185: Retinoids Flashcards
(130 cards)
1
Q
What are retinoids and how do they function in the body?
A
Retinoids are prescription drugs and cosmeceuticals that elicit skin responses by mediating their effects through intranuclear retinoid receptors, acting as transcription factors. They bind to retinoic acid receptors (RARs) and retinoid X receptors (RXRs), activating retinoic acid-responsive genes and resulting in specific biological responses.
2
Q
What are the structural components of all-trans-retinoic acid (tretinoin)?
A
All-trans-retinoic acid (tretinoin) is a 20-carbon molecule that consists of: 1. A cyclohexenyl ring 2. A side chain with four double bonds (all arranged in trans-configuration) 3. A carboxylic-acid end group.
3
Q
How are retinoids classified and what are examples of each generation?
A
Retinoids are classified into three generations: 1. First: All-trans-retinoic acid (tretinoin), 13-cis-retinoic acid (isotretinoin), 9-cis-retinoic acid (alitretinoin) 2. Second: Etretinate (an ethyl ester), Acitretin (free acid metabolite of etretinate) 3. Third: Adapalene, Tazarotene, Bexarotene.
4
Q
What is the role of retinoid receptors in gene transcription?
A
Retinoid receptors have molecular features similar to steroid and thyroid hormone receptors. They bind to regulatory regions in DNA called hormone response elements (target sequences) and activate gene transcription in a ligand-dependent manner.
5
Q
What are the clinical implications of the structural modifications in retinoids?
A
Structural modifications in retinoids, such as the addition of a hydroxyl group to the cyclohexenyl ring, can enhance the polarity of the molecule, making it more amenable to excretion and elimination. This can affect the pharmacokinetics and therapeutic efficacy of the retinoid, influencing its clinical use and safety profile.
6
Q
What are retinoids used for?
A
As prescription drugs and cosmeceuticals to elicit skin responses.
7
Q
What do retinoic acid receptors (RARs) and retinoid X receptors (RXRs) do?
A
They act as transcription factors that mediate the effects of retinoids.
8
Q
What is the structure of all-trans-retinoic acid (tretinoin)?
A
It consists of a cyclohexenyl ring, a side chain with four double bonds, and a carboxylic-acid end group.
9
Q
What is the significance of the 4th carbon atom in retinoic acid?
A
It is involved in a hydroxylation reaction to generate 4-hydroxy-retinoic acid, making the molecule more polar.
10
Q
How are retinyl esters formed?
A
By esterification of retinol with fatty acids, serving as a molecular storage form of retinol.
11
Q
What distinguishes first-generation retinoids from second and third generations?
A
First-generation retinoids include all-trans-retinoic acid and its isomers, while second and third generations involve structural modifications and receptor specificity.
12
Q
What are some examples of third-generation retinoids?
A
Adapalene, tazarotene, and bexarotene.
13
Q
What is the physiological ligand for RXR?
A
9-cis-retinoic acid.
14
Q
What is the function of cellular retinoic acid binding protein (CRABP) II?
A
It plays a role in the transport and metabolism of retinoic acid in skin cells.
15
Q
What are the clinical implications of using all-trans-retinoic acid (tretinoin) in treating skin conditions?
A
All-trans-retinoic acid (tretinoin) is effective in treating conditions such as acne, psoriasis, and photoaging due to its ability to bind and activate retinoic acid receptors (RARs), leading to transcriptional activation of retinoic acid-responsive genes. This results in improved skin cell turnover, reduced inflammation, and enhanced collagen production.
16
Q
How do the structural differences between first-generation and second-generation retinoids affect their pharmacological properties?
A
First-generation retinoids, such as all-trans-retinoic acid and isotretinoin, primarily act through RAR activation. In contrast, second-generation retinoids, like etretinate and acitretin, have modified structures that enhance their receptor specificity and may lead to different pharmacokinetic profiles, potentially resulting in improved efficacy and reduced side effects.
17
Q
What role do retinoid receptors play in the mechanism of action of retinoids, and how does this influence therapeutic outcomes?
A
Retinoid receptors, including RARs and RXRs, bind to specific DNA sequences and regulate gene transcription in a ligand-dependent manner. This binding activates retinoic acid-responsive elements (RARE) in gene promoters, influencing cellular processes such as differentiation and proliferation, which are crucial for the therapeutic effects of retinoids in skin conditions.
18
Q
Discuss the significance of the stereoisomers of all-trans-retinoic acid in clinical applications and their potential effects on treatment outcomes.
A
The stereoisomers of all-trans-retinoic acid, such as 9-cis-retinoic acid (alitretinoin) and 13-cis-retinoic acid (isotretinoin), exhibit different binding affinities and biological activities at retinoid receptors. This can lead to variations in therapeutic effects, side effects, and overall treatment outcomes, making the choice of stereoisomer important in clinical practice.
19
Q
What are the potential side effects associated with the use of retinoids, and how can they be managed in clinical practice?
A
Common side effects of retinoids include skin irritation, dryness, and photosensitivity. Management strategies include gradual dose escalation, using moisturizers, and advising patients on sun protection measures. Monitoring for more severe effects, such as teratogenicity in pregnant patients, is also crucial to ensure safe use of retinoids.
20
Q
What is the effect of all-trans-retinol or retinaldehyde on retinyl ester levels in the epidermal layer?
A
Treatment with all-trans-retinol or retinaldehyde increases retinyl ester levels in the epidermal layer by more than 10-fold.
21
Q
What are the two enzymes that catalyze the esterification and oxidation of retinol?
A
The two enzymes are: 1. Lecithin/retinol acyltransferase - predominant retinol-esterifying activity in human keratinocytes. 2. Acyl-coenzyme A/retinol acyltransferase.
22
Q
What are the histologic and molecular alterations that occur after treatment with all-trans-retinoic acid?
A
The alterations include: - Epidermal hyperplasia - Epidermal spongiosis - Compaction of the stratum corneum - Induction of CRBP, CRABP-II, and CYP26.
23
Q
How does the bioavailability of oral retinoids change when administered with food?
A
The oral bioavailability of all retinoids is markedly enhanced when they are administered with food, especially with fatty meals.
24
Q
What is the major metabolite of isotretinoin and its bioactivity?
A
The major metabolite of isotretinoin is 4-oxoisotretinoin, which has reduced bioactivity.
25
What is the pharmacokinetic advantage of acitretin over etretinate?
Acitretin is eliminated more rapidly than etretinate, which has a longer half-life of up to 120 days.
26
What is the primary use of topical retinoids in acne therapy?
Topical retinoids are extremely effective for acne therapy, especially for comedonal lesions, and they help normalize abnormal follicular epithelial differentiation and desquamation in acne.
27
What are the approved indications for tazarotene?
Tazarotene is approved for acne, psoriasis, and photoaging.
28
What is the mechanism of action of alitretinoin gel in treating cutaneous Kaposi sarcoma?
Alitretinoin gel inhibits cellular proliferation and induces apoptosis, and it has an antiviral role against HHV-8.
29
What are the potential effects of topical retinoids on molluscum contagiosum and warts?
Topical retinoids may improve molluscum contagiosum, warts, and various forms of ichthyosis to a variable degree.
30
A patient on acitretin therapy for psoriasis consumes alcohol. What are the potential consequences, and what precautions should be taken?
Alcohol consumption during acitretin therapy can lead to the formation of etretinate, which has a longer half-life and extends the time of compulsory contraception to 2 years (3 years in the US). Patients must strictly avoid alcohol during treatment and for 2 months thereafter.
31
A patient with CTCL is prescribed topical bexarotene. What are its mechanisms of action?
Topical bexarotene inhibits tumor cell growth, encourages terminal differentiation, induces apoptosis, and may play a role in chemoprophylaxis.
32
What is the primary mechanism of action for all-trans-retinoic acid in human skin?
It increases retinyl ester levels in the epidermal layer by more than 10-fold.
33
What is the significance of CYP26 in the metabolism of all-trans-retinoic acid?
CYP26 activity is minimally detectable in untreated normal human skin but increases significantly with administration of retinoids.
34
What is the main difference in the pharmacokinetics of oral retinoids compared to topical retinoids?
Oral retinoids have enhanced bioavailability when administered with food, especially fatty meals.
35
What is the role of isotretinoin in acne treatment?
It normalizes follicular epithelial differentiation and desquamation, providing protection against the development of new lesions.
36
What is the recommended duration of contraception after isotretinoin treatment?
One month posttherapy provides an adequate safety margin.
37
What is the primary use of topical bexarotene?
It is used for the treatment of cutaneous T-cell lymphoma and inhibits tumor cell growth.
38
What are the indications for alitretinoin gel?
It is approved for cutaneous Kaposi sarcoma caused by human herpes virus 8 (HHV-8).
39
What is a common side effect of topical retinoids in patients with greater constitutive pigmentation?
Retinoid dermatitis does not usually lead to postinflammatory hyperpigmentation.
40
What is the effect of topical retinoids on photoaged skin?
They improve fine wrinkles and dyspigmentation, requiring several weeks of treatment for clinical improvement.
41
What are the metabolic pathways involved in the esterification and oxidation of retinol, and how do they affect skin treatment outcomes?
The metabolic pathways for retinol include: 1. Esterification: All-trans-retinol or retinaldehyde increases retinyl ester levels in the epidermal layer by more than 10-fold. Catalyzed by two enzymes: Lecithin/retinol acyltransferase (predominant in keratinocytes) and Acyl-coenzyme A/retinol acyltransferase. 2. Oxidation: Sequential oxidation of all-trans-retinol forms all-trans-retinoic acid, with all-trans-retinaldehyde as the intermediate metabolite. This oxidation is the rate-limiting step for all-trans-retinoic acid formation. These processes lead to histologic and molecular alterations in the skin, including epidermal hyperplasia and spongiosis, which mimic the effects of all-trans-retinoic acid treatment.
42
How does the pharmacokinetics of isotretinoin differ from that of acitretin, and what implications does this have for their clinical use?
The pharmacokinetics of isotretinoin and acitretin differ significantly: 1. Metabolism: Isotretinoin undergoes first-pass metabolism in the liver and enterohepatic recycling. Acitretin is a pro-drug of etretinate, undergoing extensive hydrolysis. 2. Half-life: Isotretinoin varies but is generally longer than acitretin (approximately 2 days). 3. Bioactivity: 4-oxoisotretinoin is the major metabolite of isotretinoin with reduced bioactivity, while acitretin is more lipophilic and binds strongly to plasma lipoprotein. 4. Elimination: Isotretinoin is excreted in urine and feces, while acitretin is eliminated more rapidly than etretinate. Clinical implications include the need for a 1-month post-therapy contraception period for isotretinoin due to its longer half-life and potential teratogenic effects, while acitretin requires extended contraception due to the possibility of etretinate formation when taken with alcohol.
43
What are the indications and contraindications for the use of topical retinoids in acne therapy?
Topical retinoids are indicated for: 1. Acne: Particularly effective for comedonal lesions. 2. Post-inflammatory hyperpigmentation: Especially in black individuals. 3. Actinic dyspigmentation: Notably in Chinese and Japanese individuals. 4. Early stretch marks: Can be beneficial in various age groups, with exceptions for neonates. Contraindications include: Use in pregnancy is discouraged until after delivery due to potential risks to the mother and fetus, and patients with a history of hypersensitivity to retinoids should avoid these treatments.
44
What is the mechanism of action of alitretinoin gel in the treatment of cutaneous Kaposi sarcoma, and what are its clinical implications?
Alitretinoin gel is approved for the treatment of cutaneous Kaposi sarcoma (KS) caused by human herpes virus 8 (HHV-8). Its mechanism of action includes: 1. Inhibition of cellular proliferation: Alitretinoin inhibits the growth of malignant cells. 2. Induction of apoptosis: It promotes programmed cell death in affected cells. 3. Antiviral activity: It has a role against HHV-8, which is significant in KS. Clinical implications include improvement in skin lesions typically observed after 4 to 8 weeks of treatment, with the most significant response occurring after 14 weeks.
45
What is the primary use of topical tazarotene?
Topical tazarotene is primarily approved for the treatment of psoriasis and is typically used in combination with topical steroids due to irritation issues.
46
What are the clinical features improved by isotretinoin in the treatment of acne?
Isotretinoin significantly improves the following clinical features in acne treatment: 1. Sebum production 2. Comedogenesis 3. Colonization with Propionibacterium acnes.
47
What are the clinical features improved by isotretinoin in the treatment of acne?
Isotretinoin significantly improves the following clinical features in acne treatment:
1. Sebum production
2. Comedogenesis
3. Colonization with Propionibacterium acnes
4. Photoaging
5. Increased collagen
6. Elastic fiber density
48
What is the recommended dosage of oral bexarotene for CTCL treatment?
The recommended dosage of oral bexarotene for the treatment of CTCL is 300 mg/m² or more per day within the first 2 months.
49
What is the significance of acitretin in the treatment of psoriasis?
Acitretin is the retinoid of choice for psoriasis, particularly effective in pustular psoriasis of the palmoplantar or generalized type, showing significant improvement in about 50% of treated patients and a decrease in psoriasis area and severity index by approximately 60% to 70% depending on dosage.
50
What are the expected side effects of topical retinoid therapy?
Expected side effects of topical retinoid therapy include local skin irritation, such as redness and peeling. It is important to educate patients that clinical improvement correlates with the degree of irritation, and that administration should be individualized based on skin reaction.
51
What is the role of alitretinoin in dermatological treatment?
Alitretinoin is approved in Europe and Canada for the treatment of treatment-resistant chronic hand eczema, requiring between 3 and 6 months of therapy to fully appreciate its effects.
52
What are the key mechanisms by which isotretinoin treats acne?
Isotretinoin treats acne by reducing sebum production (caused by atrophy of sebaceous glands), inhibiting comedogenesis, and reducing colonization with Propionibacterium acnes.
53
What are the expected improvements in photoaged skin with topical tretinoin?
Topical tretinoin improves fine wrinkles and dyspigmentation in photoaged skin.
54
What is the mechanism of action of alitretinoin gel in treating Kaposi sarcoma?
Alitretinoin gel inhibits cellular proliferation and induces apoptosis, with a potential antiviral role against HHV-8.
55
What are the best results achieved by acitretin for specific types of psoriasis?
Acitretin achieves the best results in pustular psoriasis of the palmoplantar or generalized (von Zumbusch) type.
56
What is the recommended initial dosage of acitretin for Darier-White disease?
The recommended initial dosage of acitretin for Darier-White disease is 10 mg/day to prevent initial exacerbation of the disease.
57
What are the best results achieved by acitretin for specific types of ichthyosis?
Acitretin achieves the best results for autosomal recessive congenital ichthyoses, such as lamellar ichthyosis.
58
What is the expected outcome of tretinoin 0.05%/hydroquinone 4%/fluocinolone 0.1% for melasma?
This combination therapy is effective for treating melasma.
59
What are the response rates for early and advanced stages of CTCL with oral bexarotene?
Response rates for oral bexarotene are approximately 60% for early stages (IA–IIA) and 50% for advanced stages (IIB–IVB) of CTCL.
60
What are the mixed findings regarding isotretinoin's efficacy on photoaging?
Some studies show isotretinoin significantly improves clinical features of photoaging, while others show no significant differences compared to topical retinoic acid or daily sunscreen use.
61
What is the expected improvement in the psoriasis area and severity index with acitretin?
Acitretin therapy decreases the psoriasis area and severity index by approximately 60% to 70%, depending on the dosage.
62
What is topical tazarotene approved for?
Psoriasis.
63
What is isotretinoin primarily used to treat?
Acne.
64
What are the effects of isotretinoin on photoaging?
It may improve clinical features like photo-aging, increased collagen, and elastic fiber density, but data is mixed.
65
What is acitretin the retinoid of choice for?
Psoriasis, particularly pustular psoriasis of the palmoplantar or generalized type.
66
What is the typical dosage of acitretin for treating psoriasis?
Initiate with low dosage, usually 10 mg/day, increasing to 20 mg/day for significant improvement.
67
What is alitretinoin approved for in Europe and Canada?
Treatment-resistant chronic hand eczema.
68
What is the FDA-approved use of bexarotene?
Oral therapy for the treatment of CTCL that is refractory to at least one systemic therapy.
69
What is the importance of patient education in topical retinoid therapy?
To explain that local skin irritation is expected and that clinical improvement correlates with the degree of irritation.
70
What should be considered when choosing oral retinoids for skin aging?
The potential adverse effects of oral retinoids.
71
What is the response rate for early-stage CTCL with oral bexarotene monotherapy?
Approximately 60%.
72
What are the clinical implications of using low-dose oral retinoids for photoaging?
The use of low-dose oral retinoids for photoaging has shown mixed results:
- One study indicated that isotretinoin significantly improved clinical features such as photo-aging, increased collagen, and elastic fiber density.
- Other studies found no significant differences in clinical and histologic improvement when comparing isotretinoin to topical retinoic acid (0.05%) or daily sunscreen use.
- More rigorous studies are needed to further elucidate these effects and consider the potential adverse effects of oral retinoids when choosing this treatment modality for skin aging.
73
What is the recommended approach for initiating acitretin therapy in patients with moderate to severe forms of Darier-White disease?
The recommended approach for initiating acitretin therapy in patients with moderate to severe forms of Darier-White disease includes:
1. Start with a low dosage: Initiate treatment with acitretin at 10 mg/day to prevent initial exacerbation of the disease.
2. Adjust dosage: Usually, 20 mg/day is sufficient for significant improvement.
3. Long-term treatment: Long-term treatment is typically needed to prevent relapse.
74
How does the treatment of psoriasis with acitretin differ from other retinoids?
Acitretin is the retinoid of choice for treating psoriasis, particularly in pustular psoriasis of the palmoplantar or generalized type (von Zumbusch). The expected outcomes include:
- Rebound effects: Rebound does not usually occur after cessation of therapy.
- Reintroduction: Reintroduction of acitretin produces a beneficial response.
- Clearance: Complete clearing of plaque-type psoriasis occurs in approximately 30% of treated patients.
- Improvement: Significant improvement is observed in about 50% of patients, with a decrease in the psoriasis area and severity index of approximately 60% to 70%, depending on the dosage.
75
What are the key considerations for patient education when prescribing topical retinoids?
Key considerations for patient education when prescribing topical retinoids include:
- Local skin irritation: Patients should be informed that local skin irritation (redness and peeling) is expected.
- Clinical improvement: Explain that clinical improvement correlates with the degree of irritation, as shown in studies comparing different concentrations of tretinoin.
- Individualized treatment: Administration of a topical retinoid should be individualized and titrated based on the patient's skin reaction.
- Nonprescription products: Discuss the existence of various 'natural retinoid' preparations and their efficacy, emphasizing that many contain less active forms like retinyl esters.
76
What is the optimal daily dose of isotretinoin for acne treatment?
The optimal daily dose of isotretinoin for acne treatment is approximately 0.5 to 1 mg/kg of body weight per day.
77
What is the recommended cumulative dose of isotretinoin to minimize posttherapy relapse?
To minimize posttherapy relapse, a cumulative dose of at least 120 mg/kg is recommended, which implies a treatment duration of 6 to 8 months.
78
What are the common adverse effects associated with oral retinoids?
Common adverse effects of oral retinoids include:
- Dryness of the lips, skin, and mucous membranes
- Retinoid dermatitis
- Blepharoconjunctivitis
- Alterations in visual function
- Hair loss (telogen effluvium)
- Bone pain
- Muscle pain and cramps
79
What is the most serious adverse effect of oral retinoids?
The most serious adverse effect of oral retinoids is teratogenesis, which can lead to various birth defects including auditory, cardiovascular, craniofacial, ocular, and central nervous system abnormalities.
80
What is the recommended dose of alitretinoin for chronic hand eczema?
The recommended dose of alitretinoin for chronic hand eczema is 10 to 30 mg/day.
81
What should be monitored in patients receiving high-dose retinoid treatment?
In patients receiving high-dose retinoid treatment, it is important to monitor for:
- Bone changes and calcification of tendons and ligaments
- Signs of hyperostosis
- Visual function alterations
- Skin reactions
82
What is the initial recommended dosage of bexarotene for CTCL treatment?
The initial recommended dosage of bexarotene for CTCL treatment is 300 mg/m²/day as a single oral dose with meals.
83
What is the relationship between isotretinoin and Staphylococcus aureus colonization?
Staphylococcus aureus colonization tends to correlate with isotretinoin-induced reduction in sebum production and may lead to overt cutaneous infections.
84
What is the significance of a lag period in isotretinoin therapy?
A lag period of 1 to 3 months may occur before the onset of the therapeutic effect of isotretinoin, indicating that initial flare-ups of acne may be observed during the first few weeks of treatment.
85
What precautions should men take when using systemic retinoids?
Men who are actively trying to father children should avoid systemic retinoid therapy due to the potential risks of teratogenic effects.
86
How long should therapy with alitretinoin continue before evaluating its full effects?
Therapy with alitretinoin should continue for 3 to 6 months before a full evaluation of its therapeutic effects can be made.
87
What is the recommended initial dosage of bexarotene for CTCL treatment and how should it be adjusted if adverse effects occur?
The recommended initial dosage of bexarotene is 300 mg/m²/day with meals. If adverse effects occur, the dosage can be reduced to 100 or 200 mg/m²/day, or therapy may be temporarily suspended.
88
What should be done if a patient on isotretinoin therapy reports poor night vision and excessive glare sensitivity?
These symptoms are likely due to alterations in visual function caused by isotretinoin. The patient should be referred to an ophthalmologist for further evaluation.
89
What combination therapies may be required for total clearing of psoriasis lesions?
Combination therapies for psoriasis may include retinoids plus topical glucocorticoids, topical vitamin D derivatives, dithranol (anthralin), ultraviolet B irradiation, or photochemotherapy (PUVA).
90
What should be done if a patient on isotretinoin therapy develops blepharoconjunctivitis?
Blepharoconjunctivitis is likely related to isotretinoin's effects on meibomian glands. If artificial tears fail to alleviate the condition, an ophthalmologic consultation should be sought.
91
What should be done if a patient on isotretinoin therapy develops a flare-up of acne during the first few weeks?
A flare-up of acne during the first few weeks of isotretinoin therapy is common and does not require discontinuation. Therapy should be continued as the condition typically improves over time.
92
What is the initial dosage of acitretin for psoriasis and how should it be adjusted?
The initial dosage of acitretin for psoriasis is 10 to 25 mg/day, followed by progressively increasing doses based on the patient's response.
93
What should be done if a patient on isotretinoin therapy develops diffuse hair loss?
Diffuse hair loss (telogen effluvium) is a common complaint with isotretinoin therapy, especially at higher dosage levels or after several months of therapy. Management may include dosage adjustment or discontinuation if necessary.
94
What is the likely cause and management if a patient on isotretinoin therapy develops Staphylococcus aureus colonization?
Staphylococcus aureus colonization is likely due to isotretinoin-induced reduction in sebum production, which may lead to overt cutaneous infections.
95
How should retinoid dermatitis be managed in a patient on isotretinoin therapy?
Retinoid dermatitis can be managed by reducing the frequency or amount of retinoid application and using liberal emollients.
96
What is the likely cause and management if a patient on isotretinoin therapy develops nail thinning and periungual granulation tissue?
Nail thinning and periungual granulation tissue are side effects of isotretinoin therapy. Management may include dosage adjustment or discontinuation if necessary.
97
What is the likely cause and management if a patient on isotretinoin therapy develops bone pain?
Bone pain is a frequent side effect of retinoid therapy, often without objective abnormalities. Management may include symptomatic treatment or discontinuation if necessary.
98
What are the common side effects of topical tazarotene and how should they be managed?
Common side effects of topical tazarotene include local skin irritation, which can be managed by reducing the frequency or amount of application and using emollients.
99
What is the recommended dosage adjustment for oral bexarotene if CTCL does not respond after 8 weeks?
If CTCL does not respond after 8 weeks of therapy, the dosage of oral bexarotene may be increased to 400 mg/m²/day with careful monitoring.
100
What is the optimal daily dose of isotretinoin for acne treatment?
The optimal daily dose of isotretinoin for acne treatment is approximately 0.5 to 1 mg/kg of body weight.
101
What is the typical duration of therapy for isotretinoin?
6 to 8 months.
102
What is a common side effect of topical retinoids?
Local skin irritation.
103
What serious adverse effect is associated with oral retinoids?
Teratogenesis, leading to birth defects.
104
What should men trying to father children avoid?
Systemic retinoid therapy.
105
What is a common mucocutaneous side effect of isotretinoin?
Blepharoconjunctivitis.
106
What is a potential effect of retinoids on bone health?
Bone pain without objective evidence of abnormalities.
107
What is the relationship between isotretinoin and Staphylococcus aureus colonization?
It tends to correlate with isotretinoin-induced reduction in sebum production and may lead to overt cutaneous infections.
108
What is a common complaint among patients treated with acitretin?
Diffuse or localized hair loss (telogen effluvium).
109
What are the recommended dosages and treatment durations for alitretinoin and acitretin?
For alitretinoin, the recommended dosage is 10 to 30 mg/day for chronic hand eczema, with treatment periods of up to 6 months often needed. For acitretin in psoriasis, an initial low dose of 10 to 25 mg/day is followed by progressively increasing doses.
110
What are the most common adverse effects associated with topical retinoids?
The most common adverse effect of topical retinoids is local skin irritation, which typically peaks within the first month of treatment.
111
What serious adverse effects are associated with oral retinoids, particularly regarding teratogenesis?
The most serious adverse effect of oral retinoids is teratogenesis, which can lead to various birth defects including auditory, cardiovascular, craniofacial, ocular, axial and acral skeletal, and central nervous system abnormalities.
112
What are the recommendations for monitoring and managing ocular side effects in patients treated with isotretinoin?
Patients treated with isotretinoin may develop blepharoconjunctivitis. Recommendations include seeking ophthalmologic consultation if artificial tears fail and monitoring for alterations in visual function.
113
What are the common side effects associated with isotretinoin therapy?
Common side effects include increased muscle tone, axial muscle rigidity, myopathy, rare central nervous system side effects, increased intracranial pressure, severe depression, and clinical and biochemical central hypothyroidism.
114
What monitoring is required for patients on retinoid therapy?
Monitoring includes proper patient selection, dosage adjustments, discontinuation of treatment if necessary, routine monitoring for potential toxicity, and baseline serum lipid measurement.
115
What are the drug interactions to avoid when using retinoids?
Avoid tetracyclines, alcohol, methotrexate, vitamin A supplements, and bexarotene with gemfibrozil.
116
At what triglyceride level should retinoid therapy be discontinued?
Retinoid therapy should be discontinued if triglyceride levels reach 800 mg/dL.
117
What precautions should be taken for women of childbearing potential when prescribing isotretinoin?
Women of childbearing potential must have 2 negative pregnancy tests spaced 30 days apart and practice effective contraception.
118
What is the appropriate course of action for a patient on isotretinoin therapy with a triglyceride level of 850 mg/dL?
Discontinue retinoid therapy immediately.
119
What is the expected outcome upon discontinuation of bexarotene therapy for central hypothyroidism?
Central hypothyroidism caused by bexarotene therapy is rapidly and completely reversible upon cessation of therapy.
120
Why is coadministration of atorvastatin recommended for a patient with severe retinoid-induced hypertriglyceridemia?
Coadministration of atorvastatin is recommended to manage severe retinoid-induced hypertriglyceridemia.
121
At what threshold should isotretinoin therapy be discontinued due to elevated serum transaminase levels?
Retinoid therapy should be discontinued if serum transaminase levels exceed three times the upper normal range.
122
What is the likely cause of muscle pain and cramps in a patient on isotretinoin therapy?
Muscle pain and cramps are common with isotretinoin therapy, especially in individuals involved in vigorous physical activity.
123
What is the major risk factor for developing pseudotumor cerebri in patients on isotretinoin?
The major risk factor is the concomitant use of isotretinoin and tetracyclines.
124
What does evidence suggest about isotretinoin and psychiatric disorders?
Large-scale epidemiologic studies provide no evidence that isotretinoin exposure is associated with a greater risk of psychiatric disorders.
125
What are the common lipid changes observed in patients on isotretinoin therapy?
Retinoid-induced hyperlipidemia commonly includes elevated triglyceride levels and elevated cholesterol levels.
126
What is the mechanism behind central hypothyroidism in patients on isotretinoin?
Central hypothyroidism is caused by isotretinoin binding to RXR, which dimerizes with the nuclear thyroid receptor.
127
What is the likely cause of acute pancreatitis in a patient on isotretinoin therapy?
Acute pancreatitis may occur due to severe retinoid-induced hypertriglyceridemia.
128
What potential drug interactions may exacerbate hepatotoxicity in patients on isotretinoin?
Concomitant use of isotretinoin with alcohol or methotrexate may exacerbate hepatotoxicity.
129
What is the clinical significance of hyperlipidemia in patients treated with retinoids?
Retinoid-induced hyperlipidemia is not associated with an increased risk of atherosclerosis or cardiovascular disease.
130
What precautions should be taken before initiating oral retinoid therapy?
Before initiating oral retinoid therapy, measure baseline serum lipid levels, complete blood count, assess thyroid function, evaluate liver enzyme levels, and check for any history of skeletal abnormalities.
