2 - Topical and Intralesional Antiviral Agents Flashcards Preview

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Flashcards in 2 - Topical and Intralesional Antiviral Agents Deck (114):
1

Topical and intralesional agents can be:
(1) viricidal
(2) immune-enhancing
(3) cytodestructive

True

2

The topical viricidal agents include:
(1) acyclovir
(2) penciclovir
(3) cidofovir
(4) foscarnet
(5) idoxuridine

True

3

The topical/intralesional immune enhancers include:
(1) topical imiquimod
(2) topical and intralesional interferon

True

4

The topical/intralesional cytodestructive agents include:
(1) intralesional bleomycin
(2) topical podophyllin/podofilox
(3) topical trichloroacetic acid
(4) topical cantharidin
(5) topical salicylic acid
(6) topical 5-fluorouracil

True

5

Topical acyclovir 5% cream and ointment are FDA approved for the treatment of HSV

True

6

Even when acyclovir is applied topically to damaged skin including localised VZV infection, systemic absorption is limited

True

7

Topical acyclovir is specific for HSV-infected cells because the drug requires phosphorylation by the viral enzyme thymidine kinase

True

8

Topical acyclovir is most effective against HSV-1 and HSV-2 and less effective against VZV due to less efficient phosphorylation by the VZV viral thymidine kinase

True

9

Topical acyclovir is not effective against CMV because CMV does not encode for thymidine kinase

True (acyclovir needs to be phosphorylated by viral thymidine kinase to be able to be incorporated into viral DNA by viral-DNA polymerase)

10

Topical acyclovir 5% ointment is approved of the management of initial genital HSV in immunocompetent patients

True (early application within 24 hours of onset of prodrome is important)
Initial = every 3 hours up to 6 X daily for 7 days
Recurrent = 5 X daily for 4 days
A finger cot or rubber glove should be used when applying the medication to prevent autoinoculation or transmission to other persons

11

Topical acyclovir 5% ointment/cream is approved of the management of limited non-life threatening mucocutaneous genital HSV and HSV labialis in immunocompetent patients

True (early application within 24 hours of onset of prodrome is important)

12

Topical acyclovir may cause application site reactions including mild pain and burning, although placebo patients experienced similar adverse effects

True

13

Both topical acyclovir and penciclovir are classified as pregnancy category B

True

14

Topical cidofovir and foscarnet are classified as pregnancy category C

True (listed for the injectable version of the drug)

15

Topical acyclovir has limited use as monotherapy for genital HSV and HSV labialis and when medically tolerable, oral acyclovir is preferred over topical acyclovir for recurrent genital herpes given the greater efficacy in reducing the duration of viral shedding and time to crusting and healing of lesions

True

16

Penciclovir is only available in topical preparation because of poor oral availability

True (Famciclovir, the prodrug of penciclovir is available in oral form)

17

Penciclovir is selectively phosphorylated to the monophosphate from by viral thymidine kinase, and then further phosphorylated by human cellular kinases to the active triphosphate for, which inhibits viral replication by competitively binding to viral DNA polymerase

True

18

Even though acyclovir and penciclovir are qualitatively similar (with similar mode of action), penciclovir exhibits more efficient phosphorylation, a higher affinity to viral DNA polymerase, and increased stability of its active triphosphate form; thus leading to longer duration of activity

True

19

Penciclovir exhibits inhibitory activity against HSV-1, HSV-2, VZV and EBV

True (limited activity against CMV)

20

Penciclovir exhibits limited in vitro inhibitory activity against CMV

True

21

Penciclovir 1% cream is indicated for the treatment of recurrent HSV labialis in immunocompetent individuals 12 years and older

True (Penciclovir 1% cream should be applied at the earliest sign/symptom to all lesions every 2 hours/at least 6X daily for 4 days)

22

Penciclovir 1% cream reduced pain and viral shedding associated with HSV labialis independent of the timing of medication initiation

True

23

The most frequently reported adverse effect with topical Penciclovir is headache

True

24

Given the inconvenience or frequent application of topical Penciclovir (every 2 hours, or at least 6X daily), the expense and the reduction of symptoms of viral shedding by half a day; the clinical benefit of penciclovir over oral antiviral therapy is limited

True

25

If oral therapy is contraindicated or not available, topical Penciclovir is an alternative option to topical acyclovir for HSV labialis

True (although no head to head studies performed between these 2)

26

Cidofovir is an acyclic nucleotide that exhibits antiviral activity against a broad range of DNA viruses including HPV, human herpes viruses, and some pox viruses

True

27

IV Cidofovir is used to treat CMV retinitis in AIDS patients

True

28

No oral preparations of cidofovir are available, however cidofovir has been compounded in topical formulations for verruca vulgaris (HPV)

True (reported anecdotally or in small studies including children with recalcitrant disease)

29

Unlike acyclovir and penciclovir, cidofovir does not depend on thymidine kinase for its phosphorylation

True

30

Cidofovir acts as a competitive inhibitor for incorporation into viral DNA by viral DNA polymerase and blocks viral DNA synthesis

True

31

No oral preparations of cidofovir are available, however cidofovir has been compounded in topical formulations for condyloma acuminata/genital warts (HPV)

True (reported anecdotally or in small studies in immunocompetent patients)

32

No oral preparations of cidofovir are available, however cidofovir has been compounded in topical formulations for herpes simplex (HSV)

True (reported anecdotally or in small studies in AIDS patients with acyclovir-resistant HSV as well as immunocompetent patients)

33

No oral preparations of cidofovir are available, however cidofovir has been compounded in topical formulations for orf (parapox virus)

True (reported anecdotally or in small studies)

34

No oral preparations of cidofovir are available, however cidofovir has been compounded in topical formulations for molluscum contagiosum (pox virus)

True (reported anecdotally or in small studies in children and adults with HIV with recalcitrant disease)

35

Topical cidofovir may cause headaches, nausea, and pharyngitis, though with similar frequency to placebo

True

36

Application site pruritus, rash, pain, paraesthesia and ulceration are increased with higher concentrations of topical cidofovir

True

37

Foscarnet is a pyrophosphate (not a nucleoside) analog with activity against all herpes viruses

True

38

Foscarnet is used in the treatment of CMV infection in immunocompromised patients

True

39

Foscarnet is the oral drug of choice for acyclovir-resistant HSV

True (does not require activation by either cellular or viral enzymes)

40

Foscarnet does not require activation by either cellular or viral enzymes

True (drug of choice for acyclovir-resistant HSV)
NB. Acyclovir relies on viral thymidine kinase for phosphorylation and subsequent inhibition of viral replication

41

Foscarnet is not a nucleoside analog, and so nucleoside-resistant viral DNA polymerase are susceptible/sensitive to Foscarnet

True (foscarnet is a pyrophosphate analog instead)
NB. Acyclovir and Penciclovir are nucleoside analogs (Valacyclovir is the prodrug or acyclovir and Famciclovir is the prodrug of Penciclovir)

42

Idoxuridine is a thymidine analog which has limited efficacy in genital HSV, HSV labialis, and VZV infections

True (only available as an ophthalmic solution for the treatment of herpes keratitis)

43

Idoxuridine is only available as an ophthalmic solution for the treatment of herpes keratitis

True (has limited efficacy in genital HSV, HSV labialis, and VZV infections)

44

Imiquimod is a topical immunomodulating agent approved by the FDA for treatment of external genital and perianal warts/condylomata acuminata (HPV) for patients 12 years and older

True
5% cream once daily 3 X weekly application for up to 16 weeks
3.75% cream daily for 8 weeks

45

5% topical Imiquimod is a topical immunomodulating agent approved by the FDA for treatment of superficial small <2cm non-facial superficial BCC if surgery is inappropriate and patient follow up can be assured

True
5% cream once daily 5 days/week for 6-12 weeks

46

Imiquimod is a topical immunomodulating agent approved by the FDA for treatment of actinic keratoses on the face and scalp

True (poor efficacy for sites other than face and scalp + application more than 3X weekly for these non-scalp and non-facial sites are poorly tolerated)
5% cream twice weekly for 16 weeks to 25cm2 area
5% cream 3 X weekly for 4 weeks to 25cm2 area, to repeat course if patients failed to clear with first course (alternative regimen)
3.75% cream daily to full face/balding scalp for 2 week on/off/on regimen or 3 week on/off/on

47

Imiquimod is a non-nucleoside heterocyclic amine

True

48

Imiquimod is an activator of Toll-like receptor-7 (TLR-7) that induces a potent antiviral and antitumour effect in vivo by inducing secretion of a host of inflammatory cytokines such as TNF-alpha, interferons, interleukins

True

49

When assessing a superficial BCC site already treated with topical imiquimod, there is no way to ensure the tumour is fully eradicated without a biopsy

True (hence the indication to only use imiquimod in low risk tumours as a second line treatment I.e. Superficial subtype, non-facial locations, and small tumours <2cm)

50

Imiquimod-induced hypopigmented or hypertrophic scarring can mask residual tumour underneath the scar

True

51

Erythema and ulceration caused by imiquimod can be difficult to differentiate from the tumour

True

52

Imiquimod cream should be applied to clean skin prior to normal sleeping hours (bedtime), left in place for approximately 6-10 hours, then washed off with soap and water

True (occlusive dressings or wrappings are not recommended because of an increased risk of irritation)

53

Local skin reaction such as redness and burning are common in imiquimod application and may require a rest period of several days

True (rest periods should not extend treatment beyond 16 weeks)

54

Clearance of AKs is more common in imiquimod patients who developed intense erythema or other local reactions in treatment areas

True

55

Imiquimod is one of many treatment options available for patients with AK who are unable to tolerate other topical first line treatments including 5-FU

True

56

Imiquimod is a topical immunomodulating agent with some benefit for cutaneous warts although monotherapy has limited efficacy

True
Overnight application 5X weekly

57

Imiquimod monotherapy has limited efficacy on cutaneous warts due to suspected lack of penetrance and absorption of of imiquimod through common wart tissue, and combination of cytodestructive methods such as cryotherapy, salicylic acid, and occlusion Ma enhance the imiquimod efficacy

True

58

Imiquimod is not FDA approved for use in children under 12 years of age, but has be reported as an effective treatment (complete clearance) with BD application for 6 months

True

59

Imiquimod has been used in the treatment of molluscum contagiousum (pox virus)

True

60

Imiquimod is undergoing trial for the treatment of lentigo maligna melanoma

True

61

Topical imiquimod is well tolerated, it's the most frequent adverse reactions being local skin reactions with erythema, pruritus, ulceration and pain with no serious systemic effects

True

62

Interferon-gamma has an integral role in genital wart clearance and exhibits indirect antiviral activity with minimal systemic absorption

True (although Topical interferon-gamma preparations have not proved to be efficacious over placebo)

63

Bleomycin has antitumour activity

True

64

Bleomycin has antibacterial activity

True

65

Bleomycin has antiviral activity

True

66

Although the mechanism against HPV infection is unclear, Bleomycin acts during the M and G2 phases of the cell cycle by binding to DNA which lead to single-strand breakage

True (it is unlikely that Bleomycin binds specifically to HPV)

67

Bleomycin affects protein synthesis which may cause biochemical changes leading to apoptosis and necrosis of keratinocytes

True

68

Bleomycin has been associated with detectable plasma concentrations, but there are no reports of systemic toxicity to date

True

69

Intralesional Bleomycin has been used for the treatment of verruca vulgaris and has been shown to be more effective than cryotherapy

True (not FDA approved)

70

Intralesional Bleomycin is associated with significant localised adverse effects and its use should be limited

True

71

Intralesional Bleomycin should not be used in pregnant women

True

72

Intralesional Bleomycin should not be used in children

True

73

Intralesional Bleomycin should not be used in immunosuppressed patients

True

74

Intralesional Bleomycin should not be used in patients with possible vascular compromise

True (Raynaud's phenomenon is an uncommon adverse effect from Intralesional Bleomycin, and remains localised to only the digits that receive the injection)

75

The most common adverse effect of Intralesional Bleomycin is injection site pain

True (Techniques to minimise pain include pretreatment local anaesthesia, reconstitution with injectable anaesthetic without adrenaline instead of normal saline, ice packs or vibration analgesia) - ice water soaks for 10-15 mins BD for 4 days may reduce pain after the injection

76

Within 24-72 hours of Intralesional Bleomycin there may be erythema, swelling, and pain before a blackened eschar forms

True

77

Scarring is an uncommon adverse effect from Intralesional Bleomycin

True

78

Raynaud's phenomenon is an uncommon adverse effect from Intralesional Bleomycin, and remains localised to only the digits that receive the injection

True

79

Permanent loss of the nail plate is an uncommon adverse effect from Intralesional Bleomycin

True

80

Persistent nail dystrophy is an uncommon adverse effect from Intralesional Bleomycin

True

81

Flagellate hyperpigmentation is an uncommon adverse effect from Intralesional Bleomycin

True

82

Each individual wart lesion receives 0.1mL of 1U/mL Bleomycin in a 0.1% solution with normal saline and treatment is repeated every 2-3 weeks until resolution

True (no more than a total of 2mL of Bleomycin should be administered per treatment I.e. Approximately 10-20 warts)

83

No more than a total of 2mL of Bleomycin should be administered per treatment I.e. Approximately 10-20 warts

True

84

Podophyllin is a crude extract of cytotoxic material from the May apple plant used to treat condyloma acuminata (genital warts)

True

85

The most active ingredient and the cytodestructive agent in podophyllin is podophyllotoxin

True

86

The concentration of podophyllotoxin (the cytodestructive agent) in office-based podophyllin is not standardised, however the commercial product podofilox in a solution or gel has a stable concentration of 0.5% podophyllotoxin

True

87

Even though the concentration of podophyllotoxin in the commercial product podofilox is lower than that found in office-based podophyllin, podofilox does not contain the known mutagens quercetin or kaemperol and is safe to use on an outpatient basis

True

88

Podophyllotoxin (active cytodestructive agent on podophyllin) is an Antimitotic agent that arrests cells in metaphase by binding reversibly to tubulin

True

89

Even though podofilox (commercial proprietary product) reports greater safety issues especially in women of childbearing potential (no mutagens), office applied podophyllin used as monotherapy or in combination with other cytodestructive therapies can be especially efficacious in pedunculated and cauliflower anogenital condyloma

True

90

Podophyllin (office based formula) is contraindicated in pregnancy due to its mutagenic properties and must be used carefully in women of child bearing potential

True (birth defects, Fetal death and stillbirth has been reported, and appropriate pregnancy testing is recommended prior to use) - podofilox on the other hand is classified as pregnancy category C

91

Podofilox (commercial proprietary product without mutagens) is classified as pregnancy category C

True

92

The most common adverse effects from podophyllin/podofilox are inflammation, burning, erythema, and erosions

True

93

Trichloroacetic acid (TCAA) works through the destruction of tissue by causing non-specific hydrolysis of cellular proteins leading to inflammation and cell death

True (as the drug is non-specific in its effect on virus-infected cells, care must be taken when applying TCAA so that surrounding tissue is not destroyed)

94

As TCAA is non-specific in its effect on virus-infected cells, care must be taken when applying TCAA so that surrounding tissue is not destroyed

True (adequate application is achieved when the wart and surrounding area turn white)

95

TCAA is advantageous over podophyllin as it can be used in treating genital warts in pregnant patients

True

96

The major adverse effects following treatment with TCAA are local pain and ulceration

True

97

Cantharidin is a vesiculating agent derived from the 'blister beetle', also known as the Spanish fly

True

98

Cantharidin acts by interfering with mitochondria leading to epidermal cell death, acantholysis and clinical blister formation (no direct antiviral effect)

True

99

Cantharidin has no direct antiviral effect

True

100

Cantharidin is limited to topical treatment of verruca vulgaris with cure rates as high as 80% for common, plantar and periungual warts

True (solution applied directly to the wart with the wooden end of a cotton applicator or toothpick, and lesion occluded for 4-24 hours with adhesive tape; a blister usually forms within 6-48 hours and often heals within 1 week) - retreatment at 1-3 week intervals

101

The benefits of topical cantharidin on verruca vulgaris is that it is painless and there is no scarring

True

102

The major adverse effect of topical cantharidin is blister-associated pain

True

103

Less commonly, a ring wart (annular wart formed at the periphery of a resolving blister) is induced by cantharidin

True (less frequently also noted post cryotherapy)

104

Topical cantharidin has also been used for molluscum contagiousum in a similar fashion as for verruca vulgaris

True (generally without occlusion, except for large papules or persistent lesions)

105

Combination therapy using topical cantharidin and imiquimod for the treatment of molluscum contagiousum in children has been effective and well tolerated

True

106

Salicylic acid is a topical keratolytic agent that is a common component of OTC verruca vulgaris treatments

True (ranging in concentrations between 10% and 60%)

107

Salicylic acid is recommended for use in treatment of warts located on the hands and feet

True (for best results, soak the wart in warm water for 5 mins and remove the dead tissue it's an emery board or pumice stone, followed by application of salicylic acid and occlusion)

108

Among all local treatment for cutaneous non-genital warts in immunocompetent patients, the best available evidence supports the use of simple topical treatment containing salicylic acid

True

109

5-FU is a pyrimidine analog with cytotoxic effects that penetrates abnormal skin to a greater extent than normal skin

True

110

5-FU has demonstrated some degree of efficacy in the treatment of resistant genital condylomas/warts, verruca plana and verruca vulgaris

True (once weekly application is as effective as daily treatment, and with fewer adverse effects)
NB. FDA approval is for multiple AKs and superficial BCCs

111

Adverse effects from topical 5-FU include erythema, oedema, possible erosive dermatitis and mucositis

True

112

Sinecathechin is a FDA approved topical high grade green tea polyphenol extract for treatment of external genital and perianal warts

True

113

Sinecathechin contain epigallocathechin gallate which protects cells from oxidative damage, induces apoptosis, and inhibits telomerase activity

True

114

Adverse effects of sinecathechin include erythema, pruritus, ulceration, pain and oedema

True