True
Alternate day applications of topical retinoid (especially early in therapy) and drug holidays should be suggested if skin irritation in problematic
True
Retinoid dermatitis (erythema and peeling) is most problematic during the first weeks of therapy
True
It generally takes 3-6 months of continuous use of a topical retinoid to note a significant clinical improvement in photoaging
True
Topical retinoids can increase the sensitivity to sunlight owing to reduced stratum corneum thickness
True (therefore sunscreen use is particularly stressed and patients are instructed to apply sunscreen daily)
Topical Bexarotene may be used in psoriasis especially in combination with UVB treatment
True
Application of Tretinoin to the skin 2 weeks or more before wounding has been demonstrated to enhance wound healing and speed the healing time
True (pretreatment with topical retinoids before dermabrasion, medium depth chemical peels and CO2 resurfacing results in decreased healing time overall increase improvement in cosmetic outcome)
Pretreatment with topical retinoids (Tretinoin) before dermabrasion, medium depth chemical peels and CO2 resurfacing results in decreased healing time overall increase improvement in cosmetic outcome
True
