1 - SYSTEMIC RETINOIDS Flashcards
1
Q
Tretinoin (Retrieve cream) is all-trans-retinoic acid
A
True
2
Q
Isotretinoin is 13-cis retinoic acid
A
True
3
Q
Isotretinoin (13-cis retinoic acid) and tretinoin (all-trans-retinoic acid) are first generation retinoids (non-aromatic retinoids)
A
True
4
Q
Acitretin is a second generation retinoid (monoaromatic retinoids)
A
True
5
Q
Acitretin is an acid metabolite of another second generation retinoid etretinate (phased out due to prolonged presence in subcutaneous fat)
A
True
6
Q
Topical Tazarotene, topical Adapalene, Bexarotene are third generation retinoids (polyaromatic retinoids)
A
True
7
Q
Tretinoin, Isotretinoin (both first generation retinoids), Acitretin (second generation retinoid) and bexarotene (third generation retinoid) are bound to plasma proteins with the former 3 bound specifically to albumin
A
True
8
Q
All retinoids are metabolised in the liver by CYP3A4
A
True
9
Q
Acitretin has a higher bioavailability than Isotretinoin
A
True (60% vs 25%)
10
Q
Tretinoin, Isotretinoin and Acitretin are excreted in the bile (faeces) and urine
A
True
11
Q
Bexarotene is excreted in the bile and urine
A
False (only hepatobiliary)
12
Q
Retinoids are vitamin A derivatives
A
True
13
Q
Vitamin A can be synthesised in vivo
A
False (must be acquired through the diet)
14
Q
Beta-carotene (a carotenoid) is a precursor of vitamin A and is converted to retinal (vitamin A aldehyde)
A
True
15
Q
Retinal (vitamin A aldehyde) the 11-cis isomer and 11-trans isomer is important in the biochemical reaction of visual function
A
True
16
Q
Retinol (vitamin A alcohol) is essential to reproduction
A
True
17
Q
Retinol (vitamin A alcohol) and retinal (vitamin A aldehyde) can be converted interchangeably
A
True
18
Q
Retinol (vitamin A alcohol) is irreversibly metabolised to retinoic acid
A
True
19
Q
Retinal (vitamin A aldehyde) and retinoic acid play an essential role in epithelial differentiation and normal growth
A
True
20
Q
Third generation retinoids are more potent than earlier generation retinoids and their therapeutic index (efficacy:toxicity ratio) shows no signs of improvement due to increased toxicity
A
True
21
Q
The oral bioavailability of retinoids is reduced with food intake
A
False (enhanced with food intake especially fatty food)
22
Q
Isotretinoin, Acitretin and Bexarotene are relatively water soluble
A
True (Isotretinoin and Acitretin undetectable in serum within 1 month after stopping therapy)
23
Q
The hepatic metabolism of retinoids is induced mainly by retinoids themselves but also by other agents known to induce hepatic CYP3A4
A
True
24
Q
Tretinoin has the shortest half life
A
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
25
Acitretin has the longest half life
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
26
Acitretin (50 hours) has a longer half life than Isotretinoin (10-20 hours)
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
27
Isotretinoin (10-20 hours) has a longer half life than bexarotene (7-9 hours)
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
28
Alcohol indirectly enhances the re-esterification of Acitretin to Etretinate (lipophilic second generation retinoid that preceded its acid metabolite Acitretin which is stored and slowly released from adipose tissue resulting in a prolonged half life of 2.9 years)
True (this re-esterification is the reason why contraception for 3 years after cessation of Acitretin is recommended in women of child bearing age)
29
Retinoids are small molecule hormones that elicit their biological effects by activating nuclear receptors and regulating gene transcription
True
30
Retinoids exert their physiologic effects by binding to receptors present in the nucleus
True
31
There are 2 families of retinoid receptors - retinoic acid receptor (RAR) family and retinoid X receptor (RXR) family
True
32
The retinoic acid receptor (RAR) family has 3 Isoforms - alpha, beta and gamma
True (same as RXR)
33
The retinoid X receptor (RXR) family has 3 Isoforms - alpha, beta and gamma
True (same as RAR)
34
Retinoic acid receptors (RAR) are always and exclusively paired with Retinoid X receptors (RXR)
True
35
Retinoid X receptor (RXR) can exist as a homodimer with another retinoid X receptor (RXR)
True (whereas RAR needs to be paired with an RXR)
36
Retinoid X receptor (RXR) may be paired with another RXR, a Retinoic acid receptor (RAR), vitamin-D3 receptor, thyroid hormone receptor, and peroxisome proliferator-activated receptor
True
37
There are a total of 6 Isoforms of retinoid receptors - RAR alpha, beta, gamma and RXR alpha, beta, gamma receptors
True
38
Retinoid receptors are part of a large superfamily of receptors consisting also of glucocorticosteroid, thyroid hormone and vitamin-D3 receptors
True
39
Acitretin (second generation retinoid) has a weak interaction with multiple Retinoid Acid Receptors (RAR) by activating these receptors but not binding to them
True
40
Alitretinoin (third generation retinoid) is a pan-retinoid receptor and binds to all 6 known retinoid receptors (RAR alpha, beta, gamma and RXR alpha, beta, gamma)
True
41
Tretinoin (First generation retinoid) binds to RAR
True
42
Isotretinoin (First generation retinoid) has no clearly identified affinity for any retinoid receptor (RAR or RXR)
True
43
There is a higher affinity for RXR than RAR with the higher generation retinoids
True (third generation Retinoids Alitretinoin and Bexarotene have a higher affinity for RXR)
44
Topical retinoids Adapalene and Tazarotene (third generation retinoids) binds to RAR beta and gamma Isoforms
True (in contrast to the other systemic and topical third generation retinoid Bexarotene which has an affinity for RXR instead of RAR)
45
Systemic retinoids affect the pathways involved in inflammation
True
46
Systemic retinoids affect the pathways involved in cellular differentiation
True
47
Systemic retinoids affect the pathways involved in apoptosis
True
48
Systemic retinoids affect the pathways involved in sebaceous gland activity
True
49
Patients on systemic retinoids may concomitantly take vitamin A supplementation as long as this is < 5000 IU daily
True
50
Oral administration of retinoids with milk or fatty foods reduces retinoid absorption
False (enhances retinoid absorption, though patients should avoid excessively fatty diet)
51
Women with childbearing potential must not consume alcohol during and up to 2 months after cessation of Acitretin therapy
True (alcohol enhances the re-esterification of Acitretin to Etretinate which is more lipophilic and able to be stored in tissue and slowly released for up to 2.9 years)
52
In males and females of non-child bearing potential, the consumption of alcohol with the risk of re-esterification of Acitretin to Etretinate is not a clinically important issue
True
53
Isotretinoin (First generation retinoid) is FDA approved for acne vulgaris
True
54
Acitretin (second generation retinoid) is FDA approved for psoriasis
True
55
Bexarotene (third generation retinoid) is FDA approved for selected cases of mycosis fungoides and Sezary syndrome
True
56
The initial clinical effects of Acitretin in psoriasis are often seen in 4-6 weeks but it may take up to 3-4 months or longer to see the full clinical benefit
True
57
Combination therapy with systemic retinoids (Acitretin) and phototherapy for psoriasis is more effective than monotherapy with either modality
True
58
Current recommendations for combination Acitretin and UV therapy for psoriasis include instituting low dose (25mg) Acitretin 2 weeks prior to the initiation of phototherapy
True
59
If combination Acitretin and UV therapy is used in psoriasis, the UV dose should be adjusted downward to accommodate the Acitretin effect
True
60
Acitretin can be used in combination with methotrexate, however every attempt should be made to limit the period for which patients are taking both medications due to the potential adverse liver effects
True
61
Acitretin can be used in combination with CsA, however every attempt should be made to limit the period for which patients are taking both medications due to the possible elevations in serum triglycerides
True
62
Retinoids are immunosuppressive
False (generally not considered to be immunosuppressive and so may be ideal candidates for combination therapy with biological agents)
63
Patients taking Isotretinoin for acne vulgaris may expect that their complexion may worsen for the first 4-6 weeks of Isotretinoin therapy
True
64
Retinoids are teratogenic
True
65
Effective contraception or abstinence should commence 1 month prior to starting Isotretinoin and Acitretin therapy
True
66
Effective contraception must be continued 1 month after discontinuation of Isotretinoin therapy
True
67
Effective contraception must be continued 3 years following the discontinuation of Acitretin due to the re-esterification to etretinate with concomitant alcohol use
True (etretinate has an exceptionally long elimination half life)
68
It is not clear what quantity of ingested alcohol is required for the re-esterification of Acitretin to Etretinate
True
69
There is a risk of retinoid embryopathy in fetuses fathered by men taking systemic retinoids
False (there is little, if any risk)
70
Patients should have 2 negative urine or serum pregnancy tests before receiving the initial Isotretinoin prescription
True
71
The second pregnancy test should be done during the first 5 days of the menstrual period immediately preceding the start of Isotretinoin therapy
True
72
For patients who are amenorrhea, the second pregnancy test should be done at least 11 days after the last unprotected sexual intercourse (without using 2 effective forms of contraception, prior to starting Isotretinoin therapy
True
73
Each month of Isotretinoin therapy, the patient must have a negative pregnancy test result
True
74
Patients on Isotretinoin therapy must commit to 2 forms of contraception
True
75
Hypersensitivity to parabens is a contraindication to Isotretinoin therapy
True (Parabens are present in Isotretinoin capsules)
76
Systemic retinoids can cause spontaneous abortion
True
77
Pancreatitis is a risk of Bexarotene, but also reported with Isotretinoin
True
78
Dry mucous membranes (cheilitis and nasal mucosa) and skin (xerosis) is common in patients taking Isotretinoin and Acitretin
True
79
Cutaneous xerosis associated with Isotretinoin and Acitretin is more common in patients with a history of atopy
True
80
Acitretin may induce 'sticky skin' especially on the palms
True
81
Systemic retinoids may cause an exuberant granulation tissue response in previous acne lesions, around nail folds, and at sites of trauma
True
82
Acne fulminans can occur with Isotretinoin use
True
83
Elevated serum lipids, especially triglyceride levels is much greater with Bexarotene than other systemic retinoids
True (occurred within the first or second week of therapy)
84
Statins and fenofibrate (fibric acid derivative) can be used as lipid lowering agents in conjunction with Bexarotene
True (both lipid lowering agents are not inhibitors of the Cytochrome P450 pathway and so do not affect the metabolism of Bexarotene with the risk of increase Bexarotene and triglyceride levels)
85
Gemfibrozil (also a fibric acid derivative) is contraindicated with Bexarotene as it is a Cytochrome P450 pathway inhibitor which causes an increase of Bexarotene and triglyceride levels
True (Bexarotene is metabolised by the Cytochrome P450 pathway in the liver)
86
Lipid elevations associated with systemic retinoid therapy are reversible upon cessation of therapy
True
87
There is contradictory evidence that Isotretinoin is a cause of depression
True
88
The data regarding Isotretinoin use as a cause of Inflammatory Bowel Disease is conflicting
True
89
There is potential for systemic retinoids to cause diffuse interstitial skeletal hyperostosis (DISH), similar bone effects in chronic vitamin A toxicity
True (may be asymptomatic risk in Isotretinoin, although true risk is only when systemic retinoids are given in high doses and prolonged period)
90
If diffuse interstitial skeletal hyperostosis (DISH) involves the posterior longitudinal ligament, this may lead to spinal cord compression and neurological deficits and therefore consideration should be given to discontinuing the retinoid
True
91
Systemic retinoids may cause premature epiphyseal closure
True (rare and only occurring in higher doses)
92
Blepharoconjunctivitis has been associated with Isotretinoin and Acitretin
True
93
Corneal opacities can also occur in patients taking systemic retinoids
True (occur in central and peripheral cornea and do not adversely affect vision)
94
Decreased night vision is exclusively associated with Isotretinoin
True
95
Bacterial conjunctivitis has been associated with Isotretinoin (uncommon)
True
96
Both Acitretin and Isotretinoin may cause elevated transaminases
True
97
Elevated transaminases in Isotretinoin use are mild and return to normal despite continued therapy
True
98
There have been cases of severe hepatitis reported with Acitretin use
True
99
Elevated transaminases which are more persistent in Acitretin therapy are usually mild and not considered to be clinically significant
True (Acitretin should be discontinued for severe (> 3 fold) increase of liver transaminases elevations)
100
Elevated Transaminases as a result of Bexarotene therapy occur less frequently
True
101
Acitretin is more likely to cause an idiosyncratic fatal hepatitis reaction than the other systemic retinoids
True
102
Acitretin should be discontinued for severe (> 3 fold) increase of liver transaminases elevations
True
103
Thyroid effects (Central hypothyroidism) is most commonly reported for Bexarotene
True (RXR heterodimers with thyroid receptors)
104
Systemic retinoids may cause pseudotumour cerebri (headaches with nausea, vomiting and visual changes), especially with concomitant tetracycline, doxycycline, and minocycline
True
105
Muscle effects (myalgias) are associated mostly with Isotretinoin therapy
True
106
Telogen effluvium is greater with Acitretin than Isotretinoin or Bexarotene
True
107
Nail fragility may be associated with systemic retinoids
True
108
The incidence of Nail dystrophy and onycholysis is higher with Acitretin
True
109
Patients on Bexarotene (third generation retinoid) are at risk of reversible leukopenia and neutropenia
True (less frequent with first and second generation retinoids)
110
Systemic retinoids may cause photosensitivity
True
111
Concomitant Vitamin A supplementation and systemic retinoids may induce hypervitaminosis A-like toxicities
True
112
CYP3A4 inhibitors I.e. Macrolide antibiotics (erythromycin, clarithromycin, roxithromycin) and Azole antifungals may increase systemic retinoid drug levels and result in potential toxicity
True (retinoids are metabolised on the liver by CYP3A4)
113
CYP3A4 Inducers I.e. Antituberculosis drugs (rifampicin) and Anticonvulsants (Phenytoin, carbamazepine) may reduce systemic retinoid drug levels
True (retinoids are metabolised on the liver by CYP3A4)
114
Systemic retinoids may increase CsA levels and result in potential toxicity via competition with retinoids for CYP3A4 metabolism
True (both retinoids and CsA are CYP3A4 substrates)
115
Retinoids may reduce the drug levels of progestin only contraceptives causing reduced efficacy of these contraceptives
True
