1 - SYSTEMIC RETINOIDS Flashcards Preview

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Flashcards in 1 - SYSTEMIC RETINOIDS Deck (115):
1

Tretinoin (Retrieve cream) is all-trans-retinoic acid

True

2

Isotretinoin is 13-cis retinoic acid

True

3

Isotretinoin (13-cis retinoic acid) and tretinoin (all-trans-retinoic acid) are first generation retinoids (non-aromatic retinoids)

True

4

Acitretin is a second generation retinoid (monoaromatic retinoids)

True

5

Acitretin is an acid metabolite of another second generation retinoid etretinate (phased out due to prolonged presence in subcutaneous fat)

True

6

Topical Tazarotene, topical Adapalene, Bexarotene are third generation retinoids (polyaromatic retinoids)

True

7

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

True

8

All retinoids are metabolised in the liver by CYP3A4

True

9

Acitretin has a higher bioavailability than Isotretinoin

True (60% vs 25%)

10

Tretinoin, Isotretinoin and Acitretin are excreted in the bile (faeces) and urine

True

11

Bexarotene is excreted in the bile and urine

False (only hepatobiliary)

12

Retinoids are vitamin A derivatives

True

13

Vitamin A can be synthesised in vivo

False (must be acquired through the diet)

14

Beta-carotene (a carotenoid) is a precursor of vitamin A and is converted to retinal (vitamin A aldehyde)

True

15

Retinal (vitamin A aldehyde) the 11-cis isomer and 11-trans isomer is important in the biochemical reaction of visual function

True

16

Retinol (vitamin A alcohol) is essential to reproduction

True

17

Retinol (vitamin A alcohol) and retinal (vitamin A aldehyde) can be converted interchangeably

True

18

Retinol (vitamin A alcohol) is irreversibly metabolised to retinoic acid

True

19

Retinal (vitamin A aldehyde) and retinoic acid play an essential role in epithelial differentiation and normal growth

True

20

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

True

21

The oral bioavailability of retinoids is reduced with food intake

False (enhanced with food intake especially fatty food)

22

Isotretinoin, Acitretin and Bexarotene are relatively water soluble

True (Isotretinoin and Acitretin undetectable in serum within 1 month after stopping therapy)

23

The hepatic metabolism of retinoids is induced mainly by retinoids themselves but also by other agents known to induce hepatic CYP3A4

True

24

Tretinoin has the shortest half life

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